Risk factors of chronic course of anxiety and depressive disorders: a 3-year longitudinal study in the general population.

BACKGROUND: Risk factors of a chronic course of anxiety and depressive disorders were previously studied using a limited definition of recovery, i.e. remission of the index disorder. However, frequently, other mental disorders are present at follow-up. Thus, the course of anxiety and depressive disorders was represented too rosy and the identified determinants may not apply when using a broader, more realistic definition. Additionally, physical health risk factors have often been ignored. METHODS: Data were used from two waves of the Netherlands Mental Health Survey and Incidence Study-2 including 509 respondents with 12-month anxiety disorder (panic disorder, social phobia, agoraphobia or generalized anxiety disorder) or/and major depressive disorder at baseline. Chronic course was defined as (1) presence of index disorder; and (2) presence of any anxiety, mood or substance use disorder (overall course) during the subsequent three years. Regression models were built with sociodemographic, clinical, and lifestyle/physical health indicators. Predictive accuracy was evaluated with area under the curve (AUC). RESULTS: Chronic course of the index disorder was present among 24.8% of cases, whereas 38.7% had a chronic overall course. The accuracy of prediction of chronic course of the index disorder was suboptimal (AUC = 0.68) compared to prediction of overall course (AUC = 0.75). The main risk factors were baseline number of mental disorders, neuroticism, childhood abuse, parental psychopathology and alcohol use. Lifestyle and physical health indicators were marginally relevant. CONCLUSION: Transdiagnostic risk factors are important in predicting overall course of anxiety and depressive disorders but cannot accurately predict chronic course of the index disorder.

Context v. algorithm: evidence that a transdiagnostic framework of contextual clinical characterization is of more clinical value than categorical diagnosis.

BACKGROUND: A transdiagnostic and contextual framework of 'clinical characterization', combining clinical, psychopathological, sociodemographic, etiological, and other personal contextual data, may add clinical value over and above categorical algorithm-based diagnosis. METHODS: Prediction of need for care and health care outcomes was examined prospectively as a function of the contextual clinical characterization diagnostic framework in a prospective general population cohort (n = 6646 at baseline), interviewed four times between 2007 and 2018 (NEMESIS-2). Measures of need, service use, and use of medication were predicted as a function of any of 13 DSM-IV diagnoses, both separately and in combination with clinical characterization across multiple domains: social circumstances/demographics, symptom dimensions, physical health, clinical/etiological factors, staging, and polygenic risk scores (PRS). Effect sizes were expressed as population attributable fractions. RESULTS: Any prediction of DSM-diagnosis in relation to need and outcome in separate models was entirely reducible to components of contextual clinical characterization in joint models, particularly the component of transdiagnostic symptom dimensions (a simple score of the number of anxiety, depression, mania, and psychosis symptoms) and staging (subthreshold, incidence, persistence), and to a lesser degree clinical factors (early adversity, family history, suicidality, slowness at interview, neuroticism, and extraversion), and sociodemographic factors. Clinical characterization components in combination predicted more than any component in isolation. PRS did not meaningfully contribute to any clinical characterization model. CONCLUSION: A transdiagnostic framework of contextual clinical characterization is of more value to patients than a categorical system of algorithmic ordering of psychopathology.

Prevalence and trends of common mental disorders from 2007-2009 to 2019-2022: results from the Netherlands Mental Health Survey and Incidence Studies (NEMESIS), including comparison of prevalence rates before vs. during the COVID-19 pandemic.

Up-to-date information on the prevalence and trends of common mental disorders is relevant to health care policy and planning, owing to the high burden associated with these disorders. In the first wave of the third Netherlands Mental Health Survey and Incidence Study (NEMESIS-3), a nationally representative sample was interviewed face-to-face from November 2019 to March 2022 (6,194 subjects; 1,576 interviewed before and 4,618 during the COVID-19 pandemic; age range: 18-75 years). A slightly modified version of the Composite International Diagnostic Interview 3.0 was used to assess DSM-IV and DSM-5 diagnoses. Trends in 12-month prevalence rates of DSM-IV mental disorders were examined by comparing these rates between NEMESIS-3 and NEMESIS-2 (6,646 subjects; age range: 18-64 years; interviewed from November 2007 to July 2009). Lifetime DSM-5 prevalence estimates in NEMESIS-3 were 28.6% for anxiety disorders, 27.6% for mood disorders, 16.7% for substance use disorders, and 3.6% for attention-deficit/hyperactivity disorder. Over the last 12 months, prevalence rates were 15.2%, 9.8%, 7.1%, and 3.2%, respectively. No differences in 12-month prevalence rates before vs. during the COVID-19 pandemic were found (26.7% pre-pandemic vs. 25.7% during the pandemic), even after controlling for differences in socio-demographic characteristics of the respondents interviewed in these two periods. This was the case for all four disorder categories. From 2007-2009 to 2019-2022, the 12-month prevalence rate of any DSM-IV disorder significantly increased from 17.4% to 26.1%. A stronger increase in prevalence was found for students, younger adults (18-34 years) and city dwellers. These data suggest that the prevalence of mental disorders has increased in the past decade, but this is not explained by the COVID-19 pandemic. The already high mental disorder risk of young adults has particularly further increased in recent years.

