Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Comparison of the structural dynamic and mitochondrial electron-transfer properties of the proapoptotic human cytochrome c variants, G41S, Y48H and A51V

Mitochondrial cytochrome c is associated with electron transfer in the respiratory chain and in apoptosis. Four cytochrome c variants have been identified in families that suffer from mild autosomal dominant thrombocytopenia, a platelet disorder associated with increased apoptosis. Three out of the four substitutions, G41S, Y48H and A51V are located on the 40–57 Ω-loop. The G41S and Y48H variants perturb key physicochemical and dynamic properties that result in enhanced functional features associated with apoptotic activity. Herein we characterise the ferric A51V variant. We show by chemical denaturation that this variant causes the native state to be destabilized. Through azide binding kinetics, the population of a pentacoordinate heme form, whereby the Met80 axial ligand is dissociated, is estimated to be of equal magnitude to that found in the Y48H variant. This pentacoordinate form gives rise to peroxidase activity, which despite the similar pentacoordinate population of the A51V variant to that of the Y48H variant, the peroxidase activity of the A51V variant is suppressed. Far-UV circular dichroism spectroscopy and pH jump studies, suggest that a combination of structural and dynamic features in addition to the population of the pentacoordinate form regulate peroxidase activity in these disease variants. Additionally, the steady-state ratio of ferric/ferrous cytochrome c when in turnover with cytochrome c oxidase has been investigated for all 40–57 Ω-loop variants. These studies show that the lower pKa of the alkaline transition for the disease causing variants increases the ferric to ferrous heme ratio, indicating a possible influence on respiration in vivo

The effect of birth cohort on well-being: the legacy of economic hard times

In the present research, we examined the effects of age, cohort, and time of measurement on well-being across adulthood. Cross-sectional and longitudinal analyses of two independent samples-one with more than 10,000 repeated assessments across 30 years (mean assessments per participant = 4.44, SD = 3.47) and one with nationally representative data-suggested that well-being declines with age. This decline, however, reversed when we controlled for birth cohort. That is, once we accounted for the fact that older cohorts had lower levels of well-being, all cohorts increased in well-being with age relative to their own baseline. Participants tested more recently had higher well-being, but time of measurement, unlike cohort, did not change the shape of the trajectory. Although well-being increased with age for everyone, cohorts that lived through the economic challenges of the early 20th century had lower well-being than those born during more prosperous times. © The Author(s) 2013

The trajectory of depressive symptoms across the adult life span

IMPORTANCE Long-term longitudinal studies are needed to delineate the trajectory of depressive symptoms across adulthood and to individuate factors that may contribute to increases in depressive symptoms in older adulthood. OBJECTIVES To estimate the trajectory of depressive symptoms across the adult life span; to test whether this trajectory varies by demographic factors (sex, ethnicity, and educational level) and antidepressant medication use; and to test whether disease burden, functional limitations, and proximity to death explain the increase in depressive symptoms in old age. DESIGN Longitudinal study. SETTING Community. PARTICIPANTS The study included 2320 participants (47.0%female; mean [SD] age at baseline, 58.1 [17.0] years; range, 19-95 years) from the Baltimore Longitudinal Study of Aging. MAIN OUTCOMES AND MEASURES Estimated trajectory of depressive symptoms modeled from 10 982 assessments (mean [SD] assessments per participant, 4.7 [3.6]; range, 1-21) based on the Center for Epidemiologic Studies Depression scale and 3 subscales (depressed affect, somatic complaints, and interpersonal problems). RESULTS The linear (?10 = 0.52; P > .01) and quadratic (?20 = 0.43; P > .01) terms were significant, which indicated that depressive symptoms were highest in young adulthood, decreased across middle adulthood, and increased again in older adulthood. The subscales followed a similar pattern.Women reported more depressed affect at younger ages, but an interaction with age suggested that this gap disappeared in old age. Accounting for comorbidity, functional limitations, and impending death slightly reduced but did not eliminate the uptick in depressive symptoms in old age. CONCLUSIONS AND RELEVANCE Symptoms of depression follow a U-shaped pattern across adulthood. Older adults experience an increase in distress that is not due solely to declines in physical health or approaching death

Impulsivity-related traits are associated with higher white blood cell counts

A chronically elevated white blood cell (WBC) count is a risk factor for morbidity and mortality. The present research tests whether facets of impulsivity - impulsiveness, excitement-seeking, self-discipline, and deliberation - are associated with chronically elevated WBC counts. Community-dwelling participants (N = 5,652) from Sardinia, Italy, completed a standard personality questionnaire and provided blood samples concurrently and again 3 years later. Higher scores on impulsivity, in particular impulsiveness and excitementseeking, were related to higher total WBC counts and higher lymphocyte counts at both time points. Impulsiveness was a predictor of chronic inflammation: for every standard deviation difference in this trait, there was an almost 25% higher risk of elevated WBC counts at both time points (OR = 1.23, 95% CI = 1.10-1.38). These associations were mediated, in part, by smoking and body mass index. The findings demonstrate that links between psychological processes and immunity are not limited to acute stressors; stable personality dispositions are associated with a chronic inflammatory state. © Springer Science+Business Media, LLC (outside the USA) 2011

I know not to, but I can't help it: weight gain and changes in impulsivity-related personality traits

Reciprocal relations between weight and psychological factors suggest that there are deep connections between mind and body. Personality traits are linked to weight gain; weight gain may likewise be associated with personality change. Using data from two diverse longitudinal samples (N = 1,919) collected at two time points an average of 10 years apart, we showed that significant weight gain is associated with increases in both impulsiveness and deliberation: In both samples, middle-aged adults who gained 10% or more of their baseline body weight by follow-up increased in their tendency to give in to temptation, yet were more thoughtful about the consequences of their actions. The present research moves beyond life events to implicate health status in adult personality development. The findings also suggest that interventions focusing on the emotional component of impulse control may be more effective because even people who become more thoughtful about the consequences of their actions may have limited success at inhibiting their behavior. © The Author(s) 2013

The association between leptin and depressive symptoms is modulated by abdominal adiposity

Background: Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies. Methods: Data were from 851 participants (65-94 years) of the InCHIANTI Study and 1064 (26-93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D≥20) was evaluated over a 9-year follow-up. Results: In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p= 0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly (p= 0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference. Conclusions: The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications. © 2014 Elsevier Ltd

Gender Stereotypes of Personality: Universal and Accurate?

Numerous studies have documented subtle but consistent sex differences in self-reports and observer-ratings of five-factor personality traits, and such effects were found to show well-defined developmental trajectories and remarkable similarity across nations. In contrast, very little is known about perceived gender differences in five-factor traits in spite of their potential implications for gender biases at the interpersonal and societal level. In particular, it is not clear how perceived gender differences in five-factor personality vary across age groups and national contexts and to what extent they accurately reflect assessed sex differences in personality. To address these questions, we analyzed responses from 3,323 individuals across 26 nations (mean age = 22.3 years, 31% male) who were asked to rate the five-factor personality traits of typical men or women in three age groups (adolescent, adult, and older adult) in their respective nations. Raters perceived women as slightly higher in openness, agreeableness, and conscientiousness as well as some aspects of extraversion and neuroticism. Perceived gender differences were fairly consistent across nations and target age groups and mapped closely onto assessed sex differences in self- and observer-rated personality. Associations between the average size of perceived gender differences and national variations in sociodemographic characteristics, value systems, or gender equality did not reach statistical significance. Findings contribute to our understanding of the underlying mechanisms of gender stereotypes of personality and suggest that perceptions of actual sex differences may play a more important role than culturally based gender roles and socialization processes. © The Author(s) 2014