Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review
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* Jordi Soler
* Lourdes Fañanás
* Mara Parellada
* Marie-Odile Krebs
* Guy A. Rouleau
* Mar Fatjó-Vilas

## Abstract

Scaffolding proteins represent an evolutionary solution to controlling the specificity of information transfer in intracellular networks. They are highly concentrated in complexes located in specific subcellular locations. One of these complexes is the postsynaptic density of the excitatory synapses. There, scaffolding proteins regulate various processes related to synaptic plasticity, such as glutamate receptor trafficking and signalling, and dendritic structure and function. Most scaffolding proteins can be grouped into 4 main families: discs large (DLG), discs-large-associated protein (DLGAP), Shank and Homer. Owing to the importance of scaffolding proteins in postsynaptic density architecture, it is not surprising that variants in the genes that code for these proteins have been associated with neuropsychiatric diagnoses, including schizophrenia and autism-spectrum disorders. Such evidence, together with the clinical, neurobiological and genetic overlap described between schizophrenia and autism-spectrum disorders, suggest that alteration of scaffolding protein dynamics could be part of the pathophysiology of both. However, despite the potential importance of scaffolding proteins in these psychiatric conditions, no systematic review has integrated the genetic and molecular data from studies conducted in the last decade. This review has the following goals: to systematically analyze the literature in which common and/or rare genetic variants (single nucleotide polymorphisms, single nucleotide variants and copy number variants) in the scaffolding family genes are associated with the risk for either schizophrenia or autism-spectrum disorders; to explore the implications of the reported genetic variants for gene expression and/or protein function; and to discuss the relationship of these genetic variants to the shared genetic, clinical and cognitive traits of schizophrenia and autism-spectrum disorders.

## Introduction

Schizophrenia and autism-spectrum disorders are neurodevelopmental psychiatric disorders that have a prevalence of approximately 1% and 2.5% worldwide, respectively,1,2 and have profound human and economic consequences.

Schizophrenia and autism-spectrum disorders were nosologically separated in the *Diagnostic and Statistical Manual Mental Disorders,* third edition (1980).3 However, evidence has been accumulating to suggest that they may partially overlap in their clinical, neurobiological, behavioural and cognitive features, and that they may have some common etiological roots.4 Regarding their clinical expression, some authors have proposed that the negative symptoms of schizophrenia can be construed more broadly as deficits in social communication and motivation, which are also found in people with autism-spectrum disorders.5 Similarly, the grossly disorganized or abnormal motor behaviour described in schizophrenia includes a number of signs and symptoms consistent with those of autism-spectrum disorders, such as repeated stereotyped movements, echolalia, unpredictable agitation and decreased interaction with or interest in one’s environment.5,6 The disorders also share some cognitive deficits7–9; in particular, deficits in social cognition have received much attention.10–15 As well, there are brain structural similarities between these disorders. For instance, lower grey matter volume in the limbic–striato–thalamic circuitry is common to schizophrenia and autism-spectrum disorders,16 and reduced volume and thickness of the insula have been found in patients with first-episode psychosis and in high-functioning patients with autism-spectrum disorders.17 Similar alterations to the white matter integrity of the left fronto-occipital fasciculus have recently been found in patients with schizophrenia and in patients with autism-spectrum disorders.18

In recent years, the field of molecular genetics has been uncovering evidence of an overlapping and complex polygenetic architecture for these disorders. Evidence suggests that studying pathways common to both may shed light on their pathophysiology and clinical heterogeneity.

Robust longitudinal and epidemiological studies have shown that 25% of people with childhood-onset schizophrenia have a history of a premorbid autism-spectrum disorder19; that the adult outcomes of children with atypical autism include psychotic disorders20; that autistic traits in infancy increase the risk for psychotic experiences later in life21; and that there is some co-occurrence of autism-spectrum disorders and psychotic disorders.22,23 This overlap is further supported by family studies, which have reported that the presence of one of these diagnoses in a first-degree relative increases the risk of the other.24–27 Similarly, schizophrenia is more common in parents of patients with autism than in parents of healthy controls.24

Twin studies have also recognized the important contribution of genetic factors to both schizophrenia and autism-spectrum disorders, with heritability estimates of *h**2* = 64%–80%28,29 and *h**2* = 64%–91%,30 respectively.

Over the last decade, molecular studies have contributed to our initial understanding of the complex genetic architecture of schizophrenia and autism-spectrum disorders, and later to identifying genes that are involved in both disorders. In this sense, it is currently accepted that an individual’s genetic risk of schizophrenia or an autism-spectrum disorder can be attributed to either many common variants with a frequency of > 1% (single nucleotide polymorphisms [SNPs]), each conferring a modest level of risk (odds ratio = 1.1–1.5); or rare mutations with a frequency of < 1% (single nucleotide variants [SNVs] and copy number variants [CNVs]) that are usually associated with a larger penetrance on the phenotype (odds ratio > 2).31,32

The most recent studies to examine genome-wide SNPs contributing to these disorders have estimated that genetic variation from SNPs accounts for 23% and 17% of the variance in risk of schizophrenia and autism-spectrum disorders, respectively.33 Based on the significant but small correlation between SNP heritability estimates in both disorders, the coheritability between them has been quantified at around 4%.33 In this regard, genome-wide association studies have identified several SNPs associated with schizophrenia and/or autism-spectrum disorders.34–37

Meanwhile, genome-wide and microarray-based comparative genomic hybridizations have found that the CNV burden is also increased in patients with schizophrenia or autism-spectrum disorders compared with healthy controls.38–41 For example, microduplications of 1q21.1 or 16p11.2 and deletions at 2p16.3, 15q11.2 or 22q11.21 have been reported in patients with schizophrenia and autism-spectrum disorders.42 De novo gene-disrupting SNVs have also been found to occur at higher rates in patients with autism-spectrum disorders than in controls.43–46 In schizophrenia, the initially reported increased rates of putatively functional mutations47,48 have not been replicated in 2 larger studies,49,50 but those later studies found that the enrichment of loss-of-function de novo mutations was relatively concentrated in genes that overlapped with those affected by de novo mutations in autism-spectrum disorders. In addition, an excess of de novo mutation was confirmed in an independent sample of patients with schizophrenia.51

With regard to the identification of specific genes involved in both schizophrenia and autism-spectrum disorders, findings from CNV and SNV studies have shown a notable consistency in some functionally enriched sets of genes. Genetic studies assessing common or rare variants show a certain convergence on reporting genes involved in glutamatergic synapse plasticity.49,52–55 A structure located in glutamatergic synapses that has been associated with both disorders is the postsynaptic density (PSD).50,56–61 For example, Bayés and colleagues found that mutations in 199 human PSD genes were involved in more than 200 diseases, half being nervous-system disorders.61 That study suggested that impairments in PSD proteins might underlie psychiatric disorders and their associated cognitive, behavioural and clinical phenotypes, but no systematic review based on this hypothesis has integrated the molecular data generated across studies in the last decade. Another example has been provided by Purcell and colleagues, who, after analyzing the exome sequences of 2536 patients with schizophrenia and 2543 controls, reported that SNVs were significantly more frequent in cases than controls, and that these SNVs were especially enriched in the activity-regulated cytoskeleton-associated (ARC) complex of PSD.50

### PSD proteins and pathophysiological hypotheses

The PSD is a specialized matrix located at the excitatory postsynaptic terminals with a dish-shaped aspect, a surface area of 0.07 μm2 and a thickness of 30 to 40 nm on electron microscopy (Fig. 1A).62 The PSD can also be described as a highly organized and dynamic macromolecular complex consisting of several hundred proteins that process, integrate and converge the excitatory glutamatergic synaptic signals on the nucleus. As a point of convergence for the glutamatergic signalling pathways with other neurotransmitter systems, the composition and regulation of the PSD is essential for ensuring normal synaptic neurotransmission and plasticity.63,64

![Fig. 1](http://jpn.ca/https://www.jpn.ca/content/jpn/43/4/223/F1.medium.gif)

[Fig. 1](http://jpn.ca/content/43/4/223/F1)

Fig. 1 
Image of the postsynaptic density (PSD) and scheme of the scaffolding proteins at the PSD that have been analyzed in the present review. (**A**) An electronic microscope image of a synapse; vesicles can be observed in the presynaptic neuron (asterisk). The electron-dense structure observed in the postsynaptic element is the PSD (arrowhead). Scale bar, 250 nm. Image retrieved under the Creative Commons Attribution License from Heupel et al. *Neural Devel* 2008, [https://doi.org/10.1186/1749-8104-3-25](https://doi.org/10.1186/1749-8104-3-25). (**B**) A scheme of the PSD (grey shading). Multimerization of Shank1 to 3 proteins generate a network that links numerous proteins to the postsynaptic receptors. Homer proteins, including Homer1b/c, Homer2 and Homer3, also act as adaptors and interact with several PSD proteins, such as type I-mGluRs. The DLGAP1 to 4 proteins interact with DLG proteins, including the DLG1/SAP-97, DLG2/PSD-93, DLG3/SAP-102 and DLG4/PSD-95, to coregulate different ion channels, such as the NMDAR and AMPAR. AMPAR = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; DLG = discs large; DLGAP = discs-large-associated protein; mGluR = metabotropic glutamate receptor; NMDAR = *N*-methyl-d-aspartate receptor; SAP = synapse-associated protein.

The PSD is enriched with different membrane components, such as glutamate receptors, tyrosine kinases, G protein–coupled receptors, ion channels or cell adhesion molecules, which are assembled by cytoplasmatic scaffolding proteins.65 Among the proteins that make up the PSD, studies have reported associations between genes coding for scaffolding proteins and both schizophrenia and autism-spectrum disorders, suggesting that variants in these genes might increase the risk of these disorders. For instance, recent studies have found that SNPs and CNVs in autism-spectrum disorders and schizophrenia are particularly concentrated in scaffolding genes and other PSD-related genes.66,67 Other studies have indicated changes in the expression of scaffolding genes in schizophrenia and autism-spectrum disorders compared with healthy controls.68,69 A recent study reported that gene-disrupting ultra-rare variants were more abundant in schizophrenia cases than in controls, and that these mutations were particularly enriched in scaffolding genes and other PSD genes.70

Scaffolding proteins can be defined as molecular circuit boards that can organize a wide variety of circuit relationships between signalling proteins. More specifically, the main function of scaffolding proteins is to bring together 2 or more proteins to facilitate their interaction and functions, linked to critical roles in cellular signalling. This is possible because scaffolding proteins are composed of several protein–protein interaction modules, most notably the PSD-95/discs large/zona occludens-1 (PDZ) and Src homology 3 (SH3) domains.71 Since scaffolding protein complexes are dynamic, they have the ability to change specific protein interactions to rapidly adapt to changing environmental requirements or diverse signalling cues.72 This versatility is related to their modularity, which allows for recombination of protein interaction domains to generate variability in signalling pathways. Such properties are seen as a simple evolutionary solution to controlling the specificity of information flow in intracellular networks, generating precise signalling behaviours.73

Owing to their dynamic configuration, postsynaptic scaffolding molecules not only establish the internal organization of the PSD, allowing neurons to respond efficiently to stimuli, but they also regulate processes related to synaptic plasticity, such as glutamate receptor trafficking and signalling, and dendritic structure and function,74,75 which critically determine the characteristics of excitatory synaptic transmission (Fig. 1B).

Disruption of scaffolding genes might alter the homeostasis of the PSD and contribute to the synaptic dysfunctions associated with schizophrenia and autism-spectrum disorders.76 However, despite the potential importance of scaffolding proteins in these psychiatric conditions, no systematic review has addressed the integration of genetic and molecular data generated across studies.

The nature and function of the different families of scaffolding proteins included in this review, and the characteristics of the genes encoding them, are shown in Figure 1 and briefly summarized below.

#### The discs large protein subfamily

The discs large (DLG) subfamily is a group of proteins in the membrane-associated guanylate kinase (MAGUK) family, and consists of DLG1, DLG2, DLG3 and DLG4. These proteins have 3 PDZ domains in their N-terminus, which allow them to interact with a variety of binding partners in the PSD, such as glutamatergic receptors, as well as other cytoplasmic scaffolding proteins. The DLG proteins control the transmission of extracellular signals to downstream signalling molecules of the PSD and regulate the localization of glutamatergic receptors *N*-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) at neuronal synapses and dendrites.77 Moreover, they regulate the trafficking and clustering of ionic channels and the excitability of the presynaptic terminals, affecting the amount of neurotransmitter released.78 Since their temporal and spatial expression differ, it is believed that DLG members complement each other in performing these functions from embryonic to adult stages.79

The *DLG1* gene (also known as SAP-97) maps on chromosome 3q29 and encodes the synapse-associated protein 97 (SAP-97 or DLG1), which is thought to play a role in synaptogenesis80 and glutamatergic receptor trafficking during development.77

The *DLG2* gene (also known as PSD-93) is located on chromosome 11q14.1. Different studies have suggested that the protein it encodes (PSD-93, DLG2) plays a role in the regulation of synaptic plasticity. The DLG2 protein interacts with the tyrosine kinase Fyn, which is involved in the phosphorylation-based regulation of NMDA receptors that is required for the induction of NMDA-receptor-dependent long-term potentiation.81

The *DLG3* gene (also known as SAP-102) is located on Xq13.1, and the protein it encodes (DLG3) is the first protein related to intellectual disability that has been directly linked to glutamate receptor signalling and trafficking.82 Later studies have replicated the association of this gene with intellectual disability,83,84 suggesting that DLG3 somehow modulates cognition. This is consistent with the observed embryonic expression of this protein and its role in the regulation of synaptic formation and plasticity during brain development.85

The *DLG4* gene is located on chromosome 17p13.1, and the protein it encodes (PSD-95, DLG4) is involved in the maturation of synapse formation and the NMDA receptor signalling pathway**.** It participates in the clustering and trafficking of NMDA and AMPA receptors in the PSD.63,79 Moreover, DLG4 interacts with the dopamine receptor D1 (DRD1) and the NMDA receptor, and regulates positive feedback between them.86 The degradation of DLG4 is regulated by other proteins that have also been associated with autism-spectrum disorders.87

#### The discs-large-associated protein family

The discs-large-associated protein (DLGAP) family is made up of 4 proteins encoded by different homonymous genes: *DLGAP1* (18p11), *DLGAP2* (8p23), *DLGAP3* (1p34), and *DLGAP4* (20q11). All proteins have 5 repeats of 14 amino acids in the middle region, followed by a proline-rich sequence and a C-terminal PDZ-binding motif that mediate interactions with other PSD proteins.88

Although the differential roles of each family member are unknown, all DLGAP proteins play an important role in organizing the postsynaptic signalling complex in glutamatergic synapses,89 and are especially involved in the stabilization of synaptic junctions and regulation of neurotransmission.90 In addition, DLGAP proteins clearly have a central role in the regulation of synaptic ion channels, including both NMDA and AMPA receptors.91

DLGAP2 (also known as SAPAP2 or GKAP) is the most studied of the proteins in this family. It interacts directly with DLG4 and Shank proteins to form a complex that plays critical roles in synaptic morphogenesis and function.90,92

It has been proposed that SAPAP proteins provide a link between the PSD-95 family of proteins and the actincytoskeleton through interactions with the Shank/ProSAP proteins, which in turn bind the actin-binding protein cortactin.93–97 Additionally, Shank/ProSAP binds to Homer, which interacts with metabotropic glutamate receptors.98 Therefore, in the current scaffolding model, PSD-95/SAPAP/Shank interactions play an important role in organizing the large postsynaptic signalling complex at glutamatergic synapses.96,97,99,100

#### The Shank protein family

Another PSD scaffolding protein group is the SH3 and multiple ankyrin repeat domains (Shank) family, which consists of 3 proteins encoded by different genes that are differently expressed in the brain97,101: *SHANK1* (19q13.33), *SHANK2* (11q13.3) and *SHANK3* (22q13.3). So far, it is unclear whether individual Shank family proteins fulfill unique physiologic functions, but the structural similarity between Shank forms has led to the observation that many interaction partners of Shank proteins in the synapse are recognized equally by all 3 family members.93

In this regard, Shank proteins crosslink Homer, DLGAP2 and DLG4 proteins in the PSD and participate in glutamatergic downstream signalling by assembling glutamate receptors with other scaffolding proteins, cytoskeleton factors and intracellular effectors.102 Multimerization of Shank1–3 proteins can generate a network in the PSD that links numerous proteins to the postsynaptic receptors. In addition, Shank proteins promote the formation, maturation and enlargement of dendritic spines.103

#### The Homer protein family

Homer proteins include 3 different members that are encoded by 3 different homonymous genes: *HOMER1* (5q14), *HOMER2* (15q25) and *HOMER3* (19p13). Homer proteins can also be classified into constitutively expressed isoforms (i.e., Homer1b/c, Homer2 and Homer3), which are bimodal proteins with an N-terminal domain that mediates the interaction with other PSD proteins, and a C-terminal coiled-coil domain that enables self-assembly, as well as short splice variants (Homer1a and Ania-3) that lack the C-terminal domain and cannot self-assemble.104 The various protein forms are differentially expressed over time and place.105

Homer proteins act as multimodal adaptors by interacting with several PSD proteins, such as type I metabotropic glutamate receptors (mGLuR1–5), Shank proteins or synaptic signalling molecules such as inositol 1,4,5-triphosphate receptors (IP3Rs), and binding them to the cytoskeleton.102 Homer proteins are also involved in glutamatergic synapses by regulating glutamatergic receptor trafficking, the function of plasma membrane ion channels and intracellular messenger systems.106 For these reasons, Homer proteins are important for cell signalling, cell excitability, synaptic neurotransmission and neuronal plasticity.107,108

### Objectives

The objectives of this review were as follows: to conduct a systematic review of the literature in which variations within the above-mentioned scaffolding genes are associated with either schizophrenia or autism-spectrum disorders, and to describe the degree of overlap between both diagnoses; to explore whether the reported genetic variants putatively associated with schizophrenia or autism-spectrum disorders are involved in changes of gene expression or protein functionality according to basic research data; and to consider the implications of the reported associations for the development of these disorders and their associated phenotypes.

## Methods

We conducted a systematic search of the PubMed, PsycINFO and Web of Science databases. The search terms were “Schizophrenia or autism” and “postsynaptic density proteins or PSD or scaffold* proteins” without date restrictions. Inclusion criteria were original articles that reported i) the association of genetic variants (SNPs, SNVs and CNVs) of the genes in the DLG protein subfamily or the DLGAP, Shank or Homer protein families with schizophrenia or autism-spectrum disorders; and ii) genetic variations in these genes and their functional consequences, based on animal-model or in vitro studies.

This search initially retrieved 366 articles. After evaluating whether they fulfilled the inclusion criteria, we excluded 261 articles. Another 25 studies and reviews that were relevant for the topic were found from cross-referencing and included in this review. The final pool of articles comprised 130 papers (Fig. 2).

![Fig. 2](http://jpn.ca/https://www.jpn.ca/content/jpn/43/4/223/F2.medium.gif)

[Fig. 2](http://jpn.ca/content/43/4/223/F2)

Fig. 2 
Flow diagram of the literature search. PSD = postsynaptic density.

## Results

Table 1 describes SNPs in scaffolding genes that have been associated with schizophrenia or autism-spectrum disorders. Table 2 describes SNVs, and Table 3 describes CNVs. Table 4 describes expression and functional information on scaffolding genes obtained from basic studies. Table 5 describes the SNPs, SNVs and CNVs of risk that are shared by both schizophrenia and autism-spectrum disorders.

View this table:
[Table 1](http://jpn.ca/content/43/4/223/T1)

Table 1 
Single nucleotide polymorphisms in scaffolding genes associated with schizophrenia, autism-spectrum disorders and other clinical phenotypes of interest

View this table:
[Table 2](http://jpn.ca/content/43/4/223/T2)

Table 2 
Single nucleotide variants in scaffolding genes associated with schizophrenia, autism-spectrum disorders and other clinical phenotypes of interest

View this table:
[Table 3](http://jpn.ca/content/43/4/223/T3)

Table 3 
Copy number variants in scaffolding genes associated with schizophrenia, autism-spectrum disorders and other clinical phenotypes of interest

View this table:
[Table 4](http://jpn.ca/content/43/4/223/T4)

Table 4 
Expression, animal model and pharmacological studies on the reviewed scaffolding genes

View this table:
[Table 5](http://jpn.ca/content/43/4/223/T5)

Table 5 
Summary of variants in scaffolding genes associated with both schizophrenia and autism-spectrum disorders

### DLG protein subfamily

#### Protein DLG1

Both SNPs in *DLG1* have been associated with schizophrenia (Table 1). An SNV has been associated with autism-spectrum disorders (Table 2). Furthermore, deletions of the chromosomal region 3q29 have been related to schizophrenia and autism-spectrum disorders (Table 3) and have been associated with impaired cognition and social dysfunction (Table 3).

Two studies reported reduced expression of *DLG1* in the prefrontal cortex of postmortem brain samples of patients with schizophrenia (Table 4). To the best of our knowledge, there are no expression studies in autism-spectrum disorders samples.

An animal-model study reported that glutamate-receptor NMDA antagonists upregulate *DLG1* mRNA expression in the cerebral cortex of mice (Table 4).

#### Protein DLG2

Different studies have identified rare mutations in the *DLG2* gene in schizophrenia and autism-spectrum disorders. While SNVs have been detected only in schizophrenia (Table 2), CNVs have been identified in both disorders (Table 3). Interestingly, a deletion identified in intron 6 of the gene in patients with autism-spectrum disorders157 partially overlaps with another deletion spanning from intron 2 to intron 6 in patients with schizophrenia.57

Although still not tested in patients with autism-spectrum disorders, alterations in mRNA and protein expression have been reported in the prefrontal cortex of postmortem brain samples of patients with schizophrenia (Table 4).

Animal-model studies seem to support the function of DLG2 as a regulator of synaptic plasticity; they have shown that *DLG2* mutant mice display cognitive abnormalities and long-term potentiation deficits (Table 4).

#### Protein DLG3

To our knowledge, only 1 genetic study has associated 6 intronic SNPs in *DLG3* with autism-spectrum disorders (Table 1), although their consequences for protein function or expression are unknown.

Despite conflicting results in postmortem brain expression studies, it seems that alterations in *DLG3* could underlie the neurobiology of schizophrenia. In this regard, both increased and decreased *DLG3* mRNA and protein expression have been reported in the thalamus of schizophrenia patients (Table 4).

Animal-model studies support a role for this gene in cognition; mice lacking *DLG3* exhibit impaired learning (Table 4).

#### Protein DLG4

For the *DLG4* gene, SNPs (Table 1) and CNVs (Table 3) have been identified only in patients with schizophrenia and with autism-spectrum disorders, respectively. In contrast, SNVs have been associated with both disorders (Table 2).

Among these variants, the SNP rs13331 (T/C), located at the 3′UTR of the gene, is especially interesting because the T allele was first associated with schizophrenia, and a posterior reporter gene assay indicated that subjects carrying this allele had decreased DLG4 protein activity. Based on these results, the authors suggested that reduced DLG4 activity or expression may increase the risk of developing schizophrenia.112

Alterations in mRNA and protein expression have been reported in postmortem brain samples of patients with schizophrenia (Table 4), although the direction of the results is inconsistent. Up to now, no expression studies have been performed in patients with autism-spectrum disorders.

Animal-model studies also appear to support an important role for DLG4 in regulating excitatory synapses and synaptic plasticity, while mutant mice also displayed clinical phenotypes related to schizophrenia and autism-spectrum disorders, such as impaired learning, abnormal communication, altered motor coordination or other abnormal behaviour (Table 4).

#### Summary

These findings suggest that mutations in DLG genes might increase the risk of developing schizophrenia and autism-spectrum disorders, as well as related cognitive deficits, by contributing to the disruption of glutamatergic synapses. Although the neurobiological mechanisms underlying these disruptions are still unknown, some pathways can be inferred. For instance, mutations affecting *DLG2* might modify the tyrosine phosphorylation-based regulation of NMDA receptors, altering NMDA-receptor-related signalling. Similarly, mutations in *DLG4* might dysregulate NMDA receptor activity, because this protein also anchors different protein tyrosine kinases.229 Other mechanisms might explain the association between *DLG4* and both schizophrenia and autism-spectrum disorders. It has been reported that DLG4 inhibits the interaction between dopamine receptor D1 and the NMDA receptor, preventing a reciprocal damaging overactivation of both receptors.86 This suggests that reduced expression or dysfunction of this protein might dysregulate glutamatergic and dopaminergic homeostasis. Finally, since DLG4 enhances the expression of NMDA receptor subunits NR2A and NR2B230 and the traffic of the NMDA receptor to synapses,231 diminished expression or alterations in protein function might also compromise NMDA-receptor-mediated signalling transduction.

