There is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon.

Here we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth.

Neither genetic measure was associated with season or month of birth within the UKBB sample.

As our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure.

Non-psychotic affective symptoms are important components of psychotic syndromes. They are frequent and are now thought to influence the emergence of paranoia and hallucinations. Evidence supporting this model of psychosis comes from recent cross-fertilising epidemiological and intervention studies. Epidemiological studies identify plausible targets for intervention but must be interpreted cautiously. Nevertheless, causal inference can be strengthened substantially using modern statistical methods.

Directed Acyclic Graphs were used in a dynamic Bayesian network approach to learn the overall dependence structure of chosen variables. DAG-based inference identifies the most likely directional links between multiple variables, thereby locating them in a putative causal cascade. We used initial and 18-month follow-up data from the 2000 British National Psychiatric Morbidity survey (N = 8580 and N = 2406).

We analysed persecutory ideation, hallucinations, a range of affective symptoms and the effects of cannabis and problematic alcohol use. Worry was central to the links between symptoms, with plausible direct effects on insomnia, depressed mood and generalised anxiety, and recent cannabis use. Worry linked the other affective phenomena with paranoia. Hallucinations were connected only to worry and persecutory ideation. General anxiety, worry, sleep problems, and persecutory ideation were strongly self-predicting. Worry and persecutory ideation were connected over the 18-month interval in an apparent feedback loop.

These results have implications for understanding dynamic processes in psychosis and for targeting psychological interventions. The reciprocal influence of worry and paranoia implies that treating either symptom is likely to ameliorate the other.

Major depressive disorder (MDD), represent a major source of risk for suicidality. However, knowledge about risk factors for future suicide attempts (SAs) within MDD is limited. The present longitudinal study examined a wide range of putative non-clinical risk factors (demographic, social, lifestyle, personality) and clinical risk factors (depressive and suicidal indicators) for future SAs among persons with MDD. Furthermore, we examined the relationship between a number of significant predictors and the incidence of a future SA.

Data are from 1713 persons (18–65 years) with a lifetime MDD at the baseline measurement of the Netherlands Study of Depression and Anxiety who were subsequently followed up 2, 4 and 6 years. SAs were assessed in the face-to-face measurements. Cox proportional hazard regression analyses were used to examine a wide range of possible non-clinical and clinical predictors for subsequent SAs during 6-year follow-up.

Over a period of 6 years, 3.4% of the respondents attempted suicide. Younger age, lower education, unemployment, insomnia, antidepressant use, a previous SA and current suicidal thoughts independently predicted a future SA. The number of significant risk factors (ranging from 0 to 7) linearly predicted the incidence of future SAs: in those with 0 predictors the SA incidence was 0%, which increased to 32% incidence in those with 6+ predictors.

Of the non-clinical factors, particularly socio-economic factors predicted a SA independently. Furthermore, preexisting suicidal ideation and insomnia appear to be important clinical risk factors for subsequent SA that are open to preventative intervention.

The jumping to conclusions (JTC) reasoning bias and decreased working memory performance (WMP) are associated with psychosis, but associations with affective disturbances (i.e. depression, anxiety, mania) remain inconclusive. Recent findings also suggest a transdiagnostic phenotype of co-occurring affective disturbances and psychotic experiences (PEs). This study investigated whether JTC bias and decreased WMP are associated with co-occurring affective disturbances and PEs.

Data were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). Trained interviewers administered the Composite International Diagnostic Interview (CIDI) at three time points in a general population sample (N = 4618). The beads and digit-span task were completed to assess JTC bias and WMP, respectively. CIDI was used to measure affective disturbances and an add-on instrument to measure PEs.

Compared to individuals with neither affective disturbances nor PEs, the JTC bias was more likely to occur in individuals with co-occurring affective disturbances and PEs [moderate psychosis (1–2 PEs): adjusted relative risk ratio (RRR) 1.17, 95% CI 0.98–1.41; and high psychosis (3 or more PEs or psychosis-related help-seeking behaviour): adjusted RRR 1.57, 95% CI 1.19–2.08], but not with affective disturbances and PEs alone, whereas decreased WMP was more likely in all groups. There was some evidence of a dose–response relationship, as JTC bias and decreased WMP were more likely in individuals with affective disturbances as the level of PEs increased or help-seeking behaviour was reported.

The findings suggest that JTC bias and decreased WMP may contribute to a transdiagnostic phenotype of co-occurring affective disturbances and PEs.

