Yann Quide

Effects of common GRM5 genetic variants on cognition, hippocampal volume and mGluR5 protein levels in schizophrenia.

Matosin N, Newell KA, Quidé Y, Andrews JL, Teroganova N, Green MJ, Fernandez F

Brain Imaging Behav. 2017 Apr;():. doi: 28405888. Epub 2017 Apr.

GRM5 (coding for metabotropic glutamate receptor 5, mGluR5) is a promising target for the treatment of cognitive deficits in schizophrenia, but there has been little investigation of its association with cognitive and brain phenotypes within this disorder. We examined the effects of common genetic variation in GRM5 with cognitive function, hippocampal volume, and hippocampal mGluR5 protein levels in schizophrenia patients relative to healthy controls. Two independent GRM5 variants rs60954128 [C>T] and rs3824927 [G>T] were genotyped in a schizophrenia case/control cohort (n=249/261). High-resolution anatomical brain scans were available for a subset of the cohort (n=103 schizophrenia /78 control). All participants completed a standard set of neuropsychological tests. In a separate postmortem cohort (n=19 schizophrenia/20 controls), hippocampal mGluR5 protein levels were examined among individuals of different GRM5 genotypes. Schizophrenia minor allele carriers of rs60954128 had reduced right hippocampal volume relative to healthy controls of the same genotype (-12.3%); this effect was exaggerated in males with schizophrenia (-15.6%). For rs3824927, compared to major allele homozygotes, minor allele carriers with schizophrenia had lower Intelligence Quotients (IQ). Examination in hippocampal postmortem tissue showed no difference in mGluR5 protein expression according to genotype for either rs60954128 or rs3824927. While these genetic variants in GRM5 were associated with cognitive impairments and right hippocampal volume reduction in schizophrenia, they did not affect protein expression. Further study of these mechanisms may help to delineate new targets for the treatment of cognitive deficits in schizophrenia, and may be relevant to other disorders.

Effects of childhood trauma on working memory in affective and non-affective psychotic disorders.

Quidé Y, O'Reilly N, Rowland JE, Carr VJ, Elzinga BM, Green MJ

Brain Imaging Behav. 2016 Apr;():. doi: 27090803. Epub 2016 Apr.

Childhood trauma-related alterations in brain function during a Theory-of-Mind task in schizophrenia.

Quidé Y, Ong XH, Mohnke S, Schnell K, Walter H, Carr VJ, Green MJ

Schizophr. Res.. 2017 Feb;():. doi: 28215391. Epub 2016 Feb.

Childhood trauma is a risk factor for schizophrenia that affects brain functions associated with higher cognitive processes, including social cognition. Alterations in Theory-of-Mind (ToM), or mentalizing skills, are a hallmark feature of schizophrenia, and are also evident in individuals exposed to childhood trauma. However, the impact of childhood trauma exposure on brain function during social cognition in schizophrenia remains unclear. We thus examined the association between childhood trauma and brain function during the performance of a ToM task in 47 patients diagnosed with schizophrenia or schizoaffective disorder. All participants completed the Childhood Trauma Questionnaire (CTQ) and underwent functional magnetic resonance imaging while performing an established visual-cartoon affective ToM task. Whole-brain multiple regression analysis was performed on ToM-related brain activation, with CTQ total score as regressor of interest, while accounting for the effects of age, sex, diagnosis, symptom severity, behavioural performance, intelligence and medications levels. First, using a small-volume correction approach within a mask made of key regions for ToM [including bilateral temporo-parietal junctions (TPJ), medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC)/precuneus], total CTQ scores were positively associated with activation of the PCC/precuneus. Second, exploratory analyses for the rest of the brain (i.e., ROIs masked-out), revealed a positive association between trauma exposure and activation of the dorsomedial prefrontal cortex (dmPFC), and a negative association with activation of the anterior section of the TPJ. These results suggest that childhood trauma exposure may, at least partially, contribute to functional alterations of brain regions essential for effective mental state inference in schizophrenia.