Experimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment.

Here, we explored the prospective association between typical variation in maternal sensitivity and offspring epigenome-wide DNAm, in a population-based cohort of children (N = 235). Maternal sensitivity was observed when children were 3- and 4-years-old. DNAm, quantified with the Infinium 450 K array, was extracted at age 6 (whole blood). The influence of methylation quantitative trait loci (mQTLs), DNAm at birth (cord blood), and confounders (socioeconomic status, maternal psychopathology) was considered in follow-up analyses.

Genome-wide significant associations between maternal sensitivity and offspring DNAm were observed at 13 regions (p < 1.06 × 10−07), but not at single sites. Follow-up analyses indicated that associations at these regions were in part related to genetic factors, confounders, and baseline DNAm levels at birth, as evidenced by the presence of mQTLs at five regions and estimate attenuations. Robust associations with maternal sensitivity were found at four regions, annotated to ZBTB22, TAPBP, ZBTB12, and DOCK4.

These findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses.

For a small minority of personnel, military service can have a negative impact on their mental health. Yet no studies have assessed how the mental health of UK veterans (who served during the recent operations in Afghanistan or Iraq) compares to non-veterans, to determine if they are at a disadvantage. We examine the prevalence of mental disorders and alcohol misuse in UK veterans compared to non-veterans.

Veteran data were taken from the third phase of the King's Centre for Military Health Research cohort study (n = 2917). These data were compared with data on non-veterans taken from two large general population surveys: 2014 Adult Psychiatric Morbidity Survey (n = 5871) and wave 6 of the UK Household Longitudinal Study (UKHLS, n = 22 760).

We found that, overall, UK veterans who served at the time of recent military operations were more likely to report a significantly higher prevalence of common mental disorders (CMD) (23% v. 16%), post-traumatic stress disorder (PTSD) (8% v. 5%) and alcohol misuse (11% v. 6%) than non-veterans. Stratifying by gender showed that the negative impact of being a veteran on mental health and alcohol misuse was restricted to male veterans. Being ill or disabled was associated with a higher prevalence of CMD and PTSD for both veterans and non-veterans.

Whilst the same sociodemographic groups within the veteran and non-veteran populations seemed to have an increased risk of mental health problems (e.g. those who were unemployed), male veterans, in particular, appear to be at a distinct disadvantage compared to those who have never served.

Genetically informed studies have provided mixed findings as to what extent parental substance misuse is associated with offspring substance misuse and antisocial behavior due to shared environmental and genetic factors.

We linked data from nationwide registries for a cohort of 2 476 198 offspring born in Sweden 1958–1995 and their parents. Substance misuse was defined as International Classification of Diseases diagnoses of alcohol/drug use disorders or alcohol/drug-related criminal convictions. Quantitative genetic offspring-of-siblings analyses in offspring of monozygotic and dizygotic twin, full-sibling, and half-sibling parents were conducted.

Both maternal and paternal substance misuse were robustly associated with offspring substance misuse [maternal adjusted hazard ratio (aHR) = 1.83 (95% confidence interval (CI) 1.80–1.87); paternal aHR = 1.96 (1.94–1.98)] and criminal convictions [maternal aHR = 1.56 (1.54–1.58); paternal aHR = 1.66 (1.64–1.67)]. Additive genetic effects explained 42% (95% CI 25–56%) and 46% (36–55%) of the variance in maternal and paternal substance misuse, respectively, and between 36 and 44% of the variance in substance misuse and criminality in offspring. The associations between parental substance misuse and offspring outcomes were mostly due to additive genetic effects, which explained 54–85% of the parent-offspring covariance. However, both nuclear and extended family environmental factors also contributed to the associations, especially with offspring substance misuse.

Our findings from a large offspring-of-siblings study indicate that shared genetic influences mostly explain the associations between parental substance misuse and both offspring substance misuse and criminality, but we also found evidence for the contribution of environmental factors shared by members of nuclear and extended families.

Cluster analyses have become popular tools for data-driven classification in biological psychiatric research. However, these analyses are known to be sensitive to the chosen methods and/or modelling options, which may hamper generalizability and replicability of findings. To gain more insight into this problem, we used Specification-Curve Analysis (SCA) to investigate the influence of methodological variation on biomarker-based cluster-analysis results.

