Bipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.

Among the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.

FDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.

Our study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.

Vulnerability to depression can be measured in different ways. We here examine how genetic risk factors are inter-related for lifetime major depression (MD), self-report current depressive symptoms and the personality trait Neuroticism.

We obtained data from three population-based adult twin samples (Virginia n = 4672, Australia #1 n = 3598 and Australia #2 n = 1878) to which we fitted a common factor model where risk for ‘broadly defined depression’ was indexed by (i) lifetime MD assessed at personal interview, (ii) depressive symptoms, and (iii) neuroticism. We examined the proportion of genetic risk for MD deriving from the common factor v. specific to MD in each sample and then analyzed them jointly. Structural equation modeling was conducted in Mx.

The best fit models in all samples included additive genetic and unique environmental effects. The proportion of genetic effects unique to lifetime MD and not shared with the broad depression common factor in the three samples were estimated as 77, 61, and 65%, respectively. A cross-sample mega-analysis model fit well and estimated that 65% of the genetic risk for MD was unique.

A large proportion of genetic risk factors for lifetime MD was not, in the samples studied, captured by a common factor for broadly defined depression utilizing MD and self-report measures of current depressive symptoms and Neuroticism. The genetic substrate for MD may reflect neurobiological processes underlying the episodic nature of its cognitive, motor and neurovegetative manifestations, which are not well indexed by current depressive symptom and neuroticism.

UK veterans suffering from a psychological or psychiatric illness as a consequence of service in the Second World War were entitled to a war pension. Their case files, which include regular medical assessments, are a valuable resource to investigate the nature, distribution and duration of symptoms.

A standardised form was used to collect data from pension records of a random sample of 500 UK army veterans from the first presentation in the 1940s until 1980. Data were also gathered from 50 civilians and 54 emergency responders with a pension for post-traumatic illness following air-raids.

The 10 most common symptoms reported by veterans were anxiety, depression, sleep problems, headache, irritability/anger, tremor/shaking, difficulty completing tasks, poor concentration, repeated fears and avoidance of social contact. Nine of the 10 were widely distributed across the veteran population when symptoms were ranked by the number of subjects who reported them. Nine symptoms persisted significantly longer in the veteran sample than in emergency responders. These included seven of the most common symptoms, together with two others: muscle pain and restlessness. The persistence of these symptoms in the veteran group suggests a post-traumatic illness linked to lengthy overseas service in combat units.

The nature and duration of symptoms exhibited by veterans may be associated with their experience of heightened risks. Exposure to severe or prolonged trauma seems to be associated with chronic multi-symptom illness, symptoms of post-traumatic stress and somatic expressions of pain that may delay or complicate the recovery process.

Decreased white matter (WM) integrity in patients with psychotic disorder has been a consistent finding in diffusion tensor imaging (DTI) studies. However, the contribution of environmental risk factors to these WM alterations is rarely investigated. The current study examines whether individuals with (increased risk for) psychotic disorder will show increased WM integrity change over time with increasing levels of childhood trauma and cannabis exposure.

DTI scans were obtained from 85 patients with a psychotic disorder, 93 non-psychotic siblings and 80 healthy controls, of which 60% were rescanned 3 years later. In a whole-brain voxel-based analysis, associations between change in fractional anisotropy (ΔFA) and environmental exposures as well as interactions between group and environmental exposure in the model of FA and ΔFA were investigated. Analyses were adjusted for a priori hypothesized confounding variables: age, sex, and level of education.

At baseline, no significant associations were found between FA and both environmental risk factors. At follow-up as well as over a 3-year interval, significant interactions between group and, respectively, cannabis exposure and childhood trauma exposure in the model of FA and ΔFA were found. Patients showed more FA decrease over time compared with both controls and siblings when exposed to higher levels of cannabis or childhood trauma.

Higher levels of cannabis or childhood trauma may compromise connectivity over the course of the illness in patients, but not in individuals at low or higher than average genetic risk for psychotic disorder, suggesting interactions between the environment and illness-related factors.

People with schizophrenia process language in unusual ways, but the causes of these abnormalities are unclear. In particular, it has proven difficult to empirically disentangle explanations based on impairments in the top-down processing of higher level information from those based on the bottom-up processing of lower level information.

