This meta-analysis seeks to quantify the prospective association between neuroticism and the common mental disorders (CMDs, including anxiety, depression, and substance abuse) as well as thought disorders (psychosis/schizophrenia) and non-specific mental distress. Data on the degree of confounding of the prospective association of neuroticism by baseline symptoms and psychiatric history, and the rate of decay of neuroticism's effect over time, can inform theories about the structure of psychopathology and role of neuroticism, in particular the vulnerability theory.

This meta-analysis included 59 longitudinal/prospective studies with 443 313 participants.

The results showed large unadjusted prospective associations between neuroticism and symptoms/diagnosis of anxiety, depression, and non-specific mental distress (d = 0.50–0.70). Adjustment for baseline symptoms and psychiatric history reduced the associations by half (d = 0.10–0.40). Unadjusted prospective associations for substance abuse and thought disorders/symptoms were considerably weaker (d = 0.03–0.20), but were not attenuated by adjustment for baseline problems. Unadjusted prospective associations were four times larger over short (<4 year) than long (⩾4 years) follow-up intervals, suggesting a substantial decay of the association with increasing time intervals. Adjusted effects, however, were only slightly larger over short v. long time intervals. This indicates that confounding by baseline symptoms and psychiatric history masks the long-term stability of the neuroticism vulnerability effect.

High neuroticism indexes a risk constellation that exists prior to the development and onset of any CMD. The adjusted prospective neuroticism effect remains robust and hardly decays with time. Our results underscore the need to focus on the mechanisms underlying this prospective association.

Social functioning (SF) difficulties are ubiquitous among individuals at clinical high risk for psychosis (CHR), but it is not yet clear why. One possibility is suggested by the observation that effective SF requires adaptive emotion awareness and regulation. Previous reports have documented deficits in emotion awareness and regulation in individuals with schizophrenia, and have shown that such deficits predicted SF. However, it is unknown whether these deficits are present prior to the onset of psychosis or whether they are linked to SF in CHR individuals.

We conducted a cross-sectional comparison of emotion awareness and regulation in 54 individuals at CHR, 87 with schizophrenia and 50 healthy controls (HC). Then, within the CHR group, we examined links between emotion awareness, emotion regulation and SF as indexed by the Global Functioning Scale: Social (Cornblatt et al. 2007).

Group comparisons indicated significant differences between HC and the two clinical groups in their ability to identify and describe feelings, as well as the use of suppression and reappraisal emotion-regulation strategies. Specifically, the CHR and schizophrenia groups displayed comparable deficits in all domains of emotion awareness and emotion regulation. A hierarchical multiple regression analysis indicated that difficulties describing feelings accounted for 23.2% of the SF variance.

The results indicate that CHR individuals display substantial emotion awareness and emotion-regulation deficits, at severity comparable with those observed in individuals with schizophrenia. Such deficits, in particular difficulties describing feelings, predate the onset of psychosis and contribute significantly to poor SF in this population.

Mental health disorders commonly co-occur, even between conceptually distinct syndromes, such as internalizing and externalizing disorders. The current study investigated whether phenotypic, genetic, and environmental variance in negative emotionality and behavioral control account for the covariation between major depressive disorder (MDD) and alcohol use disorder (AUD).

A total of 3623 members of a national twin registry were administered structured diagnostic telephone interviews that included assessments of lifetime histories of MDD and AUD, and were mailed self-report personality questionnaires that assessed stress reactivity (SR) and behavioral control (CON). A series of biometric models were fitted to partition the proportion of covariance between MDD and AUD into SR and CON.

A statistically significant proportion of the correlation between MDD and AUD was due to variance specific to SR (men = 0.31, women = 0.27) and CON (men = 0.20, women = 0.19). Further, genetic factors explained a large proportion of this correlation (0.63), with unique environmental factors explaining the rest. SR explained a significant proportion of the genetic (0.33) and environmental (0.23) overlap between MDD and AUD. In contrast, variance specific to CON accounted for genetic overlap (0.32), but not environmental overlap (0.004). In total, SR and CON accounted for approximately 70% of the genetic and 20% of the environmental covariation between MDD and AUD.

