Limits...
Genetic Variation in the Catechol-O-Methyl Transferase Val108/158Met Is Linked to the Caudate and Posterior Cingulate Cortex Volume in Healthy Subjects: Voxel-Based Morphometry Analysis of Brain Magnetic Resonance Imaging.

Watanabe K, Kakeda S, Yoshimura R, Ide S, Hayashi K, Katsuki A, Umene-Nakano W, Watanabe R, Abe O, Korogi Y - PLoS ONE (2015)

Bottom Line: The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial.We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings.Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048].

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, University of Occupational and Environmental Health, Fukuoka, Japan.

ABSTRACT
The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects.

Show MeSH
Hypothetical inverted U-shaped relationship between prefrontal cortex (PFC) brain function and dopamine levels.Intermediate COMT activity and dopamine levels present in Val/Met individuals are thought to be optimal for PFC-mediated brain function.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4643939&req=5

pone.0142862.g001: Hypothetical inverted U-shaped relationship between prefrontal cortex (PFC) brain function and dopamine levels.Intermediate COMT activity and dopamine levels present in Val/Met individuals are thought to be optimal for PFC-mediated brain function.

Mentions: The relationship between dopamine levels and brain function/morphology is complicated. There appears to be an inverted U-shaped dose-response curve by which both deficient and excessive amounts of dopamine activity predict poor performance on cognitive tasks [13–15]. Preclinical data has suggested that these functional effects are related to a lawful effect of extracellular dopamine stimulation on the firing rate and tuning of prefrontal neurons, which exhibit optimal function with a middle range of dopamine [13, 16]. A previous study that assessed the relationship between COMT genotypes and cognitive tasks in adolescents also suggested that Val/Met individuals, who have intermediate COMT activity and dopamine levels, displayed optimal performance [17] (Fig 1).


Genetic Variation in the Catechol-O-Methyl Transferase Val108/158Met Is Linked to the Caudate and Posterior Cingulate Cortex Volume in Healthy Subjects: Voxel-Based Morphometry Analysis of Brain Magnetic Resonance Imaging.

Watanabe K, Kakeda S, Yoshimura R, Ide S, Hayashi K, Katsuki A, Umene-Nakano W, Watanabe R, Abe O, Korogi Y - PLoS ONE (2015)

Hypothetical inverted U-shaped relationship between prefrontal cortex (PFC) brain function and dopamine levels.Intermediate COMT activity and dopamine levels present in Val/Met individuals are thought to be optimal for PFC-mediated brain function.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643939&req=5

pone.0142862.g001: Hypothetical inverted U-shaped relationship between prefrontal cortex (PFC) brain function and dopamine levels.Intermediate COMT activity and dopamine levels present in Val/Met individuals are thought to be optimal for PFC-mediated brain function.
Mentions: The relationship between dopamine levels and brain function/morphology is complicated. There appears to be an inverted U-shaped dose-response curve by which both deficient and excessive amounts of dopamine activity predict poor performance on cognitive tasks [13–15]. Preclinical data has suggested that these functional effects are related to a lawful effect of extracellular dopamine stimulation on the firing rate and tuning of prefrontal neurons, which exhibit optimal function with a middle range of dopamine [13, 16]. A previous study that assessed the relationship between COMT genotypes and cognitive tasks in adolescents also suggested that Val/Met individuals, who have intermediate COMT activity and dopamine levels, displayed optimal performance [17] (Fig 1).

Bottom Line: The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial.We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings.Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048].

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, University of Occupational and Environmental Health, Fukuoka, Japan.

ABSTRACT
The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects.

Show MeSH