Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.

The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.

There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.

Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.

Computerized cognitive remediation therapy (CCRT) is generally effective for the cognitive deficits of schizophrenia. However, there is much uncertainty about what factors mediate or moderate effectiveness and are therefore important to personalize treatment and boost its effects.

In total, 311 Chinese inpatients with Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia were randomized to receive CCRT or Active control for 12 weeks with four to five sessions per week. All participants were assessed at baseline, post-treatment and 3-month follow-up. The outcomes were cognition, clinical symptoms and functional outcomes.

There was a significant benefit in the MATRICS Consensus Cognitive Battery (MCCB) total score for CCRT (F1,258 = 5.62; p = 0.02; effect size was 0.27, 95% confidence interval 0.04–0.49). There were no specific moderators of CCRT improvements. However, across both groups, Wisconsin Card Sort Test improvement mediated a positive effect on functional capacity and Digit Span benefit mediated decreases in positive symptoms. In exploratory analyses younger and older participants showed cognitive improvements but on different tests (younger on Symbol Coding Test, while older on the Spatial Span Test). Only the older age group showed MSCEIT benefits at post-treatment. In addition, cognition at baseline negatively correlated with cognitive improvement and those whose MCCB baseline total score was around 31 seem to derive the most benefit.

CCRT can improve the cognitive function of patients with schizophrenia. Changes in cognitive outcomes also contributed to improvements in functional outcomes either directly or solely in the context of CCRT. Age and the basic cognitive level of the participants seem to affect the cognitive benefits from CCRT.

Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis.

We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L).

After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21–34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22–1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47–69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18–1.82).

About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.

Major depression (MD) is a risk factor for cardiovascular disease. Reduced heart rate variability (HRV) has been observed in MD. Given the predictive value of HRV for cardiovascular health, reduced HRV might be one physiological factor that mediates this association.

The purpose of this study was to provide up-to-date random-effects meta-analyses of studies which compare resting-state measures of HRV between unmedicated adults with MD and controls. Database search considered English and German literature to July 2018.

A total of 21 studies including 2250 patients and 1982 controls were extracted. Significant differences between patients and controls were found for (i) frequency domains such as HF-HRV [Hedges' g = −0.318; 95% CI (−0.388 to −0.247)], LF-HRV (Hedges' g = −0.195; 95% CI (−0.332 to −0.059)], LF/HF-HRV (Hedges' g = 0.195; 95% CI (0.086–0.303)] and VLF-HRV (Hedges' g = −0.096; 95% CI (−0.179 to −0.013)), and for (ii) time-domains such as IBI (Hedges' g = −0.163; 95% CI (−0.304 to −0.022)], RMSSD (Hedges' g = −0.462; 95% CI (−0.612 to −0.312)] and SDNN (Hedges' g = −0.266; 95% CI (−0.431 to −0.100)].

Our findings demonstrate that all HRV-measures were lower in MD than in healthy controls and thus strengthens evidence for lower HRV as a potential cardiovascular risk factor in these patients.

Exposure to stressful life events is an established risk factor for the development of adolescent mental disorder. Growing evidence also suggests that neighbourhood social environments, including strong social cohesion, could have a protective effect on mental health. However, little is known about how neighbourhood social cohesion may buffer against the effects of stressful life events on adolescent mental health. Our aim was to assess whether neighbourhood social cohesion modifies the association between stressful life events and adolescent mental health outcomes.

Data were drawn from a nationally-representative prospective sample of Canadian adolescents, including 5183 adolescents aged 12/13 years at T1 and 14/15 years at T2. Caregivers reported neighbourhood social cohesion at T1, and exposure to stressful life events between T1 and T2. Symptoms of mental health and behaviour problems were self-reported by adolescents at T1 and T2. Multivariable logistic regression was used to determine whether the relationship between stressful life events and outcomes was modified by neighbourhood social cohesion.

Associations between stressful life events and adolescent outcomes were statistically significantly lower in neighbourhoods with greater social cohesion for: depression/anxiety (high cohesion OR = 0.98 v. low cohesion OR = 3.11), suicidal ideation (ORhigh = 1.30 v. ORlow = 5.25), aggression/conduct disorder (ORhigh = 1.09 v. ORlow = 4.27), and property offence (ORhigh = 1.21 v. ORlow = 4.21).

Greater neighbourhood social cohesion appeared to buffer the effects of stressful life events on several domains of adolescent mental health. This potentially presents a target for public health intervention to improve adolescent mental health and behavioural outcomes.

