Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.

Childhood adversity patterns differentially cluster with mental disorders and socioeconomic indicators in a large Swiss community sample.

BACKGROUND: Exposure to childhood adversities (CHAD) has been found to be strongly associated with individuals' mental health and social development. Recently, it has been suggested that certain CHAD patterns exist in the population, which are more closely related to individuals' later mental health than the simple summation of adversities. The current study aims 1) to establish CHAD patterns based on self-reported child abuse and family dysfunction and 2) to assess their associations with mental disorders and sociodemographic indicators reported in adulthood. METHODS: Data used in this cross-sectional study were derived from the representative CoLaus/PsyCoLaus population-based cohort (N = 5111, 35 to 88 years). Latent class analysis was conducted for the identification of CHAD patterns, while their associations with mental disorders and socioeconomic achievements (e. g. education and income) were investigated using correspondence analysis. RESULTS: Four CHAD patterns emerged. While the majority (70.7%) of the sample showed an overall low adversity pattern (c1), 13.6% had not been raised by both of their biological parents due to divorce or being placed in foster home (c2), 11.0% had been raised by conflictive / dysfunctional / abusive parents (c3), and 4.7% showed high overall adversities (c4). Patterns c3 and c4 were most strongly associated with various mental disorders, especially c3 with internalizing anxiety disorders, while c2 was closely related to lower educational achievement. CONCLUSIONS: Four CHAD patterns characterised by varying levels of child abuse and family dysfunction existed in this community sample. They yielded distinct associations with mental disorders and socioeconomic indicators.

Psychopathological precursors of the onset of mood disorders in offspring of parents with and without mood disorders: results of a 13-year prospective cohort high-risk study.

BACKGROUND: There is still limited evidence from prospective high-risk research on the evolution of specific disorders that may emerge early in the development of mood disorders. Moreover, few studies have examined the specificity of mood disorder subtypes among offspring of parents with both major subtypes of mood disorders and controls based on prospective tracking across the transition from childhood to adulthood. Our specific objectives were to (a) identify differences in patterns of psychopathological precursors among youth with (hypo)mania compared to MDD and (b) examine whether these patterns differ by subtypes of parental mood disorders. METHODS: Our data stem from a prospective cohort study of 449 directly interviewed offspring (51% female, mean age 10.1 years at study intake) of 88 patients with BPD, 71 with MDD, 30 with substance use disorders and 60 medical controls. The mean duration of follow-up was 13.2 years with evaluations conducted every three years. RESULTS: Within the whole cohort of offspring, MDE (Hazard Ratio = 4.44; 95%CI: 2.19-9.02), CD (HR = 3.31;1.55-7.07) and DUD (HR = 2.54; 1.15-5.59) predicted the onset of (hypo)manic episodes, whereas MDD in offspring was predicted by SAD (HR = 1.53; 1.09-2.15), generalized anxiety (HR = 2.56; 1.05-6.24), and panic disorder (HR = 3.13; 1.06-9.23). The early predictors of (hypo)mania in the whole cohort were also significantly associated with the onset of (hypo)mania among the offspring of parents with BPD. CONCLUSIONS: The onset of mood disorders is frequently preceded by identifiable depressive episodes and nonmood disorders. These precursors differed by mood subtype in offspring. High-risk offspring with these precursors should be closely monitored to prevent the further development of MDD or conversion to BPD.

Factors associated with subjective cognitive decline in dementia-free older adults-A population-based study.

BACKGROUND: Subjective cognitive decline (SCD) is common in older adults, affects quality of life (QoL), and may represent the earliest clinical manifestation of cognitive decline evolving to dementia. Still little is known about factors associated with SCD. OBJECTIVES: (1) Assess the associations between SCD and demographic, social, clinical, and personality characteristics as well as QoL, with and without adjustment for objective cognitive performance, and (2) investigate the relations between neuroticism, QoL, and SCD. METHODS: Cross-sectional analysis of a cohort of 1567 dementia-free community-dwellers from the urban area of Lausanne, Switzerland, aged 64 years and older (mean age 70.9 ± 4.7 years), from CoLaus/PsyCoLaus. SCD was assessed using a validated 10-item questionnaire. Personality traits, QoL, and perceived social support were evaluated using self-report measures. Information on depression and anxiety status and socioeconomic characteristics including professional activity were elicited using a semi-structured interview. Cognitive functioning was assessed through a comprehensive neuropsychological test battery. Statistical analysis was based on logistic regression. RESULTS: SCD was present in 18.5% of the sample and it was associated with lower performance in memory and verbal fluency tasks. After controlling for possible confounders, professional activity, neuroticism, and current depression were associated with SCD. Exploratory analysis revealed associations of SCD with QoL, neuroticism, and their interaction. CONCLUSION: Besides objective cognitive performance, SCD is related to several psychosocial factors in dementia-free community-dwelling older people. These findings are relevant for the development of healthcare interventions to reduce cognitive complaints, improve QoL, and prevent cognitive decline in general population.