Proteomics data (31 biomarkers) were used from patients (n = 688) and healthy controls (n = 426) in the Netherlands Study of Depression and Anxiety. In SCAs, consistency of results was evaluated across 1200 k-means and hierarchical clustering analyses, each with a unique combination of the clustering algorithm, fit-index, and distance metric. Next, SCAs were run in simulated datasets with varying cluster numbers and noise/outlier levels to evaluate the effect of data properties on SCA outcomes.

The real data SCA showed no robust patterns of biological clustering in either the MDD or a combined MDD/healthy dataset. The simulation results showed that the correct number of clusters could be identified quite consistently across the 1200 model specifications, but that correct cluster identification became harder when the number of clusters and noise levels increased.

SCA can provide useful insights into the presence of clusters in biomarker data. However, SCA is likely to show inconsistent results in real-world biomarker datasets that are complex and contain considerable levels of noise. Here, the number and nature of the observed clusters may depend strongly on the chosen model-specification, precluding conclusions about the existence of biological clusters among psychiatric patients.

Childbirth may pose many challenges to the psychological well-being of marriage-based immigrant mothers in interracial marriages, who must negotiate bi-dimensional acculturation – adaptation to the host culture and maintenance of her own heritage culture. We examined the temporal relationships between bi-dimensional acculturation and depressive symptoms from pregnancy to 1 year postpartum among marriage-based immigrant mothers in Taiwan using the cross-lagged structural equation modeling.

This study recruited 310 immigrant mothers, who were examined in the second and third trimesters, and again at 1 month, 3 months, 6 months, and 1 year postpartum from March 2013 to December 2015. Depressive symptoms and bi-dimensional acculturation were measured using the Edinburgh Postnatal Depression Scale and Bidimensional Acculturation Scale for Marriage-Based Immigrant Women, respectively.

The study found that adaptation to the host culture followed a downward linear trajectory, while maintenance of the mother's own heritage culture followed an upward linear trajectory from pregnancy to 1 year postpartum. All but one cross-lagged path between bi-dimensional acculturation and depressive symptoms was statistically insignificant, though almost all cross-sectional associations were significant. Adaptation to host culture was negatively associated with depressive symptoms at all time points. The association between maintenance of heritage culture and depressive symptoms reversed from positive to negative after 6 months postpartum.

Adaptation to the host culture and maintenance of the mother's heritage culture differed in their associations with maternal depressive symptoms. Health professionals should assist immigrant mothers in adapting to the host culture while supporting their heritage culture in the childbearing period.

Aerobic exercise has demonstrated antidepressant efficacy among adults with major depression. There is a poor understanding of the neural mechanisms associated with these effects. Deficits in reward processing and cognitive control may be two candidate targets and predictors of treatment outcome to exercise in depression.

Sixty-six young adults aged 20.23 years (s.d. = 2.39) with major depression were randomized to 8 weeks of moderate-intensity aerobic exercise (n = 35) or light stretching (n = 31). Depressive symptoms were assessed across the intervention to track symptom reduction. Reward processing [reward positivity (RewP)] and cognitive control [error-related negativity (ERN)] were assessed before and after the intervention using event-related brain potentials.

Compared to stretching, aerobic exercise resulted in greater symptom reduction (gs = 0.66). Aerobic exercise had no impact on the RewP (gav = 0.08) or ERN (gav = 0.21). In the aerobic exercise group, individuals with a larger pre-treatment RewP [odds ratio (OR) = 1.45] and increased baseline depressive symptom severity (OR = 1.18) were more likely to respond to an aerobic exercise program. Pre-treatment ERN did not predict response (OR = 0.74).

Aerobic exercise is effective in alleviating depressive symptoms in adults with major depression, particularly for those with increased depressive symptom severity and a larger RewP at baseline. Although aerobic exercise did not modify the RewP or ERN, there is preliminary support for the utility of the RewP in predicting who is most likely to respond to exercise as a treatment for depression.

Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association.

We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide.

In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73–2.78 after 1 month of use, and 1.25–1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period.

Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.

