The typically poor outcomes of schizophrenia could be improved through interventions that reduce cardiometabolic risk, negative symptoms and cognitive deficits; aspects of the illness which often go untreated. The present review and meta-analysis aimed to establish the effectiveness of exercise for improving both physical and mental health outcomes in schizophrenia patients.

We conducted a systematic literature search to identify all studies that examined the physical or mental effects of exercise interventions in non-affective psychotic disorders. Of 1581 references, 20 eligible studies were identified. Data on study design, sample characteristics, outcomes and feasibility were extracted from all studies and systematically reviewed. Meta-analyses were also conducted on the physical and mental health outcomes of randomized controlled trials.

Exercise interventions had no significant effect on body mass index, but can improve physical fitness and other cardiometabolic risk factors. Psychiatric symptoms were significantly reduced by interventions using around 90 min of moderate-to-vigorous exercise per week (standardized mean difference: 0.72, 95% confidence interval −1.14 to −0.29). This amount of exercise was also reported to significantly improve functioning, co-morbid disorders and neurocognition.

Interventions that implement a sufficient dose of exercise, in supervised or group settings, can be feasible and effective interventions for schizophrenia.

The association between childhood trauma and psychotic and depressive symptomatology is well established. However, less is known about the specificity and course of these symptoms in relation to childhood trauma.

In a large sample (n = 2765) of patients with psychosis (n = 1119), their siblings (n = 1057) and controls (n = 589), multivariate (mixed-effects) regression analyses with multiple outcomes were performed to examine the association between childhood trauma and psychotic and depressive symptomatology over a 3-year period.

A dose–response relationship was found between childhood trauma and psychosis. Abuse was more strongly associated with positive symptoms than with negative symptoms whereas the strength of the associations between neglect and positive and negative symptoms was comparable. In patients, similar associations between childhood trauma and psychotic or depressive symptoms were found, and in siblings and controls, stronger associations were found between trauma and depressive symptomatology. Childhood trauma was not related to a differential course of symptoms over a 3-year time period.

In congruence with earlier work, our findings suggest that childhood trauma, and abuse in particular, is associated with (subthreshold) psychosis. However, childhood trauma does not seem to be associated with a differential course of symptoms, nor does it uniquely heighten the chance of developing (subthreshold) psychotic symptomatology. Our results indicate that trauma may instead contribute to a shared vulnerability for psychotic and depressive symptoms.

Findings from family and twin studies support a genetic contribution to the development of sexual orientation in men. However, previous studies have yielded conflicting evidence for linkage to chromosome Xq28.

We conducted a genome-wide linkage scan on 409 independent pairs of homosexual brothers (908 analyzed individuals in 384 families), by far the largest study of its kind to date.

We identified two regions of linkage: the pericentromeric region on chromosome 8 (maximum two-point LOD = 4.08, maximum multipoint LOD = 2.59), which overlaps with the second strongest region from a previous separate linkage scan of 155 brother pairs; and Xq28 (maximum two-point LOD = 2.99, maximum multipoint LOD = 2.76), which was also implicated in prior research.

Results, especially in the context of past studies, support the existence of genes on pericentromeric chromosome 8 and chromosome Xq28 influencing development of male sexual orientation.

Several psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study.

The present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter–Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test – immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms.

Compared with no-grief participants, participants with complicated grief had lower scores for the Letter–Digit Substitution Test [Z-score −0.16 v. 0.04, 95% confidence interval (CI) −0.36 to −0.04, p = 0.01] and Word Fluency Task (Z-score −0.15 v. 0.03, 95% CI −0.35 to −0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI −37.6 to −0.10, p = 0.04).

Participants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.

Although depression is a common problem among non-professional caregivers, only one trial has evaluated the efficacy of indicated prevention targeting this population and the long-term efficacy is unknown. The aim of this study was to evaluate the long-term efficacy of a brief intervention for the indicated prevention of depression in a sample of female caregivers.

A randomized controlled trial was conducted involving 173 participants (mean age 53.9 years) who were allocated to the intervention (n = 89) or the usual-care control group (n = 84). Blinded interviewers conducted assessments at 1, 3, 6 and 12 months of follow-up. The main outcome measure was the incidence of major depression and the secondary outcomes were compliance with treatment, depressive symptoms, emotional distress and caregiver burden.