### The DLGAP protein family

Some SNPs (Table 1) and SNVs (Table 2) in the *DLGAP1* gene and SNVs (Table 2) in the *DLGAP3* gene have been associated with schizophrenia. No studies have assessed the association between *DLGAP4* and schizophrenia or autism-spectrum disorders.

There is more evidence for an association between the *DLGAP2* gene and both disorders. The SNPs (Table 1), SNVs (Table 2) and CNVs (Table 3) in this gene have been associated with both schizophrenia and autism-spectrum disorders. Interestingly, some variants were coincident in both disorders (Table 1, Table 2 and Table 3).

On one hand, the SNP rs2906569 (A>G) in intron 1 and the missense SNP rs2301963 (C>A; P384Q) in exon 3 have been associated with both autism-spectrum disorders115 and schizophrenia.116 Although the functional significance of rs2906569 is difficult to infer, it could affect either the final protein function or the regulation of gene expression by altering different processes, such as splicing, translation regulation or mRNA polyadenylation.232 The missense variant rs2301963, in which CC homozygotes were overrepresented in patients with schizophrenia and patients with autism-spectrum disorders, could affect final protein activity according to bioinformatics analyses.115

On the other hand, 3 nonsynonymous exonic de novo variants (c.841C>G, c.2135C>T and c.2750C>T) have been identified in both schizophrenia116 and autism spectrum disorders.115 The c.841C>G and c.2750C>T mutations were predicted to damage protein function using PolyPhen-2 or Pmut.

Moreover, deletion of the chromosomic region 8p23.3 has been detected in patients with schizophrenia and patients with autism-spectrum disorders. This deletion and other CNVs spanning this gene have been found in patients with schizophrenia and patients with autism-spectrum disorders who have intellectual disability.40,161

To the best of our knowledge, there are no studies of the expression of *DLGAP2* in either autism-spectrum disorders or schizophrenia. Animal-model studies have suggested that alterations in this gene might lead to disadaptative social behaviour (Table 4).

Taken together, these findings suggest that disruptions of this gene might alter the function or expression of DLGAP2 and ultimately dysregulate its interplay with other PSD proteins, which could underlie the development of both schizophrenia and autism-spectrum disorders, as well as the manifestation of related clinical phenotypes, such as abnormal social behaviour. Interestingly, animal studies have found that DLGAP2 is vital for normal synaptic structure and function of the orbitofrontal cortex, a brain region that is implicated in the self-regulation of social-emotional behaviour.233 There is also evidence that the orbitofrontal cortex is disrupted in patients with autism, and animal studies have indicated that a lesion of the orbitofrontal cortex may cause aggressive behaviour.234

### The Shank protein family

#### Protein Shank1

Up to now, most of the SNVs in *SHANK1* have been associated with autism-spectrum disorders and not schizophrenia (Table 2). Deletions in *SHANK1* have also been associated with autism-spectrum disorders (Table 3), with some detected in patients with pronounced social dysfunction.

No expression studies have been carried out for either schizophrenia or autism-spectrum disorders, but animal-model studies seem to indicate that alterations in *SHANK1* could lead to impaired social skills (Table 4).

#### Protein Shank2

While SNVs in this gene have been identified in patients with schizophrenia and patients with autism-spectrum disorders (Table 2), CNVs have been found only in people with autismspectrum disorders, particularly with respect to intellectual disability or language delay (Table 3).

Among these mutations, the SNV (A1731S) detected in patients with schizophrenia is noteworthy. The authors of a study involving a functional assay in HEK293 cells reported that this variant has a significant effect on the F/G-actin ratio and concluded that diminished actin polymerization could lead to impairments in synapse formation and maintenance by reducing the presynaptic contacts.131

To the best of our knowledge, no expression studies have been performed for this gene. However, animal-model studies suggest that disruption of this gene could lead to the cognitive and social dysfunction associated with schizophrenia or autism-spectrum disorders by altering NMDA receptor function (Table 4).

#### Protein Shank3

There is accumulating evidence that *SHANK3* mutations contribute to the pathology of neurodevelopment disorders. Two SNVs in the *SHANK3* gene have been identified in patients with schizophrenia (Table 2), and different variants (SNPs, SNVs and CNVs) have been associated with autismspectrum disorders (Table 1, Table 2 and Table 3). Among them, the missense variant G1011V (g.49506159G>T) located in exon 21 has been identified in patients with schizophrenia and patients with autism-spectrum disorders (Table 2). Further studies are needed to test whether this variant has any consequence for the protein function.

The R1117X nonsense mutation (g.49484091C>T) has been identified in exon 21 of the *SHANK3* gene in patients with schizophrenia and intellectual disability. This amino acid change resulted in a truncated form of the Shank3 protein that lacked the Homer-binding site, causing its loss of function.46,135

The A198G (g.51117341C>G) identified in people with autism-spectrum disorders generated a frameshift mutation that introduced a premature STOP codon at position 1227, leading to a truncated form of Shank3 that also caused its loss of function. This mutation disrupted actin polymerization, the regulation of spine formation and the molecular organization of the PSD.136

Two frameshift mutations causing premature STOP codons (g.51117094C>G and g.51160615G>T) resulted in the loss of protein function by losing the C-terminal region of the protein, which is crucial for interactions with other PSD proteins.137

Regarding CNVs, different studies have identified deletions in the *SHANK3* gene in patients with schizophrenia and patients with autism-spectrum disorders with intellectual disability, developmental delay, language alterations or impaired social interaction (Table 3). Similarly, Phelan McDermid Syndrome (22q13.3 deletion syndrome), which includes deletion of the *SHANK3* gene, is characterized by neonatal hypotonia, global developmental delay, absence of speech, autistic behaviour and intellectual disability.235

Animal-model studies also appear to support a role for this gene in the cognitive and behavioural clinical phenotypes related to schizophrenia and autism-spectrum disorders. Shank3 mutant mice display reduced social interaction, affiliation behaviour, repetitive behaviour and communicative deficits (Table 4).

#### Summary

In summary, results for Shank proteins suggest that their disruption might underlie some of the cognitive and social dysfunction present in schizophrenia and autism-spectrum disorders. This is in line with the latest data showing that the prevalence of *SHANK3* mutations in people with autismspectrum disorders is 0.5% to 0.7%, and that a *SHANK3* mutation is present in approximately 2% of people with both an autism-spectrum disorder and intellectual disability.129,138,236 More specifically, from animal-model studies it has been suggested that these dysfunctions might be caused by alterations in the NMDA-receptor-related signalling pathway. There is evidence that *SHANK2* (−/−) mutant mice display abnormal NMDA receptor function and show alterations in behaviour and social skills.201 Interestingly, when mutant mice were stimulated with NMDA receptor agonists, NMDA receptor function was normalized and their social interactions improved.202 Regarding the pathophysiological mechanisms underlying the social deficits in *SHANK3* mutation, it has been reported that knockdown of the *SHANK3* gene in rat cortical cultures causes a loss of NMDA receptor function and alterations in its membrane trafficking through the disruption of the actin cytoskeleton.237 Furthermore, Arons and colleagues showed that the loss of function of the *SHANK3* gene resulted in reduced glutamatergic synaptic transmission, whereas overexpression of this gene increased the number and size of excitatory synapses and the expression levels of other PSD proteins, such as DLG4 and Homer1.204 Therefore, the behavioural and cognitive alterations present in patients carrying mutations in *SHANK* genes might be related to dysfunctions in NMDA-receptor-related glutamatergic signalling, which in turn might be caused by abnormalities in the interactions between Shank and other PSD proteins or anomalies in the actin polymerization processes.

#### The Homer protein family

Although 1 study reported a putative role for the *HOMER2* gene in schizophrenia (Table 1), it is principally the *HOMER1* gene that has been associated with schizophrenia and autism-spectrum disorders.

Three SNPs in *HOMER1* have been associated with schizophrenia (Table 1). Among them, rs4704560 has also been associated with the risk of developing psychotic symptoms in Parkinson disease (Table 1). In addition, 1 SNV and 1 CNV have been found in patients with schizophrenia (Table 2 and Table 3). As well, SNVs (Table 2) and CNVs (Table 3) have been detected in people with autism-spectrum disorders.

Expression studies have reported increases in Homer1a protein and decreases in Homer1b in the hippocampus of postmortem brain samples of schizophrenia (Table 4).

Animal-model studies suggest that *HOMER1* transcripts might control cognitive and behaviour functions (Table 4). It has also been suggested that mutations in *HOMER1* might increase the risk of developing schizophrenia by dysregulating NMDA receptors and their associated signalling pathway. Pharmacological studies have shown that the NMDR inhibitor phencyclidine (PCP) and the NMDA receptor antagonist ketamine increase *HOMER1* mRNA in rat prefrontal cortex and ventral striatum and nucleus accumbens, respectively. Other studies show that *HOMER1* mRNA and/or related protein expression levels are modified by psychotomimetic drugs and the antipsychotic haloperidol (Table 3).

#### Summary

Overall, although *HOMER1* has been associated with both schizophrenia and autism-spectrum disorders, genetic, expression and animal model studies do not provide conclusive results. This could be because different Homer1 isoforms have different functions. It has been suggested that the long isoform Homer1c is implicated in the regulation of working memory and sensorimotor function, whereas Homer1a could modulate the behavioural and emotional area.217 Additionally, some studies report that the balance between long and short Homer forms determines the normal functioning of the synaptic architecture and function and influences synaptic plasticity dynamics238; therefore, an alteration of this balance could dysregulate synaptic signalling, leading to neurochemical, structural and behavioural changes.217,218

## Discussion

Accumulating evidence supporting biological overlap between schizophrenia and autism-spectrum disorders has fuelled research into common underlying mechanisms to provide a better understanding of the etiology of these disorders, their diagnosis and treatment. One such mechanism involves the synaptic plasticity in which the PSD structure plays a key role. This review has summarized genetic variants in the main scaffolding genes of the PSD that have been associated with schizophrenia and/or autism-spectrum disorders to date. Moreover, evidence coming from genetic, brain expression and animal model studies suggests that genetic variants in scaffolding genes could contribute to the deregulation of the glutamate receptor signalling pathways of the PSD, which may be involved in the pathophysiology of schizophrenia and autism-spectrum disorders, and the development of related shared phenotypes, such as cognitive or social dysfunction.

Such a cross-disorder effect of scaffolding gene and protein dysregulation seems consistent with their role as a dynamic complex that regulates cell signalling pathways and determines the specificity of information flow in intracellular networks.72 Because scaffolding proteins coordinate the excitatory synaptic transmission and mediate functional changes at the synapse, thus regulating synaptic plasticity among other processes, 73 they can be seen as crucial pieces of the complex puzzle of synaptic homeostasis maintenance. The fact that common (SNPs) and rare (SNVs and CNVs) variants have been identified in scaffolding genes in both schizophrenia and autism-spectrum disorders is in agreement with the view that both kinds of variants complementarily and heterogeneously underlie the shared genetic susceptibility to these disorders (Table 5) by generating synaptic instability.

From the present review, it is possible to infer that patients with schizophrenia or autism-spectrum disorders primarily share CNVs that include the complete length of one or more genes. In this regard, CNVs in the PSD genes seem to increase the risk of developing either schizophrenia or autism-spectrum disorders. For instance, deletions of the chromosomal region 3q29, which includes the *DLG1* gene, have been related to both schizophrenia and autism-spectrum disorders.45,49 Taking into account the usually large effect size of rare variants on a phenotype, we should not be surprised that alterations in the number of copies (deletions or duplications) of these genes have an impact on PSD functioning and plasticity. In addition to being associated with specific disorders, these variants have been associated with certain phenotypes in these or other disorders, or even in healthy controls. Pocklington and colleagues showed that rare CNV burden may be relevant to cognitive dysfunction in patients with schizophrenia,239 and Stefansson and colleagues found that CNVs conferring risk of either schizophrenia or autism-spectrum disorders, including CNVs in the *DLG1* and *DLG2* genes, also affect cognitive function in healthy controls.240 Other studies have similarly detected that mutations in PSD genes, including some of the scaffolding genes reviewed here, such as *DLG3*83 or *SHANK3*,241 are present in patients with intellectual disability.