Eating-disorder severity indicators should theoretically index symptom intensity, impairment, and level of needed treatment. Two severity indicators for binge-eating disorder (BED) have been proposed (categories of binge-eating frequency and shape/weight overvaluation) but have mixed empirical support including modest clinical utility. This project uses structural equation model (SEM) trees – a form of exploratory data mining – to empirically determine the precise levels of binge-eating frequency and/or shape/weight overvaluation that most significantly differentiate BED severities.

Participants were 788 adults with BED enrolled in BED treatment studies. Participants completed interviews and self-report measures assessing eating-disorder and comorbid symptoms. SEM Tree analyses were performed by specifying an outcome model of BED severity and then recursively partitioning the outcome model into subgroups. Subgroups were split based on empirically determined values of binge-eating frequency and/or shape/weight overvaluation. SEM Forests also quantified which variable contributed more improvement in model fit.

SEM Tree analyses yielded five subgroups, presented in ascending order of severity: overvaluation <1.25, overvaluation = 1.25–2.74, overvaluation = 2.75–4.24, overvaluation ⩾4.25 with weekly binge-eating frequency <4.875, and overvaluation ⩾4.25 with weekly binge-eating frequency ⩾4.875. SEM Forest analyses revealed that splits that occurred on shape/weight overvaluation resulted in much more improvement in model fit than splits that occurred on binge-eating frequency.

Shape/weight overvaluation differentiated BED severity more strongly than binge-eating frequency. Findings indicate a nuanced potential BED severity indicator scheme, based on a combination of cognitive and behavioral eating-disorder symptoms. These results inform BED classification and may allow for the provision of more specific and need-matched treatment formulations.

Evidence on inequalities in mental health in lesbian, gay, and bisexual people arises primarily from non-random samples.

To use a probability sample to study change in mental health inequalities between two survey points, 7 years apart; the contribution of minority stress; and whether associations vary by age, gender, childhood sexual abuse, and religious identification.

We analysed data from 10 443 people, in two English population-based surveys (2007 and 2014), on common mental disorder (CMD), hazardous alcohol use, and illicit drug use. Multivariable models were adjusted for age, gender, and economic factors, adding interaction terms for survey year, age, gender, childhood sexual abuse, and religious identification. We explored bullying and discrimination as mediators.

Inequalities in risks of CMD or substance misuse were unchanged between 2007 and 2014. Compared to heterosexuals, bisexual, and lesbian/gay people were more likely to have CMD, particularly bisexual people [adjusted odds ratio (AOR) = 2.86; 95% CI 1.83–4.46], and to report alcohol misuse and illicit drug use. When adjusted for bullying, odds of CMD remained elevated only for bisexual people (AOR = 3.21; 95% CI 1.64–6.30), whilst odds of alcohol and drug misuse were unchanged. When adjusted for discrimination, odds of CMD and alcohol misuse remained elevated only for bisexual people (AOR = 2.91; 95% CI 1.80–4.72; and AOR = 1.63; 95% CI 1.03–2.57 respectively), whilst odds of illicit drug use remained unchanged. There were no interactions with age, gender, childhood sexual abuse, or religious identification.

Mental health inequalities in non-heterosexuals have not narrowed, despite increasing societal acceptance. Bullying and discrimination may help explain the elevated rate of CMD in lesbian women and gay men but not in bisexual people.

Individuals present in lower Manhattan during the 9/11 World Trade Center (WTC) disaster suffered from significant physical and psychological trauma. Studies of longitudinal psychological distress among those exposed to trauma have been limited to relatively short durations of follow-up among smaller samples.

The current study longitudinally assessed heterogeneity in trajectories of psychological distress among WTC Health Registry enrollees – a prospective cohort health study of responders, students, employees, passersby, and residents in the affected area (N = 30 839) – throughout a 15-year period following the WTC disaster. Rescue/recovery status and exposure to traumatic events of 9/11, as well as sociodemographic factors and health status, were assessed as risk factors for trajectories of psychological distress.