At the 12-month follow-up, a lower incidence of depression as evaluated using the Structured Clinical Interview for Axis I Disorders of the DSM-IV was found in the intervention group compared with the control group (10.1% v. 25.0%). The relative risk was 0.40 and statistically significant [χ2 = 6.68, degrees of freedom = 1, p = 0.010, 95% confidence interval (CI) 0.20–0.81], and the number needed to treat was 7 (95% CI 4–27). There was a significant delay in the onset of depression in the intervention group (p = 0.008). The good complier caregivers had a lower incidence of depression. The intervention effect on depressive symptoms, emotional distress and caregiver burden were maintained for 12 months.

This is the first study to demonstrate that a brief problem-solving intervention can prevent the onset of depression among non-professional caregivers over the longer term.

Altered corticostriatothalamic encoding of reinforcement is a core feature of depression. Here we examine reinforcement learning in late-life depression in the theoretical framework of the vascular depression hypothesis. This hypothesis attributes the co-occurrence of late-life depression and poor executive control to prefrontal/cingulate disconnection by vascular lesions.

Our fMRI study compared 31 patients aged ⩾60 years with major depression to 16 controls. Using a computational model, we estimated neural and behavioral responses to reinforcement in an uncertain, changing environment (probabilistic reversal learning).

Poor executive control and depression each explained distinct variance in corticostriatothalamic response to unexpected rewards. Depression, but not poor executive control, predicted disrupted functional connectivity between the striatum and prefrontal cortex. White-matter hyperintensities predicted diminished corticostriatothalamic responses to reinforcement, but did not mediate effects of depression or executive control. In two independent samples, poor executive control predicted a failure to persist with rewarded actions, an effect distinct from depressive oversensitivity to punishment. The findings were unchanged in a subsample of participants with vascular disease. Results were robust to effects of confounders including psychiatric comorbidities, physical illness, depressive severity, and psychotropic exposure.

Contrary to the predictions of the vascular depression hypothesis, altered encoding of rewards in late-life depression is dissociable from impaired contingency learning associated with poor executive control. Functional connectivity and behavioral analyses point to a disruption of ascending mesostriatocortical reward signals in late-life depression and a failure of cortical contingency encoding in elderly with poor executive control.

Dysfunctional attitudes are a feature of depression that has been correlated with receptor binding abnormalities in limbic and cortical regions. We sought to investigate the functional neuroanatomy of dysfunctional attitudes in major depressive disorder (MDD) and the effects of treatment with cognitive–behavioural therapy (CBT).

Participants were 16 patients with unipolar depression in an acute depressive episode (mean age 40.0 years) and 16 matched healthy controls (mean age 39.9 years). Patients were medication free and received a course of treatment with CBT. All participants underwent functional magnetic resonance imaging (fMRI) scans at baseline and at week 16, prior to the initiation of therapy and following the course of CBT for patients. During each fMRI scan, participants indicated their attributions to statements from a modified Dysfunctional Attitudes Scale (mDAS-48).

MDD patients in an acute depressive episode endorsed a greater number of extreme responses to DAS statements, which normalized following CBT treatment. Extreme attributions were associated with greater activation in the left hippocampal region, inferior parietal lobe and precuneus in MDD patients as compared with healthy controls as a main effect of group. An interaction effect was found in the left parahippocampal region, which showed less attenuation in MDD patients at the follow-up scan relative to healthy controls.

Attenuation of activity in the parahippocampal region may be indicative of an improvement in dysfunctional thinking following CBT treatment in depression, while persistent engagement of regions involved in attentional processing and memory retrieval with extreme attributions reflects a trait feature of depression.

Although there is evidence for the effectiveness of interventions for psychosis among ultra-high-risk (UHR) groups, health economic evaluations are lacking. This study aimed to determine the cost effectiveness and cost–utility of cognitive–behavioural therapy (CBT) to prevent first-episode psychosis.

The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients with an 18-month follow-up. All participants were treated with routine care (RC) for non-psychotic disorders. The experimental group (n = 95) received add-on CBT to prevent first-episode psychosis. We report the intervention, medical and travel costs, as well as costs arising from loss of productivity. Treatment response was defined as psychosis-free survival and quality-adjusted life years (QALYs) gained.

In the cost-effectiveness analysis, the proportion of averted psychoses was significantly higher in the CBT condition (89.5% v. 76.2%). CBT showed a 63.7% probability of being more cost effective, because it was less costly than RC by US$844 (£551) per prevented psychosis. In the cost–utility analysis, QALY health gains were slightly higher for CBT than for RC (0.60 v. 0.57) and the CBT intervention had a 52.3% probability of being the superior treatment because, for equal or better QALY gains, the costs of CBT were lower than those of RC.

Add-on preventive CBT for UHR resulted in a significant reduction in the incidence of first psychosis. QALY gains show little difference between the two conditions. The CBT intervention proved to be cost saving.

Negative cognitive bias and aberrant neural processing of emotional faces are trait-marks of depression. Yet it is unclear whether these changes constitute an endophenotype for depression and are also present in healthy individuals with hereditary risk for depression.

Thirty healthy, never-depressed monozygotic (MZ) twins with a co-twin history of depression (high risk group: n = 13) or without co-twin history of depression (low-risk group: n = 17) were enrolled in a functional magnetic resonance imaging (fMRI) study. During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping strategies.

High-risk twins showed increased neural response to happy and fearful faces in dorsal anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), pre-supplementary motor area and occipito-parietal regions compared to low-risk twins. They also displayed stronger negative coupling between amygdala and pregenual ACC, dmPFC and temporo-parietal regions during emotional face processing. These task-related changes in neural responses in high-risk twins were accompanied by impaired gender discrimination performance during face processing. They also displayed increased attention vigilance for fearful faces and were slower at recognizing facial expressions relative to low-risk controls. These effects occurred in the absence of differences between groups in mood, subjective state or coping.

Different neural response and functional connectivity within fronto-limbic and occipito-parietal regions during emotional face processing and enhanced fear vigilance may be key endophenotypes for depression.

Electroconvulsive therapy (ECT) is widely applied to treat severe depression resistant to standard treatment. Results from previous studies comparing the cost-effectiveness of this technique with treatment alternatives such as repetitive transcranial magnetic stimulation (rTMS) are conflicting.

We conducted a cost-effectiveness analysis comparing ECT alone, rTMS alone and rTMS followed by ECT when rTMS fails under the perspective of the Spanish National Health Service. The analysis is based on a Markov model which simulates the costs and health outcomes of individuals treated under these alternatives over a 12-month period. Data to populate this model were extracted and synthesized from a series of randomized controlled trials and other studies that have compared these techniques on the patient group of interest. We measure effectiveness using quality-adjusted life years (QALYs) and characterize the uncertainty using probabilistic sensitivity analyses.

ECT alone was found to be less costly and more effective than rTMS alone, while the strategy of providing rTMS followed by ECT when rTMS fails is the most expensive and effective option. The incremental cost per QALY gained of this latter strategy was found to be above the reference willingness-to-pay threshold used in these types of studies in Spain and other countries. The probability that ECT alone is the most cost-effective alternative was estimated to be around 70%.

ECT is likely to be the most cost-effective option in the treatment of resistant severe depression for a willingness to pay of €30 000 per QALY.

Previous studies have reported strong genetic and environmental overlap between antisocial-externalizing (factor 2; F2) features of psychopathy and borderline personality disorder (BPD) tendencies. However, this line of research has yet to examine etiological associations of affective-interpersonal (factor 1, F1) features of psychopathy with BPD tendencies.

The current study investigated differential phenotypic and genetic overlap of psychopathy factors 1 and 2 with BPD tendencies in a sample of over 250 male and female community-recruited adult twin pairs.

Consistent with previous research, biometric analyses revealed strong genetic and non-shared environmental correlations of F2 with BPD tendencies, suggesting that common genetic and non-shared environmental factors contribute to both phenotypes. In contrast, negative genetic and non-shared environmental correlations were observed between F1 and BPD tendencies, indicating that the genetic factors underlying F1 serve as protective factors against BPD. No gender differences emerged in the analyses.

