Differential association of the COMT Val158Met polymorphism with clinical phenotypes in schizophrenia and bipolar disorder

Abstract

Schizophrenia and bipolar disorder, although diagnostically separate, likely share elements of their genetic etiology. This study assessed whether COMT Val158Met polymorphism has shared or specific associations with clinical phenotypes evident in schizophrenia and bipolar disorder. Schizophrenia and bipolar patients completed a clinical assessment encompassing premorbid functioning and current and lifetime symptomatology. Multivariate analyses yielded a three-way interaction of diagnosis, COMT genotype, and lifetime symptomatology. The COMT Val allele was associated with greater positive symptomatology in schizophrenia, whereas Met homozygosity was associated with greater positive symptomatology in bipolar disorder. Findings support the COMT Val158Met polymorphism conferring vulnerability for different clinical phenotypes in schizophrenia and bipolar disorder. Lifetime symptomatology may be particularly useful in determining the relationship between genes and clinical phenotypes across mental disorders.

Prefrontal-Related Functional Connectivities within the Default Network Are Modulated by COMTval158metin Healthy Young Adults

“…Additionally, evidence suggests that prefrontal dopamine plays a critical role in the normal cognitive process, especially in working memory, planning and attention (Seamans and Yang, 2004). Some studies have found that dysfunctions in prefrontal DA may underlie neuropsychiatric pathologies, such as the cognitive deficits associated with schizophrenia and bipolar disorder (Egan et al, 2001;Seamans and Yang, 2004;Tunbridge et al, 2006;Goghari and Sponheim, 2008). Moreover, one recent study suggests a reciprocal interplay between working memory capacity and cortical dopamine neurotransmission (McNab et al, 2009).…”

Do COMT, BDNF and NRG1 polymorphisms influence P50 sensory gating in psychosis?

“…Many studies have implicated the genes coding for the catechol-O-methyltransferase (COMT ) enzyme, brain-derived neurotrophic factor (BDNF ) and notably neuregulin 1 (NRG1) as candidate genes for schizophrenia (Li et al 1996 ;Egan et al 2001 ;Shifman et al 2002Shifman et al , 2004Glatt et al 2003 ;Handoko et al 2005 ;Lohoff et al 2005 ;Owen et al 2005 ;Chen et al 2006 ;Jonsson et al 2006 ;Ehlis et al 2007 ;Goghari & Sponheim, 2008 ;Okochi et al 2009 ;Zhang et al 2009). There is also a large body of evidence demonstrating the inconsistency of association between polymorphisms in COMT, BDNF and NRG1 genes and psychotic disorders in samples across the globe (Munafo et al 2005 ;Prata et al 2006 ;Kanazawa et al 2007 ;Ikeda et al 2008 ;Sanders et al 2008 ;Jonsson et al 2009 ;Kawashima et al 2009 ;Okochi et al 2009).…”

Gender‐specific COMT Val158Met polymorphism association in Spanish schizophrenic patients

“…A number of studies have identified an association between SZ and the Val158 allele [Li et al, 1996;de Chaldee et al, 1999;Egan et al, 2001;Kremer et al, 2003;Wonodi et al, 2003;Abdolmaleky et al, 2006;Goghari and Sponheim, 2008], although the last meta-analyses have brought about negative results [Fan et al, 2005;Munafo et al, 2005]. Strongest evidences of a significant association between the COMT Val158 allele gene and SZ have been observed in haplotype studies [Shifman et al, 2002;Sanders et al, 2005].…”