Fledgling pathoconnectomics of psychiatric disorders

doi:10.1016/j.tics.2013.10.007

Trends in Cognitive Sciences

Volume 17, Issue 12, December 2013, Pages 641-647

https://doi.org/10.1016/j.tics.2013.10.007 Get rights and content

Highlights

•
We evaluate the conceptual foundations of pathoconnectomics.
•
We overview the construction and analysis of empirical models of brain networks or connectomes.
•
We summarize recent reports of large-scale whole-brain connectome abnormalities of two candidate brain-network disorders, schizophrenia and autism.

Pathoconnectomics, the mapping of abnormal brain networks, is a popular current framework for the study of brain dysfunction in psychiatric disorders. In this review we evaluate the conceptual foundations of this framework, describe the construction and analysis of empirical models of brain networks or connectomes, and summarize recent reports of the large-scale whole-brain connectome organization of two candidate brain-network disorders, schizophrenia and autism. We consider the evidence for the abnormal brain-network nature of psychiatric disorders and find it inconclusive. For instance, although there is some evidence for more random whole-brain network organization in schizophrenia and autism, future studies need to determine if these and other observed brain-network abnormalities represent sufficient phenotypes of psychiatric disorders, in order to validate pathoconnectomics as a scientific and clinical framework.

Section snippets

Promises and challenges of pathoconnectomics

Connectomics, the mapping of brain networks (see Glossary), is a popular current framework for the study of brain function [1]. Connectomics postulates that brain functions, especially higher perceptual and cognitive functions, are contingent on brain-network interactions 2, 3 and that an understanding of these higher functions requires an understanding of brain-network organization 4, 5, 6.

Abnormalities of higher brain functions are a prominent feature of major psychiatric disorders such as

Sufficient phenotypes of psychiatric disorders

Objective delineation of psychiatric disorders is a central and perennial problem of psychiatry. In the current absence of such definitions, psychiatrists define psychiatric disorders using convenient, but not biologically validated, clinical phenotypes or groupings of symptoms and signs 16, 17.

A biological phenotype objectively defines a disorder when it is specific for the disorder, such that its presence implies the presence of the disorder. Modern medicine uses the simplest-known specific

Empirical models of connectomes

The connectome is broadly defined as the complete structural- or functional-network organization of the brain 1, 3. There are multiple microscopy- and neuroimaging-based model realizations of this concept (Table 1). Each of these empirical models has distinct spatial and sometimes temporal resolution, spatial coverage, and susceptibility to noise. The models balance the demands of biological realism and complexity. Neuronal-scale models may be too complex to construct and analyze, whereas

Abnormalities of connectomes in psychiatric disorders

In this section we provide an overview of recently reported whole-brain abnormalities of anatomical and functional MRI-based connectome models of schizophrenia and autism. The focus on schizophrenia and autism reflects the weight of the current literature; there are considerably fewer and less conclusive results of whole-brain connectome organization for other psychiatric disorders, such as major depression, bipolar disorder, and attention-deficit/hyperactivity disorder.

MRI-based structural

Concluding remarks

We examined the conceptual and methodological foundations of the emerging framework of pathoconnectomics and reviewed recent studies of large-scale whole-brain network abnormalities in schizophrenia and autism. These studies find some evidence for more random-like brain-network organization in schizophrenia and autism. The challenge for future studies is to show that such a biological marker represents a sufficient – specific and simplest-known – phenotype of these psychiatric disorders (Box 1

Acknowledgments

We are grateful to Catie Chang, Rolf Ypma, and two anonymous reviewers for helpful comments on an earlier version of the manuscript. M.R. is supported by the NARSAD Young Investigator Grant and the Isaac Newton Trust. E.B. is employed part time by GlaxoSmithKline and part time by the University of Cambridge. The Behavioural and Clinical Neuroscience Institute is supported by the Wellcome Trust and the Medical Research Council.

Glossary

Autism: a disorder, or spectrum of disorders, characterized by impairment in social interaction and communication and the presence of repetitive, stereotyped behaviors.
Connectome: strictly defined, the complete structural ‘wiring diagram’ of the brain. More loosely defined, the complete or partial ‘wiring diagrams’ or networks of structural and functional interactions in the brain.
Diffusion MRI: a method for mapping large-scale structural connectomes based on the inference of uneven (anisotropic)

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View full text

Trends in Cognitive Sciences

ReviewSpecial Issue: The ConnectomeFledgling pathoconnectomics of psychiatric disorders

Highlights

Section snippets

Promises and challenges of pathoconnectomics

Sufficient phenotypes of psychiatric disorders

Empirical models of connectomes

Abnormalities of connectomes in psychiatric disorders

Concluding remarks

Acknowledgments

Glossary

Neuron

Schizophr. Res.

Neuroimage

Neuroimage

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Biol. Psychiatry

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The human connectome: a structural description of the human brain

PLoS Comput. Biol.

The human connectome: a complex network

Ann. N. Y. Acad. Sci.

Discovering the Human Connectome

Connectome: How the Brain's Wiring Makes Us Who We Are

Structural neurobiology: missing link to a mechanistic understanding of neural computation

Nat. Rev. Neurosci.

Faulty circuits

Sci. Am.

Complex brain networks: graph theoretical analysis of structural and functional systems

Nat. Rev. Neurosci.

Psychiatry and Clinical Neuroscience: A Primer

Research domain criteria (RDoC): toward a new classification framework for research on mental disorders

Am. J. Psychiatry

The Structure of Scientific Revolutions

In retrospect: the structure of scientific revolutions

Nature

Disruptive insights in psychiatry: transforming a clinical discipline

J. Clin. Invest.

The neuron doctrine, redux

Science

Dissecting complex disease: the quest for the Philosopher's Stone?

Int. J. Epidemiol.

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)

International Statistical Classification of Diseases and Related Health Problems

Systems biology and the future of medicine

Wiley Interdiscip. Rev. Syst. Biol. Med.

Diabetes: The Biography

Natural kinds

Can neuroscience be integrated into the DSM-V?

Nat. Rev. Neurosci.

Autism and abnormal development of brain connectivity

J. Neurosci.

The dopamine hypothesis of schizophrenia: an historical and philosophical analysis

Philos. Psychiatry Psychol.

Serotonin and depression: a disconnect between the advertisements and the scientific literature

PLoS Med.

A critical look at connectomics

Nat. Neurosci.

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Nat. Genet.

Review
Special Issue: The Connectome
Fledgling pathoconnectomics of psychiatric disorders