Michaela Schmoeger

Brain-derived neurotrophic factor (BDNF)—Epigenetic regulation in unipolar and bipolar affective disorder

BACKGROUND Alterations of brain-derived neurotrophic factor (BDNF) DNA methylation at specific BDNF promoters and corresponding gene expressions are associated with pathology and the response to antidepressant (AD) therapy in affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). METHODS Genomic DNA was derived from peripheral blood mononuclear cells (PBMCs) and was bisulfite converted. Percentage of methylated reference (PMR) was calculated based on results from quantitative real-time PCR following the MethyLight protocol. For statistical analysis parametric procedures were performed as appropriate. RESULTS In this study 544 subjects were included, 207 MDD subjects, 59 BD subjects and 278 control subjects. The BDNF exon I promoter methylation resulted to be significantly increased in MDD subjects compared to BD subjects (p=0.0089) and control subjects (p<0.001). Furthermore, the increase of methylation in MDD subjects was significantly associated with AD therapy (p=0.0019) but not to the clinical features of depression such as the severity of symptoms (p=n.s.). None of the 12 investigated single nucleotide polymorphisms (SNP) showed significant genotype-methylation interactions. LIMITATIONS Although based on previous findings, the DNA methylation was evaluated within only one CpG island of the different alternative BDNF gene transcripts. CONCLUSIONS The results suggest that the methylation status might not only be affected by the disease phenotype but might also be further influenced by pharmacological treatment, therefore harbouring the possibility of identifying new insights for treatment options.

Comprehension of metaphors in patients with schizophrenia-spectrum disorders

BACKGROUND Metaphors, mainly proverbs and idiomatic expressions of ordinary life are commonly used as a model for concretism. Previous studies have shown impaired metaphor comprehension in patients with schizophrenia-spectrum disorders compared to either psychiatric or non-psychiatric control subject. The aim of this study was to detect possible quantitative differences in figurative processing between patients with schizophrenia-spectrum disorders and healthy controls. METHODS In order to analyse possible dissociations of different aspects of figurative speech, a range of metaphor tasks was used to distinguish between recognition of familiar metaphors, paraphrasing the meaning of the latter and generating novel metaphors: we used a standard proverb test for conventional metaphors consisting of a multiple-choice and a paraphrasing task, and the Metaphoric Triads Test for the assessment of novel metaphors. We included 40 patients with schizophrenia-spectrum disorders and 43 healthy control subjects. RESULTS Our results showed that patients had impaired figurative speech processing regarding novel and conventional metaphors. Associations with cognitive functions were detected. Performance on the paraphrasing task was associated with the severity of negative symptoms. CONCLUSION We conclude that patients with schizophrenia-spectrum disorders do exhibit impairments in the recognition and paraphrasing of conventional and the generation of novel metaphors and that some cognitive domains as well the extent of negative symptoms might be associated with these deficits.

Meta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of gender

Abstract Objectives: Many studies have reported an association of the COMT Val158Met polymorphism and major depressive disorder (MDD), although with conflicting results. The role of gender is a possible modulator. To overcome the problem of poor sample size detecting genes of small effect, we perform a meta-analysis of the current literature, investigating the influence of the COMT Val158Met polymorphism on the pathogenesis of MDD, with a major focus on the effect of gender. Methods: Out of 977 retrieved articles, 21 included case–control studies allowed the analysis of 9005 patients with MDD and 12,095 controls. Allelic and genotypic pooled odds ratios (OR) were calculated for the total sample and gender-subgroups. Results: In the absence of publication bias, allelic and genotypic analyses showed no significant association in the total sample, as well as in gender-specific subgroups. Sensitivity analysis did not alter the ORs. Conclusions: The results imply a complex nature of the genotype × phenotype interaction. Further studies of the COMT gene or the locus remain to be justified given the important positional and functional relevance and the plethora of gender-specific findings. A possible way to further dissect this topic is shifting the focus to gene-based or genome-wide analyses of intermediate phenotypes.

Cognitive and emotional demands of black humour processing: the role of intelligence, aggressiveness and mood.

Humour processing is a complex information-processing task that is dependent on cognitive and emotional aspects which presumably influence frame-shifting and conceptual blending, mental operations that underlie humour processing. The aim of the current study was to find distinctive groups of subjects with respect to black humour processing, intellectual capacities, mood disturbance and aggressiveness. A total of 156 adults rated black humour cartoons and conducted measurements of verbal and nonverbal intelligence, mood disturbance and aggressiveness. Cluster analysis yields three groups comprising following properties: (1) moderate black humour preference and moderate comprehension; average nonverbal and verbal intelligence; low mood disturbance and moderate aggressiveness; (2) low black humour preference and moderate comprehension; average nonverbal and verbal intelligence, high mood disturbance and high aggressiveness; and (3) high black humour preference and high comprehension; high nonverbal and verbal intelligence; no mood disturbance and low aggressiveness. Age and gender do not differ significantly, differences in education level can be found. Black humour preference and comprehension are positively associated with higher verbal and nonverbal intelligence as well as higher levels of education. Emotional instability and higher aggressiveness apparently lead to decreased levels of pleasure when dealing with black humour. These results support the hypothesis that humour processing involves cognitive as well as affective components and suggest that these variables influence the execution of frame-shifting and conceptual blending in the course of humour processing.