COMT val158met influence on electroconvulsive therapy response in major depression.

There is strong evidence for a genetic contribution to the pathogenesis of depression, with the functional catechol-O-methyltransferase (COMT) val158met polymorphism having been suggested as a potential susceptibility factor. In the present study, the effect of COMT val158met on response to electroconvulsive therapy (ECT) was analyzed in a sample of 104 Caucasian patients (f = 71, m = 33) with pharmacologically treatment-resistant Major Depression. The higher active COMT 158val allele was found to be associated with (1) higher pre-ECT severity of depression and (2) better treatment response to ECT particularly regarding the core symptoms of depression as well as sleep-related symptoms. These findings were restricted to the female subgroup of patients. In summary, the present study supports a potentially gender-specific significant impact of COMT gene variation on electroconvulsive therapy response, with COMT 158val risk allele carriers suffering from more severe, pharmacologically less efficiently treatable depression and thus possibly deriving greater benefit from ECT in the first place.

fMRI amygdala activation during a spontaneous panic attack in a patient with panic disorder.

Previous studies on neuronal activation correlates of panic attacks were mostly based on challenge tests, sensory-related stimulation or fear conditioning in healthy subjects. In the present study, we report on a female patient with panic disorder experiencing a spontaneous panic attack under an auditory habituation paradigm in the last stimulation block with sine tones captured with fMRI at 3T. The panic attack was associated with a significantly increased activity in the right amygdala. This is the first report on neuronal activation correlates of a spontaneous panic attack in a patient with panic disorder as measured by fMRI, which lends further support to a pivotal role of the amygdala in the pathogenesis of the disease.

Genetics of panic disorder: focus on association studies and therapeutic perspectives.

There is evidence for either genetic heterogeneity or complex inheritance with an interaction of environmental factors and multiple single genes in the etiology of panic disorder. Although linkage analyses of panic disorder have implicated several chromosomal regions including 1q, 2q, 4q, 7p, 9q, 12q, 13q, 15q and 22q, they so far have not been able to identify a major gene responsible for panic disorder. Several genes of classical candidate neurotransmitter systems have been reported to be associated with panic disorder. Genetic variation in genes of monoamine oxidase A, catechol-O-methyltransferase, adenosine receptor (ADORA2A) and cholecystokinin B receptor have been inconsistently replicated. There are multiple lines of evidence for highly relevant effects of gender and ethnicity. Future research strategies might focus on broad phenotypes defined by comorbidity or intermediate phenotypes and include the use of animal models for identifying candidate genes, such as the regulator of G-protein signaling (RGS2) gene, genome-wide association studies in large samples, studies of gene-gene and gene-environment interactions and pharmacogenetic studies. The identification of novel pathophysiological pathways may provide the basis for the development of novel therapeutic interventions.

Meta-analysis of COMT val158met in panic disorder: ethnic heterogeneity and gender specificity.

There is strong evidence for a genetic contribution to the pathogenesis of panic disorder, with the functional catechol-O-methyltransferase (COMT) val158met polymorphism having been suggested as a potential susceptibility factor. In the present study, a meta-analysis of six available case-control studies (557 patients with panic disorder and 763 healthy controls in total) on the role of the COMT val158met polymorphism in panic disorder was conducted in an attempt to reconcile previous conflicting results and to facilitate evaluation of the role of COMT gene variation in panic disorder. Overall, no significant association, but strong between-study heterogeneity, was discerned. Analysis of studies pooled by ancestry yielded a significant association of the COMT 158val allele with panic disorder in Caucasian samples and, conversely, a trend towards association of the COMT 158met allele with the disorder in Asian samples. Interestingly, stratification for gender as well as ethnicity revealed that association of the 158val allele in Caucasians and, reciprocally, the 158met allele in Asian samples was restricted to females. The present meta-analysis provides tentative support for the COMT val158met polymorphism as a possible risk factor for panic disorder, with differential effects in Caucasian and Asian populations, and suggests a female-specific effect. However, given the relatively small number of case-control studies presently available, several more association studies, preferably including a larger number of family-based studies, are warranted for conclusive evaluation of the COMT val158met polymorphism as a vulnerability factor in panic disorder.