This is the first study to demonstrate that negative emotionality and behavioral control confer risk for the co-occurrence of MDD and AUD via genetic factors. These findings are consistent with the aims of NIMH's RDoC proposal to elucidate how transdiagnostic risk factors drive psychopathology.

Poor impulse control is a common feature in patients with Parkinson's disease (PD). However, before testing whether patients with PD and controls differ in impulsivity, one must assess whether impulsivity measures are invariant across groups. Consequently, we examined (a) the measurement and structural invariance of a scale assessing changes in four dimensions of impulsivity (urgency, lack of premeditation, lack of perseverance and sensation seeking) among patients with PD and controls; and (b) whether the four impulsivity traits relate differentially to risky decisions by patients.

Close relatives of 78 patients with idiopathic PD and 96 control participants were given the short Urgency–Premeditation–Perseverance–Sensation seeking Impulsive Behaviour Scale (UPPS), which assesses changes in four dimensions of impulsivity. Participants also completed the Game of Dice Task (GDT), a laboratory measure of risk taking.

Multigroup confirmatory factor analyses supported measurement invariance across groups, whereas structural invariance was not confirmed. Patients with PD showed greater variability and higher impulsivity than controls. Furthermore, patients with impulse control disorders (ICDs) demonstrated even greater levels of sensation seeking than patients without ICDs. Finally, lower premeditation and greater perseverance were significantly associated with greater risk taking in patients with PD, and higher agonist dopaminergic doses with less risky choices on the GDT.

The questionnaire appears to function comparably across patients and controls. Thus, group comparisons on the questionnaire can be considered valid. Mean differences between groups on the dimensions of impulsivity may reflect executive impairments and/or abnormal reward processing in patients with PD, which may lead to risky behaviours.

Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions?

A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others’ fearful, angry, happy or neutral reactions.

During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others’ fearful reactions, and a trend towards decreased amygdala activation to objects associated with others’ happy and neutral reactions.

These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments.

Although mental disorders are significant predictors of educational attainment throughout the entire educational career, most research on mental disorders among students has focused on the primary and secondary school years.

The World Health Organization World Mental Health Surveys were used to examine the associations of mental disorders with college entry and attrition by comparing college students (n = 1572) and non-students in the same age range (18–22 years; n = 4178), including non-students who recently left college without graduating (n = 702) based on surveys in 21 countries (four low/lower-middle income, five upper-middle-income, one lower-middle or upper-middle at the times of two different surveys, and 11 high income). Lifetime and 12-month prevalence and age-of-onset of DSM-IV anxiety, mood, behavioral and substance disorders were assessed with the Composite International Diagnostic Interview (CIDI).

One-fifth (20.3%) of college students had 12-month DSM-IV/CIDI disorders; 83.1% of these cases had pre-matriculation onsets. Disorders with pre-matriculation onsets were more important than those with post-matriculation onsets in predicting subsequent college attrition, with substance disorders and, among women, major depression the most important such disorders. Only 16.4% of students with 12-month disorders received any 12-month healthcare treatment for their mental disorders.

Mental disorders are common among college students, have onsets that mostly occur prior to college entry, in the case of pre-matriculation disorders are associated with college attrition, and are typically untreated. Detection and effective treatment of these disorders early in the college career might reduce attrition and improve educational and psychosocial functioning.

Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR–stress interaction has been distorted by citation bias and a selective focus on positive findings.

A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined.

In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%.

Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR–stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.

Advancing paternal age has been linked to psychiatric disorders. These associations might be caused by the increased number of de novo mutations transmitted to offspring of older men. It has also been suggested that the associations are confounded by a genetic liability for psychiatric disorders in parents. The aim of this study was to indirectly test the confounding hypotheses by examining if there is a genetic component to advancing paternal age and if men with a genetic liability for psychiatric disorders have children at older ages.