Schizophrenia has been associated with changes in both cortical thickness and surface area, but antipsychotic exposure, illness progression and substance use may confound observations. In antipsychotic-naïve schizophrenia patients, we investigated cortical thickness and surface area as well as mean curvature before and after monotherapy with amisulpride, a relatively selective dopamine D2/3 receptor antagonist.

Fifty-six patients and 59 matched healthy controls (HCs) underwent T1-weighted 3T magnetic resonance imaging. Forty-one patients and 51 HCs were re-scanned. FreeSurfer-processed baseline, follow-up values and symmetrized percentage changes (SPC) in cortical structures were analysed using univariate analysis of variance. Clinical measures comprised psychopathology ratings, assessment of functioning and tests of premorbid and current intelligence. We applied false discovery rate correction to account for multiple comparisons.

At baseline, groups did not differ in cortical thickness or surface area; however, curvature in the left hemisphere was higher in patients (p = 0.015). In both patients and HCs, higher curvature was associated with lower premorbid (p = 0.009) and current intelligence (p < 0.001). Lower surface area was associated with lower premorbid intelligence (p = 0.017). After 6 weeks, the cortical structures did not differ between groups. Amisulpride dose (275.0 mg/day) did not correlate with any cortical structures (p > 0.43). Cortical thickness SPC was negatively associated with symptom improvement (p = 0.002).

Schizophrenia appears associated with subtle, yet clinically relevant aberrations in cortical structures. Mean curvature holds promise as a sensitive supplement to cortical thickness and surface area to detect complex structural brain abnormalities.

Non-motor features of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), such as auditory hallucinations (AH), contribute to disease burden but are not well understood.

Systematic review and random-effects meta-analyses of studies reporting AH associated with PD or DLB. Prevalence of visual hallucinations (VH) in identified studies meeting eligibility criteria were included in meta-analyses, facilitating comparison with AH. Synthesis of qualitative descriptions of AH was performed. PubMed, Web of Science and Scopus databases were searched for primary journal articles, written in English, published from 1970 to 2017. Studies reporting AH prevalence in PD or DLB were screened using PRISMA methods.

Searches identified 4542 unique studies for consideration, of which, 26 met inclusion criteria. AH pooled prevalence in PD was estimated to be 8.9% [95% confidence interval (CI) 5.3–14.5], while in DLB was estimated to be 30.8% (±23.4 to 39.3). Verbal hallucinations, perceived as originating outside the head, were the most common form of AH. Non-verbal AH were also common while musical AH were rare. VH were more prevalent, with an estimated pooled prevalence in PD of 28.2% (±19.1 to 39.5), while in DLB they were estimated to be 61.8% (±49.1 to 73.0). Meta-regression determined that the use of validated methodologies to identify hallucinations produced higher prevalence estimates.

AH and VH present in a substantial proportion of PD and DLB cases, with VH reported more frequently in both conditions. Both AH and VH are more prevalent in DLB than PD. There is a need for standardised use of validated methods to detect and monitor hallucinations.

Various childhood social experiences have been reported to predict adult outcomes. However, it is unclear how different social contexts may influence each other's effects in the long run. This study examined the joint contribution of adolescent family and peer experiences to young adult wellbeing and functioning.

Participants came from the TRacking Adolescents’ Individual Lives Survey (TRAILS) study (n = 2230). We measured family and peer relations at ages 11 and 16 (i.e. family functioning, perceived parenting, peer status, peer relationship quality), and functioning as the combination of subjective wellbeing, physical and mental health, and socio-academic functioning at age 22. Using structural equation modelling, overall functioning was indicated by two latent variables for positive and negative functioning. Positive, negative and overall functioning at young adulthood were regressed on adolescent family experiences, peer experiences and interactions between the two.

Family experiences during early and mid-adolescence were most predictive for later functioning; peer experiences did not independently predict functioning. Interactions between family and peer experiences showed that both protective and risk factors can have context-dependent effects, being exacerbated or overshadowed by negative experiences or buffered by positive experiences in other contexts. Overall the effect sizes were modest at best.

Adolescent family relations as well as the interplay with peer experiences predict young adult functioning. This emphasizes the importance of considering the relative effects of one context in relation to the other.

Emotion dysregulation is a core feature of borderline personality disorder (BPD), which often co-occurs with posttraumatic stress disorder (PTSD). Difficulties in emotion regulation (ER) have been linked to lower high-frequency heart rate variability (HF-HRV), a measure of autonomous nervous system functioning. However, previous research on vagally-mediated heart rate in BPD revealed heterogeneous findings and the effects of comorbid PTSD and dissociation on HF-HRV are not yet completely understood. This study aim to investigate HF-HRV during resting-state and an ER task in female BPD patients with comorbid PTSD (BPD + PTSD), patients without this comorbidity (BPD), and healthy controls (HC).

57 BPD patients (BPD: n = 37, BPD + PTSD: n = 20) and 27 HC performed an ER task with neutral, positive, and negative images. Participants were instructed to either attend these pictures or to down-regulate their upcoming emotions using cognitive reappraisal. Subjective arousal and wellbeing, self-reported dissociation, and electrocardiogram data were assessed.

Independent of ER instruction and picture valence, both patient groups (BPD and BPD + PTSD) reported higher subjective arousal and lower wellbeing; patients with BPD + PTSD further exhibited significantly lower HF-HRV compared with the other groups. Higher self-reported state dissociation predicted higher HF-HRV during down-regulating v. attending negative pictures in BPD + PTSD.

Findings suggest increased emotional reactivity to negative, positive, and neutral pictures, but do not provide evidence for deficits in instructed ER in BPD. Reduced HF-HRV appears to be particularly linked to comorbid PTSD, while dissociation may underlie attempts to increase ER and HF-HRV in BPD patients with this comorbidity.

This study aimed to develop and test the feasibility of a primary care worker-led psychological intervention as the main feature of a collaborative stepped care for depression that is effective, affordable, culturally acceptable, tailored to patients’ clinical condition and easily integrate-able into the primary care schedule in Nigeria.

Using the Medical Research Council framework, in the first stage (modelling/theoretical development), experts reviewed and distilled evidence from literature to form the intervention components. In the second (formative) stage, local stakeholders were consulted on the practical application and feasibility of the proposed intervention. The third (piloting) stage involved testing for the clinical efficacy and acceptability of the components of the draft intervention

The final intervention components included a 2-stage screening (red-flagging and further evaluation), psychoeducation, low-intensity psychological therapy (problem-solving therapy for primary care), antidepressant prescription, proactive mobile telephony adherence support and referral to the mental health specialist if needed. At 3 months, 71.6% of depressed patients on the intervention improved. The intervention was perceived to be acceptable and useful by over 70% of health workers and clients and had high ratings (>70% score) by expert panels on intervention simplicity, facilitation strategies, and quality of delivery.

The development and feasibility testing of our integrated intervention encompassed review of current literature, expert opinions and consultation with local stakeholders and end users. Our intervention package was largely deemed acceptable, relevant, useful, and feasible. Important lessons learnt with this process will help in future intervention developments.

Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.

We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.

The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).

Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.

Methodological and ethical constraints have hampered studies into long-term lasting outcomes of stimulant treatment in individuals with attention-deficit/hyperactivity disorder (ADHD). Lasting effects may be beneficial (i.e. improved functioning even when treatment is temporarily ceased) or detrimental (i.e. worse functioning while off medication), but both hypotheses currently lack empirical support. Here we investigate whether stimulant treatment history predicts long-term development of ADHD symptoms, social–emotional functioning or cognition, measured after medication wash-out.

ADHD symptoms, social–emotional functioning and cognitive test performance were measured twice, 6 years apart, in two ADHD groups (stimulant-treated versus not stimulant-treated between baseline and follow-up). Groups were closely matched on baseline clinical and demographic variables (n = 148, 58% male, age = 11.1). A matched healthy control group was included for reference.

All but two outcome measures (emotional problems and prosocial behaviour) improved between baseline and follow-up. Improvement over time in the stimulant-treated group did not differ from improvement in the not stimulant-treated group on any outcome measure.

Stimulant treatment is not associated with the long-term developmental course of ADHD symptoms, social–emotional functioning, motor control, timing or verbal working memory. Adolescence is characterised by clinical improvement regardless of stimulant treatment during that time. These findings are an important source to inform the scientific and public debate.

Mood disorders and adiposity are major public health challenges. Few studies have investigated the bidirectional association of weight and waist circumference (WC) change with psychological distress in middle age, while taking into account the potential U-shape of the association. The aim of this study was to examine the bidirectional association between psychological distress and categorical change in objectively measured weight and WC.

We analysed repeated measures (up to 17 522 person-observations in adjusted analyses) of psychological distress, weight and WC from the Whitehall II cohort. Participants were recruited at age 35–55 and 67% male. Psychological distress was assessed using the General Health Questionnaire. We used random-effects regressions to model the association between weight and WC changes and psychological distress, with and without a 5-year lag period.

