Certain personality traits, in particular higher neuroticism, have been associated, on one hand, with elevated cortisol levels, and on the other hand, with poorer cognitive performance. At the same time, several studies highlighted the association between high cortisol and poor cognitive functioning. Here, we hypothesized that increased cortisol may be associated with poorer cognition and with certain personality traits (mainly high neuroticism), and that personality might explain the association between cortisol and cognition. A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a population-based study involving residents of Lausanne, Switzerland. Salivary cortisol samples (upon waking, 30 min after waking, at 11 am and at 8 pm) along with cognitive and personality measures were obtained from 643 non-demented participants aged at least 65. Personality traits were assessed using the NEO Five-Factor Inventory (NEO-FFI). We examined the links between the cortisol Area under the Curve (AUC), the Clinical Dementia Rating Sum of Boxes (CDRSOB) and the NEO-FFI scores. No association was found between personality traits and the CDRSOB or the MMSE score, controlling for age, sex, depression, education and BMI. However, the executive functioning domain z-score was negatively associated with agreeableness (p = 0.005; slope = -0.107 [-0.181; -0.033]) and openness (p = 0.029; slope = -0.081 [-0.154; -0.008]) after controlling for age, sex, depression, education and BMI. The CDRSOB score was positively associated with the cortisol AUC after controlling for age, sex, BMI, education and depression, (p = 0.003; slope = 0.686 [0.240; 1.333]). This association remained significant after controlling for personality traits and for the interaction between personality traits and the cortisol AUC (p = 0.006; slope = 0.792 [0.233; 1.352]. High agreeableness and openness might be associated with poorer executive performance in later life. Increased cortisol may be associated with both specific personality traits (high extraversion, low openness) and worse cognitive performance. Increased salivary cortisol does not mediate the relationship between personality traits and cognitive impairment.

The Family Attitude Scale (FAS) is a self-report measure of critical or hostile attitudes and behaviors towards another family member, and demonstrates an ability to predict relapse in psychoses. Data are not currently available on a French version of the scale. The present study developed a French version of the FAS, using a large general population sample to test its internal structure, criterion validity and relationships with the respondents' symptoms and psychiatric diagnoses, and examined the reciprocity of FAS ratings by respondents and their partners. A total of 2072 adults from an urban population undertook a diagnostic interview and completed self-report measures, including an FAS about their partner. A subset of participants had partners who also completed the FAS. Confirmatory factor analyses revealed an excellent fit by a single-factor model, and the FAS demonstrated a strong association with dyadic adjustment. FAS scores of respondents were affected by their anxiety levels and mood, alcohol and anxiety diagnoses, and moderate reciprocity of attitudes and behaviors between the partners was seen. The French version of the FAS has similarly strong psychometric properties to the original English version. Future research should assess the ability of the French FAS to predict relapse of psychiatric disorders.

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.

The factors involved in the transmission of mood disorders are only partially elucidated. Aside from genes, the family environment might play a crucial role in parent-child transmission. Our goals were to (1) assess the associations of parental bipolar disorder (BPD) and Major Depressive Disorder (MDD) with individual or shared family environmental factors, including traumatic events in offspring, parental separation, family cohesion and parental attitudes; and 2) test whether these factors were mediators of the association between exposure to parental mood disorders and the onset of these disorders in offspring.

Dysregulations in cholesterol metabolism are associated with neurodegenerative and vascular pathologies, and dementia. Diet-derived plant sterols (phytosterols) have cholesterol-lowering, anti-inflammatory, and antioxidant properties and may interfere with neurodegeneration and cognitive decline. Here we performed multivariate analysis in 720 individuals enrolled in a population-based prospective study to determine whether circulating cholesterol precursors and metabolites, triglycerides, and phytosterols, are associated with cognitive impairment and decline in the older population. We report specific dysregulations of endogenous cholesterol synthesis and metabolism, and diet-derived phytosterols, and their changes over time associated with cognitive impairment, and decline in the general population. These findings suggest circulating sterols levels could be considered in risk evaluation and are relevant for the development of strategies to prevent cognitive decline in older people.

Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset.

Objective: Among the major dimensions of personality, high Neuroticism and low Conscientiousness have frequently been linked to worse health-related behaviors and poor health outcomes. However, studies on the association between personality traits and biomarkers of chronic low-grade inflammation reflecting increased morbidity and mortality risk are sparse; therefore, the aim of this study was to explore this association. Methods: A population-based Swiss sample of 2,182 persons (40-82 years, 42% men) completed a comprehensive personality questionnaire (NEO Five-Factor Inventory-Revised). Circulating levels of inflammatory markers, including C-reactive protein, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and levels of the "cardioprotective" adipo(cyto)kine adiponectin were also determined. Analyses controlled for sociodemographic factors, traditional cardiovascular risk factors and lifetime psychiatric disorders using a validated semi-structured psychiatric interview. The role of gender as a moderator of the personality-inflammation link was additionally explored. Results: Controlling for all covariates, higher Extraversion (β = 0.092, 95%CI 0.004-0.180) was positively associated with higher IL-6 levels, and higher Conscientiousness (β = -0.095, 95%CI -0.180-[-0.009]) were significantly associated with lower IL-6 levels (all p-values < 0.05). Neuroticism and Agreeableness showed no significant association with any inflammatory biomarker. The associations between personality traits and inflammatory markers were not moderated by gender. Conclusions: Conscientiousness seems to be inversely related to chronic low-grade inflammation as measured by IL-6 levels, compatible with protection from the cardiovascular risk. The opposite may apply to Extraversion. Further research is needed to better understand the underlying mechanisms and their impact for health outcomes in the community.

