Risk prediction algorithms have long been used in health research and practice (e.g. prediction of cardiovascular disease and diabetes). However, similar tools have not been developed for mental health. For example, for psychotic disorders, attempts to sum environmental risk are rare, unsystematic and dictated by available data. In light of this, we sought to develop a valid, easy to use measure of the aggregate environmental risk score (ERS) for psychotic disorders.

We reviewed the literature to identify well-replicated and validated environmental risk factors for psychosis that combine a significant effect and large-enough prevalence. Pooled estimates of relative risks were taken from the largest available meta-analyses. We devised a method of scoring the level of exposure to each risk factor to estimate ERS. Relative risks were rounded as, due to the heterogeneity of the original studies, risk effects are imprecisely measured.

Six risk factors (ethnic minority status, urbanicity, high paternal age, obstetric complications, cannabis use and childhood adversity) were used to generate the ERS. A distribution for different levels of risk based on simulated data showed that most of the population would be at low/moderate risk with a small minority at increased environmental risk for psychosis.

This is the first systematic approach to develop an aggregate measure of environmental risk for psychoses in asymptomatic individuals. This can be used as a continuous measure of liability to disease; mostly relevant to areas where the original studies took place. Its predictive ability will improve with the collection of additional, population-specific data.

Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity.

We analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators.

Affective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data.

Affective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.

Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).

Thirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.

Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.

Glutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

Individual differences in cognitive responses to trauma may represent modifiable risk factors that could allow early identification, targeted early treatment and possibly prevention of chronic posttraumatic stress disorder (PTSD). Ehlers and Clark's cognitive model of PTSD suggests that negative appraisals, disjointed trauma memories, and unhelpful coping strategies maintain PTSD. These are thought to be influenced by cognitive processing during trauma. The aim of this study was to test this model prospectively with path analyses.

Participants (N = 828) were recruited from an emergency department following injury in a violent assault or road traffic collision and 700 participated in the 6-month assessments. Cognitive processing was assessed shortly after the event, negative appraisals, disjointed memories, and unhelpful coping strategies at 1 month, persistent PTSD symptom severity at 6 months, and early PTSD symptom severity at 2 weeks.

Cognitive variables, with trauma type and gender, explained 52% of the variance in PTSD symptom severity at 6 months. Including early symptom severity in the model did not explain more variance (53%). Early PTSD symptom severity, with trauma type and gender, only predicted 40%. Negative appraisals and disjointed memories predicted persistent symptom severity both directly and indirectly via unhelpful strategies. Peritraumatic processing predicted persistent symptom severity mainly indirectly. The effects of trauma type and gender were fully mediated by the cognitive factors.

The results are consistent with theoretically derived predictions and support cognitive factors as indicators of risk for chronic PTSD and as a target for the treatment and prevention of PTSD.

Postpartum depression is a major mental health issue. It not only adversely affects the mother's quality of life, but also mother-infant bonding. However, the relationship between postpartum depression (at multiple points after childbirth) and mother-infant bonding failure one year after birth is not well understood. This study investigates the relationship between postpartum depression at 1-month and 6-month after birth and mother-infant bonding failure at 1 year after birth with a large cohort.

Data from 83 109 mothers from the Japan Environment and Children's Study were analyzed. Mother-infant bonding 1-year after delivery was assessed using the Mother-to-Infant Bonding Scale Japanese version (MIBS-J). Postpartum depression was measured using the Edinburgh Postnatal Depression Scale (EPDS) at 1-month and 6-month after delivery. Twenty covariates during pregnancy and one month after delivery were controlled for deriving the odds ratios (ORs) describing postpartum depression to mother-infant bonding.

EPDS Total Score crude ORs and adjusted ORs against the MIBS-J Total Score at 1-month and 6-month after delivery were calculated. Crude ORs were 1.111 (95% CI 1.110–1.112) and 1.122 (95% CI 1.121–1.124) respectively. In the fully adjusted model, ORs were 1.088 (95% CI 1.086–1.089) and 1.085 (95% CI 1.083–1.087), respectively.