To distinguish these accounts, we used visual-world eye tracking, a paradigm that measures spoken language processing during real-world interactions. Participants listened to and then acted out syntactically ambiguous spoken instructions (e.g. ‘tickle the frog with the feather’, which could either specify how to tickle a frog, or which frog to tickle). We contrasted how 24 people with schizophrenia and 24 demographically matched controls used two types of lower level information (prosody and lexical representations) and two types of higher level information (pragmatic and discourse-level representations) to resolve the ambiguous meanings of these instructions. Eye tracking allowed us to assess how participants arrived at their interpretation in real time, while recordings of participants’ actions measured how they ultimately interpreted the instructions.

We found a striking dissociation in participants’ eye movements: the two groups were similarly adept at using lower level information to immediately constrain their interpretations of the instructions, but only controls showed evidence of fast top-down use of higher level information. People with schizophrenia, nonetheless, did eventually reach the same interpretations as controls.

These data suggest that language abnormalities in schizophrenia partially result from a failure to use higher level information in a top-down fashion, to constrain the interpretation of language as it unfolds in real time.

The atypical processing of eye contact is a characteristic hallmark of autism spectrum disorder (ASD). The severity of these symptoms, however, is thought to lie on a continuum that extends into the typical population. While behavioural evidence shows that differences in social cognitive tasks in typically developed (TD) adults are related to the levels of autistic-like traits, it remains unknown whether such a relation exists for the sensitivity to direct gaze.

In two experiments, we measured reaction times to detect the faces with direct and averted gaze, suppressed from awareness, i.e. the access to awareness. In experiment 1, we tested N = 19 clinically diagnosed adults with ASD and N = 22 TD matched controls, while in experiment 2, we tested an independent sample of N = 20 TD adults.

In line with the literature, experiment 1 showed preferential processing of direct gaze in the TD group but not in the ASD group. Importantly, we found a linear relationship in both experiments between the levels of autistic traits within the groups of TD participants and their sensitivity to direct gaze: with increasing autistic characteristics, there was a decrease in sensitivity to direct gaze.

These results provide the first evidence that differences in gaze processing and the sensitivity to direct gaze are already present in individuals with subclinical levels of autistic traits. Furthermore, they lend support to the continuum view of the disorder and could potentially help in an earlier diagnosis of individuals at high risk for autism.

The aim of this study was to explore the relationship between patient self-reported Patient Health Questionnaire-9 (PHQ-9) symptoms and doctor diagnosis of depression using a tree analysis approach.

This was a secondary analysis on a dataset obtained from 10 179 adult primary care patients and 59 primary care physicians (PCPs) across Hong Kong. Patients completed a waiting room survey collecting data on socio-demographics and the PHQ-9. Blinded doctors documented whether they thought the patient had depression. Data were analyzed using multiple logistic regression and conditional inference decision tree modeling.

PCPs diagnosed 594 patients with depression. Logistic regression identified gender, age, employment status, past history of depression, family history of mental illness and recent doctor visit as factors associated with a depression diagnosis. Tree analyses revealed different pathways of association between PHQ-9 symptoms and depression diagnosis for patients with and without past depression. The PHQ-9 symptom model revealed low mood, sense of worthlessness, fatigue, sleep disturbance and functional impairment as early classifiers. The PHQ-9 total score model revealed cut-off scores of >12 and >15 were most frequently associated with depression diagnoses in patients with and without past depression.

A past history of depression is the most significant factor associated with the diagnosis of depression. PCPs appear to utilize a hypothetical-deductive problem-solving approach incorporating pre-test probability, with different associated factors for patients with and without past depression. Diagnostic thresholds may be too low for patients with past depression and too high for those without, potentially leading to over and under diagnosis of depression.

Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode.

Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning.

Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders.

Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP.

Persisting symptoms after treatment for major depressive disorder (MDD) contribute to ongoing impairment and relapse risk. Whether cognitive behavior therapy (CBT) or antidepressant medications result in different profiles of residual symptoms after treatment is largely unknown.