Major depression subtypes are differentially associated with migraine subtype, prevalence and severity.

OBJECTIVE: Migraine and major depressive disorder show a high rate of comorbidity, but little is known about the associations between the subtypes of major depressive disorder and migraine. In this cross-sectional study we aimed at investigating a) the lifetime associations between the atypical, melancholic, combined and unspecified subtype of major depressive disorder and migraine with and without aura and b) the associations between major depressive disorder and its subtypes and the severity of migraine. METHODS: A total of 446 subjects with migraine (migraine without aura: n = 294; migraine with aura: n = 152) and 2511 controls from the population-based CoLaus/PsyCoLaus study, Switzerland, were included. Associations between major depressive disorder subtypes and migraine characteristics were tested using binary logistic or linear regression. RESULTS: Melancholic, combined and unspecified major depressive disorder were associated with increased frequency of migraine with aura, whereas only melancholic major depressive disorder was associated with increased frequency of migraine without aura. Lifetime and unspecified major depressive disorder were associated with severe migraine intensity among subjects with migraine with aura but not migraine without aura, while combined major depressive disorder was associated with higher migraine frequency independently from migraine subtype. CONCLUSION: This study suggests that melancholic but not atypical major depressive disorder is associated with migraine and migraine subtypes. Future studies exploring pathophysiological mechanisms shared between melancholic depression and migraine are warranted.

A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants.

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.

A step beyond the hygiene hypothesis-immune-mediated classes determined in a population-based study.

BACKGROUND: Comorbidity patterns of childhood infections, atopic diseases, and adverse childhood experiences (ACE) are related to immune system programming conditions. The aim of this study was to make a step beyond the hygiene hypothesis and to comprehensively classify these patterns with latent class analysis (LCA). A second aim was to characterize the classes by associations with immunological, clinical, and sociodemographic variables. METHODS: LCA was applied to data from the CoLaus|PsyCoLaus study (N = 4874, age range 35-82 years) separately for men and women. It was based on survey information on chickenpox, measles, mumps, rubella, herpes simplex, pertussis, scarlet fever, hay fever, asthma, eczema, urticaria, drug allergy, interparental violence, parental maltreatment, and trauma in early childhood. Subsequently, we examined how immune-mediated classes were reflected in leukocyte counts, inflammatory markers (IL-1ß, IL-6, TNF-α, hsCRP), chronic inflammatory diseases, and mental disorders, and how they differed across social classes and birth cohorts. RESULTS: LCA results with five classes were selected for further analysis. Latent classes were similar in both sexes and were labeled according to their associations as neutral, resilient, atopic, mixed (comprising infectious and atopic diseases), and ACE class. They came across with specific differences in biomarker levels. Mental disorders typically displayed increased lifetime prevalence rates in the atopic, the mixed, and the ACE classes, and decreased rates in the resilient class. The same patterns were apparent in chronic inflammatory diseases, except that the ACE class was relevant specifically in women but not in men. CONCLUSIONS: This is the first study to systematically determine immune-mediated classes that evolve early in life. They display characteristic associations with biomarker levels and somatic and psychiatric diseases occurring later in life. Moreover, they show different distributions across social classes and allow to better understand the mechanisms beyond the changes in the prevalence of chronic somatic and psychiatric diseases.

Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community.