This study demonstrated prospectively, in a large-scale cohort, that depression at multiple postpartum points, including associations with each EPDS and MIBS-J factors, may be a robust predictor of mother-infant bonding failure 1-year after birth.

Substance use disorder explains much of the excess risk of violent behaviour in psychotic disorders. However, it is unclear to what extent the pharmacological properties and subthreshold use of illicit substances are associated with violence.

Individuals with psychotic disorders were recruited for two nationwide projects: GROUP (N = 871) in the Netherlands and NEDEN (N = 921) in the United Kingdom. Substance use and violent behaviour were assessed with standardized instruments and multiple sources of information. First, we used logistic regression models to estimate the associations of daily and nondaily use with violence for cannabis, stimulants, depressants and hallucinogens in the GROUP and NEDEN samples separately. Adjustments were made for age, sex and educational level. We then combined the results in random-effects meta-analyses.

Daily use, compared with nondaily or no use, and nondaily use, compared with no use, increased the pooled odds of violence in people with psychotic disorders for all substance categories. The increases were significant for daily use of cannabis [pooled odds ratio (pOR) 1.6, 95% confidence interval (CI) 1.2–2.0), stimulants (pOR 2.8, 95% CI 1.7–4.5) and depressants (pOR 2.2, 95% CI 1.1–4.5), and nondaily use of stimulants (pOR 1.6, 95% CI 1.2–2.0) and hallucinogens (pOR 1.5, 95% CI 1.1–2.1). Daily use of hallucinogens, which could only be analysed in the NEDEN sample, significantly increased the risk of violence (adjusted odds ratio 3.3, 95% CI 1.2–9.3).

Strategies to prevent violent behaviour in psychotic disorders should target any substance use.

Across psychopathologies, trauma-exposed individuals suffer from difficulties in inhibiting emotions and regulating attention. In trauma-exposed individuals without psychopathology, only subtle alterations of neural activity involved in regulating emotions have been reported. It remains unclear how these neural systems react to demanding environments, when acute (non-traumatic but ordinary) stress serves to perturbate the system. Moreover, associations with subthreshold clinical symptoms are poorly understood.

The present fMRI study investigated response inhibition of emotional faces before and after psychosocial stress situations. Specifically, it compared 25 women (mean age 31.5 ± 9.7 years) who had suffered severe early life trauma but who did not have a history of or current psychiatric disorder, with 25 age- and education-matched trauma-naïve women.

Under stress, response inhibition related to fearful faces was reduced in both groups. Compared to controls, trauma-exposed women showed decreased left inferior frontal gyrus (IFG) activation under stress when inhibiting responses to fearful faces, while activation of the right anterior insula was slightly increased. Also, groups differed in brain–behaviour correlations. Whereas stress-induced false alarm rates on fearful stimuli negatively correlated with stress-induced IFG signal in controls, in trauma-exposed participants, they positively correlated with stress-induced insula activation.

Neural facilitation of emotion inhibition during stress appears to be altered in trauma-exposed women, even without a history of or current psychopathology. Decreased activation of the IFG in concert with heightened bottom-up salience of fear related cues may increase vulnerability to stress-related diseases.

Previous studies of pubertal timing and self-harm are limited by subjective measures of pubertal timing or by the conflation of self-harm with suicide attempts and ideation. The current study investigates the association between an objective measure of pubertal timing – age at menarche – and self-harm with and without suicidal intent in adolescence and adulthood in females.

Birth cohort study based on 4042 females from the Avon Longitudinal Study of Parents and Children (ALSPAC). Age at menarche was assessed prospectively between ages 8 and 17 years. Lifetime history of self-harm was self-reported at ages 16 and 21 years. Associations between age at menarche and self-harm, both with and without suicidal intent, were examined using multivariable logistic regression.