This review has also provided evidence that, although several SNPs and SNVs in the scaffolding genes have been associated with schizophrenia or autism-spectrum disorders, only a few have been reported in both: 2 SNPs and 3 SNVs in the *DLGAP2* gene and 1 SNV in the *SHANK3* gene (Table 5). Variants that occur in both diagnoses might be targets of special interest for our understanding of common pathophysiological mechanisms and shared clinical features. Although it is difficult to infer the functional significance of these variants, bioinformatic analyses have indicated that some of the *DLGAP2* gene variants (rs2301963, c.841C>G and c.2750C>T) might affect final protein function or expression. In relation to *SHANK3*, to our knowledge, there is no available information about the functionality of the missense SNV (G1011V) that has also been found associated with both disorders.

Nevertheless, the general lack of specificity observed here can be explained in terms of the pleiotropic nature of scaffolding genes. Variants in different scaffolding genes, either at the allelic or the gene level, may dysregulate the homeostasis of the PSD, which is finally expressed as features associated with different neurodevelopment disorders. In addition to this pleiotropy, the polygenic nature of psychiatric disorders and the polygenic nature of the intermediate molecular pathways known to underlie at least part of the autism-spectrum disorders/schizophrenia pathology (such as the proper functioning of the PSD) should also be considered. This directly links with additional genetic phenomena, such as gene–gene interactions. In recent years, the gene-pathways methodology has been developed to study whether different genes with similar functions are jointly associated with a single phenotype. So far, only a few studies have assessed the effect of common variance in scaffolding genes as a functional gene set or the epistatic effects of other related PSD functional gene sets on the risk of schizophrenia or autism-spectrum disorders. One recent study explored the enrichment of schizophrenia-associated ultra-rare variants and found a significant enrichment of disrupting ultrarare variants among genes defined as encoding interactors with DLG4 and ARC and NMDA receptors.70 Another study observed an enrichment of SNPs associated with autismspectrum disorders in gene sets related to synaptic structure and function, including genes related to scaffolding proteins, β-catenin nuclear pathways, glutamate receptor activity and adherents junctions.67 In addition, although not significant after correction, a nominal association between a PSD protein defined gene set (including ARC and NMDA receptor complexes) with schizophrenia has been reported.36 In all, the effect of common and rare variants in scaffolding genes on schizophrenia and autism-spectrum disorders reflects the complex and heterogeneous genetic architecture of these disorders, and further analyses of gene sets could facilitate the untangling of this complexity.

In addition to genetic data, expression and animal-model studies have indicated the importance of scaffolding genes in schizophrenia and autism-spectrum disorders. There is evidence that patients with schizophrenia or autism-spectrum disorders display deviations from normal scaffolding protein brain expression levels, supporting the hypothesis that the deregulation of these genes might underlie the neurobiology of both disorders. However, to our knowledge, there are no brain expression studies of the 2 genes (*DLGAP2* and *SHANK3*) in which overlapping variants that predispose individuals to schizophrenia and/or autismspectrum disorders were found.52,115,116,135,242 Further research is required to test whether these coincident genetic variants contribute to modifying protein expression levels. In contrast, studies with animal models have shown the importance of scaffolding genes in ensuring cognitive and social function. We have reviewed different studies in which mice with scaffolding protein mutations show schizophrenia and autistim-like phenotypes.184,205 The use of animal models is extremely useful for understanding how changes in the gene sequence can affect phenotypes. As an example of the potential importance of animal models, there are *SHANK3*-deficient mice in which synaptic deficits were reversed with insulin-like growth factor-1.206 In a recent pilot study, insulin-like growth factor-1 has been used to treat 9 children with autism, and preliminary results have shown a reduction in social deficits.243

### Limitations

Some limitations of this review should be acknowledged. First, since the reviewed association studies do not always include the same genetic regions or variants, coincident variants can be linked to shared genetic variability between schizophrenia and autism-spectrum disorders, but noncoincidence cannot be interpreted as a lack of it. Second, patients with low IQ scores are generally excluded from association studies. Since the scaffolding genes reviewed here seem to contribute to cognitive phenotypes, it is plausible to hypothesize that the effects of SNPs and SNVs in these genes were detected less often than they actually occur. Third, the relationship between the effect size associated with common and rare variants, the statistical power needed to detect these effects and the sample sizes in the studies reported in the different articles reviewed should be considered. The odds ratios associated with schizophrenia risk SNPs are typically about 1.10 to 1.50, whereas schizophrenia-associated CNVs confer a significantly increased risk of illness (odds ratios for several CNVs exceed 8).244 Therefore, rare variants can more easily create significant genome-wide associations than common variants.245

## Conclusion

Advances in genetic technologies, together with the assembly of large patient cohorts, have made it possible to identify some genes and biological pathways involved in both schizophrenia and autism-spectrum disorders. Among them, scaffolding genes implicated in the PSD have been repeatedly associated with schizophrenia and autism-spectrum disorders, pointing toward these genes’ common involvement in the neurobiology of these disorders and in some shared clinical phenotypes, such as cognitive and social impairment. This review summarizes evidence that many different variants could introduce numerous slight alterations in the PSD pathway, leading to its inappropriate development or insufficiently robust response to environmental insults.

## Acknowledgements

This study was supported by: the Network of European Funding for Neuroscience Research, ERA-NET NEURON (PiM2010ERN-00642); Instituto de Salud Carlos III through the project PI15/01420 (co-funded by European Regional Development Fund /European Social Fund, “Investing in your future”); and SAF 2015-71526-REDT; and Ajuts de Personal Investigador predoctoral en Formació (APIF) to J Soler, 2017-2018. Thanks to the Comissionat per a Universitats i Recerca del DIUE (2014SGR1636).

## Footnotes

*   **Competing interests:** M. Parellada reports personal fees from Fundación Orange, outside the submitted work. M.-O. Krebs reports personal fees or travel grant from Janssen and Otsuka-Lundbeck, outside the submitted work. No other competing interests declared.

*   **Contributors:** J. Soler and M. Fatjó-Vilas designed the study and acquired the data, which all authors analzyed. J. Soler and M. FatjóVilas wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

*   Received April 5, 2017.
*   Revision received October 18, 2017.
*   Accepted November 13, 2017.

## References

1.  McGrath J, Saha S, Chant D, et al.Schizophrenia: a concise overview of incidence, prevalence, and mortality.Epidemiol Rev 2008;30:67–76.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1093/epirev/mxn001&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18480098&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000260555900004&link_type=ISI) 

2.  Elsabbagh M, Divan G, Koh YJ, et al.Global prevalence of autism and other pervasive developmental disorders.Autism Res 2012;5:160–79.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/aur.239&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22495912&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000305072800003&link_type=ISI) 

3.  American Psychiatric Association (1980) Diagnostic and statistical manual of mental disorders III (APA, Washington (DC)).
    
    

4.  Stone WS, Iguchi L.Do apparent overlaps between schizophrenia and autistic spectrum disorders reflect superficial similarities or etiological commonalities?.N Am J Med Sci (Boston) 2011;4:124–33.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22563520&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

5.  Hommer RE, Swedo SE.Schizophrenia and autism-related disorders.Schizophr Bull 2015;41:313–4.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1093/schbul/sbu188&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25634913&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

6.  American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5) (APA, Arlington (VA)).
    
    

7.  Eack SM, Bahorik AL, McKnight SA, et al.Commonalities in social and non-social cognitive impairments in adults with autism spectrum disorder and schizophrenia.Schizophr Res 2013;148:24–8.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.schres.2013.05.013&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23768814&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

8.  Lai MC, Lombardo MV, Baron-Cohen S.Autism.Lancet 2014;383:896–910.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/S0140-6736(13)61539-1&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24074734&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000332399500030&link_type=ISI) 

9.  Green MF.Cognitive impairment and functional outcome in schizophrenia and bipolar disorder.J Clin Psychiatry 2006;67:36–42.
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000239988900007&link_type=ISI) 

10. Fett A-KJ, Viechtbauer W, Dominguez MD, et al.The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis.Neurosci Biobehav Rev 2011;35:573–88.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neubiorev.2010.07.001&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20620163&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000286639900017&link_type=ISI) 

11. Horan WP, Kern RS, Shokat-Fadai K, et al.Social cognitive skills training in schizophrenia: an initial efficacy study of stabilized outpatients.Schizophr Res 2009;107:47–54.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.schres.2008.09.006&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18930378&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000263151500006&link_type=ISI) 

12. Dalton KM, Nacewicz BM, Johnstone T, et al.Gaze fixation and the neural circuitry of face processing in autism.Nat Neurosci 2005;8:519–26.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nn1421&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15750588&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000228040400024&link_type=ISI) 

13. Spezio ML, Adolphs R, Hurley RSE, et al.Analysis of face gaze in autism using ‘Bubbles’.Neuropsychologia 2007;45:144–51.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neuropsychologia.2006.04.027&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=16824559&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000243439900012&link_type=ISI) 

14. Chung YS, Barch D, Strube M.A meta-analysis of mentalizing impairments in adults with schizophrenia and autism spectrum disorder.Schizophr Bull 2014;40:602–16.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1093/schbul/sbt048&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23686020&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

15. Bora E, Yucel M, Pantelis C.Theory of mind impairment in schizophrenia: meta-analysis.Schizophr Res 2009;109:1–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.schres.2008.12.020&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19195844&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000265516300001&link_type=ISI) 

16. Cheung C, Yu K, Fung G, et al.Autistic disorders and schizophrenia: related or remote? an anatomical likelihood estimation.PLoS One 2010;5:e12233
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1371/journal.pone.0012233&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20805880&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

17. Parellada M, et al.Insular pathology in young people with high-functioning autism and first-episode psychosis.Psychol Med 2017;47:2472–82.
    
    

18. Katz J, et al.Similar white matter but opposite grey matter changes in schizophrenia and high-functioning autism.Acta Psychiatr Scand 2016;134:31–9.
    
    

19. Rapoport J, Chavez A, Greenstein D, et al.Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited.J Am Acad Child Adolesc Psychiatry 2009;48:10–8.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1097/CHI.0b013e31818b1c63&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19218893&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000261894400003&link_type=ISI) 

20. Mouridsen SE, Rich B, Isager T, et al.Psychiatric disorders in individuals diagnosed with infantile autism as children: a case control study.J Psychiatr Pract 2008;14:5–12.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18212598&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

21. Bevan Jones R, Thapar A, Lewis G, Zammit S.The association between early autistic traits and psychotic experiences in adolescence.Schizophr Res 2012;135:164–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.schres.2011.11.037&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22245185&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

22. Sullivan S, Rai D, Golding J, et al.The association between autism spectrum disorder and psychotic experiences in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.J Am Acad Child Adolesc Psychiatry 2013;52:806–814.e2.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.jaac.2013.05.010&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23880491&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

23. Stahlberg O, Soderstrom H, Rastam M, et al.Bipolar disorder, schizophrenia, and other psychotic disorders in adults with childhood onset AD/HD and/or autism spectrum disorders.J Neural Transm 2004;111:891–902.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15206005&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000222514400010&link_type=ISI) 

24. Daniels JL, et al.Parental psychiatric disorders associated with autism spectrum disorders in the offspring.Pediatrics 2008;121:e1357–62.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTA6InBlZGlhdHJpY3MiO3M6NToicmVzaWQiO3M6MTE6IjEyMS81L2UxMzU3IjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

25. Mortensen PB, Pedersen MG, Pedersen CB.Psychiatric family history and schizophrenia risk in Denmark: Which mental disorders are relevant?.Psychol Med 2010;40:201–10.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1017/S0033291709990419&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19607751&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000274422600004&link_type=ISI) 

26. Larsson HJ, Eaton WW, Madsen KM, et al.Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status.Am J Epidemiol 2005;161:916–25.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1093/aje/kwi123&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15870155&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000228930000002&link_type=ISI) 