Depression, cardiometabolic disease, and their co-occurrence after childhood maltreatment: an individual participant data meta-analysis including over 200,000 participants.

BACKGROUND: Childhood maltreatment is associated with depression and cardiometabolic disease in adulthood. However, the relationships with these two diseases have so far only been evaluated in different samples and with different methodology. Thus, it remains unknown how the effect sizes magnitudes for depression and cardiometabolic disease compare with each other and whether childhood maltreatment is especially associated with the co-occurrence ("comorbidity") of depression and cardiometabolic disease. This pooled analysis examined the association of childhood maltreatment with depression, cardiometabolic disease, and their comorbidity in adulthood. METHODS: We carried out an individual participant data meta-analysis on 13 international observational studies (N = 217,929). Childhood maltreatment comprised self-reports of physical, emotional, and/or sexual abuse before 18 years. Presence of depression was established with clinical interviews or validated symptom scales and presence of cardiometabolic disease with self-reported diagnoses. In included studies, binomial and multinomial logistic regressions estimated sociodemographic-adjusted associations of childhood maltreatment with depression, cardiometabolic disease, and their comorbidity. We then additionally adjusted these associations for lifestyle factors (smoking status, alcohol consumption, and physical activity). Finally, random-effects models were used to pool these estimates across studies and examined differences in associations across sex and maltreatment types. RESULTS: Childhood maltreatment was associated with progressively higher odds of cardiometabolic disease without depression (OR [95% CI] = 1.27 [1.18; 1.37]), depression without cardiometabolic disease (OR [95% CI] = 2.68 [2.39; 3.00]), and comorbidity between both conditions (OR [95% CI] = 3.04 [2.51; 3.68]) in adulthood. Post hoc analyses showed that the association with comorbidity was stronger than with either disease alone, and the association with depression was stronger than with cardiometabolic disease. Associations remained significant after additionally adjusting for lifestyle factors, and were present in both males and females, and for all maltreatment types. CONCLUSIONS: This meta-analysis revealed that adults with a history of childhood maltreatment suffer more often from depression and cardiometabolic disease than their non-exposed peers. These adults are also three times more likely to have comorbid depression and cardiometabolic disease. Childhood maltreatment may therefore be a clinically relevant indicator connecting poor mental and somatic health. Future research should investigate the potential benefits of early intervention in individuals with a history of maltreatment on their distal mental and somatic health (PROSPERO CRD42021239288).

Alcohol use as a predictor of the course of major depressive disorder: a prospective population-based study.

AIMS: There are indications that problematic alcohol use may negatively impact the course of major depressive disorder (MDD). However, most studies on alcohol use and adverse MDD outcomes are conducted amongst MDD populations with (severe) alcohol use disorder in psychiatric treatment settings. Therefore, it remains unclear whether these results can be generalised to the general population. In light of this, we examined the longitudinal relationship between alcohol use and MDD persistence after a 3-year follow-up amongst people with MDD from the general population. METHODS: Data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a psychiatric epidemiological prospective study comprising four waves amongst the adult Dutch general population (n = 6.646). The study sample (n = 642) consisted of those with 12-month MDD who participated at the follow-up wave. The outcome was 12-month MDD persistence after the 3-year follow-up, which was assessed via the Composite International Diagnostic Interview version 3.0. Weekly alcohol consumption was operationalised as non-drinking (0 drinks), low-risk drinking (⩽7 drinks; reference), at-risk drinking (women 8-13 drinks, men 8-20 drinks) and high-risk drinking (women ⩾14, men ⩾21 drinks). We performed univariate and multiple logistic regression analyses, which were adjusted for various socio-demographic and health-related factors. RESULTS: The majority (67.4%) of the MDD sample were female, while the mean age was 47.1 years. Amongst these, 23.8% were non-drinkers, 52.0% were low-risk drinkers and 14.3% and 9.4% were at-risk and high-risk drinkers, respectively. Around one-quarter of the sample (23.6%) met the criteria for a persistent MDD after 3-year follow-up. No statistically significant association was found between alcohol use and MDD persistence, either for the crude model or the adjusted models. In comparison to low-risk drinking, the full adjusted model showed no statistically significant associations between MDD persistence and non-drinking (odds ratio (OR) = 1.15, p = 0.620), at-risk drinking (OR = 1.25, p = 0.423), or high-risk drinking (OR = 0.74, p = 0.501). CONCLUSIONS: Contrary to our expectations, our findings showed that alcohol use was not a predictor of MDD persistence after 3-year follow-up amongst people with MDD from the general population.

