Neuropsychopharmacology (1997) 16 385–398. doi:10.1016/S0893-133X(96)00277-1

Development of the Prefrontal Cortex during Adolescence: Insights into Vulnerable Neural Circuits in Schizophrenia

David A Lewis MD1

1From the Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania

Correspondence: David A Lewis, MD, BST W1650, Western Psychiatric Institute and Clinic, University of Pittsburgh, 3811 O′Hara Street, Pittsburgh, Pennsylvania 15213

Received 10 September 1996; Accepted 26 November 1996



Multiple lines of evidence suggest that the prefrontal cortex is a site of dysfunction in schizophrenia. In addition, one of the characteristics of this disorder is the tendency for clinical symptoms to appear first during late adolescence or early adulthood. Recent studies in nonhuman primates have shown that the connectivity of the prefrontal cortex is substantially refined during adolescence, suggesting that these developmental changes may be critical for the appearance of the clinical features of schizophrenia. This article reviews data demonstrating that these late developmental changes are selective for particular neural elements in the prefrontal cortex and that they are synaptically linked. It is suggested that these neural elements comprise a functional circuit that is likely to be especially vulnerable in schizophrenia, a hypothesis that can be directly tested in postmortem studies.


Cortical development; Dopamine; Local circuit neurons; Prefrontal cortex; Pyramidal neurons; Schizophrenia

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