We examined the genetic component to advancing paternal age by utilizing the twin model in a cohort of male twins (N = 14 679). We also studied ages at childbirth in men with or without schizophrenia, bipolar disorder and/or autism spectrum disorder. Ages were examined in: (1) healthy men, (2) affected men, (3) healthy men with an affected sibling, (4) men with healthy spouses, (5) men with affected spouses, and (6) men with healthy spouses with an affected sibling.

The twin analyses showed that late fatherhood is under genetic influence (heritability = 0.33). However, affected men or men with affected spouses did not have children at older ages. The same was found for healthy individuals with affected siblings. Instead, these men were generally having children at younger ages.

Although there is a genetic component influencing late fatherhood, our data suggest that the associations are not explained by psychiatric disorders or a genetic liability for psychiatric disorders in the parent.

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) often co-occur with somatic symptomatology. Little is known about the contributions of individual symptoms to this association and more insight into their relationships could help to identify symptoms that are central in the processes behind the co-occurrence. This study explores associations between individual MDD/GAD symptoms and somatic symptoms by using the network approach.

MDD/GAD symptoms were assessed in 2704 participants (mean age 41.7 years, 66.1% female) from the Netherlands Study of Depression and Anxiety using the Inventory of Depressive Symptomatology. Somatic symptoms were assessed with the somatization scale of the Four-Dimensional Symptom Questionnaire. The technique eLasso was used to estimate the network of MDD/GAD and somatic symptoms.

The network structure showed numerous associations between MDD/GAD and somatic symptoms. In general, neurovegetative and cognitive/affective MDD/GAD symptoms showed a similar strength of connections to the somatic domain. However, associations varied substantially across individual symptoms. MDD/GAD symptoms with many and strong associations to the somatic domain included anxiety and fatigue, whereas hypersomnia and insomnia showed no connections to somatic symptoms. Among somatic symptoms, excessive perspiration and pressure/tight feeling in chest were associated with the MDD/GAD domain, while muscle pain and tingling in fingers showed only a few weak associations.

Individual symptoms show differential associations in the co-occurrence of MDD/GAD with somatic symptomatology. Strongly interconnected symptoms are important in furthering our understanding of the interaction between the symptom domains, and may be valuable targets for future research and treatment.

Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression.

A diagnosis of depression during pregnancy was recorded from Manchester cohort participants’ medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression.

In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively).

This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.

While trauma-focused cognitive–behavioral therapy (TF-CBT) is the ‘gold standard’ treatment for pediatric post-traumatic stress disorder (PTSD), little is known about the neural mechanisms by which TF-CBT produces clinical benefit. Here, we test the hypothesis that PTSD symptom reduction during TF-CBT among adolescent girls with PTSD is associated with changes in patterns of brain functional connectivity (FC) with the amygdala during cognitive reappraisal.

Adolescent girls with PTSD related to physical or sexual assault (n = 34) were enrolled in TF-CBT, delivered in an approximately 12-session format, in an open trial. Before and after treatment, they were engaged in a cognitive reappraisal task, probing neural mechanisms of explicit emotion regulation, during 3 T functional magnetic resonance imaging.

Among adolescent girls completing TF-CBT with usable pre- and post-treatment scans (n = 20), improvements in self-reported emotion from pre- to post-treatment were positively related to improvements in PTSD symptoms. Adolescent girls with greater post-treatment symptom reduction were also able to suppress amygdala–insula FC while re-appraising, which was not evident in girls with less symptom reduction. Pre- to post-treatment changes in right amygdala to left insula FC that scaled with PTSD symptom reduction also scaled with improvements in emotion regulation.

These preliminary results suggest the neurocircuitry mechanisms through which TF-CBT produces clinical outcomes, providing putative brain targets for augmenting TF-CBT response.

