Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground

doi:10.1016/0920-9964(95)00013-C

Schizophrenia Research

Volume 16, Issue 2, 1 August 1995, Pages 87-110

https://doi.org/10.1016/0920-9964(95)00013-C Get rights and content

Abstract

Two of the favorite hypotheses of schizophrenia research — maldevelopment of cerebral cortex and malfunction of brain dopamine systems — have often seemed difficult to reconcile. This article reviews recent research that suggests a heuristically useful reconciliation centered on the functional neuroanatomical concept of prefrontal-temporolimbic cortical connectivity. Anatomical findings from postmortem studies and neuropsychological and neuroimaging studies of brain function in patients with schizophrenia have implicated a developmental ‘dysconnection’ of temporolimbic-prefrontal cortices. The possibility that such dysconnection can account for the principal phenomenology of the illness, including its delayed onset and its treatment, is suggested by neurologic disease analogies such as metachromatic leukodystrophy and by recent studies in animals with developmental cortical lesions. Studies mapping neuronal gene expression indicate that all antipsychotic drugs modulate DNA transcription in a region of the nucleus accumbens that receives converging inputs from prefrontal and temporolimbic cortices, suggesting that indirect compensation for dysfunctional communication between prefrontal and temporolimbic cortices is a therapeutic mechanism of these drugs. Treatments aimed at direct cortical compensation may be more effective.

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Review articleCortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground

Abstract

Psychiatry Res.

Biol. Psychiatry

Neuroscience

Brain Res.

Pharmacol. Biochem. Behav.

Schizophr. Res.

Life Sci.

Biol. Psychiatry

Cognition

Mol. Cell Neurosci

Schizophr. Res.

J. Neurosci. Meth.

Neuroscience

Neurosci Lett.

Biol. Psychiatry

Neuroscience

Neuroscience

Neroscience

Neuron

Neuroscience

Eur. J. Pharmacol.

Brain Res.

Semin. Neurosci.

Pharmacol. Biochem. Behav

Biol. Psychiatry

Neuroscience

Fos and Jun cooperate in transcriptional regulation via heterologous activation domains

Mol. Cell Biol.

Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenic implies disturbances of cortical development

Arch. Gen. Psychiatry

Typical and atypical antipsychotic occupancy of D-2 and S-2 receptors: An autoradiographic analysis in rat brain

Brain Res. Bull.

The hippocampus and parahippocampus in schizophrenic, suicide, and control brains

Arch. Gen. Psychiatry

Effect of clozapine on turnover of dopamine in the corpus striatum and in the limbic system

J. Pharm. Pharmac.

Evidence for different states of the dopamine D1 receptor: Clozapine and fluperlapine may preferentially label an adenylate cyclase-coupled state of the D1 receptor

J. Neurochem.

Magnetic resonance imaging of the brain in schizophrenia: The pathophysiologic significance of structural abnormalities

Arch. Gen. Psychiatry

Structural abnormalities in the frontal system in schizophrenia

Arch. Gen. Psychiatry

Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia: Assessment with Xenon133 single-photon emission computed tomography and the Tower of London

Arch. Gen. Psychiatry

Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia

Arch. Gen. Psychiatry

Pharmacology of mesocortical dopamine neurons

Pharmacol. Rev.

Development of the hippocampal region in the rat. I. Neurogenesis examined with 3H-thymidine autoradiography

J. Comp. Neurol.

An analysis of the arrangement of neurons in the cingulate cortex of schizophrenic patients

Arch. Gen. Psychiatry

Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics

Arch. Gen. Psychiatry

Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients

Arch. Gen. Psychiatry

Functional localization in the brain in schizophrenia

Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia

Arch. Gen. Psychiatry

Basal ganglia and limbic system pathology in schizophrenia: A morphometric study of brain volume and shrinkage

Arch. Gen. Psychiatry

Regional differences in homovanillic acid concentrations after acute and chronic administration of antipsychotic drugs

J. Pharm. Pharmac.

Sensorimotor gating and schizophrenia

Arch. Gen. Psychiatry

The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results

Arch. Gen. Psychiatry

Brain morphology and schizophrenia: A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures

Arch. Gen. Psychiatry

Neurodevelopmental implications of findings from brain imaging studies of schizophrenia

Postmortem evidence of structural brain changes in schizophrenia

Arch. Gen. Psychiatry

Review article
Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground