The loss of a close relative is one of the most stressful life events. In pregnancy, this experience has been associated with a higher risk of fetal death and under-five mortality, but little is known about potential effects on long-term mortality in offspring. We examined the association between prenatal maternal bereavement and mortality in a cohort of 5.3 million children followed until up to 37 years of age.

The population-based cohort study included 5 253 508 live singleton births in Denmark (1973–2004) and Sweden (1973–2006). Children born to mothers who lost a child, spouse, sibling, or parent during or 1 year before pregnancy were categorized as exposed.

Prenatal maternal bereavement was associated with a 10% increased all-cause mortality risk in offspring [mortality rate ratio (MRR) 1.10, 95% confidence interval (CI) 1.03–1.18]. The association was the most pronounced for children of mothers who lost a child/spouse (MRR 1.28, 95% CI 1.14–1.44) and was stronger during the first 10 years of life. Prenatal maternal bereavement may have stronger effects on natural causes of death in offspring, including infectious/parasitic disease (MRR 1.86, 95% CI 1.07–3.23), endocrine/nutritional/metabolic diseases (MRR 3.23, 95% CI 2.02–5.17), diseases of nervous system (MRR 3.36, 95% CI 2.47–4.58), and congenital malformations (MRR 1.39, 95% CI 1.08–1.80). No excess mortality risk in offspring was observed for unnatural causes of death.

Prenatal maternal bereavement was associated with an increased long-term mortality risk in offspring, particularly for selected natural causes of diseases and medical conditions. Our results support the fetal programming hypothesis that prenatal stress may contribute to ill health from physical diseases later in life.

There is growing recognition of the importance of both functioning and quality of life (QoL) outcomes in the treatment of depressive disorders, but the meta-analytic evidence is scarce. The objective of this meta-analysis of randomized controlled trials (RCTs) was to determine the absolute and relative effects of psychotherapy, pharmacotherapy and their combination on functioning and QoL in patients with depression.

One hundred and fifty-three outcome trials involving 29 879 participants with depressive disorders were identified through database searches in Pubmed, PsycINFO and the Cochrane Central Register of Controlled Trials.

Compared to control conditions, psychotherapy and pharmacotherapy yielded small to moderate effect sizes for functioning and QoL, ranging from g = 0.31 to g = 0.43. When compared directly, initial analysis yielded no evidence that one of them was superior. After adjusting for publication bias, psychotherapy was more efficacious than pharmacotherapy (g = 0.21) for QoL. The combination of psychotherapy and medication performed significantly better for both outcomes compared to each treatment alone yielding small effect sizes (g = 0.32 to g = 0.39). Both interventions improved depression symptom severity more than functioning and QoL.

Despite the small number of comparative trials for some of the analyses, this study reveals that combined treatment is superior, but psychotherapy and pharmacotherapy alone are also efficacious for improving functioning and QoL. The overall relatively modest effects suggest that future tailoring of therapies could be warranted to better meet the needs of individuals with functioning and QoL problems.

The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment.

Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement.

Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint.

This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.

Sleep problems are associated with increased risk of physical and mental illness. Identifying risk factors is an important method of reducing public health impact. We examined the association between maternal postnatal depression (PND) and offspring adolescent sleep problems.

The sample was derived from Avon Longitudinal Study of Parents and Children (ALSPAC) participants. A sample with complete data across all variables was used, with four outcome variables. A sensitivity analysis imputing for missing data was conducted (n = 9633).

PND was associated with increased risk of sleep problems in offspring at ages 16 and 18 years. The most robust effects were sleep problems at 18 years [adjusted odds ratio (OR) for a 1 s.d. increase in PND, 1.26, 95% confidence interval (CI) 1.15–1.39, p < 0.001] and waking more often (adjusted OR 1.14, 95% CI 1.05–1.25, p = 0.003). This remained after controlling for confounding variables including antenatal depression and early sleep problems in infancy.

PND is associated with adolescent offspring sleep problems. Maternal interventions should consider the child's increased risk. Early sleep screening and interventions could be introduced within this group.

This study investigated the potential environmental effects of peer victimization and the quality of relationships with parents and friends on diurnal cortisol secretion in mid-adolescence.

This study used the monozygotic (MZ) twin-difference design to control for genetic effects and thus estimate the unique environmental influences on diurnal cortisol. Participants were 136 MZ twin pairs (74 female pairs) for whom cortisol was assessed four times per day over four collection days grouped in a 2-week period in grade 8 (mean age = 14.07 years). Participants also provided self-reports of peer victimization from grade 4 to grade 8 and of the relationship quality with the mother, father and best friend in grade 8.

The expected pattern of diurnal cortisol secretion was observed, with high levels at awakening followed by an increase 30 min later and a progressive decrease subsequently. Controlling for a host of confounders, only within-twin pair differences in peer victimization and a problematic relationship with the mother were significantly linked to twin differences in diurnal cortisol secretion. Specifically, whereas a more problematic mother–child relationship was associated with morning cortisol secretion, peer victimization was linked to cortisol secretion later in the day (diurnal slope).

Controlling for genetic influences and other confounders, stressful relationships with peers and the mother exert unique and time-specific environmental influences on the pattern of diurnal cortisol secretion in mid-adolescence.

Altered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results.

Study participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol.

Cortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size).

Our findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.

Laboratory tasks to delineate anxiety disorder features are used to refine classification and inform our understanding of etiological mechanisms. The present study examines laboratory measures of response inhibition, specifically the inhibition of a pre-potent motor response, in clinical anxiety. Data on associations between anxiety and response inhibition remain inconsistent, perhaps because of dissociable effects of clinical anxiety and experimentally manipulated state anxiety. Few studies directly assess the independent and interacting effects of these two anxiety types (state v. disorder) on response inhibition. The current study accomplished this goal, by manipulating state anxiety in healthy and clinically anxious individuals while they complete a response inhibition task.

The study employs the threat-of-shock paradigm, one of the best-established manipulations for robustly increasing state anxiety. Participants included 82 adults (41 healthy; 41 patients with an anxiety disorder). A go/nogo task with highly frequent go trials was administered during alternating periods of safety and shock threat. Signal detection theory was used to quantify response bias and signal-detection sensitivity.

There were independent effects of anxiety and clinical anxiety on response inhibition. In both groups, heightened anxiety facilitated response inhibition, leading to reduced nogo commission errors. Compared with the healthy group, clinical anxiety was associated with excessive response inhibition and increased go omission errors in both the safe and threat conditions.

Response inhibition and its impact on go omission errors appear to be a promising behavioral marker of clinical anxiety. These results have implications for a dimensional view of clinical anxiety.

While group-level functional alterations have been identified in many brain regions of psychotic patients, multivariate machine-learning methods provide a tool to test whether some of such alterations could be used to differentiate an individual patient. Earlier machine-learning studies have focused on data collected from chronic patients during rest or simple tasks. We set out to unravel brain activation patterns during naturalistic stimulation in first-episode psychosis (FEP).

We recorded brain activity from 46 FEP patients and 32 control subjects viewing scenes from the fantasy film Alice in Wonderland. Scenes with varying degrees of fantasy were selected based on the distortion of the ‘sense of reality’ in psychosis. After cleaning the data with a novel maxCorr method, we used machine learning to classify patients and healthy control subjects on the basis of voxel- and time-point patterns.

Most (136/194) of the voxels that best classified the groups were clustered in a bilateral region of the precuneus. Classification accuracies were up to 79.5% (p = 5.69 × 10−8), and correct classification was more likely the higher the patient's positive-symptom score. Precuneus functioning was related to the fantasy content of the movie, and the relationship was stronger in control subjects than patients.

These findings are the first to show abnormalities in precuneus functioning during naturalistic information processing in FEP patients. Correlational findings suggest that these alterations are associated with positive psychotic symptoms and processing of fantasy. The results may provide new insights into the neuronal basis of reality distortion in psychosis.

Previous studies suggest that adults with Tourette syndrome (TS) can respond unconventionally on tasks involving social cognition. We therefore hypothesized that these patients would exhibit different neural responses to healthy controls in response to emotionally salient expressions of human eyes.

Twenty-five adults with TS and 25 matched healthy controls were scanned using fMRI during the standard version of the Reading the Mind in the Eyes Task which requires mental state judgements, and a novel comparison version requiring judgements about age.