Course of subthreshold manic symptoms and related risk factors in the general population: A three-year follow-up study.

OBJECTIVES: Subthreshold manic symptoms (subM) are a risk factor for the onset and recurrence of bipolar disorder (BD). Individuals with subM may benefit from preventive interventions, however, their development is hampered by a lack of knowledge on subM prevalence and subsequent course. This study examines subM characteristics, course, and risk factors for an unfavourable course. METHODS: In a Dutch representative, population-based sample aged 18-64 (N = 4618), we assessed subM, defined as the occurrence of manic core symptoms (elation/irritability), without meeting full DSM-IV criteria for BD I or II in the past 3 years. Comparison groups had either no manic symptoms (noM) or hypomania/mania in the context of BD (mBD) in the past 3 years. Furthermore, we differentiated a mild and moderate type of subM, based on the number of manic symptoms. A subsequent three-year course was assessed prospectively. RESULTS: SubM had a three-year prevalence of 4.9%. Its prevalence, characteristics, and course were in between noM and mBD, and there were few differences between mild and moderate subM. Over the 3-year follow-up, 25.0% of individuals with subM had persistent subM and another 6.1% transitioned to mBD. Eleven significant risk factors for this unfavourable course were found. The most important were a history of depression/dysthymia (OR 3.75, p ≤ 0.001), living alone (OR 2.61, p ≤ 0.01) and elevated neuroticism score (OR 1.21, p ≤ 0.001). CONCLUSIONS: This study supports the validity and clinical relevance of subM as a BD prodrome. It demonstrates that subM symptoms often persist or increase during follow-up and identifies 11 risk factors that are associated with an unfavourable course.

Age- and sex-specific associations between risk scores for schizophrenia and self-reported health in the general population.

PURPOSE: The health correlates of polygenic risk (PRS-SCZ) and exposome (ES-SCZ) scores for schizophrenia may vary depending on age and sex. We aimed to examine age- and sex-specific associations of PRS-SCZ and ES-SCZ with self-reported health in the general population. METHODS: Participants were from the population-based Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). Mental and physical health were measured with the 36-item Short Form Survey 4 times between 2007 and 2018. The PRS-SCZ and ES-SCZ were respectively calculated from common genetic variants and exposures (cannabis use, winter birth, hearing impairment, and five childhood adversity categories). Moderation by age and sex was examined in linear mixed models. RESULTS: For PRS-SCZ and ES-SCZ analyses, we included 3099 and 6264 participants, respectively (age range 18-65 years; 55.7-56.1% female). Age and sex did not interact with PRS-SCZ. Age moderated the association between ES-SCZ and mental (interaction: p = 0.02) and physical health (p = 0.0007): at age 18, + 1.00 of ES-SCZ was associated with - 0.10 of mental health and - 0.08 of physical health, whereas at age 65, it was associated with - 0.21 and - 0.23, respectively (all units in standard deviations). Sex moderated the association between ES-SCZ and physical health (p < .0001): + 1.00 of ES-SCZ was associated with - 0.19 of physical health among female and - 0.11 among male individuals. CONCLUSION: There were larger associations between higher ES-SCZ and poorer health among female and older individuals. Accounting for these interactions may increase ES-SCZ precision and help uncover populational determinants of environmental influences on health.

The impact of borderline personality disorder symptoms on onset and course of anxiety disorders: Results of a general population study.

