Impact of catechol-O-methyltransferase Val108/158 Met genotype on hippocampal and prefrontal gray matter volume

A variation in catechol-O-methyltransferase (COMT) gene (Val108/158Met) affects the physiological response of hippocampal–prefrontal circuits, predicts variation in human memory and is associated with increased risk for psychiatric disorders. Using optimized voxel-based morphometry we studied the effect of this functional polymorphism on the anatomy of the hippocampus, and the prefrontal cortex. Fifty-seven healthy participants were investigated (nine had Met/Met, 30 Val/Met, and 14 Val/Val). Voxel-based morphometry showed that individuals who are homozygous for the Val–COMT allele had greater gray matter volume of the prefrontal cortex bilaterally, whereas Met–COMT carriers were associated with increased tissue volume of the hippocampus bilaterally. This study provides evidence that the Val108/158Met polymorphism of the COMT gene might be responsible for individual variation in the human brain morphology.

[1]  B. Lipska,et al.  Catechol O-methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function , 2003, Neuroscience.

[2]  Thomas E. Nichols,et al.  Impact of complex genetic variation in COMT on human brain function , 2006, Molecular Psychiatry.

[3]  Andreas Heinz,et al.  Catechol-O-Methyltransferase val158met Genotype Affects Processing of Emotional Stimuli in the Amygdala and Prefrontal Cortex , 2005, The Journal of Neuroscience.

[4]  R. Straub,et al.  Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A. Ghezzi,et al.  Italian version of the Chicago multiscale depression inventory: translation, adaptation and testing in people with multiple sclerosis , 2004, Neurological Sciences.

[6]  P. Buckley,et al.  Catechol O-methyltransferase Val158Met Genotype and Neural Mechanisms Related to Affective Arousal and Regulation , 2008 .

[7]  Daniel R. Weinberger,et al.  Prefrontal neurons and the genetics of schizophrenia , 2001, Biological Psychiatry.

[8]  Kenneth K Kidd,et al.  Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles , 1999, Biological Psychiatry.

[9]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[10]  A. Meyer-Lindenberg,et al.  The Brain-derived Neurotrophic Factor Val66met Polymorphism and Variation in Human Cortical Morphology , 2022 .

[11]  M. Egan,et al.  Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[13]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[14]  D. Wechsler.  Manual for the Wechsler Adult Intelligence Scale. , 1955 .

[15]  R. Coppola,et al.  Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. , 2003, Archives of general psychiatry.

[16]  Venkata S Mattay,et al.  Imaging genetic influences in human brain function , 2004, Current Opinion in Neurobiology.

[17]  P. Buckley,et al.  Catechol-O-Methyltransferase (COMT) Genotypes and Working Memory: Associations with Differing Cognitive Operations , 2007 .

[18]  M. Hamilton.  The assessment of anxiety states by rating. , 1959, The British journal of medical psychology.

[19]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[20]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[21]  M. Egan,et al.  Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. , 2004, American journal of human genetics.

[22]  D. Noh,et al.  Relationship between the Val158Met polymorphism of catechol O-methyl transferase and breast cancer. , 2001, Pharmacogenetics.

[23]  Tommaso Scarabino,et al.  Additive Effects of Genetic Variation in Dopamine Regulating Genes on Working Memory Cortical Activity in Human Brain , 2006, The Journal of Neuroscience.