Adverse health and social outcomes are known to occur more frequently following parental death during childhood, but evidence is lacking for comparing long-term risks of internalised v. externalised harm.

This national register-based cohort study consisted of Danish persons born 1970–2000. The Civil Registration System and National Causes of Death Register were linked to ascertain parental deaths by cause before cohort members' 15th birthdays. From age 15 years, hospital-treated self-harm episodes were ascertained through linkage to the National Patient Register and the Psychiatric Central Research Register, and violent crimes were identified via linkage to the National Crime Register. Hazard ratio and cumulative incidence values were estimated.

Self-harm and violent criminality risks were elevated following parental death during childhood. Covariate adjustment for gender, birth year and first-degree relatives' mental illnesses attenuated these associations, although significantly heightened risks persisted. The estimated hazard ratios did not differ greatly according to which parent died, but losing both parents conferred particularly large risk increases. Risks for both adverse outcomes were higher in relation to unnatural v. natural parental death; violent criminality risk was especially raised among individuals exposed to parental death by unnatural causes other than suicide. The association was strongest when pre-school age children experienced parental death.

Effective early intervention is needed to help youngsters who have experienced the death of one or both parents to develop immediate and sustained coping strategies. Enhanced cooperation between health and social services and criminal justice agencies may mitigate risks for these two destructive behaviours.

Preterm birth is associated with an increased risk for cognitive-neurophysiological impairments and attention-deficit/hyperactivity disorder (ADHD). Whether the associations are due to the preterm birth insult per se, or due to other risk factors that characterise families with preterm-born children, is largely unknown.

We employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task.

Within-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms (β = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ (β = −0.20, p = 0.02, 95% CI −0.40 to −0.01), preparation-vigilance measures and measures of error processing (ranging from β = 0.71, −0.35). There was a negligible within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, β = −0.07, p = 0.45, 95% CI −0.33 to 0.15) or verbal working memory (digit span backward, β = −0.05, p = 0.63, 95% CI −0.30 to 0.18).

Our results suggest that the relationship between preterm birth with ADHD symptoms and specific cognitive-neurophysiological impairments (IQ, preparation-vigilance and error processing) is independent of family-level risk and consistent with a causal inference. In contrast, our results suggest that previously observed associations between preterm birth with executive control processes of inhibition and working memory are instead linked to background characteristics of families with a preterm-born child rather than preterm birth insult per se. These findings suggest that interventions need to target both preterm-birth specific and family-level risk factors.

To estimate the lifetime prevalence and potential determinants of psychotic experience(s) (PEs) in the general population of Qatar – a small non-war afflicted, conservative, high-income, middle-eastern country with recent rapid urbanization including an influx of migrants.

A probability-based sample (n = 1353) of non-migrants and migrants were interviewed face-to-face and administered a 7-item psychosis screener adapted from the Composite International Diagnostic Interview, the Kessler 6-item psychological distress scale, and the 5 items assessing odd (paranormal) beliefs and magical thinking (OBMT) from the Schizotypal Personality Questionnaire. Using bivariate and logistic regression analyses, lifetime prevalence rates of PEs were estimated then compared before and after adjustment for socio-demographics, Arab ethnicity, psychological distress, and OBMT.

Prevalence of PEs was 27.9%. Visual hallucinations were most common (12.8%), followed by persecutory delusions (6.7%) and auditory hallucinations (6.9%). Ideas of reference (3.6%) were least prevalent. PEs were significantly higher in Arabs (34.7%) compared with non-Arabs (16.4%, p < 0.001) with the exception of ideas of reference and paranoid delusions. Female gender was associated with a higher prevalence of PEs in the Arab group only (p < 0.001). Prevalence of PEs was significantly higher among Arabs (48.8% v. 15.8%, p < 0.001) and non-Arabs (35.2% v. 7.3%, p < 0.001) with OBMT. Arab ethnicity (OR = 2.10, p = 0.015), psychological distress (OR = 2.29 p = 0.003), and OBMT (OR = 6.25, p < 0.001) were independently associated with PEs after adjustment for all variables.

Ethnicity, but not migration was independently associated with PEs. Evidence linking Arab ethnicity, female gender, and psychological distress to PEs through associations with OBMT was identified for future prospective investigations.

Fatigue syndromes (FSs) affect large numbers of individuals, yet evidence from epidemiological studies on adverse outcomes, such as premature death, is limited.