Five psychological distress trajectory groups were found: none-stable, low-stable, moderate-increasing, moderate-decreasing, and high-stable. Of the study sample, 78.2% were classified as belonging to the none-stable or low-stable groups. Female sex, being younger at the time of 9/11, lower education and income were associated with a higher probability of being in a greater distress trajectory group relative to the none-stable group. Greater exposure to traumatic events of 9/11 was associated with a higher probability of a greater distress trajectory, and community members (passerby, residents, and employees) were more likely to be in greater distress trajectory groups – especially in the moderate-increasing [odds ratios (OR) 2.31 (1.97–2.72)] and high-stable groups [OR 2.37 (1.81–3.09)] – compared to the none-stable group.

The current study illustrated the heterogeneity in psychological distress trajectories following the 9/11 WTC disaster, and identified potential avenues for intervention in future disasters.

For decades confirmatory factor analysis (CFA) has been the preeminent method to study the underlying structure of posttraumatic stress disorder (PTSD); however, methodological limitations of CFA have led to the emergence of other analytic approaches. In particular, network analysis has become a gold standard to investigate the structure and relationships between PTSD symptoms. A key methodological limitation, however, which has significant clinical implications, is the lack of data on the potential impact of item order effects on the conclusions reached through network analyses.

The current study, involving a large sample (N = 5055) of active duty army soldiers following deployment to Iraq, assessed the vulnerability of network analyses and prevalence rate to item order effects. This was done by comparing symptom networks of the DSM-IV PTSD checklist items to these same items distributed in random order. Half of the participants rated their symptoms on traditionally ordered items and half the participants rated the same items, but in random order and interspersed between items from other validated scales. Differences in prevalence rate and network composition were examined.

The prevalence rate differed between the ordered and random item samples. Network analyses using the ordered survey closely replicated the conclusions reached in the existing network analyses literature. However, in the random item survey, network composition differed considerably.

Order effects appear to have a significant impact on conclusions reached from PTSD network analysis. Prevalence rates were also impacted by order effects. These findings have important diagnostic and clinical treatment implications.

Even though recent research indicates that sexual symptoms are highly prevalent in post-traumatic stress disorder following childhood sexual abuse and cause severe distress, current treatments neither address them nor are they effective in reducing them. This might be due to a lack of understanding of sexual symptoms' specific role in the often complex and comorbid psychopathology of post-traumatic stress disorder following childhood abuse.

Post-traumatic, dissociative, depressive, and sexual symptoms were assessed in 445 inpatients with post-traumatic stress disorder following childhood sexual abuse. Comorbidity structure was analyzed using a partial correlation network with regularization.

A total of 360 patients (81%) reported difficulties engaging in sexual activities and 102 patients (23%) reported to suffer from their sexual preferences. Difficulties engaging in sexual activities were linked to depressive and hyperarousal symptoms, whereas sexual preferences causing distress were linked to anger and dissociation. Dissociative amnesia, visual intrusions, and physical reactions to trauma reminders were of central importance for the network. Dissociative amnesia, depressed mood, lack of energy, and difficulties engaging in sexual activities were identified as bridge symptoms. Local clustering analysis indicated the non-redundancy of sexual symptoms.

Sexual symptoms are highly prevalent in survivors of childhood sexual abuse with post-traumatic stress disorder. Further research is needed regarding the link of difficulties engaging in sexual activities, depression, and post-traumatic stress disorder, as well as regarding the association of dissociation and sexual preferences causing distress. Sexual symptoms require consideration in the treatment of post-traumatic stress disorder following childhood sexual abuse.

Voices are commonly experienced as communication with a personified ‘other’ with ascribed attitudes, intentionality and personality (their own ‘character’). Phenomenological work exploring voice characterisation informs a new wave of relational therapies. To date, no study has investigated the role of characterisation in behavioural engagement with voices or within psychological therapy for distressing voices.

Baseline characterisation (the degree to which the voice is an identifiable and characterful entity) of the dominant voice was rated (high, medium or low) using a newly developed coding framework, for n = 60 people prior to starting AVATAR therapy. Associations between degree of characterisation and (i) everyday behavioural engagement with voices (The Beliefs about Voices Questionnaire-Revised; n = 60); and (ii) interaction within avatar dialogue [Session 4 Time in Conversation (participant–avatar); n = 45 therapy completers] were explored.