Very preterm birth (VPT; <32 weeks of gestation) has been associated with impairments in emotion regulation, social competence and communicative skills. However, the neuroanatomical mechanisms underlying such impairments have not been systematically studied. Here we investigated the functional integrity of the amygdala connectivity network in relation to the ability to recognize emotions from facial expressions in VPT adults.

Thirty-six VPT-born adults and 38 age-matched controls were scanned at rest in a 3-T MRI scanner. Resting-state functional connectivity (rs-fc) was assessed with SPM8. A seed-based analysis focusing on three amygdalar subregions (centro-medial/latero-basal/superficial) was performed. Participants’ ability to recognize emotions was assessed using dynamic stimuli of human faces expressing six emotions at different intensities with the Emotion Recognition Task (ERT).

VPT individuals compared to controls showed reduced rs-fc between the superficial subregion of the left amygdala, and the right posterior cingulate cortex (p = 0.017) and the left precuneus (p = 0.002). The VPT group further showed elevated rs-fc between the left superficial amygdala and the superior temporal sulcus (p = 0.008). Performance on the ERT showed that the VPT group was less able than controls to recognize anger at low levels of intensity. Anger scores were significantly associated with rs-fc between the superficial amygdala and the posterior cingulate cortex in controls but not in VPT individuals.

These findings suggest that alterations in rs-fc between the amygdala, parietal and temporal cortices could represent the mechanism linking VPT birth and deficits in emotion processing.

Strategies are needed to identify youth developing schizophrenia. The present study aimed to determine whether adolescents treated for substance misuse were at elevated risk to develop schizophrenia, whether this risk has changed since the late 1960s, and whether substance misuse in adolescence predicted poorer outcomes through adulthood.

In a Swedish city, since the mid-1960s there has been only one clinic for adolescent substance misuse. Three samples from this clinic were studied: 1992 individuals treated from 1968 to 1971 followed to age 50 years; 1576 treated from 1980 to 1984 followed to age 35 years; and 180 treated in 2004 followed to age 22 years. Each clinical sample was matched on age, sex and place of birth to an equal, or larger, number of randomly selected individuals from the general population. Schizophrenia, substance use disorders, physical disorders related to substance misuse, criminal convictions, poverty and death were identified using national registers.

Individuals treated for substance misuse in adolescence were at increased risk to subsequently develop schizophrenia: in males the increase was approximately four-fold and in females between five- and seven-fold. There was no difference in risk for those treated in 1968–1971 and from 1980 to 1984 when cannabis use increased from 37.6% to 49.8% of the clinical samples. Among males who developed schizophrenia, treatment for substance misuse was associated with increased risk of substance use disorders and criminal convictions through adulthood.

Treatment programmes for adolescents misusing substances include a disproportionate number developing schizophrenia. Early detection and treatment have the potential to improve long-term outcomes.

It has been observed that mental disorders, such as psychosis, are more common for people in some ethnic groups in areas where their ethnic group is less common. We set out to test whether this ethnic density effect reflects minority status in general, by looking at three situations where individual characteristics differ from what is usual in a locality.

Using data from the South East London Community Health study (n = 1698) we investigated associations between minority status (defined by: ethnicity, household status and occupational social class) and risk of psychotic experiences, common mental disorders and parasuicide. We used a multilevel logistic model to examine cross-level interactions between minority status at individual and neighbourhood levels.

Being Black in an area where this was less common (10%) was associated with higher odds of psychotic experiences [odds ratio (OR) 1.34 95% confidence interval (CI) 1.07–1.67], and attempted suicide (OR 1.84 95% CI 1.19–2.85). Living alone where this was less usual (10% less) was associated with increased odds of psychotic experiences (OR 2.18 95% CI 0.91–5.26), while being in a disadvantaged social class where this was less usual (10% less) was associated with increased odds of attempted suicide (OR 1.33 95% CI 1.03–1.71). We found no evidence for an association with common mental disorders.

The relationship between minority status and mental distress was most apparent when defined in terms of broad ethnic group but was also observed for individual household status and occupational social class.