Three hundred fifteen adults with MDD randomized to treatment with either CBT or antidepressant medication in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study were analyzed for the frequency of residual symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) item scores at the end of the 12-week treatment period. Separate comparisons were made for treatment responders and non-responders.

Among treatment completers (n = 250) who responded to CBT or antidepressant medication, there were no significant differences in the persistence of residual MADRS symptoms. However, non-responders treated with medication were significantly less likely to endorse suicidal ideation (SI) at week 12 compared with those treated with CBT (non-responders to medication: 0/54, 0%, non-responders to CBT: 8/30, 26.7%; p = .001). Among patients who terminated the trial early (n = 65), residual MADRS item scores did not significantly differ between the CBT- and medication-treated groups.

Depressed adults who respond to CBT or antidepressant medication have similar residual symptom profiles. Antidepressant medications reduce SI, even among patients for whom the medication provides little overall benefit.

In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors.

In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models.

A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (β = −0.09, t = −3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (β = 0.09, t = 3.04, p = 0.002).

In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.

Evidence suggests that cannabis-induced psychotic-like experiences may be a marker of psychosis proneness. The effect of such experiences on cannabis use has not systematically been examined.

We undertook a mixed-methods online survey of 1231 cannabis users (including 926 continued users) using the Cannabis Experiences Questionnaire. We examined the effect of psychotic-like and pleasurable experiences on cessation of cannabis and intention to quit. Socio-demographic variables, cannabis use parameters and substance misuse history were included as covariates. Free-text data explored subjective reasons for changes in use.

Cessation of cannabis use was associated with greater psychotic-like experiences [p < 0.001, Exp(B) 1.262, 95% confidence interval (CI) 1.179–1.351], whilst continued cannabis users were more likely to report pleasurable experiences [p < 0.001, Exp(B) 0.717, 95% CI 0.662–0.776]. Intention to quit cannabis in continued users was associated with greater psychotic-like experiences [p < 0.003, Exp(B) 1.131, 95% CI 1.044–1.225], whilst intention to not quit was significantly associated with increased pleasurable experiences [p < 0.015, Exp(B) 0.892, 95% CI 0.814–0.978]. Whereas former users clearly ascribed cessation to negative experiences, continued users who expressed intention to quit less readily ascribed the intention to negative experiences.

Elucidation of psychotic-like experiences may form the basis of a therapeutic intervention for those who wish to quit. Cessation in those with cannabis-induced psychotomimetic experiences may offset the risk for the development of a psychotic disorder, in this higher risk group.

Trait impulsivity is thought to play a key role in predicting behaviors on the externalizing spectrum, such as drug and alcohol use and aggression. Research suggests that impulsivity may not be a unitary construct, but rather multidimensional in nature with dimensions varying across self-report assessments and laboratory behavioral tasks. Few studies with large samples have included a range of impulsivity-related measures and assessed several externalizing behaviors to clarify the predictive validity of these assessments on important life outcomes.

Community adults (N = 1295) between the ages of 30 and 54 completed a multidimensional assessment of impulsivity-related traits (including 54 self-report scales of personality traits implicated in impulsive behaviors, and four behavioral tasks purporting to assess a construct similar to impulsivity) and reported on five externalizing behavioral outcomes (i.e. drug, alcohol, and cigarette use, and physical and verbal aggression). We ran an exploratory factor analysis on the trait scales, and then a structural equation model predicting the externalizing behaviors from the three higher-order personality factors (i.e. Disinhibition v. Constraint/Conscientiousness, Neuroticism/Negative Emotionality, and Extraversion/Positive Emotionality) and the four behavioral tasks.

Relations between the self-report factors and behavioral tasks were small or nonexistent. Associations between the self-report factors and the externalizing outcomes were generally medium to large, but relationships between the behavioral tasks and externalizing outcomes were either nonexistent or small.

These results partially replicate and extend recent meta-analytic findings reported by Sharma et al. (2014) to further clarify the predictive validity of impulsivity-related trait scales and laboratory behavioral tasks on externalizing behaviors.

The aim of this study was to build a detailed, integrative profile of the correlates of young adults’ feelings of loneliness, in terms of their current health and functioning and their childhood experiences and circumstances.