27. Sullivan PF, Magnusson C, Reichenberg A, et al.Family history of schizophrenia and bipolar disorder as risk factors for autism.Arch Gen Psychiatry 2012;69:1099–103.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1001/archgenpsychiatry.2012.730&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22752149&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000310689200002&link_type=ISI) 

28. Lichtenstein P, Yip BH, Björk C, et al.Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study.Lancet 2009;373:234–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/S0140-6736(09)60072-6&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19150704&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000262537500026&link_type=ISI) 

29. Sullivan PF, Kendler KS, Neale MC.Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies.Arch Gen Psychiatry 2003;60:1187–92.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1001/archpsyc.60.12.1187&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=14662550&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000187022200002&link_type=ISI) 

30. Tick B, Bolton P, Happé F, et al.Heritability of autism spectrum disorders: a meta-analysis of twin studies.J Child Psychol Psychiatry 2016;57:585–95.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1111/jcpp.12499&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=26709141&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

31. Bodmer W, Bonilla C.Common and rare variants in multifactorial susceptibility to common diseases.Nat Genet 2008;40:695–701.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng.f.136&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18509313&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000256212000007&link_type=ISI) 

32. Geschwind DH, Flint J.Genetics and genomics of psychiatric disease.Science 2015;349:1489–94.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEzOiIzNDkvNjI1NS8xNDg5IjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

33. Lee SH, Ripke S, Neale BM, et al.Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.Nat Genet 2013;45:984–94.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng.2711&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23933821&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

34. Purcell SM, Wray NR, Stone JL, et al.Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.Nature 2009;460:748–52.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature08185&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19571811&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000268670300041&link_type=ISI) 

35. Wang K, Zhang H, Ma D, et al.Common genetic variants on 5p14.1 associate with autism spectrum disorders.Nature 2009;459:528–33.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature07999&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19404256&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000266370500030&link_type=ISI) 

36. Ripke S, Neale BM, Corvin A, et al.Biological insights from 108 schizophrenia-associated genetic loci.Nature 2014;511:421–7.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature13595&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25056061&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000339335700037&link_type=ISI) 

37. Weiss LA, Arking DE, Daly MJ, et al.A genome-wide linkage and association scan reveals novel loci for autism.Nature 2009;461:802–8.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature08490&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19812673&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000270547500038&link_type=ISI) 

38. International Schizophrenia ConsortiumRare chromosomal deletions and duplications increase risk of schizophrenia.Nature 2008;455:237–41.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature07239&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18668038&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000259090800050&link_type=ISI) 

39. Xu B, Roos JL, Levy S, et al.Strong association of de novo copy number mutations with sporadic schizophrenia.Nat Genet 2008;40:880–5.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng.162&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18511947&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000257166500023&link_type=ISI) 

40. Guilmatre A, Dubourg C, Mosca AL, et al.Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation.Arch Gen Psychiatry 2009;66:947–56.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1001/archgenpsychiatry.2009.80&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19736351&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000269590900004&link_type=ISI) 

41. Poultney CS, Goldberg AP, Drapeau E, et al.Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder.Am J Hum Genet 2013;93:607–19.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.ajhg.2013.09.001&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24094742&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

42. Malhotra D, Sebat J.CNVs: harbingers of a rare variant revolution in psychiatric genetics.Cell 2012;148:1223–41.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.cell.2012.02.039&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22424231&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000301889500018&link_type=ISI) 

43. O’Roak BJ, Deriziotis P, Lee C, et al.Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.Nat Genet 2011;43:585–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng.835&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21572417&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

44. Neale BM, Kou Y, Liu L, et al.Patterns and rates of exonic de novo mutations in autism spectrum disorders.Nature 2012;485:242–5.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature11011&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22495311&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000303799800042&link_type=ISI) 

45. Sanders SJ, Murtha MT, Gupta AR, et al.De novo mutations revealed by whole-exome sequencing are strongly associated with autism.Nature 2012;485:237–41.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature10945&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22495306&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000303799800041&link_type=ISI) 

46. Awadalla P, Gauthier J, Myers RA, et al.Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.Am J Hum Genet 2010;87:316–24.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.ajhg.2010.07.019&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20797689&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000281923500001&link_type=ISI) 

47. Girard SL, Gauthier J, Noreau A, et al.Increased exonic de novo mutation rate in individuals with schizophrenia.Nat Genet 2011;43:860–3.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng.886&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21743468&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

48. Xu B, Roos JL, Dexheimer P, et al.Exome sequencing supports a de novo mutational paradigm for schizophrenia.Nat Genet 2011;43:864–8.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng.902&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21822266&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

49. Fromer M, Pocklington AJ, Kavanagh DH, et al.De novo mutations in schizophrenia implicate synaptic networks.Nature 2014;506:179–84.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature12929&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24463507&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000331107700029&link_type=ISI) 

50. Purcell SM, Moran JL, Fromer M, et al.A polygenic burden of rare disruptive mutations in schizophrenia.Nature 2014;506:185–90.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature12975&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24463508&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000331107700030&link_type=ISI) 

51. Girard SL, Dion PA, Bourassa CV, et al.Mutation burden of rare variants in schizophrenia candidate genes.PLoS One 2015;10:e0128988
    
    

52. Iossifov I, Ronemus M, Levy D, et al.De novo gene disruptions in children on the autistic spectrum.Neuron 2012;74:285–99.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neuron.2012.04.009&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22542183&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000303361800011&link_type=ISI) 

53. Kenny EM, Cormican P, Furlong S, et al.Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.Mol Psychiatry 2014;19:872–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/mp.2013.127&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24126926&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000340040200007&link_type=ISI) 

54. Leblond CS, Nava C, Polge A, et al.Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments.PLoS Genet 2014;10:e1004580
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1371/journal.pgen.1004580&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25188300&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

55. Krumm N, O’Roak BJ, Shendure J, et al.A de novo convergence of autism genetics and molecular neuroscience.Trends Neurosci 2014;37:95–105.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.tins.2013.11.005&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24387789&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000331687300005&link_type=ISI) 

56. Föcking M, Lopez LM, English JA, et al.Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia.Mol Psychiatry 2015;20:424–32.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/mp.2014.63&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25048004&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

57. Kirov G, Pocklington AJ, Holmans P, et al.De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia.Mol Psychiatry 2012;17:142–53.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/mp.2011.154&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22083728&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000299802400007&link_type=ISI) 

58. Chen J, Yu S, Fu Y, et al.Synaptic proteins and receptors defects in autism spectrum disorders.Front Cell Neurosci 2014;8:276
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.3389/fncel.2014.00276&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25309321&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

59. Iossifov I, O’Roak BJ, Sanders SJ, et al.The contribution of de novo coding mutations to autism spectrum disorder.Nature 2014;515:216–21.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature13908&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25363768&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000344631400039&link_type=ISI) 

60. Pinto D, Pagnamenta AT, Klei L, et al.Functional impact of global rare copy number variation in autism spectrum disorders.Nature 2010;466:368–72.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature09146&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20531469&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000279867100049&link_type=ISI) 

61. Bayés A, Van de Lagemaat LN, Collins MO, et al.Characterization of the proteome, diseases and evolution of the human postsynaptic density.Nat Neurosci 2011;14:19–21.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nn.2719&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21170055&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

62. Sheng M, Hoogenraad CC.The postsynaptic architecture of excitatory synapses: a more quantitative view.Annu Rev Biochem 2007;76:823–47.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1146/annurev.biochem.76.060805.160029&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17243894&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000249336800034&link_type=ISI) 

63. de Bartolomeis A, Latte G, Tomasetti C, et al.Glutamatergic postsynaptic density protein dysfunctions in synaptic plasticity and dendritic spines morphology: relevance to schizophrenia and other behavioral disorders pathophysiology, and implications for novel therapeutic approaches.Mol Neurobiol 2014;49:484–511.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1007/s12035-013-8534-3&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23999870&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

64. MacGillvary HD, Song Y, Raghavachari S, et al.Nanoscale scaffolding domains within the postsynaptic density concentrate synaptic AMPA receptors.Neuron 2013;78:615–22.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neuron.2013.03.009&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23719161&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000319491200006&link_type=ISI) 

65. Carlin RK, Grab DJ, Cohen RS, et al.Isolation and characterization of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities.J Cell Biol 1980;86:831–45.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNiIjtzOjU6InJlc2lkIjtzOjg6Ijg2LzMvODMxIjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

66. Marshall CR, Howrigan DP, Merico D, et al.Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects.Nat Genet 2016;49:27–35.
    
    

67. Autism Spectrum Disorders Working Group of the Psychiatric Genomics ConsortiumMeta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Mol Autism 2017;8:21
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/s13229-017-0137-9&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=28540026&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

68. Dracheva S, McGurk SR, Haroutunian V.mRNA expression of AMPA receptors and AMPA receptor binding proteins in the cerebral cortex of elderly schizophrenics.J Neurosci Res 2005;79:868–78.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/jnr.20423&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15696539&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

69. Ohnuma T, Kato H, Arai H, et al.Gene expression of PSD95 in prefrontal cortex and hippocampus in schizophrenia.Neuroreport 2000;11:3133–7.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1097/00001756-200009280-00019&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=11043537&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000089833500020&link_type=ISI) 

70. Genovese G, Fromer M, Stahl EA, et al.Increased burden of ultrarare protein-altering variants among 4,877 individuals with schizophrenia.Nat Neurosci 2016;19:1433–41.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nn.4402&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=27694994&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

71. Pawson T, Nash P.Assembly of cell regulatory systems through protein interaction domains.Science 2003;300:445–52.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEyOiIzMDAvNTYxOC80NDUiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

72. Garbett D, Bretscher A.The surprising dynamics of scaffolding proteins.Mol Biol Cell 2014;25:2315–9.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTE6Im1vbGJpb2xjZWxsIjtzOjU6InJlc2lkIjtzOjEwOiIyNS8xNi8yMzE1IjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

73. Good MC, Zalatan JG, Lim WA.Scaffold proteins: hubs for controlling the flow of cellular information.Science 2011;332:680–6.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEyOiIzMzIvNjAzMC82ODAiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

74. Sheng M, Kim E.The postsynaptic organization of synapses.Cold Spring Harb Perspect Biol 2011;3pii: a005678
    
    

75. Gao C, Tronson NC, Radulovic J.Modulation of behavior by scaffolding proteins of the post-synaptic density.Neurobiol Learn Mem 2013;105:3–12.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.nlm.2013.04.014&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23701866&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

76. Verpelli C, Schmeisser MJ, Sala C, et al.Scaffold proteins at the postsynaptic density.Adv Exp Med Biol 2012;970:29–61.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1007/978-3-7091-0932-8_2&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22351050&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

77. Howard MA, Elias GM, Elias LAB, et al.The role of SAP97 in synaptic glutamate receptor dynamics.Proc Natl Acad Sci U S A 2010;107:3805–10.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czoxMDoiMTA3LzgvMzgwNSI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

78. Montgomery JM, Zamorano PL, Garner CC.MAGUKs in synapse assembly and function: an emerging view.Cell Mol Life Sci 2004;61:911–29.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1007/s00018-003-3364-5&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15095012&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000220982200015&link_type=ISI) 

79. Oliva C, Escobedo P, Astorga C, et al.Role of the MAGUK protein family in synapse formation and function.Dev Neurobiol 2012;72:57–72.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/dneu.20949&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21739617&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

80. Poglia L, Muller D, Nikonenko I.Ultrastructural modifications of spine and synapse morphology by SAP97.Hippocampus 2011;21:990–8.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/hipo.20811&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20865734&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000294182200008&link_type=ISI) 

81. Sato Y, Tao Y-X, Su Q, et al.Post-synaptic density-93 mediates tyrosine-phosphorylation of the N-methyl-D-aspartate receptors.Neuroscience 2008;153:700–8.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neuroscience.2008.03.006&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18423999&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

82. Tarpey P, Parnau J, Blow M, et al.Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation.Am J Hum Genet 2004;75:318–24.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1086/422703&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15185169&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000222702000016&link_type=ISI) 

83. Zanni G, van Esch H, Bensalem A, et al.A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation.Neurogenetics 2010;11:251–5.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1007/s10048-009-0224-y&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19795139&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000276662300011&link_type=ISI) 

84. Philips AK, et al.X-exome sequencing in Finnish families with intellectual disability–four novel mutations and two novel syndromic phenotypes.Orphanet J Rare Dis 2014;9:49
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/1750-1172-9-49&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24721225&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

