Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group.

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = -0.164 to -0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = -0.173 to -0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

[The application of the BL-38 subjective complaints scale in an epidemiological cohort study (Study of Health in Pomerania)]. / Die Anwendung der Beschwerdeliste-38 zur Erhebung subjektiver Gesundheitsbeschwerden in einer epidemiologischen Kohortenstudie (Study of Health in Pomerania, SHIP).

The application of the BL-38 subjective complaints scale in an epidemiological cohort study (Study of Health in Pomerania) Objective: We provide an overview of the application of the BL-38 complaints scale in the epidemiological Study of Health in Pomerania. We examine the influence of socio-demographic variables on complaint burden and the stability of complaint burden over time. Methods: 16 studies that used the BL-38 in analyses of SHIP-data were examined in terms of how the BL-38 was operationalised and the statistically significant results yielded. We conduct linear regression analyses to assess effects of sociodemographic variables on complaint burden in four SHIP populations and assess test-retest-reliability over a 17-year period. Results: The BL-38 is predominantly used flexibly to depict specific complaints in analyses covering a heterogeneous range of disciplines and study questions. Total, somatic and mental complaint burden have different determinant, predictive and confounding effects. Test-retest-reliability was moderate. Conclusions: The BL-38 allows consideration of (specified) health complaint patterns across many research disciplines. Cross-sectional and longitudinal reproducibility of significant results underlines its validity. The results underscore the importance of subjective health complaints in epidemiological and psychosomatic research.

Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior.

Caffeine is the most widely consumed psychoactive substance in the world and presents with wide interindividual variation in metabolism. This variation may modify potential adverse or beneficial effects of caffeine on health. We conducted a genome-wide association study (GWAS) of plasma caffeine, paraxanthine, theophylline, theobromine and paraxanthine/caffeine ratio among up to 9,876 individuals of European ancestry from six population-based studies. A single SNP at 6p23 (near CD83) and several SNPs at 7p21 (near AHR), 15q24 (near CYP1A2) and 19q13.2 (near CYP2A6) met GW-significance (P < 5 × 10-8) and were associated with one or more metabolites. Variants at 7p21 and 15q24 associated with higher plasma caffeine and lower plasma paraxanthine/caffeine (slow caffeine metabolism) were previously associated with lower coffee and caffeine consumption behavior in GWAS. Variants at 19q13.2 associated with higher plasma paraxanthine/caffeine (slow paraxanthine metabolism) were also associated with lower coffee consumption in the UK Biobank (n = 94 343, P < 1.0 × 10-6). Variants at 2p24 (in GCKR), 4q22 (in ABCG2) and 7q11.23 (near POR) that were previously associated with coffee consumption in GWAS were nominally associated with plasma caffeine or its metabolites. Taken together, we have identified genetic factors contributing to variation in caffeine metabolism and confirm an important modulating role of systemic caffeine levels in dietary caffeine consumption behavior. Moreover, candidate genes identified encode proteins with important clinical functions that extend beyond caffeine metabolism.