During prompted mental state recognition, greater activity was apparent in TS within left orbitofrontal cortex, posterior cingulate, right amygdala and right temporo-parietal junction (TPJ), while reduced activity was apparent in regions including left inferior parietal cortex. Age judgement elicited greater activity in TS within precuneus, medial prefrontal and temporal regions involved in mentalizing. The interaction between group and task revealed differential activity in areas including right inferior frontal gyrus. Task-related activity in the TPJ covaried with global ratings of the urge to tic.

While recognizing mental states, adults with TS exhibit greater activity than controls in brain areas involved in the processing of negative emotion, in addition to reduced activity in regions associated with the attribution of agency. In addition, increased recruitment of areas involved in mental state reasoning is apparent in these patients when mentalizing is not a task requirement. Our findings highlight differential neural reactivity in response to emotive social cues in TS, which may interact with tic expression.

Brief-pulse electroconvulsive therapy (ECT) is the most acutely effective treatment for severe depression though concerns persist about cognitive side-effects. While bitemporal electrode placement is the most commonly used form worldwide, right unilateral ECT causes less cognitive side-effects though historically it has been deemed less effective. Several randomized trials have now compared high-dose (>5× seizure threshold) unilateral ECT with moderate-dose (1.0–2.5× seizure threshold) bitemporal ECT to investigate if it is as effective as bitemporal ECT but still has less cognitive side-effects. We aimed to systematically review these trials and meta-analyse clinical and cognitive outcomes where appropriate.

We searched PubMed, PsycINFO, Web of Science, Cochrane Library and EMBASE for randomized trials comparing these forms of ECT using the terms ‘electroconvulsive’ OR ‘electroshock’ AND ‘trial’.

Seven trials (n = 792) met inclusion criteria. Bitemporal ECT did not differ from high-dose unilateral ECT on depression rating change scores [Hedges's g = −0.03, 95% confidence interval (CI) −0.17 to 0.11], remission (RR 1.06, 95% CI 0.93–1.20), or relapse at 12 months (RR 1.42, 95% CI 0.90–2.23). There was an advantage for unilateral ECT on reorientation time after individual ECT sessions (mean difference in minutes = −8.28, 95% CI −12.86 to −3.70) and retrograde autobiographical memory (Hedges's g = −0.46, 95% CI −0.87 to −0.04) after completing an ECT course. There were no differences for general cognition, category fluency and delayed visual and verbal memory.

High-dose unilateral ECT does not differ from moderate-dose bitemporal ECT in antidepressant efficacy but has some cognitive advantages.

The co-existence of depression and psychotic experiences (PEs) is associated with more pronounced adverse health outcomes compared to depression alone. However, data on its prevalence and correlates are lacking in the general adult population, and there is no published data on its association with chronic physical conditions.

Cross-sectional, community-based data from 201 337 adults aged ⩾18 years from 47 low- and middle-income countries from the World Health Survey were analyzed. The presence of past 12-month PE and DSM-IV depression was assessed with the Composite International Diagnostic Interview (CIDI). Information on six chronic medical conditions (chronic back pain, edentulism, arthritis, angina, asthma, diabetes) were obtained by self-report. Multivariable logistic regression analysis was performed.

The crude overall prevalence of co-morbid depression/PEs was 2.5% [95% confidence interval (CI) 2.3–2.7%], with the age- and sex-adjusted prevalence ranging from 0.1% (Sri Lanka, Vietnam) to 9.03% (Brazil). Younger age, urban setting, current smoking, alcohol consumption, and anxiety were significant correlates of co-existing depression/PEs. Co-occurring depression/PEs was associated with significantly higher odds for arthritis, angina, and diabetes beyond that of depression alone after adjusting for sociodemographics, anxiety, and country, with odds ratios (depression/PEs v. depression only) being: arthritis 1.30 (95% CI 1.07–1.59, p = 0.0086); angina 1.40 (95% CI 1.18–1.67, p = 0.0002); diabetes 1.65 (95% CI 1.21–2.26, p = 0.0017).

The prevalence of co-existing depression/PEs was non-negligible in most countries. Our study suggests that when depression/PE or a chronic condition (e.g. arthritis, angina, diabetes) is detected, screening for the other may be important to improve clinical outcomes.

