Neuroimaging and molecular genetics of schizophrenia: pathophysiological advances and therapeutic potential

British Journal of Pharmacology
Stephen M LawrieEve C Johnstone

Abstract

There is impressive evidence for the involvement of several genetic risk factors in the aetiopathogenesis of schizophrenia. Most of these genes impact on neuropharmacological systems. Examining their relationship with brain imaging indices is arguably the best currently available method of examining these effects in vivo. In a sample of young, initially healthy people at high genetic risk of schizophrenia brain structure was measured with structural magnetic resonance imaging (sMRI) and brain function was indexed with neuropsychological tests and functional MRI. Regular detailed clinical assessments established whether subjects had developed psychotic symptoms and/or schizophrenia itself. The Catechol-O-Methyl Transferase (COMT) Val allele increased the risk of schizophrenia in this cohort in a dose-dependent manner. Subjects with this allele had reduced grey matter density in anterior cingulate cortex and increased fMRI activation in lateral prefrontal cortex and anterior and posterior cingulate. The risk allele in the Neuregulin 1 (NRG1) promoter region, on the other hand, was associated with the development of psychotic symptoms, decreased premorbid IQ and decreased activation of pre-frontal and temporal lobe regions. The NR...Continue Reading

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Oct 13, 2016·Annual Review of Psychology·Thorhildur Halldorsdottir, Elisabeth B Binder
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