Morphological changes in gray matter volume correlate with catechol-O-methyl transferase gene Val158Met polymorphism in first-episode treatment-naïve patients with schizophrenia

Abstract

The catechol-O-methyltransferase (COMT) gene is a schizophrenia susceptibility gene. A common functional polymorphism of this gene, Val158/158Met, has been proposed to infl uence gray matter volume (GMV). However, the effects of this polymorphism on cortical thickness/ surface area in schizophrenic patients are less clear.In this study, we explored the relationship between the Val158Met polymorphism of the COMT gene and the GMV/ cortical thickness/cortical surface area in 150 firstepisode treatment-naïve patients with schizophrenia and 100 healthy controls. Main effects of diagnosis were found for GMV in the cerebellum and the visual, medial temporal, parietal, and middle frontal cortex. Patients with schizophrenia showed reduced GMVs in these regions. And main effects of genotype were detected for GMV in the left superior frontal gyrus. Moreover, a diagnosis × genotype interaction was found for the GMV of the left precuneus, and the effect of the COMT gene on GMV was due mainly to cortical thickness rather than cortical surface area. In addition, a pattern of increased GMV in the precuneus with increasing Met dose found in healthy controls was lost in patients with schizophrenia. These findings suggest that the COMT Met variant is associated with the disruption of dopaminergic influence on gray matter in schizophrenia, and the effect of the COMT gene on GMV in schizophrenia is mainly due to changes in cortical thickness rather than in cortical surface area.

Association of Optic Radiation Integrity with Cortical Thickness in Children with Anisometropic Amblyopia

“…Electrophysiological studies have also shown that the visual cortical response to stimulation at higher spatial frequencies is reduced in anisometropic amblyopia [11]. Global brain gray matter [12], including the visual cortex [13], has been investigated physiologically and psychopathologically using functional magnetic resonance imaging (fMRI). Furthermore, recent fMRI studies have shown that amblyopia is associated with deactivation in the striate cortex (Brodmann area 17), the occipitotemporal cortex, and the LGN [14,15].…”

The Effect of Dopamine Antagonist Treatment on Auditory Verbal Hallucinations in Healthy Individuals Is Clearly Influenced by COMT Genotype and Accompanied by Corresponding Brain Structural and Functional Alterations: An Artificially Controlled Pilot Study

“…These previous findings converge to indicate that the reciprocal interactions between COMT genotype, dopamine levels, and structural and/or functional alterations in the human brain are related to mental disorder symptoms, such as AVHs (Lu et al., 2007; Kang et al., 2010; Sagud et al., 2010; Gothelf et al., 2011; Edgar et al., 2012; Tian et al., 2013a,b; Li et al., 2015; Huang et al., 2016; Steiner et al., 2018). …”

“…The catechol-o-methyltransferase ( COMT ) genotype influences brain functional (including auditory processing, which is highly related to AVHs) and dopaminergic alterations both in healthy people and in patients with schizophrenia ( Lu et al., 2007 ; Kang et al., 2010 ; Gothelf et al., 2011 ; Edgar et al., 2012 ; Tian et al., 2013a , b ; Li et al., 2015 ; Steiner et al., 2018 ) and the efficacy of dopamine antagonists in patients with schizophrenia ( Olgiati et al., 2009 ; Sagud et al., 2010 ; Huang et al., 2016 ). These previous findings converge to indicate that the reciprocal interactions between COMT genotype, dopamine levels, and structural and/or functional alterations in the human brain are related to mental disorder symptoms, such as AVHs ( Lu et al., 2007 ; Kang et al., 2010 ; Sagud et al., 2010 ; Gothelf et al., 2011 ; Edgar et al., 2012 ; Tian et al., 2013a , b ; Li et al., 2015 ; Huang et al., 2016 ; Steiner et al., 2018 ).…”

COMT-Val158Met polymorphism modulates antipsychotic effects on auditory verbal hallucinations and temporal lobe gray matter volumes in healthy individuals—symptom relief accompanied by worrisome volume reductions

“…Hence, COMT-Val/ Val homozygotes exhibit very efficient COMT activity, COMT-Met/Met homozygotes exhibit hypo-efficient COMT activity, and Val/Met heterozygotes carrying both variants of the enzyme exhibit an intermediate activity level, generally within normal range. COMT-Val158Met genotype (COMT genotype from here forward for simplicity) has also been shown to influence structural and functional aspects of auditory processing, including dopaminergic alterations in both healthy subjects and patients with schizophrenia (Edgar et al 2012;Gothelf et al 2011;Kang et al 2010;Li et al 2015;Lu et al 2007;Steiner et al 2018;Tian et al 2013a;Tian et al 2013b). Hence, a convergence of findings indicates that there may be reciprocal interactions between COMT genotype, dopamine levels, and structural/functional brain alterations in relation to neuropsychiatric symptoms, such as AVHs (Edgar et al 2012;Gothelf et al 2011;Huang et al 2016;Kang et al 2010;Li et al 2015;Lu et al 2007;Sagud et al 2010;Steiner et al 2018;Tian et al 2013a;Tian et al 2013b).…”