Psychological distress was associated with weight and WC gain over the subsequent 5 years but not the second 5-year period. Weight gain and loss were associated with increased odds for incident psychological distress in models with and without time-lag [odds ratio (OR) for incident psychological distress after 5-year time-lag: loss 1.20, 95% confidence interval (CI) 1.00–1.43; gain>5% 1.20, 95% CI 1.02–1.40]. WC changes were only associated with psychological distress in models without time-lag (OR for incident psychological distress: loss 1.29, 95% CI 1.02–1.64; gain>5% 1.33, 95% CI 1.11–1.58).

Weight gain and loss increase the odds for psychological distress compared with stable weight over subsequent 10 years. In contrast, the association between psychological distress and subsequent weight and WC changes was limited to the first 5 years of follow-up.

The long-term outcomes of bipolar disorder range from lasting remission to chronic course or frequent recurrences requiring admissions. The distinction between bipolar I and II disorders has limited utility in outcome prediction. It is unclear to what extent the clinical course of bipolar disorder predicts long-term outcomes.

A representative sample of 191 individuals diagnosed with bipolar I or II disorder was recruited and followed for up to 5 years using a life-chart method. We previously described the clinical course over the first 18 months with dimensional course characteristics and latent classes. Now we test if these course characteristics predict long-term outcomes, including time ill (time with any mood symptoms) and hospital admissions over a second non-overlapping follow-up period in 111 individuals with available data from both 18 months and 5 years follow-ups.

Dimensional course characteristics from the first 18 months prospectively predicted outcomes over the following 3.5 years. The proportion of time depressed, the severity of depressive symptoms and the proportion of time manic predicted more time ill. The proportion of time manic, the severity of manic symptoms and depression-to-mania switching predicted a greater likelihood of hospital admissions. All predictions remained significant after controlling for age, sex and bipolar I v. II disorder.

Differential associations with long-term outcomes suggest that course characteristics may facilitate care planning with greater predictive validity than established types of bipolar disorders. A clinical course dominated by depressive symptoms predicts a greater proportion of time ill. A clinical course characterized by manic episodes predicts hospital admissions.

Research in depression has progressed rapidly over the past four decades. Yet depression rates are not subsiding and treatment success is not improving. We examine the extent to which the gap between science and practice is associated with the level of integration in how depression is considered in research and stakeholder-relevant documents.

We used a network-science perspective to analyze similar uses of depression relevant terms in the Google News corpus (approximately 1 billion words) and the Web of Science database (120 000 documents).

These analyses yielded consistent pictures of insular modules associated with: (1) patient/providers, (2) academics, and (3) industry. Within academia insular modules associated with psychology, general medical, and psychiatry/neuroscience/biology were also detected.

These analyses suggest that the domain of depression is fragmented, and that advancements of relevance to one stakeholder group (academics, industry, or patients) may not translate to the others. We consider potential causes and associated responses to this fragmentation that could help to unify and advance translation from research on depression to the clinic, largely involving harmonizing employed language, bridging conceptual domains, and increasing communication across stakeholder groups.

Few studies have investigated the patterns of posttraumatic stress disorder (PTSD) symptom change in prolonged exposure (PE) therapy. In this study, we aimed to understand the patterns of PTSD symptom change in both PE and present-centered therapy (PCT).

Participants were active duty military personnel (N = 326, 89.3% male, 61.2% white, 32.5 years old) randomized to spaced-PE (S-PE; 10 sessions over 8 weeks), PCT (10 sessions over 8 weeks), or massed-PE (M-PE; 10 sessions over 2 weeks). Using latent profile analysis, we determined the optimal number of PTSD symptom change classes over time and analyzed whether baseline and follow-up variables were associated with class membership.

Five classes, namely rapid responder (7–17%), steep linear responder (14–22%), gradual responder (30–34%), non-responder (27–33%), and symptom exacerbation (7–13%) classes, characterized each treatment. No baseline clinical characteristics predicted class membership for S-PE and M-PE; in PCT, more negative baseline trauma cognitions predicted membership in the non-responder v. gradual responder class. Class membership was robustly associated with PTSD, trauma cognitions, and depression up to 6 months after treatment for both S-PE and M-PE but not for PCT.

Distinct profiles of treatment response emerged that were similar across interventions. By and large, no baseline variables predicted responder class. Responder status was a strong predictor of future symptom severity for PE, whereas response to PCT was not as strongly associated with future symptoms.