Borderline personality disorder (BPD) has a negative impact on the onset and course of anxiety disorders. However, even though many people with anxiety disorders only have some BPD symptoms, little is known about the impact of BPD symptoms on anxiety disorders. This study examines the impact of BPD symptoms on the onset and persistence of anxiety disorders over a 3-year follow-up in the general population. Longitudinal data from the Netherlands Mental Health Survey and Incidence study were used (N = 4,618). BPD symptoms were assessed using the International Personality Examination, and anxiety disorders and other mental disorders were assessed with the Composite International Diagnostic Interview. Logistic regression analyses were performed, adjusting for a wide range of potential confounders such as childhood abuse and mood disorders. In all, 72.1% of the participants reported no BPD symptoms, 24.0% reported one to two symptoms, 3.1% reported three to four symptoms, and 0.8% reported ≥ 5 symptoms. There was a clear dose-response relation, with more BPD symptoms being associated with a higher risk for onset and persistence of anxiety disorders (both p for trend < .001). Even one to two BPD symptoms significantly impacted the onset (odds ratio = 3.32, 95% confidence interval [1.68, 6.54]) and persistence (odds ratio = 3.12, 95% confidence interval [1.01, 9.64]). Results appeared to be independent of multiple potential confounders. Even a low number of BPD symptoms impact the onset and persistence of anxiety disorders. Targeting these symptoms may improve the outcome of anxiety disorders. Future research should study the effect of various interventions for people with anxiety disorders and BPD symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Netherlands Mental Health Survey and Incidence Study-3 (NEMESIS-3): Objectives, methods and baseline characteristics of the sample.

OBJECTIVES: NEMESIS-3 (Netherlands Mental Health Survey and Incidence Study-3) is a psychiatric epidemiological cohort study of the Dutch general population that replicates and expands on two previous NEMESIS-studies conducted in 1996-1999 and 2007-2018 respectively. The main aims of NEMESIS-3 are to provide up-to-date information on the prevalence, incidence, course and consequences of mental disorders, their risk indicators, and to study the relevant time trends. This paper gives an overview of the objectives and methods of NEMESIS-3, especially of the recently completed first wave, and describes the sample characteristics. METHODS: NEMESIS-3 is based on a multistage, stratified random sampling of individuals aged 18-75 years. Face-to-face interviews were laptop computer-assisted and held at the respondent's home. A slightly modified Composite International Diagnostic Interview (CIDI) version 3.0 was used to assess both Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) and DSM-5 mental disorders. Two follow-up waves are planned three and six years after baseline. RESULTS: In the first wave, performed from November 2019 to March 2022, 6194 individuals were interviewed: 1576 respondents before and 4618 respondents during the COVID-19 pandemic. The average interview duration was 91 min and the response rate was 54.6%. The sample consisted of 50.4% women and had a mean age of 47.9 years. The sample was reasonable nationally representative, although some sociodemographic groups were somewhat underrepresented. CONCLUSIONS: Despite the COVID-19 restrictions, we were able to build a large and comprehensive dataset of good quality, permitting us to investigate the latest trends in mental health status, various new topics related to mental health, and the extent to which the pandemic has had an effect on the population's mental health.

Recurrence of anxiety disorders and its predictors in the general population.

BACKGROUND: Anxiety disorders frequently recur in clinical populations, but the risk of recurrence of anxiety disorders is largely unknown in the general population. In this study, recurrence of anxiety and its predictors were studied in a large cohort of the adult general population. METHODS: Baseline, 3-year and 6-year follow-up data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). Respondents (N = 468) who had been in remission for at least a year prior to baseline were included. Recurrence was assessed at 3 and 6 years after baseline, using the Composite International Diagnostic Interview version 3.0. Cumulative recurrence rates were estimated using the number of years since remission of the last anxiety disorder. Furthermore, Cox regression analyses were conducted to investigate predictors of recurrence, using a broad range of putative predictors. RESULTS: The estimated cumulative recurrence rate was 2.1% at 1 year, 6.6% at 5 years, 10.6% at 10 years, and 16.2% at 20 years. Univariate regression analyses predicted a shorter time to recurrence for several variables, of which younger age at interview, parental psychopathology, neuroticism and a current depressive disorder remained significant in the, age and gender-adjusted, multivariable regression analysis. CONCLUSIONS: Recurrence of anxiety disorders in the general population is common and the risk of recurrence extends over a lengthy period of time. In clinical practice, alertness to recurrence, monitoring of symptoms, and quick access to health care in case of recurrence are needed.

