Two common functional polymorphisms in catechol-O-methyltransferase (COMTVal158Met) and brain-derived neurotrophic factor (BDNF Val66Met) genes have been implicated in the neurobiology of anxiety and depression.
We show that Val/Val but neither Met/Met nor Val/Met carriers of the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism-a prime candidate for anxiety vulnerability-became significantly more anxious during the fMRI experiment (N=97 females: 24 Val/Val, 51 Val/Met, and 22 Met/Met).
These data suggest that involvement of the COMT locus in susceptibility to anxiety-related traits (ie low extraversion and high neuroticism) is unlikely to be wholly accounted for by the well-studied rs4680 ('val/met') polymorphism.
Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype.
In the 22q11.2 deletion syndrome group, baseline subthreshold psychotic symptoms interacted both with the COMT genotype and with baseline symptoms of anxiety or depression to predict 61% of the variance in severity of psychosis at follow-up evaluation.
Association between the COMTVal158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health.
The present results provide further support for a-potentially female-specific-role of the COMTval158met polymorphism in the genetic and neural underpinnings of anxiety- and depression-related intermediate phenotypes and may aid in further clarifying the differential role of COMT genotype driven dopaminergic tonus in the processing of emotionally salient stimuli.
Catechol O-methyltransferase (COMT), the major enzyme determining cortical dopamine flux, has a common functional polymorphism (val(158)met) that affects prefrontal function and working memory capacity and has also been associated with anxiety and emotional dysregulation.
Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.
We investigated and provided evidence of lower PPI: (i) in healthy pregnant women compared to healthy non-pregnant controls, (ii) in pregnant women with anxiety disorders compared to healthy pregnant women, (iii) in pregnant women with anxiety disorders using SSRI compared to un-medicated pregnant women with anxiety disorders, and (iv) in healthy pregnant women carrying the COMTVal158Met Val/Val genotype compared to Met carriers.
Two COMT variants were associated with the specific symptoms of anxiety and QOL measures prior to the initiation of chemotherapy as well as pain interference and severity during and after treatment.
Early aversive life experiences therefore might increase the vulnerability to anxiety disorders in the presence of homozygosity for the COMT 158met allele or low-active MAOA-uVNTR alleles.
Many of these differences are unconfirmed or minor, but some appear to be of reasonable robustness and magnitude; eg the functional Val(158)Met polymorphism in COMT is associated with obsessive-compulsive disorder in men, with anxiety phenotypes in women, and has a greater impact on cognitive function in boys than girls.
The paper focuses on such candidate gene polymorphisms that alter alcoholism-related intermediate phenotypes including: dopaminergic system polymorphic variants (DRD2 -141C Ins/Del in promoter region, exon 8 and DRD2 TaqI A and DAT 40bp VNTR genes polymorphisms) that cause predisposition to severe alcoholism (haplotype Ins/G/A2); COMTVal158Met gene polymorphism related to differences in executive cognitive function and 5-HTT gene promoter polymorphism, which alters stress response and affects anxiety and dysphoria.
The COMT gene contains a functional polymorphism changing enzyme activity that has been associated with some neuropsychiatric (endo)phenotypes, e.g. cognitive performance and anxiety.
The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been found to affect fear extinction and might play a role in the etiology of anxiety disorders.
Results indicate a main as well as a GxE effect of the COMTVal158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.
A coding variant in one such gene, encoding the dopamine catabolic enzyme catechol-O-methyltransferase (COMTVal158Met), has previously been associated with anxiety and with anxiety-related temperament and altered neural responses to affective stimuli in healthy individuals.
Given that catechol-O-methyltransferase (COMT) is widely distributed in the hippocampus and its genetic variation is thought to contribute to the interindividual variability in pain perception and anxiety regulation, whether or not migraine and COMT val(158) met genotype have an interactive effect in the key brain area related to maladaptive stress, the hippocampus, is still poorly understood.