American Journal of Psychiatry | Transcriptional Profiles of Somatostatin and Parvalbumin Interneuron Subtypes in the Human Dorsolateral Prefrontal Cortex: Implications for Schizophrenia
The dorsolateral prefrontal cortex is crucial for higher-order cognitive processes, such as attention and working memory, which are impaired in schizophrenia. Alterations in the somatostatin and parvalbumin classes of inhibitory GABAergic interneurons in the dorsolateral prefrontal cortex are thought to contribute to these cognitive impairments of schizophrenia. Both somatostatin and parvalbumin interneurons are composed of multiple subtypes, but questions remain regarding whether specific subtypes are selectively affected in schizophrenia—either in their relative proportions or in the expression of gene products.
In a study published in the American Journal of Psychiatry, investigators including John Enwright III, PhD (Research Assistant Professor of Psychiatry); Kenneth Fish, PhD (Associate Professor of Psychiatry); Dominique Arion (Research Principal Senior); Guillermo Gonzalez-Burgos, PhD (Associate Professor of Psychiatry); and David Lewis, MD (Distinguished Professor of Psychiatry and Neuroscience), from Pitt Psychiatry, used single-nucleus RNA sequencing to analyze somatostatin and parvalbumin interneuron subtypes in postmortem brain tissue samples from young and middle-age adults with no known psychiatric disorders.
The investigators found that the relative proportions of five major interneuron classes and of 37 interneuron subtypes were highly consistent across 19 individuals. Eleven somatostatin subtypes were identified, including two rare subtypes that likely produce dopamine or regulate blood flow, and a subtype derived from the caudal ganglionic eminence. Among the nine parvalbumin subtypes identified, chandelier cells were transcriptionally distinct from parvalbumin basket cells (PVBCs) and PVBC subtypes. Moreover, subsets of PVBCs were distinguished by high versus low parvalbumin expression and had distinctive molecular features consistent with differences in anatomical and electrophysiological characteristics.
“These findings help establish the molecular characteristics of distinct types of inhibitory neurons in the human prefrontal cortex, and the stability of the proportions of these subtypes across individuals. These data provide the means to determine which specific subtypes are altered in proportional representation and/or gene expression in schizophrenia,” said Dr. Lewis, senior author of the study.
Enwright JF, Tamburino AM, Tumkaya T, Lovatt D, Pan J, Gunaratna R, Fagegaltier D, Wang X, Marino MJ, Fish K, Arion D, Gonzalez-Burgos G, Lewis DA.
American Journal of Psychiatry. (2026) doi:10.1176/appi.ajp.20250355