Dataset Information

Genetic variation in GAD1 is associated with cortical thickness in the parahippocampal gyrus.

ABSTRACT: Patients with schizophrenia show widespread cortical thickness reductions throughout the brain. Likewise, reduced expression of the ?-Aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD1) and a single nucleotide polymorphism (SNP) rs3749034 in the corresponding gene have been associated with schizophrenia. We tested whether this SNP is associated with reduced cortical thickness, an intermediate phenotype for schizophrenia. Because of the well known interactions between the GABAergic and dopaminergic systems, we examined whether associations between GAD1 rs3749034 and cortical thickness are modulated by the catechol-O-methyltransferase (COMT) Val158Met genotype. Structural MRI and genotype data was obtained from 94 healthy subjects enrolled in the Mind Clinical Imaging Consortium study to examine the relations between GAD1 genotype and cortical thickness. Our data show a robust reduction of cortical thickness in the left parahippocampal gyrus (PHG) in G allele homozygotes of GAD1 rs3749034. When we stratified our analyses according to the COMT Val158Met genotype, cortical thickness reductions of G allele homozygotes were only found in the presence of the Val allele. Genetic risk variants of schizophrenia in the GABAergic system might interact with the dopaminergic system and impact brain structure and functioning. Our findings point to the importance of the GABAergic system in the pathogenesis of schizophrenia.

SUBMITTER: Brauns S

PROVIDER: S-EPMC4115611 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Genetic variation in GAD1 is associated with cortical thickness in the parahippocampal gyrus.

Brauns Stefan S Gollub Randy L RL Walton Esther E Hass Johanna J Smolka Michael N MN White Tonya T Wassink Thomas H TH Calhoun Vince D VD Ehrlich Stefan S

Journal of psychiatric research 20130406 7

Patients with schizophrenia show widespread cortical thickness reductions throughout the brain. Likewise, reduced expression of the γ-Aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD1) and a single nucleotide polymorphism (SNP) rs3749034 in the corresponding gene have been associated with schizophrenia. We tested whether this SNP is associated with reduced cortical thickness, an intermediate phenotype for schizophrenia. Because of the well known interactions between ...[more]

PMID: 23566421

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Project description:BackgroundTinnitus can interfere with a patient's speech discrimination, but whether tinnitus itself or the accompanying sensorineural hearing loss (SNHL) causes this interference is still unclear. We analyzed event-related electroencephalograms (EEGs) to observe auditory-related brain function and explore the possible effects of SNHL on auditory processing in tinnitus patients.MethodsSpeech discrimination scores (SDSs) were recorded in 21 healthy control subjects, 24 tinnitus patients, 24 SNHL patients, and 27 patients with both SNHL and tinnitus. EEGs were collected under an oddball paradigm. Then, the mismatch negativity (MMN) amplitude and latency, the clustering coefficient and average path length of the whole network in the tinnitus and SNHL groups were compared with those in the control group. Additionally, we analyzed the intergroup differences in functional connectivity among the primary auditory cortex (AC), parahippocampal gyrus (PHG), and inferior frontal gyrus (IFG).ResultsSNHL patients with or without tinnitus had lower SDSs than the control subjects. Compared with control subjects, tinnitus patients with or without SNHL had decreased MMN amplitudes, and SNHL patients had longer MMN latencies. Tinnitus patients without SNHL had a smaller clustering coefficient and a longer whole-brain average path length than the control subjects. SNHL patients with or without tinnitus had a smaller clustering coefficient and a longer average path length than patients with tinnitus alone. The connectivity strength from the AC to the PHG and IFG was lower on the affected side in tinnitus patients than that in control subjects; the connectivity strength from the PHG to the IFG was also lower on the affected side in tinnitus patients than that in control subjects. However, the connectivity strength from the IFG to the AC was stronger in tinnitus patients than that in the control subjects. In SNHL patients with or without tinnitus, these changes were magnified.ConclusionChanges in auditory processing in tinnitus patients do not influence SDSs. Instead, SNHL might cause the activity of the AC, PHG and IFG to change, resulting in impaired speech recognition in tinnitus patients with SNHL.

Dataset Information

Genetic variation in GAD1 is associated with cortical thickness in the parahippocampal gyrus.

Publications

Genetic variation in GAD1 is associated with cortical thickness in the parahippocampal gyrus.

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