OBJECTIVE: The complex relationship between psychosocial stress over the lifetime, psychological factors, and cardiometabolic risk is still poorly understood. Accordingly, our aims were (1) to independently assess the associations between childhood adversity, life-event stress in remote (earlier than the last 5 years), and recent adulthood and cardiometabolic risk, and (2) to determine the role of psychological factors including personality, coping, and depression in these associations. METHODS: The sample included 2674 adults, aged 35 to 66 years, randomly selected from urban area. Participants underwent a physical examination including the assessment of obesity markers, blood pressure, and blood lipid and glucose levels. Stress during adulthood was determined using the severity scores of 52 stressful life events. Information on adverse childhood experiences and major depressive disorders was collected using semistructured interviews, whereas personality traits and coping mechanisms were evaluated through questionnaires. RESULTS: Both childhood adversity and stress in remote adulthood were associated with elevated body mass index (ß [95% confidence interval {CI}] = 0.249 [0.029 to 0.468]; 0.020 [0.006 to 0.034]), waist circumference (ß [95% CI] = 0.061 [0.024 to 0.099]; 0.08 [0.04 to 0.11]), and the global cardiometabolic risk score (ß [95% CI] = 0.278 [0.017 to 0.540]; 0.017 [0.001 to 0.033]) after adjustment for sociodemographic, lifestyle, and psychological factors. In addition, childhood adversity was associated with low high density lipoprotein levels (ß [95% CI] = -0.021 [-0.042 to 0.000]), as well as increased fat mass and systolic blood pressure levels (ß [95% CI] = 0.506 [0.165 to 0.846]; 0.952 [0.165 to 1.740]) and stress in remote adulthood with apolipoprotein B levels (ß [95% CI] = 0.607 [0.312 to 0.901]). Psychological factors did not account for these associations and were not effect modifiers. CONCLUSIONS: Our data demonstrate that psychosocial stress during childhood and remote adulthood favor adiposity and abnormal lipid metabolism.

The bidirectional relationship between anxiety disorders and circulating levels of inflammatory markers: Results from a large longitudinal population-based study.

BACKGROUND: Although there has been abundant research on chronic low-grade inflammation as a potential mechanism underlying the link between mood disorders and cardiovascular risk, less is known about the role of inflammatory factors and anxiety disorders. The aim of this paper is to evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP) with anxiety disorders and its subgroups. METHODS: The sample consisted of 3,113 participants (53.7% women; mean age: 51.0, S.D. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, S.D. 0.6). Anxiety disorders were assessed with semistructured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. RESULTS: After adjustment for potential confounders, current anxiety disorders (ß = 0.09, 95% CI 0.00-0.17) and agoraphobia (ß = 0.25, 95% CI: 0.07-0.43) at baseline were associated with a steeper increase of hsCRP levels over the follow-up period. Current posttraumatic stress disorder (PTSD) was associated with a lower increase of IL-6 levels over the follow-up period (ß = -0.52, 95% CI: -1.00/-0.04). There was no evidence for an association between inflammation markers at baseline and anxiety disorders at follow-up. CONCLUSIONS: The prospective association between agoraphobia at baseline and hsCRP levels over the follow-up period suggests that chronic low-grade inflammation may be a consequence of this condition. The decrease in IL-6 in PTSD also requires further investigation. No evidence was found for chronic low-grade inflammation as a predictor of future anxiety disorders.

A genetic risk score is differentially associated with migraine with and without aura.

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.

High leptin levels are associated with migraine with aura.

Background Migraine is a prevalent disorder characterised by recurrent headache attacks preceded or accompanied by aura in a subgroup of patients. Migraine often occurs together with major depressive disorder (MDD). Alterations of adipokine levels have been reported both in migraine and in MDD. In this cross-sectional study, we aimed to assess the associations between serum leptin and adiponectin levels and migraine or migraine subtypes. Analyses were adjusted for a lifetime history of MDD in order to investigate the association between adipokines and migraine under consideration of depression status. Methods We included 3025 participants from the CoLaus/PsyCoLaus study. The impact of leptin and adiponectin levels on a diagnosis of migraine was analysed by binary regression analyses, adjusting for variables known to influence adipokine levels. Subgroup analyses were conducted based on the presence of aura. Results Crude leptin levels were significantly higher in subjects with migraine than controls (Mann-Whitney U = 515,102, p = 6 × 10-7). When performing adjusted analyses, leptin levels were found to be significantly higher in subjects with migraine (odds ratio = 1.22, p = 0.024) and migraine with aura (odds ratio = 1.34, p = 0.004). Conclusion High leptin levels might play a role in the pathogenesis of migraine and migraine with aura.

The Lausanne-Geneva cohort study of offspring of parents with mood disorders: methodology, findings, current sample characteristics, and perspectives.

