Dataset Information

Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function.

ABSTRACT: Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain regions. The translocation showed significant linkage (LOD score 6.1) with a clinical phenotype that included schizophrenia, schizoaffective disorder, bipolar disorder, and recurrent major depressive disorder. Translocation carriers showed reduced cortical thickness in the left temporal lobe, which correlated with general psychopathology and positive psychotic symptom severity. They showed reduced gyrification in prefrontal cortex, which correlated with general psychopathology severity. Translocation carriers also showed significantly increased activation in the caudate nucleus on increasing verbal working memory load, as well as statistically significant reductions in the right dorsolateral prefrontal cortex glutamate concentrations. These findings confirm that the t(1;11) translocation is associated with a significantly increased risk of major psychiatric disorder and suggest a general vulnerability to psychopathology through altered cortical structure and function, and decreased glutamate levels.

SUBMITTER: Thomson PA

PROVIDER: S-EPMC4994153 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function.

Thomson Pippa A PA Duff Barbara B Blackwood Douglas H R DH Romaniuk Liana L Watson Andrew A Whalley Heather C HC Li Xiang X Dauvermann Maria R MR Moorhead T William J TW Bois Catherine C Ryan Niamh M NM Redpath Holly H Hall Lynsey L Morris Stewart W SW van Beek Edwin J R EJ Roberts Neil N Porteous David J DJ St Clair David D Whitcher Brandon B Dunlop John J Brandon Nicholas J NJ Hughes Zoë A ZA Hall Jeremy J McIntosh Andrew A Lawrie Stephen M SM

NPJ schizophrenia 20160810

Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain regions. The translocation showed significant linkage (LOD score 6.1) with a clinical phenotype that included schizophrenia, schizoaffective disorder, ...[more]

PMID: 27602385

Similar Datasets

Project description:The balance of excitation and inhibition in neural circuits is hypothesized to be increased in autism spectrum disorder, possibly mediated by altered signaling of the inhibitory neurotransmitter ?-aminobutyric acid (GABA), yet empirical evidence in humans is inconsistent. We used edited magnetic resonance spectroscopy (MRS) to quantify signals associated with both GABA and the excitatory neurotransmitter glutamate in multiple regions of the sensory and sensorimotor cortex, including primary visual, auditory, and motor areas in adult individuals with autism and in neurotypical controls. Despite the strong a priori hypothesis of reduced GABA in autism spectrum disorder, we found no group differences in neurometabolite concentrations in any of the examined regions and no correlations of MRS measure with psychophysical visual sensitivity or autism symptomatology. We demonstrate high data quality that is comparable across groups, with a relatively large sample of well-characterized participants, and use Bayesian statistics to corroborate the lack of any group differences. We conclude that levels of GABA and Glx (glutamate, glutamine, and glutathione) in the sensory and sensorimotor cortex, as measured with MRS at 3T, are comparable in adults with autism and neurotypical individuals. Autism Res 2020, 13: 1111-1129. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ?-Aminobutyric acid (GABA) and glutamate are the main inhibitory and excitatory neurotransmitters in the human brain, respectively, and their balanced interaction is necessary for neural function. Previous research suggests that the GABA and glutamate systems might be altered in autism. In this study, we used magnetic resonance spectroscopy to measure concentrations of these neurotransmitters in the sensory areas in the brains of young adults with autism. In contradiction to the common hypothesis of reduced GABA in autism, we demonstrate that concentrations of both GABA and glutamate, in all the brain regions examined, are comparable in individuals with autism and in neurotypical adults. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Dataset Information

Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function.

Publications

Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets