White matter alterations related to attention-deficit hyperactivity disorder and COMT val158met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus)

Abstract

IntroductionIn this article, the COMT gene val158met polymorphism and attention-deficit hyperactivity disorder (ADHD)-related differences in diffusion-tensor-imaging-measured white matter (WM) structure in children with ADHD and controls were investigated.Patients and methodsA total of 71 children diagnosed with ADHD and 24 controls aged 8–15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA).ResultsFirst, an interaction between the COMT val158met polymorphism and ADHD in the right (R) cingulum (cingulate gyrus) (CGC) was found. According to this, valine (val) homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the R-CGC than ADHD-diagnosed methionine (met) carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L)-uncinate fasciculus and lower RD in the L-posterior corona radiata and L-posterior thalamic radiation (include optic radiation) than the val homozygotes, independent of ADHD diagnosis. Third, children with ADHD had lower FA in the L-CGC and R-retrolenticular part of the internal capsule than the controls, independent of the COMT polymorphism.ConclusionSignificant differences reported here may be evidence that the COMT gene val158met polymorphism variants, as well as ADHD, could affect brain development. ADHD and the COMT polymorphism might be interactively affecting WM development in the R-CGC to alter the WM connectivity in children with val homozygote ADHD.

Complex spatial and temporally defined myelin and axonal degeneration in Huntington disease

“…An important function of this bundle is related to the communication between components of the limbic system ( Mufson and Pandya, 1984 ) as well as with the execution of top-down and bottom-up attentional signals ( Bonnelle et al, 2012 ). Disconnection of this fiber bundle has been associated with post-traumatic amnesia ( De Simoni et al, 2016 ), with attention-deficit hyperactivity ( Kabukcu Basay et al, 2016 ) and with Alzheimer's disease ( Lee et al, 2015 ). We also found an association between increases in RD in the ILF and impaired performance on the Symbol Digit.…”

Catechol-O-methyltransferase Val158Met Genotype and Early-Life Family Adversity Interactively Affect Attention-Deficit Hyperactivity Symptoms Across Childhood

“…Met-carriers exhibited smaller striatal GMV than the Val-Val genotype ( Shimada et al, 2017 , p. 2), while Val-Val ADHD-diagnosed children had significantly lower fractional anisotropy and higher radial diffusivity in the cingulate gyrus compared to ADHD-diagnosed Met-carriers ( Basay et al, 2016 ). Also, white matter connections in Met-allele carriers were weaker than those in Val-Val-allele carriers ( Hong et al, 2014 ).…”

Catechol-O-Methyltransferase Val158Met and brain-derived neurotrophic factor Val66Met gene polymorphisms in paraphilic sexual offenders

“…Several studies have shown that COMT and BDNF polymorphisms were more common in psychiatric patient groups compared to the general population. [1223242526] In our previous study performed in panic disorder patients, we found an important association in COMT Met/Met genotype in patients according to controls. [26] In the study of Šberg et al ., it is found that depressed patients had higher frequency of COMT Met/Met (LL) genotype.…”

“…COMT has also a role in drug metabolism including catechol used for the treatment of many diseases such as asthma and Parkinson's disease. [12131415] The monoamines, epinephrine, norepinephrine, serotonin, and tyramine, may play a role in the pathophysiology of paraphilias. These neurotransmitters are neuromodulators having effects on memory, motivational behavior, appetite, and sexuality of people.…”