Cohort study involving 385 general practices in England that contributed to the Clinical Practice Research Datalink (CPRD) with linked inpatient Hospital Episode Statistics (HES) and Office for National Statistics (ONS) cause of death information. A total of 10 477 patients aged 15 years and above, diagnosed with a FS during 2000–2014, were individually matched with up to 20 comparator patients without a history of having a FS. Prevalence ratios (PRs) were estimated to compare the FS and comparison cohorts on clinical characteristics. Adjusted hazard ratios (HRs) for subsequent adverse outcomes were estimated from stratified Cox regression models.

Among patients diagnosed with FSs, we found elevated baseline prevalence of: any psychiatric illness (PR 1.77; 95% CI 1.72–1.82), anxiety disorders (PR 1.92; 1.85–1.99), depression (PR 1.89; 1.83–1.96), psychotropic prescriptions (PR 1.68; 1.64–1.72) and comorbid physical illness (PR 1.28; 1.23–1.32). We found no significant differences in risks for: all-cause mortality (HR 0.99; 0.91–1.09), natural death (HR 0.99; 0.90–1.09), unnatural death (HR 1.00; 0.59–1.72) or suicide (HR 1.68; 0.78–3.63). We did, however, observe a significantly elevated non-fatal self-harm risk: HR 1.83; 1.56–2.15.

The absence of elevated premature mortality risk is reassuring. The raised prevalence of mental illness and increased non-fatal self-harm risk indicate a need for enhanced assessment and management of psychopathology associated with fatigue syndromes.

Early life maltreatment (ELM), borderline personality disorder (BPD), and major depressive disorder (MDD) have been associated with empathy deficits in different domains. Lack of maternal empathy has also been related to child behavioral problems. As ELM, BPD, and MDD often co-occur, we aimed to identify dissociable effects on empathy due to these three factors. In addition, we aimed to investigate their indirect effects via empathy on child psychopathology.

We included 251 mothers with and without MDD (in remission), BPD and ELM and their children, aged 5–12. We used the Interpersonal Reactivity Index as a measure of empathy on four different dimensions (personal distress, empathic concern, perspective taking, and fantasy) and the Child Behavior Checklist as a measure of child psychopathology.

Having included all three factors (ELM, MDD, BPD) in one analysis, we found elevated personal distress in MDD and BPD, and lower levels of perspective-taking in BPD, but no effects from ELM on any empathy subscales. Furthermore, we found indirect effects from maternal BPD and MDD on child psychopathology, via maternal personal distress.

The present study demonstrated the dissociable effects of maternal ELM, MDD, and BPD on empathy. Elevated personal distress in mothers with BPD and MDD may lead to higher levels of child psychopathology.

Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.

Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.

CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.

Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Goal neglect refers to a dissociation between intended and actual action. Although commonly associated with frontal brain damage, this phenomenon is also characteristic of clinical depression. To date, tests of goal neglect typically require individuals to switch between subtasks populated with neutral stimuli. This study examined the impact of affective and personally salient stimulus contexts on goal neglect in clinical depression.

Participants were randomly allocated to either positively or negatively-valenced versions of the Affective Six Elements Test (A-SET). We hypothesised that depressed individuals (n = 30) would exhibit an overall impairment in A-SET performance by neglecting entire subtasks and allocating suboptimal time to each task, relative to never-depressed peers (n = 30), with effects being strongest for the negatively-valenced version.

Findings showed that depressed individuals exhibited specific deficits, relative to controls on these measures in the negative A-SET only, with a magnitude comparable to that found in brain injured patients.

Individuals with depression are impaired in their ability to monitor performance and implement strategies that are optimal for the purpose of pursuing an overarching goal when the task context is negatively-valenced. Potential mechanisms are discussed.

The efficacy of psychoeducation for bipolar disorder has been demonstrated in clinical trials, but it is not known if the results translate into effectiveness in routine clinical practice. The aim was to determine the effectiveness of psychoeducation for bipolar disorder in a routine clinical setting.

We identified 2819 patients with at least three registrations in the Swedish Quality Assurance Register for Bipolar Disorder. Among those, 402 had not been exposed to psychoeducation at the first visit, but received psychoeducation during any of the following registrations. Using within-individual analyses, the risk of recurrence after having received psychoeducation was compared with the risk prior to psychoeducation.