PURPOSE: Studies focusing on the offspring of affected parents utilize the well-established familial aggregation of mood disorders as a powerful tool for the identification of risk factors, early clinical manifestations, and prodromes of mood disorders in these offspring. The major goals of the Lausanne-Geneva mood cohort study are to: (1) assess the familial aggregation of bipolar and unipolar mood disorders; (2) prospectively identify risk factors for mood disorders as well as their early signs and prodromes; (3) identify their endophenotypes including cognitive features, alterations in brain structure, HPA-axis dysregulation, and abnormalities of the circadian rhythm of activity. METHODS: Probands with bipolar disorders, major depressive disorder, and controls with at least one child aged from 4 to 17.9 years at study intake, their offspring, as well as their spouses are invited to take part in follow-up assessments at predetermined ages of the offspring. Direct semi-structured diagnostic interviews have been used for all participants. Probands, spouses, and adult offspring also undergo neurocognitive testing, anthropomorphic measures and biochemical exams, structural Magnetic Resonance Imaging, as well as objective assessments of physical activity using accelerometers in combination with ecological momentary assessments. RESULTS: Currently, our study has up to seven follow-up assessments extending over a period of 20 years. There are 214 probands and 389 offspring with one direct interview before age 18 as well as a second assessment over follow-up. Data on 236 co-parents are also available from whom 55% have been directly interviewed. First publications support the specificity of the familial aggregation of BPD and the strong influence of an early onset of the parental BPD, which amplifies the risk of developing this disorder in offspring. CONCLUSIONS: Information from clinical, biological, cognitive, and behavioral measures, based on contemporary knowledge, should further enhance our understanding of mood disorder psychopathology, its consequences, and underlying mechanisms.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BACKGROUND: Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain. AIMS: We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL. METHOD: To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals. RESULTS: Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85 × 10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54 × 10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals. CONCLUSIONS: Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

Pure animal phobia is more specific than other specific phobias: epidemiological evidence from the Zurich Study, the ZInEP and the PsyCoLaus.

Interest in subtypes of mental disorders is growing in parallel with continuing research progress in psychiatry. The aim of this study was to examine pure animal phobia in contrast to other specific phobias and a mixed subtype. Data from three representative Swiss community samples were analysed: PsyCoLaus (n = 3720), the ZInEP Epidemiology Survey (n = 1500) and the Zurich Study (n = 591). Pure animal phobia and mixed animal/other specific phobias consistently displayed a low age at onset of first symptoms (8-12 years) and clear preponderance of females (OR > 3). Meanwhile, other specific phobias started up to 10 years later and displayed almost a balanced sex ratio. Pure animal phobia showed no associations with any included risk factors and comorbid disorders, in contrast to numerous associations found in the mixed subtype and in other specific phobias. Across the whole range of epidemiological parameters examined in three different samples, pure animal phobia seems to represent a different entity compared to other specific phobias. The etiopathogenetic mechanisms and risk factors associated with pure animal phobias appear less clear than ever.

Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments.

BACKGROUND: Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11ß-HSD1 may lead to the development of MetS. METHODS: We investigated the association between seven HSD11B1 gene (encoding 11ß-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n=478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (nR1=168, nR2=188) and in several large population-based samples (n1=5338; n2=123 865; n3>100 000). RESULTS: HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (Pcorrected<0.05). These associations were exclusively detected in women (n=257) with more than 3.1 kg/m, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (Pcorrected<0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (Pcorrected=0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, Pcorrected=0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples. CONCLUSIONS: Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not play a significant role in the general population.

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

Comparing two basic subtypes in OCD across three large community samples: a pure compulsive versus a mixed obsessive-compulsive subtype.

Due to its heterogeneous phenomenology, obsessive-compulsive disorder (OCD) has been subtyped. However, these subtypes are not mutually exclusive. This study presents an alternative subtyping approach by deriving non-overlapping OCD subtypes. A pure compulsive and a mixed obsessive-compulsive subtype (including subjects manifesting obsessions with/without compulsions) were analyzed with respect to a broad pattern of psychosocial risk factors and comorbid syndromes/diagnoses in three representative Swiss community samples: the Zurich Study (n = 591), the ZInEP sample (n = 1500), and the PsyCoLaus sample (n = 3720). A selection of comorbidities was examined in a pooled database. Odds ratios were derived from logistic regressions and, in the analysis of pooled data, multilevel models. The pure compulsive subtype showed a lower age of onset and was characterized by few associations with psychosocial risk factors. The higher social popularity of the pure compulsive subjects and their families was remarkable. Comorbidities within the pure compulsive subtype were mainly restricted to phobias. In contrast, the mixed obsessive-compulsive subtype had a higher prevalence and was associated with various childhood adversities, more familial burden, and numerous comorbid disorders, including disorders characterized by high impulsivity. The current comparison study across three representative community surveys presented two basic, distinct OCD subtypes associated with differing psychosocial impairment. Such highly specific subtypes offer the opportunity to learn about pathophysiological mechanisms specifically involved in OCD.