Prevalence, incidence, and persistence of psychotic experiences in the general population: results of a 9-year follow-up study.

BACKGROUND: Psychotic experiences (PEs) frequently occur and are associated with a range of negative health outcomes. Prospective studies on PEs are scarce, and to date no study investigated PE prevalence, incidence, persistence, their risk indicators, and psychiatric comorbidity, in one dataset. Furthermore, most studies are based on self-report, and it is unclear how this compares to clinical interviews. METHODS: Data are used from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a psychiatric cohort study among a representative sample of adults (baseline characteristics: N = 6646; 49.6% female; 18-64 years). Results are presented for self-reported and clinically validated PEs. Associations are assessed for mental disorders, socio-demographic, vulnerability, physical health, and substance use factors. RESULTS: Based on self-report, at baseline 16.5% of respondents had at least one PE in their lifetime, of those, 30.1% also reported a PE at 3-year follow-up. 4.8% had a first PE at 3-year follow up. The 3-year prevalence of PE was associated with almost all studied risk indicators. Generally, the strongest associations were found for mental health disorders. Prevalence and incidence rates were two to three times higher in self-report than in clinical interview but results on associated factors were similar. CONCLUSIONS: Validated prevalence and incidence estimates of PE are substantially lower than self-reported figures but results on associated factors were similar. Therefore, future studies on associations of PEs can rely on relatively inexpensive self-reports of PEs. The associations between PE and mental disorders underline the importance of assessment of PE in general practice.

Bidirectional relationships between cannabis use, anxiety and depressive symptoms in the mediation of the association with psychotic experience: further support for an affective pathway to psychosis.

BACKGROUND: Empirical evidence suggests that people use cannabis to ameliorate anxiety and depressive symptoms, yet cannabis also acutely worsens psychosis and affective symptoms. However, the temporal relationship between cannabis use, anxiety and depressive symptoms and psychotic experiences (PE) in longitudinal studies is unclear. This may be informed by examination of mutually mediating roles of cannabis, anxiety and depressive symptoms in the emergence of PE. METHODS: Data were derived from the second longitudinal Netherlands Mental Health Survey and Incidence Study. Mediation analysis was performed to examine the relationship between cannabis use, anxiety/depressive symptoms and PE, using KHB logit in STATA while adjusting for age, sex and education status. RESULTS: Cannabis use was found to mediate the relationship between preceding anxiety, depressive symptoms and later PE incidence, but the indirect contribution of cannabis use was small (for anxiety: % of total effect attributable to cannabis use = 1.00%; for depression: % of total effect attributable to cannabis use = 1.4%). Interestingly, anxiety and depressive symptoms were found to mediate the relationship between preceding cannabis use and later PE incidence to a greater degree (% of total effect attributable to anxiety = 17%; % of total effect attributable to depression = 37%). CONCLUSION: This first longitudinal cohort study examining the mediational relationship between cannabis use, anxiety/depressive symptoms and PE, shows that there is a bidirectional relationship between cannabis use, anxiety/depressive symptoms and PE. However, the contribution of anxiety/depressive symptoms as a mediator was greater than that of cannabis.

Identification of Latent Alcohol Use Groups and Transitions over Time Using a 9-Year Follow-Up Study in the Adult General Population.

INTRODUCTION: Studies investigating latent alcohol use groups and transitions of these groups over time are scarce, while such knowledge could facilitate efficient use of screening and preventive interventions for groups with a high risk of problematic alcohol use. Therefore, the present study examines the characteristics, transitions, and long-term stability of adult alcohol use groups and explores some of the possible predictors of the transitions. METHODS: Data were used from the baseline, 3-, 6-, and 9-year follow-up waves of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a representative study of Dutch adults aged 18-64 at baseline (N = 6,646; number of data points: 20,574). Alcohol consumption, alcohol use disorder (AUD), and mental disorders were assessed with the Composite International Diagnostic Interview 3.0. Latent Markov Modelling was used to identify latent groups based on high average alcohol consumption (HAAC) and AUD and to determine transition patterns of people between groups over time (stayers vs. movers). RESULTS: The best fitting model resulted in four latent groups: one nonproblematic group (91%): no HAAC, no AUD; and three problematic alcohol use groups (9%): HAAC, no AUD (5%); no HAAC, often AUD (3%); and HAAC and AUD (1%). HAAC, no AUD was associated with a high mean age (55 years) and low educational level (41%), and no HAAC, often AUD with high proportions of males (78%) and people with high educational level (46%). Eighty-seven percent of all respondents - mostly people with no HAAC, no AUD - stayed in their original group during the whole 9-year period. Among movers, people in a problematic alcohol use group (HAAC and/or AUD) mostly transitioned to another problematic alcohol use group and not to the nonproblematic alcohol use group (no HAAC, no AUD). Explorative analyses suggested that lack of physical activity possibly plays a role in transitions both from and to problematic alcohol use groups over time. CONCLUSION: The detection of three problematic alcohol use groups - with transitions mostly between the different problematic alcohol use groups and not to the group without alcohol problems - points to the need to explicitly address both alcohol consumption and alcohol-related problems (AUD criteria) in screening measures and interventions in order not to miss and to adequately treat all problematic alcohol users. Moreover, explorative findings suggest that prevention measures should also include physical activity.

How chronic are depressive and anxiety disorders? 9-year general population study using narrow and broad course outcomes.

BACKGROUND: Existing studies on disease course usually apply relatively short follow-up periods and narrow definitions of disease course resulting in too optimistic views on disease prognosis. This study explores the relevance of using a longer and broader (cross-disorder) perspective. METHODS: Respondents with a 12-month disorder at baseline and available at 3-, 6- and 9-year follow-up were selected (major depressive disorder, MDD: n = 208; anxiety disorder: n = 220) from a general population study (N = 6646). DSM-IV disorders were assessed with the Composite International Diagnostic Interview. Disease course was described using a short and narrow perspective (i.e., 3-year follow-up, and considering presence of the index disorder only) and a long and broad perspective (9-year follow-up, and considering presence of any mood, anxiety or substance use disorder as outcome). RESULTS: The recovery rates of both MDD and anxiety disorder reduced by half when the perspective switched from short and narrow (MDD: 74.0 %; anxiety disorder: 79.5 %) to long and broad (35.6 % and 40.0 % respectively). At 9-year follow-up, the rates of a persistent disorder (a disorder at each follow-up assessment) tripled when the perspective switched from narrow to broad (MDD: from 4.8 % to 13.9 %; anxiety disorder: from 4.5 % to 15.5 %). LIMITATIONS: The findings are not generalizable to the most severe depressed and anxious patients. CONCLUSIONS: Most people with MDD or anxiety disorder in the general population have a rather favourable prognosis when a narrow perspective is applied, but an unfavourable prognosis when a long-term and broad perspective is applied. Consequently, MDD and anxiety disorder should not merely be perceived as episodic disorders, and require longer-term disease monitoring and management.

Body Mass Index and risk for onset of mood and anxiety disorders in the general population: Results from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2).

BACKGROUND: Examine the onset of a clinical diagnosis of mood (major depression, dysthymia and bipolar disorder)- and anxiety disorders (panic disorder, agoraphobia without panic disorder, social phobia, specific phobia and generalized anxiety disorder) by Body Mass Index levels at baseline in the general adult population over three years. METHODS: Data are from NEMESIS-2, a representative psychiatric cohort study in the Netherlands. A total of 5303 subjects aged 18-64 were interviewed with the CIDI (3.0 based on DSM-IV) in two waves, with an interval of three years. The first wave was performed from November 2007 to July 2009, the second wave from November 2010 to June 2012. RESULTS: Persons with obesity at baseline had a significantly increased risk of the onset of any mood -or anxiety disorder adjusting for covariates compared to persons with a normal Body Mass Index (OR = 1.71; 95% CI: 1.11-2.62). The odds ratio of the underweight category was non-significant. A dose-response effect of the continuous BMI scores on the onset of any mood or anxiety disorder was found (OR = 1.06; 95% CI: 1.02 = 1.10; p < 0.01). CONCLUSIONS: Obesity at baseline is a risk for the onset of mood -and anxiety disorders at three year follow up.

The bidirectional relationship between anxiety disorders and alcohol use disorders in adults: Findings from a longitudinal population-based study.

BACKGROUND: Anxiety disorders (AD) and alcohol use disorder (AUD) frequently co-occur, but the temporal order of the association is unclear. We have determined the association between AD and the presence and first-onset of AUD, and vice versa. METHODS: Data were used from n = 6.646 participants and four measurement waves (baseline, 3-, 6- and 9-years) of the Netherlands Mental Health Survey and Incidence Study 2 (NEMESIS-2), a cohort study of the Dutch general population aged 18-64 years. AD and AUD were assessed with the Composite International Diagnostic Interview 3.0. Multilevel logistic autoregressive models were controlled for previous-wave AD or AUD, sociodemographics (Model 1), smoking and clinical factors (Model 2). RESULTS: People with AUD had a higher risk of present (OR = 1.65, 95 % CI 1.11-2.43; Model 2) and first-onset (OR = 2.03, 95 % CI 1.17-3.51; Model 2) AD in 3-years follow-up intervals than people without AUD. Vice versa, people with AD also had a higher sociodemographics-adjusted risk of present and first-onset AUD over 3-years follow-up intervals, but these associations attenuated into insignificance after adjustment for smoking and clinical variables. Limitations For statistical power reasons we were not able to analyze 9-year follow-up data or distinguish between AD and AUD types. CONCLUSIONS: Our results indicate a bidirectional relationship between AD and AUD; especially those with severe AD (medication use, comorbid depression) are at risk of developing AUD. Health care professionals should focus on prevention of AD in AUD patients and prevention of AUD in patients with (more severe) AD. Further research should investigate the mechanisms underlying the observed associations.

Genetic Risk for Smoking: Disentangling Interplay Between Genes and Socioeconomic Status.

This study aims to disentangle the contribution of genetic liability, educational attainment (EA), and their overlap and interaction in lifetime smoking. We conducted genome-wide association studies (GWASs) in UK Biobank (N = 394,718) to (i) capture variants for lifetime smoking, (ii) variants for EA, and (iii) variants that contribute to lifetime smoking independently from EA ('smoking-without-EA'). Based on the GWASs, three polygenic scores (PGSs) were created for individuals from the Netherlands Twin Register (NTR, N = 17,805) and the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2, N = 3090). We tested gene-environment (G × E) interactions between each PGS, neighborhood socioeconomic status (SES) and EA on lifetime smoking. To assess if the PGS effects were specific to smoking or had broader implications, we repeated the analyses with measures of mental health. After subtracting EA effects from the smoking GWAS, the SNP-based heritability decreased from 9.2 to 7.2%. The genetic correlation between smoking and SES characteristics was reduced, whereas overlap with smoking traits was less affected by subtracting EA. The PGSs for smoking, EA, and smoking-without-EA all predicted smoking. For mental health, only the PGS for EA was a reliable predictor. There were suggestions for G × E for some relationships, but there were no clear patterns per PGS type. This study showed that the genetic architecture of smoking has an EA component in addition to other, possibly more direct components. PGSs based on EA and smoking-without-EA had distinct predictive profiles. This study shows how disentangling different models of genetic liability and interplay can contribute to our understanding of the etiology of smoking.

Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway.

BACKGROUND: There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. METHODS: We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. RESULTS: The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465). CONCLUSIONS: The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

Combined impact of ADHD and insomnia symptoms on quality of life, productivity, and health care use in the general population.

BACKGROUND: Both attention-deficit/hyperactivity disorder (ADHD) and insomnia have been independently related to poorer quality of life (QoL), productivity loss, and increased health care use, although most previous studies did not take the many possible comorbidities into account. Moreover, ADHD and insomnia often co-occur. Symptoms of ADHD and insomnia together may have even stronger negative effects than they do separately. We investigated the combined effects of symptoms of ADHD and insomnia, in addition to their independent effects, on QoL, productivity, and health care use, thereby controlling for a wide range of possible comorbidities and confounders. METHODS: Data from the third wave of the Netherlands Mental Health Survey and Incidence Study-2 were used, involving N = 4618 from the general population. Both the inattention and the hyperactivity ADHD symptom dimensions were studied, assessed by the ASRS Screener. RESULTS: Mental functioning and productivity were negatively associated with the co-occurrence of ADHD and insomnia symptoms, even after adjusting for comorbidity and confounders. The results show no indication of differences between inattention and hyperactivity. Poorer physical functioning and health care use were not directly influenced by the interaction between ADHD and insomnia. CONCLUSIONS: People with both ADHD and sleep problems have increased risk for poorer mental functioning and productivity loss. These results underscore the importance of screening for sleep problems when ADHD symptoms are present, and vice versa, and to target both disorders during treatment.