Thirty-three per cent reported high voice characterisation, 42% medium and 25% low. There was a significant association between characterisation and behavioural engagement [H(2) = 7.65, p = 0.022, ɛ2 = 0.130] and duration of participant–avatar conversation [F(2,42) = 6.483, p = 0.004, η2 = 0.236]. High characterisation was associated with increased behavioural engagement compared with medium (p = 0.004, r = 0.34; moderate effect) and low (p = 0.027, r = 0.25; small−moderate effect) with a similar pattern observed for the avatar dialogue [high v. medium: p = 0.008, Hedges’ g = 1.02 (large effect); high v. low: p = 0.023, Hedges' g = 1.03 (large effect)]. No differences were observed between medium and low characterisation.

Complex voice characterisation is associated with how individuals interact with their voice(s) in and out of therapy. Clinical implications and future directions for AVATAR therapy and other relational therapies are discussed.

The development of childhood anxiety disorders (CADs) is likely to depend on pathways that can be programmed by early-life risk factors. We test the hypothesis that early-life maternal factors can predict this programming effect on CAD.

Data were obtained from 198 women and children from the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a cohort study with data collected across pregnancy, postpartum and until 4 years of age. Maternal antenatal depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV), together with antenatal hair cortisol concentrations, maternal childhood trauma and parenting stress at 6 months postpartum. CAD was assessed with the Preschool Age Psychiatric Assessment and the Child Behaviour Checklist.

Antenatal depression, a history of maternal childhood trauma and lower gestational age at birth were each associated with anxiety disorders at 4 years of age in their children. A multivariate binary logistic model with these early predictors explained approximately 9% of variance in CAD outcome at 4 years of age; however, only maternal trauma and gestational age were significant predictors in the model. The effect of early parenting stress on CAD was found to vary by the concentration of maternal antenatal hair cortisol, whereby postpartum parenting stress was associated with CAD only when there were higher maternal antenatal cortisol levels.

This study suggests the importance of maternal factors pre-conception, pregnancy and in the postnatal period, which predict CADs and this is consistent with a developmental programming hypothesis for CAD.

Large variations in prevalence rates of common mental disorder (CMD) amongst refugees and forcibly displaced populations have raised questions about the accuracy and value of epidemiological surveys in these cross-cultural settings. We examined the associations of sociodemographic indices, premigration traumatic events (TEs), postmigration living difficulties (PMLDs), and psychosocial disruptions based on the Adaptive Stress Index (ASI) in relation to CMD prevalence amongst the Rohingya, Chin and Kachin refugees originating from Myanmar and relocated to Malaysia.

Parallel epidemiological studies were conducted in areas where the three groups were concentrated in and around Malaysia (response rates: 80–83%).

TE exposure, PMLDs and ASI were significantly associated with CMD prevalence in each group but the Rohingya recorded the highest exposure to all three of these former indices relative to Chin and Kachin (TE: mean = 11.1 v. 8.2 v. 11; PMLD: mean = 13.5 v. 7.4 v. 8.7; ASI: mean = 128.9 v. 32.1 v. 35.5). Multiple logistic regression analyses based on the pooled sample (n = 2058) controlling for gender and age, found that ethnic group membership, premigration TEs (16 or more TEs: OR, 2.00; 95% CI, 1.39–2.88; p < 0.001), PMLDs (10–15 PMLDs: OR, 4.19; 95% CI, 3.17–5.54; 16 or more PMLDs: OR, 7.23; 95% CI, 5.24–9.98; p < 0.001) and ASI score (ASI score 100 or greater: OR, 2.19; 95% CI, 1.46–3.30; p < 0.001) contributed to CMD.

Factors specific to each ethnic group and differences in the quantum of exposure to TEs, PMLDs and psychosocial disruptions appeared to account in large part for differences in prevalence rates of CMDs observed across these three groups.

Suicide and cardiovascular disease rank among the leading causes of disability and premature mortality worldwide. Young adult suicide attempters are at increased risk of mortality from cardiovascular disease even compared to those with major depressive disorder suggesting an increased burden of cardiovascular risk factors. We compared the cardiovascular risk burden between youth attempters and other high-risk individuals.