Later age at menarche was associated with a lower risk of lifetime self-harm at age 16 years (OR per-year increase in age at menarche 0.87; 95% CI 0.80–0.95). Compared with normative timing, early menarche (<11.5 years) was associated with an increased risk of self-harm (OR 1.31, 95% CI 1.04–1.64) and later menarche (>13.8 years) with a reduced risk (OR 0.74, 95% CI 0.58–0.93). The pattern of association was similar at age 21 years (OR per-year increase in age at menarche 0.92, 95% CI 0.85–1.00). There was no strong evidence for a difference in associations with suicidal v. non-suicidal self-harm.

Risk of self-harm is higher in females with early menarche onset. Future research is needed to establish whether this association is causal and to identify potential mechanisms.

Whether severe obstetric complications (OCs), which harm neural function in offspring, contribute to impaired cognition found in psychiatric disorders is currently unknown. Here, we sought to evaluate how a history of severe OCs is associated with cognitive functioning, indicated by Intelligence Quotient (IQ).

We evaluated the associations of a history of OCs and IQ in 622 healthy controls (HC) and 870 patients on the schizophrenia (SCZ) – bipolar disorder (BIP) spectrum from the ongoing Thematically Organized Psychosis study cohort, Oslo, Norway. Participants underwent assessments using the NART (premorbid IQ) and the WASI (current IQ). Information about OCs was obtained from the Medical Birth Registry of Norway. Multiple linear regression models were used for analysis.

Severe OCs were equally common across groups. SCZ patients with OCs had lower performances on both premorbid and current IQ measures, compared to those without OCs. However, having experienced more than one co-occurring severe OC was associated with lower current IQ in all groups.

Severe OCs were associated with lower IQ in the SCZ group and in the BIP and HC groups, but only if they had experienced more than one severe OC. Low IQ might be a neurodevelopmental marker for SCZ; wherein, severe OCs influence cognitive abilities and increase the risk of developing SCZ. Considering OCs as a variable of neurodevelopmental risk for severe mental illness may promote the development of neuroprotective interventions, improve outcome in vulnerable newborns and advance our ability to make clinical prognoses.

Previous research has shown an association between subjective wellbeing and incident diabetes. Less is known about the role of wellbeing for subclinical disease trajectories as captured via glycated hemoglobin (HbA1c). We aimed to explore the association between subjective wellbeing and future HbA1c levels, and the role of sociodemographic, behavioral and clinical factors in this association.

We used data from the English Longitudinal Study of Ageing for this study (N = 2161). Subjective wellbeing (CASP-19) was measured at wave 2 and HbA1c was measured 8 years later at wave 6. Participants were free from diabetes at baseline. We conducted a series of analyses to examine the extent to which the association was accounted for by a range of sociodemographic, behavioral and clinical factors in linear regression models.

Models showed that subjective wellbeing (CASP-19 total score) was inversely associated with HbA1c 8 years later after controlling for depressive symptoms, age, sex, and baseline HbA1c (B = −0.035, 95% CI −0.060 to –0.011, p = 0.005). Inclusion of sociodemographic variables and behavioral factors in models accounted for a large proportion (17.0% and 24.5%, respectively) of the relationship between wellbeing and later HbA1c; clinical risk factors explained a smaller proportion of the relationship (3.4%).

Poorer subjective wellbeing is associated with greater HbA1c over 8 years of follow-up and this relationship can in part be explained by sociodemographic, behavioral and clinical factors among older adults.

Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this propensity. This study provides an update regarding the efficacy of agents with some anti-inflammatory actions for schizophrenia symptoms tested in randomized controlled trials (RCTs).

PubMed, Embase, the National Institutes of Health website (http://www.clinicaltrials.gov), and the Cochrane Database of Systematic Reviews were systematically searched for RCTs that investigated clinical outcomes.