Data were drawn from the Environmental Risk Longitudinal Twin Study, a birth cohort of 2232 individuals born in England and Wales in 1994 and 1995. Loneliness was measured when participants were aged 18. Regression analyses were used to test concurrent associations between loneliness and health and functioning in young adulthood. Longitudinal analyses were conducted to examine childhood factors associated with young adult loneliness.

Lonelier young adults were more likely to experience mental health problems, to engage in physical health risk behaviours, and to use more negative strategies to cope with stress. They were less confident in their employment prospects and were more likely to be out of work. Lonelier young adults were, as children, more likely to have had mental health difficulties and to have experienced bullying and social isolation. Loneliness was evenly distributed across genders and socioeconomic backgrounds.

Young adults’ experience of loneliness co-occurs with a diverse range of problems, with potential implications for health in later life. The findings underscore the importance of early intervention to prevent lonely young adults from being trapped in loneliness as they age.

There is limited research that explores the association between exclusion from school and mental health, but it seems intuitively plausible that the recognition of mental difficulties by key teachers and parents would influence the likelihood of exclusion from school.

A secondary analysis of the British Child and Adolescent Mental Health survey 2004, (n = 7997) and the 2007 follow-up (n = 5326) was conducted. Recognition of difficulty was assessed via a derived variable that combined the first item of the Impact supplement of the Strengths and Difficulties Questionnaire which asked parents and teachers if they thought that the child has difficulties with emotions, behaviour and concentration, and the presence/absence of psychiatric disorder measured by the Development and Well-being Assessment.

Adjusted logistic regression models demonstrated that children with recognised difficulties were more likely to be excluded [adjusted odds ratio (OR) 5.78, confidence interval 3.45–9.64, p < 0.001], but children with unrecognised difficulties [adjusted OR 3.58 (1.46–8.81) p < 0.005] or recognised subclinical difficulties [adjusted OR 3.42 (2.04–5.73) p < 0.001] were also more likely to be excluded than children with no difficulties. Children with conduct disorder and attention deficit hyperactivity disorder were most likely to be excluded compared with other types of disorder.

Exclusion from school may result from a failure to provide timely and effective support rather than a failure to recognise psychopathology.

Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.

We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.

Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.

Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.

Depressive symptoms and inflammation are risk factors for cardiovascular disease (CVD) and mortality. We investigated the combined association of these factors with the prediction of CVD and all-cause mortality in a representative cohort of older men and women.

We measured C-reactive protein (CRP) and depressive symptoms in 5328 men and women aged 52–89 years in the English Longitudinal Study of Ageing. Depressive symptoms were measured using the eight-item Centre for Epidemiological Studies Depression Scale. CRP was analysed from peripheral blood. Mortality was ascertained from national registers and associations with depressive symptoms and inflammation were estimated using Cox proportional hazard models.

We identified 112 CVD related deaths out of 420 all-cause deaths in men and 109 CVD related deaths out of 334 all-cause deaths in women over a mean follow-up of 7.7 years. Men with both depressive symptoms and high CRP (3–20 mg/L) had an increased risk of CVD mortality (hazard ratio; 95% confidence interval: 3.89; 2.04–7.44) and all-cause mortality (2.40; 1.65–3.48) after adjusting for age, socioeconomic variables and health behaviours. This considerably exceeds the risks associated with high CRP alone (CVD 2.43; 1.59–3.71, all-cause 1.49; 1.20–1.84). There was no significant increase in mortality risk associated with depressive symptoms alone in men. In women, neither depressive symptoms or inflammation alone or the combination of both significantly predicted CVD or all-cause mortality.

The combination of depressive symptoms and increased inflammation confers a considerable increase in CVD mortality risk for men. These effects appear to be independent, suggesting an additive role.

Suicide attempt (SA), which is one of the strongest predictors of completed suicide, is common in major depressive disorder (MDD) but its prevalence across epidemiological studies has been mixed. The aim of this comprehensive meta-analysis was to examine the pooled prevalence of SA in individuals with MDD.