These findings provide further insight into associations of psychopathic features – F1 as well as F2 – and BPD tendencies. Implications for treatment and intervention are discussed, along with how psychopathic traits may differentially influence the manifestation of BPD tendencies.

Psychotic phenomena are common in the general population but are excluded from diagnostic criteria for mild to moderate depression and anxiety despite their co-occurrence and shared risk factors. We used item response theory modelling to examine whether the co-occurrence of depressive, anxiety and psychotic phenomena is best explained by: (1) a single underlying factor; (2) two separate, uncorrelated factors; (3) two separate yet linked factors; or (4) two separate domains along with an underlying ‘common mental distress’ (CMD) factor. We defined where, along any latent continuum, the psychopathological items contributed most information.

We performed a secondary analysis of cross-sectional, item-level information from measures of depression, anxiety and psychotic experiences in 6617 participants aged 13 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and 977 participants aged 18 years from the ROOTS schools-based sample. We replicated results from one sample in the other and validated the latent factors against an earlier parental measure of mental state.

In both cohorts depression, anxiety and psychotic items were best represented as a bi-factor model with a single, unitary CMD factor on which psychotic items conveyed information about the more severe end (model 4); residual variation remained for psychotic items. The CMD factor was significantly associated with the prior parental measure.

Psychotic phenomena co-occur with depression and anxiety in teenagers and may be a marker of severity in a single, unitary dimension of CMD. Psychotic phenomena should be routinely included in epidemiological assessments of psychiatric morbidity, otherwise the most severe symptomatology remains unmeasured.

A growing body of research has investigated associations between insecure attachment styles and psychosis. However, despite good theoretical and epidemiological reasons for hypothesising that insecure attachment may be specifically implicated in paranoid delusions, few studies have considered the role it plays in specific symptoms.

We examined the relationship between attachment style, paranoid beliefs and hallucinatory experiences in a sample of 176 people with a diagnosis of schizophrenia spectrum disorders and 113 healthy controls. We also investigated the possible role of negative self-esteem in mediating this association.

Insecure attachment predicted paranoia but not hallucinations after co-morbidity between the symptoms was controlled for. Negative self-esteem partially mediated the association between attachment anxiety and clinical paranoia, and fully mediated the relationship between attachment avoidance and clinical paranoia.

It may be fruitful to explore attachment representations in psychological treatments for paranoid patients. If future research confirms the importance of disrupted attachment as a risk factor for persecutory delusions, consideration might be given to how to protect vulnerable young people, for example those raised in children's homes.

We investigated the course of decline in multiple cognitive domains in non-demented subjects from a memory clinic setting, and compared pattern, onset and magnitude of decline between subjects who progressed to Alzheimer's disease (AD) dementia at follow-up and subjects who did not progress.

In this retrospective cohort study 819 consecutive non-demented patients who visited the memory clinics in Maastricht or Amsterdam between 1987 and 2010 were followed until they became demented or for a maximum of 10 years (range 0.5–10 years). Differences in trajectories of episodic memory, executive functioning, verbal fluency, and information processing speed/attention between converters to AD dementia and subjects remaining non-demented were compared by means of random effects modelling.

The cognitive performance of converters and non-converters could already be differentiated seven (episodic memory) to three (verbal fluency and executive functioning) years prior to dementia diagnosis. Converters declined in these three domains, while non-converters remained stable on episodic memory and executive functioning and showed modest decline in verbal fluency. There was no evidence of decline in information processing speed/attention in either group.

Differences in cognitive performance between converters to AD dementia and subjects remaining non-demented could be established 7 years prior to diagnosis for episodic memory, with verbal fluency and executive functioning following several years later. Therefore, in addition to early episodic memory decline, decline in executive functions may also flag incident AD dementia. By contrast, change in information processing speed/attention seems less informative.

Severe stress in social situations is a core symptom of social anxiety disorder (SAD). Connectivity between the amygdala and cortical regions is thought to be important for emotion regulation, a function that is compromised in SAD. However, it has never been tested if and how this connectivity pattern changes under conditions of stress-inducing social evaluative threat. Here we investigate changes in cortical-amygdala coupling in SAD during the anticipation of giving a public speech.