The present study tested the hypothesis of a differential pattern of reward and punishment responsiveness in depression measuring effort mobilization during anticipation and facial expressions during consumption.

Twenty patients with major depressive disorder (MDD) and 20 control participants worked on a memory task under neutral, reward, and punishment instructions. Effort mobilization was operationalized as cardiovascular reactivity, while facial expressions were measured by facial electromyographic reactivity. Self-report measures for each phase complemented this multi-method approach.

During anticipation, MDD patients showed weaker cardiac pre-ejection period (PEP) reactivity to reward and blunted self-reported wanting, but weaker PEP reactivity to punishment and unchanged self-reported avoidance motivation. During consumption, MDD patients showed reduced zygomaticus major muscle reactivity to reward and blunted self-reported liking, but unchanged corrugator supercilii muscle reactivity to punishment and unchanged self-reported disliking.

These findings demonstrate reduced effort mobilization during reward and punishment anticipation in depression. Moreover, they show reduced facial expressions during reward consumption and unchanged facial expressions during punishment consumption in depression.

Patients with the deficit form of schizophrenia (D-SZ) are characterized by severe primary negative symptoms and differ from patients with the non-deficit form of schizophrenia (ND-SZ) in several aspects. No study has measured brain gyrification, which is a potential marker of neurodevelopment, in D-SZ and ND-SZ.

We obtained magnetic resonance scans from 135 schizophrenia patients and 50 healthy controls. The proxy scale for deficit syndrome (PDS) was used for the classification of D-SZ and ND-SZ. The local gyrification index (LGI) of the entire cortex was measured using FreeSurfer. Thirty-seven D-SZ and 36 ND-SZ patients were included in the LGI analyses. We compared LGI across the groups.

SZ patients exhibited hyper-gyral patterns in the bilateral dorsal medial prefrontal and ventromedial prefrontal cortices, bilateral anterior cingulate gyri and right lateral parietal/occipital cortices as compared with HCs. Although patients with D-SZ or ND-SZ had higher LGI in similar regions compared with HC, the hyper-gyral patterns were broader in ND-SZ. ND-SZ patients exhibited a significantly higher LGI in the left inferior parietal lobule relative to D-SZ patients. Duration of illness inversely associated with LGI in broad regions only among ND-SZ patients.

The common hyper-gyral patterns among D-SZ and ND-SZ suggest that D-SZ and ND-SZ may share neurodevelopmental abnormalities. The different degrees of cortical gyrification seen in the left parietal regions, and the distinct correlation between illness chronicity and LGI observed in the prefrontal and insular cortices may be related to the differences in the clinical manifestations among D-SZ and ND-SZ.

There is a growing concern about the mental health of children and young people (CYP) in the UK, with increasing demand for counselling services, admissions for self-harm and referrals to mental health services. We investigated whether there have been similar recent trends in selected mental health outcomes among CYP in national health surveys from England, Scotland and Wales.

Data were analysed from 140 830 participants (4–24 years, stratified into 4–12, 13–15, 16–24 years) in 36 national surveys in England, Scotland and Wales, 1995–2014. Regression models were used to examine time trends in seven parent/self-reported variables: general health, any long-standing health condition, long-standing mental health condition; Warwick–Edinburgh Mental Wellbeing Score (WEMWBS), above-threshold Strengths and Difficulties Questionnaire Total (SDQT) score, SDQ Emotion (SDQE) score, General Health Questionnaire (GHQ) score.

Across all participants aged 4–24, long-standing mental health conditions increased in England (0.8–4.8% over 19 years), Scotland (2.3–6.0%, 11 years) and Wales (2.6–4.1%, 7 years) (all p < 0.001). Among young children (4–12 years), the proportion reporting high SDQT and SDQE scores decreased significantly among both boys and girls in England [SDQE: odds ratio (OR) 0.97 (0.96–0.98), p < 0.001] and girls in Scotland [SDQE: OR 0.96 (0.93–0.99), p = 0.005]. The proportion with high SDQE scores (13–15 years) decreased in England [OR 0.98 (0.96–0.99), p = 0.006] but increased in Wales [OR 1.07 (1.03–1.10), p < 0.001]. The proportion with high GHQ scores decreased among English women (16–24 years) [OR 0.98 (0.98–0.99), p = 0.002].

Despite a striking increase in the reported prevalence of long-standing mental health conditions among UK CYP, there was relatively little change in questionnaire scores reflecting psychological distress and emotional well-being.