The heterogeneous aetiology of major depressive disorder (MDD) might affect the presentation of depressive symptoms across the lifespan. We examined to what extent a range of mood, cognitive, and somatic/vegetative depressive symptoms were differentially present depending on patient's age.

Data came from 1404 participants with current MDD (aged 18–88 years) from two cohort studies: the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Study of Depression in Older Persons (NESDO). Associations between age (per 10 years) and 30 depressive symptoms as well as three symptom clusters (mood, cognitive, somatic/vegetative) were assessed using logistic and linear regression analyses.

Depression severity was found to be stable with increasing age. Nevertheless, 20 (67%) out of 30 symptoms were associated with age. Most clearly, with ageing there was more often early morning awakening [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.36–1.60], reduced interest in sex (OR 1.42, 95% CI 1.31–1.53), and problems sleeping during the night (OR 1.33, 95% CI 1.24–1.43), whereas symptoms most strongly associated with younger age were interpersonal sensitivity (OR 0.72, 95% CI 0.66–0.79), feeling irritable (OR 0.73, 95% CI 0.67–0.79), and sleeping too much (OR 0.75, 95% CI 0.68–0.83). The sum score of somatic/vegetative symptoms was associated with older age (B = 0.23, p < 0.001), whereas the mood and cognitive sum scores were associated with younger age (B = −0.20, p < 0.001; B = −0.04, p = 0.004).

Depression severity was found to be stable across the lifespan, yet depressive symptoms tend to shift with age from being predominantly mood-related to being more somatic/vegetative. Due to the increasing somatic presentation of depression with age, diagnoses may be missed.

Mental health morbidity in post-conflict settings is high. Nevertheless, randomized controlled trials of psychotherapy on site are rare. Our aim was to integrate rigorous research procedures into a humanitarian programme and test the efficacy of resource activation (ROTATE) in treating post-traumatic stress disorder (PTSD), co-morbid symptoms and impaired functioning in Cambodia.

A total of 86 out-patients with PTSD were randomly assigned to five sessions of ROTATE (n = 53) or a 5-week waiting-list control (WLC) condition (n = 33). Treatment was provided by six Cambodian psychologists who had received extensive training in ROTATE. Masked assessments were made before and after therapy.

PTSD remission rates according to the DSM-IV algorithm of the Harvard Trauma Questionnaire were 95.9% in ROTATE and 24.1% in the WLC condition. Thus, patients receiving ROTATE had a significantly higher likelihood of PTSD remission (odds ratio 0.012, 95% confidence interval 0.002–0.071, p < 0.00001). Additionally, levels of anxiety, depression and impaired functioning were significantly reduced compared with the WLC condition (p < 0.00001, between-group effect sizes d = 2.41, 2.26 and 2.54, respectively). No harms were reported.

ROTATE was efficacious in treating Cambodian patients with high symptom levels of PTSD, emotional distress and impaired functioning. ROTATE is a brief, culturally adaptable intervention focusing on stabilization and strengthening resources rather than trauma confrontation. It can be taught to local professionals and paraprofessionals and enhance access to mental health care for patients in need.

Stigma related to mental health is a major barrier to help-seeking resulting in a large treatment gap in low- and middle-income countries (LMIC). This study assessed changes in knowledge, attitude and behaviour, and stigma related to help-seeking among participants exposed to an anti-stigma campaign.

The campaign, using multi-media interventions, was part of the SMART Mental Health Project, conducted for 3 months, across 42 villages in rural Andhra Pradesh, in South India. Mixed-methods evaluation was conducted in two villages using a pre-post design.

A total of 1576 and 2100 participants were interviewed, at pre- and post-intervention phases of the campaign. Knowledge was not increased. Attitudes and behaviours improved significantly (p < 0.01). Stigma related to help-seeking reduced significantly (p < 0.05). Social contact and drama were the most beneficial interventions identified during qualitative interviews.

The results showed that the campaign was beneficial and led to improvement of attitude and behaviours related to mental health and reduction in stigma related to help-seeking. Social contact was the most effective intervention. The study had implications for future research in LMIC.

Advanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age's relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence.

Data for 2 276 809 individuals born in Sweden 1979–2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987–2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history.

Even after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25–29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14–1.53] for AN and 1.26 (95% CI 1.13–1.40) for AED.

In this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline.