Conserved Regional Patterns of GABA-Related Transcript Expression in the Neocortex of Subjects With Schizophrenia

• Published in: The American journal of psychiatry Vol. 165; no. 4; pp. 479 - 489
• Main Authors: Hashimoto, Takanori, Bazmi, H. Holly, Mirnics, Karoly, Wu, Qiang, Sampson, Allan R., Lewis, David A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Association 01.04.2008
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Biological and medical sciences; Brain; Cause of Death; Female; gamma-Aminobutyric Acid - genetics; gamma-Aminobutyric Acid - metabolism; Gene Expression Profiling; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - metabolism; Gyrus Cinguli - metabolism; Humans; Male; Medical sciences; Middle Aged; Motor Cortex - metabolism; Neocortex - chemistry; Neocortex - metabolism; Neurology; Neurons; Parvalbumins - genetics; Parvalbumins - metabolism; Polymerase Chain Reaction; Prefrontal Cortex - chemistry; Prefrontal Cortex - metabolism; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Schizophrenia; Schizophrenia - genetics; Schizophrenia - metabolism; Schizophrenia - mortality; Somatostatin - genetics; Somatostatin - metabolism; Synaptic Transmission - genetics; Synaptic Transmission - physiology; Tissue Distribution - genetics; Human; Cerebral cortex; Central nervous system; Postmortem; Schizophrenia; Gene expression; Genetic determinism; Encephalon; Psychosis; Neurotransmitter; GABA; Genetics; Transcription factor
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.2007.07081223

Objective: Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia. Method: Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects. Results: Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the 1 and subunits of GABA A receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. Conclusions: Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.