Our search yielded 56 studies that provided information on the efficacy of the following components on symptom severity: aspirin, bexarotene, celecoxib, davunetide, dextromethorphan, estrogens, fatty acids, melatonin, minocycline, N-acetylcysteine (NAC), pioglitazone, piracetam, pregnenolone, statins, varenicline, and withania somnifera extract. The results of aspirin [mean weighted effect size (ES): 0.30; n = 270; 95% CI (CI) 0.06–0.54], estrogens (ES: 0.78; n = 723; CI 0.36–1.19), minocycline (ES: 0.40; n = 946; CI 0.11–0.68), and NAC (ES: 1.00; n = 442; CI 0.60–1.41) were significant in meta-analysis of at least two studies. Subgroup analysis yielded larger positive effects for first-episode psychosis (FEP) or early-phase schizophrenia studies. Bexarotene, celecoxib, davunetide, dextromethorphan, fatty acids, pregnenolone, statins, and varenicline showed no significant effect.

Some, but not all agents with anti-inflammatory properties showed efficacy. Effective agents were aspirin, estrogens, minocycline, and NAC. We observed greater beneficial results on symptom severity in FEP or early-phase schizophrenia.

Social support has been shown to be associated with a reduced likelihood of developing psychotic experiences in the general population and even amongst those at high risk due to exposure to multiple forms of victimisation (poly-victimised). However, it is unclear whether this association is merely due to the confounding effects of shared environmental and genetic influences, or reverse causality. Therefore, we investigated whether social support has a unique environmentally mediated effect on adolescent psychotic experiences after accounting for familial factors, including genetic factors, and also prior psychopathology.

Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 UK-born twins. Adolescents were interviewed at age 18 about psychotic experiences and victimisation exposure since age 12, and their perceptions of social support. Prior childhood mental health problems and psychotic symptoms were assessed at age 12. The discordant twin method was used to disentangle the relative family-wide and unique-environmental effects of social support on psychotic experiences in the general population and among poly-victimised adolescents.

Perceived social support, particularly from friends, was found to have a unique environmentally mediated buffering effect on adolescent psychotic experiences in the whole sample and in the high-risk poly-victimised group.

The protective effects of social support on adolescent psychotic experiences cannot be accounted for by shared environmental or genetic factors, nor by earlier psychopathology. Our findings suggest that early intervention programmes focused on increasing perceptions of social support have the potential to prevent the emergence of psychotic experiences amongst adolescents.

Cross-sectional evidence suggests females in late adolescence exhibit higher rates of post-traumatic stress symptoms (PTSS) than males and younger age groups. However, longitudinal evidence is limited, and underlying factors are not well understood. We investigated the emergence of sex differences in PTSS from childhood to adolescence in a large, longitudinal UK cohort, and tested whether these could be explained by overlap between PTSS and depressive symptoms, or onset of puberty.

Trauma exposure and PTSS were assessed at ages 8, 10, 13 (parent-report) and 15 (self-report) years in a sub-sample of 9966 children and adolescents from the ALSPAC cohort-study. Analyses of PTSS focused on those who reported potential trauma-exposure at each time-point (ranged from n = 654 at 15 years to n = 1231 at 10 years). Age at peak-height velocity (APHV) was used as an indicator of pubertal timing.

There was no evidence of sex differences in PTSS at ages 8 and 10, but females were more likely to show PTSS at ages 13 (OR 1.54, p = 0.002) and 15 (OR 2.04, p = .001), even once symptoms related to depression were excluded. We found little evidence that the emergence of sex differences was related to pubertal timing (as indexed by APHV).

Results indicate that females show higher levels of PTSS in adolescence but not during childhood. The emergence of this sex difference does not seem to be explained by overlap with depressive symptoms, while the influence of pubertal status requires further investigation.

Review findings on the role of dietary patterns in preventing depression are inconsistent, possibly due to variation in assessment of dietary exposure and depression. We studied the association between dietary patterns and depressive symptoms in six population-based cohorts and meta-analysed the findings using a standardised approach that defined dietary exposure, depression assessment and covariates.