A systematic literature search was conducted in PubMed, Embase, PsycINFO, Web of Science and Cochrane Library from their commencement date until 27 December 2017. Original studies containing data on prevalence of SA in individuals with MDD were analyzed.

In all, 65 studies with a total of 27 340 individuals with MDD were included. Using the random effects model, the pooled lifetime prevalence of SA was 31% [95% confidence interval (CI) 27–34%], 1-year prevalence was 8% (95% CI 3–14%) and 1-month prevalence was 24% (95% CI 15–34%). Subgroup analyses revealed that the lifetime prevalence of SA was significantly associated with the patient setting, study region and income level, while the 1-month prevalence of SA was associated with only the patient setting.

This meta-analysis confirmed that SA was common in individuals with MDD across the world. Careful screening and appropriate interventions should be implemented for SA in the MDD population.

Research has revealed that negative expectations impact depressive symptoms. However, research on the change of dysfunctional expectations in depression is lacking so far. Therefore, the present research aimed to fill this gap by testing the hypothesis that people with the major depressive disorder (MDD), contrary to healthy individuals, maintain their expectations despite experiences that positively disconfirm expectations. Further, it was hypothesized that cognitive immunization (a cognitive reappraisal of the disconfirming evidence) is a mechanism underlying the persistence of expectations.

In Study 1, we compared individuals with MDD (N = 58) to healthy individuals (N = 59). Participants worked on the same performance test and received standardized feedback that either confirmed or disconfirmed their initial performance expectations. In Study 2, we investigated the effects of cognitive immunization on expectation change among 59 individuals reporting elevated levels of depression by varying the appraisal of expectation-disconfirming feedback.

Results from Study 1 show that in the expectation-disconfirming condition, healthy individuals changed their expectations, whereas individuals with MDD did not. No such difference between the two groups was found for expectation-confirming feedback. Results from Study 2 indicated that varying cognitive immunization impacted expectation change, thus suggesting a crucial role of cognitive immunization in expectation change.

These two studies indicated that individuals suffering from depression have more difficulties in changing their expectations after disconfirming experiences than do healthy individuals, and cognitive immunization might be a core mechanism underlying expectation persistence. Therefore, psychotherapeutic interventions should aim to inhibit cognitive immunization processes to enhance expectation change.

Suicide rate among rural elderly is the highest among all age groups in China, yet little is known about the suicide risks in this rapidly growing vulnerable population.

This matched case–control psychological autopsy study was conducted during June 2014 to September 2015. Consecutive samples of suicides aged 60 or above were identified in three provinces (Shandong, Hunan, and Guangxi) in China. Living comparisons were 1:1 matched with the suicides in age (±3 years old), gender, and living location. Risk factors included demographic characteristics, being left-behind, mental disorder, depressive symptoms, stressful life events, and social support.

A total of 242 suicides and 242 comparisons were enrolled: 135 (55.8%) were male, mean (s.d.) age was 74 (8) years. The most frequently used suicide means were pesticides (125, 51.7%) and hanging (95, 39.3%). Independent risks of suicide included unstable marital status [odds ratio (OR) 4.19, 95% confidence interval (CI) 1.61–10.92], unemployed (compared with employed, OR 4.43, 95% CI 1.09–17.95), depressive symptoms (OR 1.34, 95% CI 1.21–1.48), and mental disorder (OR 6.28, 95% CI 1.75–22.54). Structural equation model indicated that the association between being left-behind and suicide was mediated by mental disorder, depressive symptoms, stressful life events, and social support.

Unstable marital status, unemployed, depressive symptoms, and mental disorder are independent risk factors for suicide in rural elderly. Being left-behind can elevate the suicide risk through increasing life stresses, depressive symptoms, mental disorder, and decreasing social support. Elderly suicide may be prevented by restricting pesticides, training rural physicians, treating mental disorders, mitigating life stress, and enhancing social connection.

Cognitive models of obsessive–compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala–prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala–prefrontal connections. However, abnormalities in amygdala–prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly.

Amygdala–prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples.

During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala–ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest.

Our finding of abnormal amygdala–prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala–prefrontal coupling in affective models of OCD.