D W Volk1, A R Sampson2, Y Zhang2, J R Edelson1, D A Lewis1. 1. Department of Psychiatry,University of Pittsburgh,Pittsburgh, PA,USA. 2. Department of Statistics,University of Pittsburgh,Pittsburgh, PA,USA.
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.
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.
Authors: S G Fillman; N Cloonan; V S Catts; L C Miller; J Wong; T McCrossin; M Cairns; C S Weickert Journal: Mol Psychiatry Date: 2012-08-07 Impact factor: 15.992
Authors: Takanori Hashimoto; H Holly Bazmi; Karoly Mirnics; Qiang Wu; Allan R Sampson; David A Lewis Journal: Am J Psychiatry Date: 2008-02-15 Impact factor: 18.112
Authors: Jo Vandesompele; Katleen De Preter; Filip Pattyn; Bruce Poppe; Nadine Van Roy; Anne De Paepe; Frank Speleman Journal: Genome Biol Date: 2002-06-18 Impact factor: 13.583
Authors: Jason Smucny; Tyler A Lesh; Keith Newton; Tara A Niendam; J Daniel Ragland; Cameron S Carter Journal: Neuropsychopharmacology Date: 2017-09-26 Impact factor: 7.853
Authors: Vicente Molina; Alba Lubeiro; Rodrigo de Luis Garcia; Javier Gomez-Pilar; Oscar Martín-Santiago; María Iglesias-Tejedor; Pedro Holgado-Madera; Rafael Segarra-Echeverría; María Recio-Barbero; Pablo Núñez; Mahmoud Karim Haidar; Jessica Fernández-Sevillano; Javier Sanz-Fuentenebro Journal: J Psychiatry Neurosci Date: 2020-09-01 Impact factor: 6.186