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Cortical GABA markers identify a molecular subtype of psychotic and bipolar disorders

Published online by Cambridge University Press:  22 June 2016

D. W. Volk ,
A. R. Sampson ,
Y. Zhang ,
J. R. Edelson  and
D. A. Lewis
D. W. Volk*
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
A. R. Sampson
Affiliation:
Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA
Y. Zhang
Affiliation:
Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA
J. R. Edelson
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
D. A. Lewis
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
*
*Address for correspondence: D. W. Volk, M.D., Ph.D., Department of Psychiatry, University of Pittsburgh, W1655 BST, 3811 O'Hara St, Pittsburgh, PA 15213, USA. (Email: volkdw@upmc.edu)
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Abstract

Background

Deficits in gamma aminobutyric acid (GABA) neuron-related markers, including the GABA-synthesizing enzyme GAD67, the calcium-binding protein parvalbumin, the neuropeptide somatostatin, and the transcription factor Lhx6, are most pronounced in a subset of schizophrenia subjects identified as having a ‘low GABA marker’ (LGM) molecular phenotype. Furthermore, schizophrenia shares degrees of genetic liability, clinical features and cortical circuitry abnormalities with schizoaffective disorder and bipolar disorder. Therefore, we determined the extent to which a similar LGM molecular phenotype may also exist in subjects with these disorders.

Method

Transcript levels for GAD67, parvalbumin, somatostatin, and Lhx6 were quantified using quantitative PCR in prefrontal cortex area 9 of 184 subjects with a diagnosis of schizophrenia (n = 39), schizoaffective disorder (n = 23) or bipolar disorder (n = 35), or with a confirmed absence of any psychiatric diagnoses (n = 87). A blinded clustering approach was employed to determine the presence of a LGM molecular phenotype across all subjects.

Results

Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype.

Conclusions

These findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.

Keywords

Inhibitorypostmortemprefrontal cortexschizoaffectiveschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 12 , September 2016 , pp. 2501 - 2512
Copyright
Copyright © Cambridge University Press 2016 

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