85. Murata Y, Constantine-Paton M.Postsynaptic density scaffold SAP102 regulates cortical synapse development through EphB and PAK signaling pathway.J Neurosci 2013;33:5040–52.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjEwOiIzMy8xMS81MDQwIjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

86. Zhang J, Xu TX, Hallett PJ, et al.PSD-95 uncouples dopamine-glutamate interaction in the D1/PSD-95/NMDA receptor complex.J Neurosci 2009;29:2948–60.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjk6IjI5LzkvMjk0OCI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

87. Tsai N-P, Wilkerson JR, Guo W, et al.Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95.Cell 2012;151:1581–94.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.cell.2012.11.040&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23260144&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000312890300021&link_type=ISI) 

88. Hirao K, Hata Y, Ide N, et al.A novel multiple PDZ domain-containing molecule interacting with N-methyl-D-aspartate receptors and neuronal cell adhesion proteins.J Biol Chem 1998;273:21105–10.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamJjIjtzOjU6InJlc2lkIjtzOjEyOiIyNzMvMzMvMjExMDUiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

89. Welch JM, Wang D, Feng G.Differential mRNA expression and protein localization of the SAP90/PSD-95-associated proteins ( SAPAPs) in the nervous system of the mouse.J Comp Neurol 2004;472:24–39.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/cne.20060&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15024750&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000220463400003&link_type=ISI) 

90. Takeuchi M, Hata Y, Hirao K, et al.SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density.J Biol Chem 1997;272:11943–51.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamJjIjtzOjU6InJlc2lkIjtzOjEyOiIyNzIvMTgvMTE5NDMiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

91. Rasmussen AH, Rasmussen HB, Silahtaroglu A.The DLGAP family: neuronal expression, function and role in brain disorders.Mol Brain 2017;10:43
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/s13041-017-0324-9&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=28870203&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

92. Ranta S, Zhang Y, Ross B, et al.Positional cloning and characterisation of the human DLGAP2 gene and its exclusion in progressive epilepsy with mental retardation.Eur J Hum Genet 2000;8:381–4.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/sj.ejhg.5200440&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=10854099&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

93. Boeckers TM, Winter C, Smalla KH, et al.Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family.Biochem Biophys Res Commun 1999;264:247–52.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1006/bbrc.1999.1489&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=10527873&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000083153500044&link_type=ISI) 

94. Du Y, Weed SA, Xiong WC, et al.Identification of a novel cortactin SH3 domain-binding protein and its localization to growth cones of cultured neurons.Mol Cell Biol 1998;18:5838–51.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoibWNiIjtzOjU6InJlc2lkIjtzOjEwOiIxOC8xMC81ODM4IjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

95. Naisbitt S, Kim E, Tu JC, et al.Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin.Neuron 1999;23:569–82.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/S0896-6273(00)80809-0&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=10433268&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000081701000020&link_type=ISI) 

96. Scannevin RH, Huganir RL.Postsynaptic organisation and regulation of excitatory synapses.Nat Rev Neurosci 2000;1:133–41.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/35039075&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=11252776&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000165764500016&link_type=ISI) 

97. Sheng M, Kim E.The Shank family of scaffold proteins.J Cell Sci 2000;113:1851–6.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToiam9jZXMiO3M6NToicmVzaWQiO3M6MTE6IjExMy8xMS8xODUxIjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

98. Tu JC, Xiao B, Naisbitt S, et al.Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins.Neuron 1999;23:583–92.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/S0896-6273(00)80810-7&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=10433269&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000081701000021&link_type=ISI) 

99. Kennedy MB.Signal-processing machines at the postsynaptic density.Science 2000;290:750–4.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEyOiIyOTAvNTQ5Mi83NTAiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

100.McGee AW, Bredt DS.Assembly and plasticity of the glutamatergic postsynaptic specialization.Curr Opin Neurobiol 2003;13:111–8.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/S0959-4388(03)00008-4&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=12593989&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000181362000014&link_type=ISI) 

101.Lim S, Naisbitt S, Yoon J, et al.Characterization of the Shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development.J Biol Chem 1999;274:29510–8.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamJjIjtzOjU6InJlc2lkIjtzOjEyOiIyNzQvNDEvMjk1MTAiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

102.Hayashi MK, Tang C, Verpelli C, et al.The postsynaptic density proteins Homer and Shank form a polymeric network structure.Cell 2009;137:159–71.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.cell.2009.01.050&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19345194&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000264813300022&link_type=ISI) 

103.Roussignol G, Ango F, Romorini S, et al.Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons.J Neurosci 2005;25:3560–70.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjEwOiIyNS8xNC8zNTYwIjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

104.Shiraishi-Yamaguchi Y, Furuichi T.The Homer family proteins.Genome Biol 2007;8:206
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/gb-2007-8-2-206&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17316461&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

105.Foa L, Gasperini R.Developmental roles for Homer: more than just a pretty scaffold.J Neurochem 2009;108:1–10.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19046353&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000261441500001&link_type=ISI) 

106.Thomas U.Modulation of synaptic signalling complexes by Homer proteins.J Neurochem 2002;81:407–13.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1046/j.1471-4159.2002.00869.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=12065649&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000175356500001&link_type=ISI) 

107.de Bartolomeis A, Aloj L, Ambesi-Impiombato A, et al.Acute administration of antipsychotics modulates Homer striatal gene expression differentially.Brain Res Mol Brain Res 2002;98:124–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/S0169-328X(01)00327-8&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=11834303&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

108.Hennou S, Kato A, Schneider EM, et al.Homer-1a/Vesl-1S enhances hippocampal synaptic transmission.Eur J Neurosci 2003;18:811–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1046/j.1460-9568.2003.02812.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=12925007&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000185069200009&link_type=ISI) 

109.Sato J, Shimazu D, Yamamoto N, et al.An association analysis of synapse-associated protein 97 (SAP97) gene in schizophrenia.J Neural Transm 2008;115:1355–65.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18665322&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

110.Uezato A, Kimura-Sato J, Yamamoto N, et al.Further evidence for a male-selective genetic association of synapse-associated protein 97 (SAP97) gene with schizophrenia.Behav Brain Funct 2012;8:2
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22225629&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

111.Kantojärvi K, Kotala I, Rehnström K, et al.Fine mapping of Xq11.1-q21.33 and mutation screening of RPS6KA6, ZNF711, ACSL4, DLG3, and IL1RAPL2 for autism spectrum disorders (ASD).Autism Res 2011;4:228–33.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/aur.187&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21384559&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000291908400007&link_type=ISI) 

112.Cheng M-C, Lu CL, Luu SU, et al.Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.PLoS One 2010;5:e15107
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1371/journal.pone.0015107&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21151988&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

113.Balan S, Yamada K, Hattori E, et al.Population-specific haplotype association of the postsynaptic density gene DLG4 with schizophrenia, in family-based association studies.PLoS One 2013;8:e70302
    
    

114.Li J-M, Lu CL, Cheng MC, et al.Genetic analysis of the DLGAP1 gene as a candidate gene for schizophrenia.Psychiatry Res 2013;205:13–7.
    
    

115.Chien WH, Gau SSF, Liao HM, et al.Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders.Mol Autism 2013;4:26
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/2040-2392-4-26&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23915500&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

116.Li J-M, Lu CL, Cheng MC, et al.Role of the DLGAP2 gene encoding the SAP90/PSD-95-associated protein 2 in schizophrenia.PLoS One 2014;9:e85373
    
    

117.Wu K, Hanna GL, Easter P, et al.Glutamate system genes and brain volume alterations in pediatric obsessive-compulsive disorder: a preliminary study.Psychiatry Res 2013;211:214–20.
    
    

118.Shao S, Xu S, Yang J, et al.A commonly carried genetic variant, rs9616915, in SHANK3 gene is associated with a reduced risk of autism spectrum disorder: replication in a Chinese population.Mol Biol Rep 2014;41:1591–5.
    
    

119.Mashayekhi F, Mizban N, Bidabadi E, et al.The association of SHANK3 gene polymorphism and autism.Minerva Pediatr 2016epub ahead of print
    
    

120.Sykes NH, Toma C, Wilson N, et al.Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection.Eur J Hum Genet 2009;17:1347–53.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ejhg.2009.47&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19384346&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000270101600017&link_type=ISI) 

121.Qin J, Jia M, Wang L, et al.Association study of SHANK3 gene polymorphisms with autism in Chinese Han population.BMC Med Genet 2009;10:61
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19566951&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

122.Spellmann I, Rujescu D, Musil R, et al.Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients.J Psychiatr Res 2011;45:234–41.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20598711&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

123.Zhao Z, Webb BT, Jia P, et al.Association study of 167 candidate genes for schizophrenia selected by a multi-domain evidence-based prioritization algorithm and neurodevelopmental hypothesis.PLoS One 2013;8:e67776
    
    

124.De Luca V, Annesi G, De Marco EV, et al.HOMER1 promoter analysis in Parkinson’s disease: association study with psychotic symptoms.Neuropsychobiology 2009;59:239–45.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19648775&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

125.Strauss J, McGregor S, Freeman N, et al.Association study of early-immediate genes in childhood-onset mood disorders and suicide attempt.Psychiatry Res 2012;197:49–54.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22460132&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

126.Gilks WP, Allott EH, Donohoe G, et al.Replicated genetic evidence supports a role for HOMER2 in schizophrenia.Neurosci Lett 2010;468:229–33.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19914345&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

127.Xing J, Kimura H, Wang C, et al.Resequencing and association analysis of six PSD-95-related genes as possible susceptibility genes for schizophrenia and autism spectrum disorders.Sci Rep 2016;6:27491
    
    

128.Li J-M, Lu CL, Cheng MC, et al.Exonic resequencing of the DLGAP3 gene as a candidate gene for schizophrenia.Psychiatry Res 2013;208:84–7.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.psychres.2012.12.015&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23414653&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

129.Leblond CS, Nava C, Polge A, et al.Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments.PLoS Genet 2014;10:e1004580
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1371/journal.pgen.1004580&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25188300&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

130.Sato D, Lionel AC, Leblond CS, et al.SHANK1 deletions in males with autism spectrum disorder.Am J Hum Genet 2012;90:879–87.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.ajhg.2012.03.017&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22503632&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

131.Peykov S, Berkel S, Schoen M, et al.Identification and functional characterization of rare SHANK2 variants in schizophrenia.Mol Psychiatry 2015;20:1489–98.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/mp.2014.172&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25560758&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

132.Homann OR, Misura K, Lamas E, et al.Whole-genome sequencing in multiplex families with psychoses reveals mutations in the SHANK2 and SMARCA1 genes segregating with illness.Mol Psychiatry 2016;21:1690–5.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/mp.2016.24&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=27001614&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

133.Berkel S, et al.Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation.Nat Genet 2010;42:489–91.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng.589&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20473310&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000278081500011&link_type=ISI) 

134.Leblond CS, Marshall CR, Weiss B, et al.Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.PLoS Genet 2012;8:e1002521
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1371/journal.pgen.1002521&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22346768&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

135.Gauthier J, Champagne N, Lafrenière RG, et al.De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia.Proc Natl Acad Sci U S A 2010;107:7863–8.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czoxMToiMTA3LzE3Lzc4NjMiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

136.Durand CM, Betancur C, Boeckers TM, et al.Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.Nat Genet 2007;39:25–7.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng1933&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17173049&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000243136500013&link_type=ISI) 

137.Boccuto L, Lauri M, Sarasua SM, et al.Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders.Eur J Hum Genet 2013;21:310–6.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ejhg.2012.175&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22892527&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

138.Soorya L, Kolevzon A, Zweifach J, et al.Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency.Mol Autism 2013;4:18
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/2040-2392-4-18&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23758760&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

139.Gauthier J, Spiegelman D, Piton A, et al.Novel de novo SHANK3 mutation in autistic patients.Am J Med Genet B Neuropsychiatr Genet 2009;150B:421–4.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/ajmg.b.30822&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18615476&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

140.Durand CM, Perroy J, Loll F, et al.SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism.Mol Psychiatry 2012;17:71–84.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/mp.2011.57&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21606927&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000299014000012&link_type=ISI) 

141.Moessner R, Marshall CR, Sutcliffe JS, et al.Contribution of SHANK3 mutations to autism spectrum disorder.Am J Hum Genet 2007;81:1289–97.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1086/522590&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17999366&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000251098800015&link_type=ISI) 

142.Waga C, Okamoto N, Ondo Y, et al.Novel variants of the SHANK3 gene in Japanese autistic patients with severe delayed speech development.Psychiatr Genet 2011;21:208–11.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1097/YPG.0b013e328341e069&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21378602&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

143.Schaaf CP, Sabo A, Sakai Y, et al.Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.Hum Mol Genet 2011;20:3366–75.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1093/hmg/ddr243&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21624971&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000293907500004&link_type=ISI) 

144.Kelleher RJ, Geigenmüller U, Hovhannisyan H, et al.High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.PLoS One 2012;7:e35003
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1371/journal.pone.0035003&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22558107&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

145.Cochoy DM, Kolevzon A, Kajiwara Y, et al.Phenotypic and functional analysis of SHANK3 stop mutations identified in individuals with ASD and/or ID.Mol Autism 2015;6:23
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/s13229-015-0020-5&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=26045941&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

146.Norton N, Williams HJ, Williams NM, et al.Mutation screening of the Homer gene family and association analysis in schizophrenia.Am J Med Genet B Neuropsychiatr Genet 2003;120B:18–21.
    
    

147.Pinto D, Delaby E, Meirco D, et al.Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.Am J Hum Genet 2014;94:677–94.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.ajhg.2014.03.018&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24768552&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

148.Levinson DF, Duan J, Oh S, et al.Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications.Am J Psychiatry 2011;168:302–16.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1176/appi.ajp.2010.10060876&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21285140&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000287916900014&link_type=ISI) 

149.Mulle JG, Dodd AF, McGrath JA, et al.Microdeletions of 3q29 confer high risk for schizophrenia.Am J Hum Genet 2010;87:229–36.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.ajhg.2010.07.013&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20691406&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

150.Magri C, Sacchetti E, Traversa M, et al.New copy number variations in schizophrenia.PLoS One 2010;5:e13422
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1371/journal.pone.0013422&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20967226&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

151.Szatkiewicz JP, O’Dushlaine C, Chen G, et al.Copy number variation in schizophrenia in Sweden.Mol Psychiatry 2014;19:762–73.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/mp.2014.40&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24776740&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000338185300005&link_type=ISI) 

152.Quintero-Rivera F, Sharifi-Hannauer P, Martinez-Agosto JA.Autistic and psychiatric findings associated with the 3q29 microdeletion syndrome: case report and review.Am J Med Genet A 2010;152A:2459–67.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/ajmg.a.33573&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20830797&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

153.Levy D, Ronemus M, Yamrom B, et al.Rare de novo and transmitted copy-number variation in autistic spectrum disorders.Neuron 2011;70:886–97.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neuron.2011.05.015&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21658582&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000291843500009&link_type=ISI) 

154.Willatt L, Cox J, Barber J, et al.3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome.Am J Hum Genet 2005;77:154–60.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1086/431653&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15918153&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000229794500016&link_type=ISI) 

155.Ballif BC, Theisen A, Coppinger J, et al.Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication.Mol Cytogenet 2008;1:8
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/1755-8166-1-8&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18471269&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

156.Sagar A, Bishop JR, Tessman DC, et al.Co-occurrence of autism, childhood psychosis, and intellectual disability associated with a de novo 3q29 microdeletion.Am J Med Genet A 2013;161A:845–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/ajmg.a.35754&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23443968&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

157.Cuscó I, Medrano A, Gener B, et al.Autism-specific copy number variants further implicate the phosphatidylinositol signaling pathway and the glutamatergic synapse in the etiology of the disorder.Hum Mol Genet 2009;18:1795–804.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1093/hmg/ddp092&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19246517&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000265525400006&link_type=ISI) 

158.Walsh T, McClellan JM, McCarthy SE, et al.Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia.Science 2008;320:539–43.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEyOiIzMjAvNTg3NS81MzkiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

159.Egger G, Roetzer KM, Noor A, et al.Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.Neurogenetics 2014;15:117–27.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1007/s10048-014-0394-0&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24643514&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

160.Sanders SJ, Ercan-Sencicek AG, Hus V, et al.Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism.Neuron 2011;70:863–85.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neuron.2011.05.002&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21658581&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000291843500008&link_type=ISI) 

161.Chien WH, Gau SS, Wu YY, et al.Identification and molecular characterization of two novel chromosomal deletions associated with autism.Clin Genet 2010;78:449–56.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1111/j.1399-0004.2010.01395.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20236125&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

162.Szatmari P, Paterson AD, Zwaigenbaum L, et al.Mapping autism risk loci using genetic linkage and chromosomal rearrangements.Nat Genet 2007;39:319–28.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng1985&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17322880&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000244480000013&link_type=ISI) 

163.Costain G, Lionel AC, Merico D, et al.Pathogenic rare copy number variants in community-based schizophrenia suggest a potential role for clinical microarrays.Hum Mol Genet 2013;22:4485–501.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1093/hmg/ddt297&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23813976&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000326675300004&link_type=ISI) 

164.Marshall CR, Noor A, Vincent JB, et al.Structural variation of chromosomes in autism spectrum disorder.Am J Hum Genet 2008;82:477–88.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.ajhg.2007.12.009&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18252227&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000253223900019&link_type=ISI) 

165.Ozgen HM, van Daalen E, Bolton PF, et al.Copy number changes of the microcephalin 1 gene (MCPH1) in patients with autism spectrum disorders.Clin Genet 2009;76:348–56.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1111/j.1399-0004.2009.01254.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19793310&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

166.Prasad A, Merico D, Thiruvahindrapuram B, et al.A discovery resource of rare copy number variations in individuals with autism spectrum disorder.G3 (Bethesda) 2012;2:1665–85.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1534/g3.112.004689&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23275889&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

167.Gai X, Xie HM, Perin JC, et al.Rare structural variation of synapse and neurotransmission genes in autism.Mol Psychiatry 2012;17:402–11.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/mp.2011.10&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21358714&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000302173900007&link_type=ISI) 

168.Nemirovsky SI, Córdoba M, Zaiat JJ, et al.Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder.PLoS One 2015;10:e0116358
    
    

169.Yuen RKC, Thiruvahindrapuram B, Merico D, et al.Whole-genome sequencing of quartet families with autism spectrum disorder.Nat Med 2015;21:185–91.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nm.3792&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25621899&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

170.Failla P, Romano C, Alberti A, et al.Schizophrenia in a patient with subtelomeric duplication of chromosome 22q.Clin Genet 2007;71:599–601.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1111/j.1399-0004.2007.00819.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17539913&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000246918000017&link_type=ISI) 

171.Crespi B, Stead P, Elliot M.Evolution in health and medicine Sackler colloquium: comparative genomics of autism and schizophrenia.Proc Natl Acad Sci U S A 2010;107Suppl1736–41.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czoxNjoiMTA3L3N1cHBsXzEvMTczNiI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

172.Sebat J, Lakshmi B, Malhotra D, et al.Strong association of de novo copy number mutations with autism.Science 2007;316:445–9.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEyOiIzMTYvNTgyMy80NDUiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

173.Wang L-S, Hranilovic D, Wang K, et al.Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia.BMC Med Genet 2010;11:134
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20858243&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

174.Bonaglia MC, Giorda R, Mani E, et al.Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome.J Med Genet 2006;43:822–8.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToiam1lZGdlbmV0IjtzOjU6InJlc2lkIjtzOjk6IjQzLzEwLzgyMiI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

175.Toyooka K, Iritani S, Makifuchi T, et al.Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia.J Neurochem 2002;83:797–806.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1046/j.1471-4159.2002.01181.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=12421351&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000179046200006&link_type=ISI) 

176.Hiraoka S, Kajii Y, Kuroda Y, et al.The development- and phencyclidine-regulated induction of synapse-associated protein-97 gene in the rat neocortex.Eur Neuropsychopharmacol 2010;20:176–86.
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19836928&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

177.Kristiansen LV, Beneyto M, Haroutunian V, et al.Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia.Mol Psychiatry 2006;11:737–47.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/sj.mp.4001844&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=16702973&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000239309800006&link_type=ISI) 

178.Carlisle HJ, Fink AE, Grant SGN, et al.Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity.J Physiol 2008;586:5885–900.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1113/jphysiol.2008.163469&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18936077&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

179.Nithianantharajah J.Synaptic scaffold evolution generated components of vertebrate cognitive complexity.Nat Neurosci 2013;16:16–24.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nn.3276&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23201973&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

180.McGee AW, Topinka JR, Hashimoto K, et al.PSD-93 knock-out mice reveal that neuronal MAGUKs are not required for development or function of parallel fiber synapses in cerebellum.J Neurosci 2001;21:3085–91.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjk6IjIxLzkvMzA4NSI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

181.Clinton SM, Haroutunian V, Davis KL, et al.Altered transcript expression of NMDA receptor-associated postsynaptic proteins in the thalamus of subjects with schizophrenia.Am J Psychiatry 2003;160:1100–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1176/appi.ajp.160.6.1100&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=12777268&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000183240800013&link_type=ISI) 

182.Clinton SM, Meador-Woodruff JH.Abnormalities of the NMDA receptor and associated intracellular molecules in the thalamus in schizophrenia and bipolar disorder.Neuropsychopharmacology 2004;29:1353–62.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/sj.npp.1300451&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15054476&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000222110700014&link_type=ISI) 

183.Cuthbert PC, Stanford LE, Coba MP, et al.Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies.J Neurosci 2007;27:2673–82.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjEwOiIyNy8xMC8yNjczIjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

184.Feyder M, Karlsson RM, Mathur P, et al.Association of mouse Dlg4 (PSD-95) gene deletion and human DLG4 gene variation with phenotypes relevant to autism spectrum disorders and Williams’ syndrome.Am J Psychiatry 2010;167:1508–17.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1176/appi.ajp.2010.10040484&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20952458&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000284937700015&link_type=ISI) 

185.Clinton SM, Haroutunian V, Meador-Woodruff JH.Up-regulation of NMDA receptor subunit and post-synaptic density protein expression in the thalamus of elderly patients with schizophrenia.J Neurochem 2006;98:1114–25.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1111/j.1471-4159.2006.03954.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=16762023&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

186.Dracheva S, Marras SA, Elhakem SL, et al.N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia.Am J Psychiatry 2001;158:1400–10.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1176/appi.ajp.158.9.1400&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=11532724&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000170769900008&link_type=ISI) 

187.Funk AJ, Mielnik CA, Koene R, et al.Postsynaptic density-95 isoform abnormalities in schizophrenia.Schizophr Bull 2017;45:sbw173
    
    

188.Toro C, Deakin JFW.NMDA receptor subunit NRI and postsynaptic protein PSD-95 in hippocampus and orbitofrontal cortex in schizophrenia and mood disorder.Schizophr Res 2005;80:323–30.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.schres.2005.07.003&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=16140506&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000234757600019&link_type=ISI) 

189.Matosin N, Fernandez-Enright F, Lum JS, et al.Molecular evidence of synaptic pathology in the CA1 region in schizophrenia.NPJ Schizophr 2016;2:16022
    
    

190.Kristiansen LV, Meador-Woodruff JH.Abnormal striatal expression of transcripts encoding NMDA interacting PSD proteins in schizophrenia, bipolar disorder and major depression.Schizophr Res 2005;78:87–93.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.schres.2005.06.012&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=16023328&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000231748600008&link_type=ISI) 

191.Nakagawa T, Futai K, Lashuel HA, et al.Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions.Neuron 2004;44:453–67.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neuron.2004.10.012&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=15504326&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000224771700008&link_type=ISI) 

192.Migaud M, Charlesworth P, Dempster M, et al.Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein.Nature 1998;396:433–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/24790&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=9853749&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000077370100044&link_type=ISI) 

193.Ehrlich I, Klein M, Rumpel S, et al.PSD-95 is required for activity-driven synapse stabilization.Proc Natl Acad Sci U S A 2007;104:4176–81.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czoxMToiMTA0LzEwLzQxNzYiO3M6NDoiYXRvbSI7czoxODoiL2pwbi80My80LzIyMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

194.Xu W, Schlüter OM, Steiner P, et al.Molecular dissociation of the role of PSD-95 in regulating synaptic strength and LTD.Neuron 2008;57:248–62.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neuron.2007.11.027&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18215622&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000252758400009&link_type=ISI) 

195.De Bartolomeis A, Sarappa C, Buonaguro EF, et al.Different effects of the NMDA receptor antagonists ketamine, MK-801, and memantine on postsynaptic density transcripts and their topography: role of Homer signaling, and implications for novel antipsychotic and pro-cognitive targets in psychosis.Prog Neuropsychopharmacol Biol Psychiatry 2013;46:1–12.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.pnpbp.2013.06.010&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23800465&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

196.Jiang-Xie L-F, Liao HM, Chen CH, et al.Autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive behaviors and orbitofrontal cortex deficits.Mol Autism 2014;5:32
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/2040-2392-5-32&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25071926&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

197.Silverman JL, Turner SM, Barkan CL, et al.Sociability and motor functions in Shank1 mutant mice.Brain Res 2011;1380:120–37.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.brainres.2010.09.026&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20868654&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000289135800011&link_type=ISI) 

198.Hung AY, Futai K, Sala C, et al.Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1.J Neurosci 2008;28:1697–708.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjk6IjI4LzcvMTY5NyI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

199.Wöhr M, Roullet FI, Hung AY, et al.Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior.PLoS One 2011;6:e20631
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1371/journal.pone.0020631&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21695253&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

200.Sungur AÖ, Schwarting RKW, Wöhr M.Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context.Autism Res 2016;9:696–709.
    