Included were cross-sectional data from 23 026 participants in six cohorts: InCHIANTI (Italy), LASA, NESDA, HELIUS (the Netherlands), ALSWH (Australia) and Whitehall II (UK). Analysis of incidence was based on three cohorts with repeated measures of depressive symptoms at 5–6 years of follow-up in 10 721 participants: Whitehall II, InCHIANTI, ALSWH. Three a priori dietary patterns, Mediterranean diet score (MDS), Alternative Healthy Eating Index (AHEI-2010), and the Dietary Approaches to Stop Hypertension (DASH) diet were investigated in relation to depressive symptoms. Analyses at the cohort-level adjusted for a fixed set of confounders, meta-analysis used a random-effects model.

Cross-sectional and prospective analyses showed statistically significant inverse associations of the three dietary patterns with depressive symptoms (continuous and dichotomous). In cross-sectional analysis, the association of diet with depressive symptoms using a cut-off yielded an adjusted OR of 0.87 (95% confidence interval 0.84–0.91) for MDS, 0.93 (0.88–0.98) for AHEI-2010, and 0.94 (0.87–1.01) for DASH. Similar associations were observed prospectively: 0.88 (0.80–0.96) for MDS; 0.95 (0.84–1.06) for AHEI-2010; 0.90 (0.84–0.97) for DASH.

Population-scale observational evidence indicates that adults following a healthy dietary pattern have fewer depressive symptoms and lower risk of developing depressive symptoms.

Previous studies using resting-state functional neuroimaging have revealed alterations in whole-brain images, connectome-wide functional connectivity and graph-based metrics in groups of patients with schizophrenia relative to groups of healthy controls. However, it is unclear which of these measures best captures the neural correlates of this disorder at the level of the individual patient.

Here we investigated the relative diagnostic value of these measures. A total of 295 patients with schizophrenia and 452 healthy controls were investigated using resting-state functional Magnetic Resonance Imaging at five research centres. Connectome-wide functional networks were constructed by thresholding correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based methods. Single-subject classification was performed using three machine learning (ML) approaches associated with varying degrees of complexity and abstraction, namely logistic regression, support vector machine and deep learning technology.

Connectome-wide functional connectivity allowed single-subject classification of patients and controls with higher accuracy (average: 81%) than both whole-brain images (average: 53%) and graph-based metrics (average: 69%). Classification based on connectome-wide functional connectivity was driven by a distributed bilateral network including the thalamus and temporal regions.

These results were replicated across the three employed ML approaches. Connectome-wide functional connectivity permits differentiation of patients with schizophrenia from healthy controls at single-subject level with greater accuracy; this pattern of results is consistent with the ‘dysconnectivity hypothesis’ of schizophrenia, which states that the neural basis of the disorder is best understood in terms of system-level functional connectivity alterations.

To determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis.

AESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up.

At 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60–7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02–7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23–6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25–8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61–41.42).

Symptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately.

Mounting evidence shows genetic overlap between multiple psychiatric disorders. However, the biological underpinnings of shared risk for psychiatric disorders are not yet fully uncovered. The identification of underlying biological mechanisms is crucial for the progress in the treatment of these disorders.

We applied gene-set analysis including 7372 gene sets, and 53 tissue-type specific gene-expression profiles to identify sets of genes that are involved in the etiology of multiple psychiatric disorders. We included genome-wide meta-association data of the five psychiatric disorders schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. The total dataset contained 159 219 cases and 262 481 controls.

We identified 19 gene sets that were significantly associated with the five psychiatric disorders combined, of which we excluded five sets because their associations were likely driven by schizophrenia only. Conditional analyses showed independent effects of several gene sets that in particular relate to the synapse. In addition, we found independent effects of gene expression levels in the cerebellum and frontal cortex.

We obtained novel evidence for shared biological mechanisms that act across psychiatric disorders and we showed that several gene sets that have been related to individual disorders play a role in a broader range of psychiatric disorders.