The occurrence of psychotic features within mood episodes in patients with bipolar I disorder (BD I) has been associated in some studies with a more severe clinical and socio-professional profile. In contrast, other studies establishing the associations of psychotic features in BD I, and in particular of mood-congruent (MC) and mood-incongruent (MI) features, with clinical characteristics have yielded contradictory results. However, many pre-existing studies have been affected by serious methodological limitations. Using a sample of thoroughly assessed patients with BD I our aims were to: (1) establish the proportion of those with MI and MC features, and (2) compare BD I patients with and without psychotic features as well as those with MI to those with MC features on a wide array of socio-demographic and clinical characteristics including course, psychiatric comorbidity and treatment.

Although the DSM-5 has suggested the two new categories of Persistent Depressive Disorders (PDD) and Other Specified Depressive Disorders (OSDD), no study so far has applied the DSM-5 criteria throughout the range of depressive disorders. The aims of the present study were to 1) establish the lifetime prevalence of specific depressive disorders according to the new DSM-5 definitions in a community sample, and 2) determine their clinical relevance in terms of socio-demographic characteristics, comorbidity, course and treatment patterns. The semi-structured Diagnostic Interview for Genetic Studies was administered by masters-level psychologists to a random sample of an urban area (n=3720). The lifetime prevalence was 15.2% for PDD with persistent major depressive episode (MDE), 3.3% for PDD with pure dysthymia, 28.2% for Major Depressive Disorder (MDD) and 9.1% for OSDD. Subjects with PDD with persistent MDE were the most severely affected, followed by those with recurrent MDD, single episode MDD, PDD with pure dysthymia and OSDD and finally those without depressive disorders. Our data provide further evidence for the clinical significance of mild depressive disorders (OSDD), but cast doubt on the pertinence of lumping together PDD with persistent MDE and the former DSM-IV dysthymic disorder within the new PDD category.

The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population-based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES-D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES-D score, occurrence of a major depressive episode (MDE) during follow-up and regular antidepressant treatment during the 6 months preceding follow-up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES-D score (p = .001). The HTR1A rs878567 variant was associated with ln CES-D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six-fold higher likelihood of regular AD therapy at follow-up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs.

Although a number of migraine-associated single-nucleotide polymorphisms (SNP) with small effect size have been identified, little is known about the additive impact of these variants on migraine risk, frequency and severity. We investigated to what extent a genetic risk score (GRS) based on recently published, novel migraine-associated SNPs is associated with migraine prevalence, subtypes and severity in a large population-based sample. The sample comprised 446 subjects with migraine and 2511 controls from the CoLaus/PsyCoLaus study. Fifty-four SNPs earlier associated with migraine were selected. SNPs with a low impact on migraine prevalence in our sample were excluded using random forest. We combined the remaining 21 SNPs into a GRS and analyzed the association with migraine using logistic regression models. The GRS was significantly associated with migraine (OR = 1.56, p = 0.02) and migraine without aura (MWOA) (OR = 2.01, p = 0.003), but not with migraine with aura (MWA). The GRS was not associated with migraine frequency, intensity or interference with daily activities. We show that a GRS combining multiple genetic risk variants is associated with MWOA but not MWA, suggesting a different genetic susceptibility background underlying the two forms of migraine.

Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia.

Neurodegenerative, vascular, and dementia diseases are linked to dysregulations in cholesterol metabolism. Dietary plant sterols, or phytosterols, may interfere to neurodegeneration and cognitive decline, and have cholesterol-lowering, anti-inflammatory, and antioxidant qualities. Here, we investigated the potential associations between circulating cholesterol precursors and metabolites, triglycerides, and phytosterols with cognitive decline in older people by performing multivariate analysis on 246 participants engaged in a population-based prospective study. In our analysis we considered the potential effect of sex and APOEe4. We reveal particular dysregulations of diet-derived phytosterols and endogenous cholesterol synthesis and metabolism, and their variations over time linked to cognitive decline in the general population. These results are significant to the development of interventions to avoid cognitive decline in older adults and suggest that levels of circulating sterols should be taken into account when evaluating risk.

Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (<45y). Interestingly, this association was totally driven by patients meeting lifetime criteria for atypical depression, i.e. major depressive episodes characterized by symptoms such as an increased appetite. Indeed, patients with atypical depression carrying rs7754794-TT had 1.17 kg/m2 (p = 0.04) lower BMI values as compared to C-allele carriers, the effect being stronger in younger individuals (-2.50 kg/m2; p = 0.03; interaction between rs7754794 and age: p-value = 0.08). This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression.

Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders.

Major depressive disorder (MDD) is the second largest cause of global disease burden. It has an estimated heritability of 37%, but published genome-wide association studies have so far identified few risk loci. Haplotype-block-based regional heritability mapping (HRHM) estimates the localized genetic variance explained by common variants within haplotype blocks, integrating the effects of multiple variants, and may be more powerful for identifying MDD-associated genomic regions.