Twenty individuals with SAD and age-, gender- and education-matched controls (n = 20) participated in this study. During the functional magnetic resonance imaging (fMRI) session, participants underwent three ‘resting-state’ fMRI scans: one before, one during, and one after the anticipation of giving a public speech. Functional connectivity between cortical emotion regulation regions and the amygdala was investigated.

Compared to controls, SAD participants showed reduced functional integration between cortical emotion regulation regions and the amygdala during the public speech anticipation. Moreover, in SAD participants cortical-amygdala connectivity changes correlated with social anxiety symptom severity.

The distinctive pattern of cortical-amygdala connectivity suggests less effective cortical-subcortical communication during social stress-provoking situations in SAD.

While cluster A personality disorders (PDs) have been shown to be moderately heritable, we know little about the temporal stability of these genetic risk factors.

Paranoid PD (PPD) and schizotypal PD (STPD) were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 twins on average 10 years later at wave 2. Using the program Mx, we fitted a longitudinal latent factor model using the number of endorsed criteria for PPD and STPD.

The stability over time of the criteria counts for PPD and STPD, estimated as polychoric correlations, were +0.34 and +0.40, respectively. The best-fit longitudinal model included only additive genetic and individual-specific environmental factors with parameter estimates constrained to equality across the two waves. The cross-wave genetic and individual-specific environmental correlations for a latent cluster A factor were estimated to equal +1.00 and +0.13, respectively. The cross-time correlations for genetic and environmental effects specific to the individual PDs were estimated at +1.00 and +0.16–0.20, respectively. We found that 68% and 71% of the temporal stability of PPD and STPD derived, respectively, from the effect of genetic factors.

Shared genetic risk factors for two of the cluster A PDs are highly stable in adults over a 10-year period while environmental risk factors are relatively transient. Over two-thirds of the long-term stability of the common cluster A PD liability can be attributed to genetic influences.

Little is known about the factors influencing the stability of obsessive–compulsive behaviour (OCB) from childhood to adolescence. The current study aimed to investigate: (1) the stability of paediatric OCB over a 12-year period; (2) the extent to which genetic and environmental factors influence stability; and (3) the extent to which these influences are stable or dynamic across development.

The sample included 14 743 twins from a population-based study. Parental ratings of severity of OCB were collected at ages 4, 7, 9 and 16 years.

OCB was found to be moderately stable over time. The genetic influence on OCB at each age was moderate, with significant effects also of non-shared environment. Genetic factors exerted a substantial influence on OCB persistence, explaining 59–80% of the stability over time. The results indicated genetic continuity, whereby genetic influences at each age continue to affect the expression of OCB at subsequent ages. However, we also found evidence for genetic attenuation in that genetic influences at one age decline in their influence over time, and genetic innovation whereby new genes ‘come on line’ at each age. Non-shared environment influenced stability of OCB to a lesser extent and effects were largely unique to each age and displayed negligible influences on OCB at later time points.

OCB appears to be moderately stable across development, and stability is largely driven by genetic factors. However, the genetic effects are not entirely constant, but rather the genetic influence on OCB appears to be a developmentally dynamic process.

Mental and substance use disorders are common and often persistent, with many emerging in early life. Compared to adult mental and substance use disorders, the global burden attributable to these disorders in children and youth has received relatively little attention.

Data from the Global Burden of Disease Study 2010 was used to investigate the burden of mental and substance disorders in children and youth aged 0–24 years. Burden was estimated in terms of disability-adjusted life years (DALYs), derived from the sum of years lived with disability (YLDs) and years of life lost (YLLs).

Globally, mental and substance use disorders are the leading cause of disability in children and youth, accounting for a quarter of all YLDs (54.2 million). In terms of DALYs, they ranked 6th with 55.5 million DALYs (5.7%) and rose to 5th when mortality burden of suicide was reattributed. While mental and substance use disorders were the leading cause of DALYs in high-income countries (HICs), they ranked 7th in low- and middle-income countries (LMICs) due to mortality attributable to infectious diseases.

Mental and substance use disorders are significant contributors to disease burden in children and youth across the globe. As reproductive health and the management of infectious diseases improves in LMICs, the proportion of disease burden in children and youth attributable to mental and substance use disorders will increase, necessitating a realignment of health services in these countries.