Participants were from the Collaborative Psychiatric Epidemiology Surveys (CPES), a U.S. population-based study, aged 18–30 years [suicide attempt (SA): n = 303; suicidal ideation (SI): n = 451; controls: n = 3671]; and psychiatric inpatients admitted for a SA (n = 38) or SI (n = 40) and healthy controls (n = 37) aged 15–30 years. We computed a cardiovascular risk score and high- and low-risk latent classes based on risk factors of high blood pressure, obesity, and smoking.

Suicide attempters showed an increased cardiovascular risk score (CPES: B = 0.43, 95% confidence interval (CI) 0.31–0.54, p < 0.001; inpatient sample: B = 1.61, 95% CI 0.53–2.68, p = 0.004) compared to controls. They were also more likely to be classified in the high cardiovascular risk group (CPES: odds ratio (OR) 3.36, 95% CI 1.67–6.78, p = 0.001; inpatient sample: OR 9.89, 95% CI 1.38–85.39, p = 0.03) compared to those with SI (CPES: OR 1.15, 95% CI 0.55–2.39, p = 0.71; inpatient sample: OR 1.91, 95% CI 0.25–15.00, p = 0.53).

Youth attempters show an increased burden for cardiovascular risk compared to other high-risk individuals in inpatient and population-based samples. Clinicians should pay particular attention to cardiovascular risk factors among suicide attempters in order to reduce their risk for cardiovascular events.

Reward dysfunction is a major dimension of depressive symptomatology, but it remains obscure if that dysfunction varies across different reward types. In this study, we focus on the abnormalities in anticipatory/consummatory processing of monetary and social reward associated with depressive symptoms.

Forty participants with depressive symptoms and forty normal controls completed the monetary incentive delay (MID) and social incentive delay (SID) tasks with event-related potential (ERP) recording.

In the SID but not the MID task, both the behavioral hit rate and the ERP component contingent negative variation (CNV; indicating reward anticipation) were sensitive to the interaction between the grouping factor and reward magnitude; that is, the depressive group showed a lower hit rate and a smaller CNV to large-magnitude (but not small-magnitude) social reward cues compared to the control group. Further, these two indexes were correlated with each other. Meanwhile, the ERP components feedback-related negativity and P3 (indicating reward consumption) were sensitive to the main effect of depression across the MID and SID tasks, though this effect was more prominent in the SID task.

Overall, we suggest that depressive symptoms are associated with deficits in both the reward anticipation and reward consumption stages, particularly for social rewards. These findings have a potential to characterize the profile of functional impairment that comprises and maintains depression.

Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.

This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).

FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50–19.67), ADHD 3.94 (CI 3.72–4.17), schizophrenia 3.05 (CI 2.74–3.40), BD 2.22 (CI 1.98–2.48) and MDD 1.88 (CI 1.76–2.00). Higher RRs of schizophrenia (4.47, CI 3.95–5.06) and ASD (18.54, CI 16.18–21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.

The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.

Classic theories posit that depression is driven by a negative learning bias. Most studies supporting this proposition used small and selected samples, excluding patients with comorbidities. However, comorbidity between psychiatric disorders occurs in up to 70% of the population. Therefore, the generalizability of the negative bias hypothesis to a naturalistic psychiatric sample as well as the specificity of the bias to depression, remain unclear. In the present study, we tested the negative learning bias hypothesis in a large naturalistic sample of psychiatric patients, including depression, anxiety, addiction, attention-deficit/hyperactivity disorder, and/or autism. First, we assessed whether the negative bias hypothesis of depression generalized to a heterogeneous (and hence more naturalistic) depression sample compared with controls. Second, we assessed whether negative bias extends to other psychiatric disorders. Third, we adopted a dimensional approach, by using symptom severity as a way to assess associations across the sample.

We administered a probabilistic reversal learning task to 217 patients and 81 healthy controls. According to the negative bias hypothesis, participants with depression should exhibit enhanced learning and flexibility based on punishment v. reward. We combined analyses of traditional measures with more sensitive computational modeling.

In contrast to previous findings, this sample of depressed patients with psychiatric comorbidities did not show a negative learning bias.

These results speak against the generalizability of the negative learning bias hypothesis to depressed patients with comorbidities. This study highlights the importance of investigating unselected samples of psychiatric patients, which represent the vast majority of the psychiatric population.