Abnormalities of the medial temporal lobe have been consistently demonstrated in schizophrenia. A common functional polymorphism, Val108/158Met, in the putative schizophrenia susceptibility gene, catechol-O-methyltransferase (COMT), has been shown to influence medial temporal lobe function. However, the effects of this polymorphism on volumes of medial temporal lobe structures, particularly in patients with schizophrenia, are less clear. Here we measured the effects of COMT Val108/158Met genotype on the volume of two regions within the medial temporal lobe, the amygdala and hippocampus, in patients with schizophrenia and healthy control subjects. We obtained MRI and genotype data for 98 schizophrenic patients and 114 matched controls. An automated atlas-based segmentation algorithm was used to generate volumetric measures of the amygdala and hippocampus. Regression analyses included COMT met allele load as an additive effect, and also controlled for age, intracranial volume, gender and acquisition site. Across patients and controls, each copy of the COMT met allele was associated on average with a 2.6% increase in right amygdala volume, a 3.8% increase in left amygdala volume and a 2.2% increase in right hippocampus volume. There were no effects of COMT genotype on volumes of the whole brain and prefrontal regions. Thus, the COMT Val108/158Met polymorphism was shown to influence medial temporal lobe volumes in a linear-additive manner, mirroring its effect on dopamine catabolism. Taken together with previous work, our data support a model in which lower COMT activity, and a resulting elevation in extracellular dopamine levels, stimulates growth of medial temporal lobe structures.
Pubmed ID: 20026221 RIS Download
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Open source software suite for processing and analyzing human brain MRI images. Used for reconstruction of brain cortical surface from structural MRI data, and overlay of functional MRI data onto reconstructed surface. Contains automatic structural imaging stream for processing cross sectional and longitudinal data. Provides anatomical analysis tools, including: representation of cortical surface between white and gray matter, representation of the pial surface, segmentation of white matter from rest of brain, skull stripping, B1 bias field correction, nonlinear registration of cortical surface of individual with stereotaxic atlas, labeling of regions of cortical surface, statistical analysis of group morphometry differences, and labeling of subcortical brain structures.Operating System: Linux, macOS.
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