Discrepancies between clinical needs and helpseeking behaviors in co-occurring posttraumatic stress and alcohol use disorders.

OBJECTIVE: The aim of the study was to compare subjects dually diagnosed with posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) to those with only one or none of these conditions regarding helpseeking needs and behaviors. METHOD: Data from a large community sample (N=3694) were used to assess the associations among lifetime PTSD and AUD, other psychiatric disorders, clinical characteristics and lifetime helpseeking behaviors derived from a semi-structured interview. RESULTS: Comorbid individuals had more severe clinical profiles and were more impaired than individuals with either PTSD or AUD alone or those with no/other psychiatric conditions. However, they did not differ in overall helpseeking behavior from any other group. Those with comorbid PTSD/AUD were even less likely than the other groups to seek help for depression and anxiety disorders through specific treatment facilities or the use of prescribed psychotropic drugs. CONCLUSIONS: Despite a greater need for treatment the comorbid group did not seek more help than the others. Their lower use of prescribed drugs supports the self-medication hypothesis, suggesting that those individuals relieve their symptoms through higher alcohol use instead. Our findings underline the need for health care facilities to encourage helpseeking behavior in the aftermath of stressful life events.

Externalizing disorders and substance use: empirically derived subtypes in a population-based sample of adults.

PURPOSE: Attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD) are common externalizing disorders of childhood. The common effects of these disorders on substance abuse need further investigation. The current study investigated the joint clusters of childhood/adolescence ADHD, CD, and ODD, and their influence on substance abuse/dependence in a population-based sample of adults. METHODS: The data were drawn from the PsyCoLaus study (n = 3,720) conducted in Lausanne, Switzerland. The population-based sample included 238 subjects meeting criteria for ADHD/ODD/CD diagnoses before the age of 15. Latent class analyses (LCA) were performed to derive comorbidity subtypes, which were subsequently characterized with respect to psychosocial correlates and substance use. RESULTS: The best fit in LCAs was achieved with three latent classes: an ADHD subtype (35.7 %); an externalizing multimorbid subtype (33.6 %) involving ODD, ADHD, and CD; and a third subtype with CD (30.7 %). The CD subtype showed the highest association with substance use. Apart from this, the externalizing multimorbid subtype was also significantly linked to substance use. The ADHD subtype had only elevated frequencies for alcohol dependence in comparison with subjects that had no history of ADHD, ODD, and CD during childhood or adolescence. Finally, important interactions between subtypes and sex were observed with regard to substance use. CONCLUSIONS: This study provides evidence showing that subtyping the externalizing disorders, ADHD, ODD and CD, along their comorbidity patterns leads to important differences regarding substance use. This could have implications for the etiology, prevention, and treatment of substance use disorders.

Factors associated with comorbidity patterns in full and partial PTSD: findings from the PsyCoLaus study.

Subtypes of comorbid conditions and their associated trauma and clinical characteristics in full and partial PTSD were examined. Data from 289 subjects from the general population that met criteria for full or partial PTSD were analyzed. Latent class analyses (LCA) were performed to derive homogeneous patterns of DSM-IV Axis-I disorders and anti-social personality comorbid to PTSD. Logistic regression models were conducted to characterize these classes by trauma-related and clinical features. The LCA revealed three classes: (1) low comorbidity; (2) high comorbidity with primarily substance-related disorders and a higher proportion of males; and (3) more severe PTSD-symptomatology and higher comorbid anxiety disorders and depression, almost entirely represented by females. Exposure to sexual abuse was more likely in the substance-dependent class and contributed strongly to the distinction between classes. Affective disorders tended to precede the onset of PTSD in the substance-dependent class, whereas phobias were more likely to follow PTSD in the depressed-anxious class. Posttrauma onset of alcohol use disorders in the substance dependent class confirmed the self-medication hypothesis. The three classes of comorbidity and their sequence of onset with PTSD suggest different mechanisms involved in their development. Our findings suggest that PTSD-related comorbidity subtypes also apply to individuals with partial PTSD.