    

201.Schmeisser MJ, Ey E, Wegener S, et al.Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2.Nature 2012;486:256–60.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature11015&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22699619&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000305189000035&link_type=ISI) 

202.Won H, Lee HR, Gee HY, et al.Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.Nature 2012;486:261–5.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature11208&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22699620&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000305189000036&link_type=ISI) 

203.Ha S, Lee D, Cho YS, et al.Cellular/molecular cerebellar Shank2 regulates excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors.J Neurosci 2016;36:12129–43.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjExOiIzNi80OC8xMjEyOSI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

204.Arons MH, Thynne CJ, Grabrucker AM, et al.Autism-associated mutations in ProSAP2/Shank3 impair synaptic transmission and neurexin-neuroligin-mediated transsynaptic signaling.J Neurosci 2012;32:14966–78.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjExOiIzMi80My8xNDk2NiI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

205.Wang X, McCoy PA, Rodriguiz RM, et al.Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.Hum Mol Genet 2011;20:3093–108.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1093/hmg/ddr212&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21558424&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000292560000017&link_type=ISI) 

206.Bozdagi O, Tavassoli T, Buxbaum JD.Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay.Mol Autism 2013;4:9
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/2040-2392-4-9&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23621888&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

207.Peça J, Feliciano C, Ting JT, et al.Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.Nature 2011;472:437–42.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature09965&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21423165&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000289949600027&link_type=ISI) 

208.Mei Y, Monteiro P, Zhou Y, et al.Adult restoration of Shank3 expression rescues selective autistic-like phenotypes.Nature 2016;530:481–4.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature16971&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=26886798&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

209.Bozdagi O, Sakurai T, Papapetrou D, et al.Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication.Mol Autism 2010;1:15
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/2040-2392-1-15&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21167025&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

210.Yang M, Bozdagi O, Scattoni ML, et al.Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice.J Neurosci 2012;32:6525–41.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjEwOiIzMi8xOS82NTI1IjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

211.Marchetto MCN, Carromeu C, Acab A, et al.A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.Cell 2010;143:527–39.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.cell.2010.10.016&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21074045&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000284149100011&link_type=ISI) 

212.Peixoto RT, Wang W, Croney DM, et al.Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B −/− mice.Nat Neurosci 2016;19:716–24.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nn.4260&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=26928064&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

213.Leber SL, Llenos IC, Miller CL, et al.Homer1a protein expression in schizophrenia, bipolar disorder, and major depression.J Neural Transm 2017;124:1261–73.
    
    

214.Inoue N, Nakao H, Migishima R, et al.Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation.Mol Brain 2009;2:7
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/1756-6606-2-7&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=19265511&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

215.Gerstein H, O’Riordan K, Osting S, et al.Rescue of synaptic plasticity and spatial learning deficits in the hippocampus of Homer1 knockout mice by recombinant Adeno-associated viral gene delivery of Homer1c.Neurobiol Learn Mem 2012;97:17–29.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.nlm.2011.08.009&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21945599&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

216.Szumlinski KK, Lominac KD, Kleschen MJ, et al.Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia.Genes Brain Behav 2005;4:273–88.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1111/j.1601-183X.2005.00120.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=16011574&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000230780700001&link_type=ISI) 

217.Lominac KD, Oleson EB, Pava M, et al.Distinct roles for different Homer1 isoforms in behaviors and associated prefrontal cortex function.J Neurosci 2005;25:11586–94.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjExOiIyNS81MC8xMTU4NiI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

218.Jaubert PJ, Golub MS, Lo YY, et al.Complex, multimodal behavioral profile of the Homer1 knockout mouse.Genes Brain Behav 2007;6:141–54.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1111/j.1601-183X.2006.00240.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=16734773&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000244543500004&link_type=ISI) 

219.Vazdarjanova A, McNaughton BL, Barnes CA, et al.Experience-dependent coincident expression of the effector immediate-early genes arc and Homer 1a in hippocampal and neocortical neuronal networks.J Neurosci 2002;22:10067–71.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjExOiIyMi8yMy8xMDA2NyI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

220.Fujiyama K, Kajii Y, Hiraoka S, et al.Differential regulation by stimulants of neocortical expression of mrt1, arc, and homer1a mRNA in the rats treated with repeated methamphetamine.Synapse 2003;49:143–9.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/syn.10220&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=12774298&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000184218000001&link_type=ISI) 

221.Cochran SM, Fujimura M, Morris BJ, et al.Acute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain.Synapse 2002;46:206–14.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/syn.10126&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=12325047&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000178619500008&link_type=ISI) 

222.Nichols CD, Sanders-Bush E.A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain.Neuropsychopharmacology 2002;26:634–42.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/S0893-133X(01)00405-5&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=11927188&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000174791600008&link_type=ISI) 

223.Iasevoli F, Polese D, Ambesi-Impiombato A, et al.Ketamine-related expression of glutamatergic postsynaptic density genes: possible implications in psychosis.Neurosci Lett 2007;416:1–5.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neulet.2007.01.041&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17317002&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

224.Iasevoli F, Fiore G, Cicale M, et al.Haloperidol induces higher Homer1a expression than risperidone, olanzapine and sulpiride in striatal sub-regions.Psychiatry Res 2010;177:255–60.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.psychres.2010.02.009&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20304506&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000278278800046&link_type=ISI) 

225.Iasevoli F, Tomasetti C, Marmo F, et al.Divergent acute and chronic modulation of glutamatergic postsynaptic density genes expression by the antipsychotics haloperidol and sertindole.Psychopharmacology (Berl) 2010;212:329–44.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1007/s00213-010-1954-0&link_type=DOI) 

226.Ambesi-Impiombato A, Panariello F, Dell’aversano C, et al.Differential expression of Homer 1 gene by acute and chronic administration of antipsychotics and dopamine transporter inhibitors in the rat forebrain.Synapse 2007;61:429–39.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1002/syn.20385&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17372981&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000245534800008&link_type=ISI) 

227.Polese D, de Serpis AA, Ambesi-Impiombato A, et al.Homer 1a gene expression modulation by antipsychotic drugs: involvement of the glutamate metabotropic system and effects of D-cycloserine.Neuropsychopharmacology 2002;27:906–13.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/S0893-133X(02)00371-8&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=12464447&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000179156900002&link_type=ISI) 

228.Tomasetti C, Dell’Aversano C, Iasevoli F, et al.Homer splice variants modulation within cortico-subcortical regions by dopamine D2 antagonists, a partial agonist, and an indirect agonist: implication for glutamatergic postsynaptic density in antipsychotics action.Neuroscience 2007;150:144–58.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neuroscience.2007.08.022&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17916411&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000251696500016&link_type=ISI) 

229.Tezuka T, Umemori H, Akiyama T, et al.PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A.Proc Natl Acad Sci U S A 1999;96:435–40.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czo4OiI5Ni8yLzQzNSI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

230.Cousins SL, Papadakis M, Rutter AR, et al.Differential interaction of NMDA receptor subtypes with the post-synaptic density-95 family of membrane associated guanylate kinase proteins.J Neurochem 2008;104:903–13.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1111/j.1471-4159.2007.05067.x&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18233995&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000253673400004&link_type=ISI) 

231.Sans N, Prybylowski K, Petralia RS, et al.NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex.Nat Cell Biol 2003;5:520–30.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ncb990&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=12738960&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000183202800012&link_type=ISI) 

232.Dunham I, Kundaje A, Aldred SF, et al.An integrated encyclopedia of DNA elements in the human genome.Nature 2012;489:57–74.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature11247&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=22955616&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000308347000039&link_type=ISI) 

233.Bachevalier J, Loveland KA.The orbitofrontal–amygdala circuit and self-regulation of social–emotional behavior in autism.Neurosci Biobehav Rev 2006;30:97–117.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.neubiorev.2005.07.002&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=16157377&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000234755000006&link_type=ISI) 

234.Nelson RJ, Trainor BC.Neural mechanisms of aggression.Nat Rev Neurosci 2007;8:536–46.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nrn2174&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17585306&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000247907800015&link_type=ISI) 

235.Phelan MC.Deletion 22q13.3 syndrome.Orphanet J Rare Dis 2008;3:14
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/1750-1172-3-14&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=18505557&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

236.Betancur C, Buxbaum JD.SHANK3 haploinsufficiency: a ‘common’ but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders.Mol Autism 2013;4:17
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/2040-2392-4-17&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=23758743&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

237.Duffney LJ, Wei J, Cheng J, et al.Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism.J Neurosci 2013;33:15767–78.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjExOiIzMy80MC8xNTc2NyI7czo0OiJhdG9tIjtzOjE4OiIvanBuLzQzLzQvMjIzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

238.Van Keuren-Jensen K, Cline HT.Visual experience regulates metabotropic glutamate receptor-mediated plasticity of AMPA receptor synaptic transmission by Homer1a Induction.J Neurosci 2006;26:7575–80.
    
    [Abstract/FREE Full Text](http://jpn.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam5ldXJvIjtzOjU6InJlc2lkIjtzOjEwOiIyNi8yOS83NTc1IjtzOjQ6ImF0b20iO3M6MTg6Ii9qcG4vNDMvNC8yMjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

239.Pocklington AJ, O’Donovan M, Owen MJ.The synapse in schizophrenia.Eur J Neurosci 2014;39:1059–67.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1111/ejn.12489&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24712986&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

240.Stefansson H, Meyer-Lindenberg A, Steinberg S, et al.CNVs conferring risk of autism or schizophrenia affect cognition in controls.Nature 2014;505:361–6.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nature12818&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=24352232&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000329621800034&link_type=ISI) 

241.Hamdan FF, Gauthier J, Araki Y, et al.Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.Am J Hum Genet 2011;88:306–16.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1016/j.ajhg.2011.02.001&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=21376300&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

242.Durand CM, Betancur C, Boeckers TM, et al.Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.Nat Genet 2007;39:25–7.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/ng1933&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=17173049&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000243136500013&link_type=ISI) 

243.Kolevzon A, Bush L, Wang AT, et al.A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome.Mol Autism 2014;5:54
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1186/2040-2392-5-54&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25685306&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

244.Harrison PJ.Recent genetic findings in schizophrenia and their therapeutic relevance.J Psychopharmacol 2015;29:85–96.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1177/0269881114553647&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=25315827&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 

245.Cirulli ET, Goldstein DB.Uncovering the roles of rare variants in common disease through whole-genome sequencing.Nat Rev Genet 2010;11:415–25.
    
    [CrossRef](http://jpn.ca/lookup/external-ref?access_num=10.1038/nrg2779&link_type=DOI) 
    
    [PubMed](http://jpn.ca/lookup/external-ref?access_num=20479773&link_type=MED&atom=%2Fjpn%2F43%2F4%2F223.atom) 
    
    [Web of Science](http://jpn.ca/lookup/external-ref?access_num=000277806700010&link_type=ISI)