In adjusted within-individuals comparisons, periods after psychoeducation was associated with decreased risks of any recurrence [odds ratio (OR) 0.57, 95% CI 0.42–0.78], (hypo-)manic or mixed episodes (OR 0.54, 95% CI 0.39–0.76), depressive episodes (OR 0.63, 95% CI 0.47–0.86), and inpatient care (OR 0.54, 95% CI 0.33–0.86) relative to periods prior to psychoeducation. There was no association with rates of involuntary sectioning or suicide attempts.

The results suggest that psychoeducation for bipolar disorder reduces the risk of mood episodes and inpatient care also when implemented in routine clinical practice.

Prenatal infections have been proposed as a putative risk factor for a number of psychiatric outcomes across a continuum of severity. Evidence on eating disorders is scarce. We investigated whether exposure to prenatal maternal infections is associated with an increased risk of disordered eating and weight and shape concerns in adolescence in a large UK birth cohort.

We used data from the Avon Longitudinal Study of Parents and Children. The primary exposure was maternal experience of infections at any time in pregnancy. Study outcomes were presence of any, monthly or weekly disordered eating at 14 and 16 years of age, and weight and shape concerns at 14 years. We defined the causal effect of the exposure on these outcomes using a counterfactual framework adjusting our analyses for a number of hypothesised confounders, and imputing missing confounder data using multiple imputation.

In total, 4884 children had complete exposure and outcome data at age 14 years, and 4124 at 16 years. Exposed children had a greater risk of reporting weekly disordered eating at both age 14 [risk difference (RD) 0.9%, 95% confidence interval (CI) −0.01 to 1.9, p = 0.08] and 16 (RD 2.3%, 95% CI 0.6–3.9, p < 0.01), though evidence of an association was weak at age 14 years. Exposed children also had greater weight and shape concerns at age 14 years (mean difference 0.15, 95% CI 0.05–0.26, p < 0.01).

Exposure to prenatal maternal infection is associated with greater risk of disordered eating in adolescence. This association could be explained by in utero processes leading to impaired neurodevelopment or altered immunological profiles. Residual confounding cannot be excluded.

Electroconvulsive therapy (ECT) is a fast-acting intervention for major depressive disorder. Previous studies indicated neurotrophic effects following ECT that might contribute to changes in white matter brain structure. We investigated the influence of ECT in a non-randomized prospective study focusing on white matter changes over time.

Twenty-nine severely depressed patients receiving ECT in addition to inpatient treatment, 69 severely depressed patients with inpatient treatment (NON-ECT) and 52 healthy controls (HC) took part in a non-randomized prospective study. Participants were scanned twice, approximately 6 weeks apart, using diffusion tensor imaging, applying tract-based spatial statistics. Additional correlational analyses were conducted in the ECT subsample to investigate the effects of seizure duration and therapeutic response.

Mean diffusivity (MD) increased after ECT in the right hemisphere, which was an ECT-group-specific effect. Seizure duration was associated with decreased fractional anisotropy (FA) following ECT. Longitudinal changes in ECT were not associated with therapy response. However, within the ECT group only, baseline FA was positively and MD negatively associated with post-ECT symptomatology.

Our data suggest that ECT changes white matter integrity, possibly reflecting increased permeability of the blood–brain barrier, resulting in disturbed communication of fibers. Further, baseline diffusion metrics were associated with therapy response. Coherent fiber structure could be a prerequisite for a generalized seizure and inhibitory brain signaling necessary to successfully inhibit increased seizure activity.

This study examined the structure of the self-concept in a sample of sexual trauma survivors with posttraumatic stress disorder (PTSD) compared to healthy controls using a self-descriptive card-sorting task. We explored whether individuals with PTSD possess a highly affectively-compartmentalized self-structure, whereby positive and negative self-attributes are sectioned off into separate components of self-concept (e.g. self as an employee, lover, mother). We also examined redundancy (i.e. overlap) of positive and negative self-attributes across the different components of self-concept.

Participants generated a set of self-aspects that reflected their own life (e.g. ‘self at work’). They were then asked to describe their self-aspects using list of positive or negative attributes.

Results revealed that, relative to the control group, the PTSD group used a greater proportion of negative attributes and had a more compartmentalized self-structure. However, there were no significant differences between the PTSD and control groups in positive or negative redundancy. Sensitivity analyses demonstrated that the key findings were not accounted for by comorbid diagnosis of depression.

Findings indicated that the self-structure is organized differently in those with PTSD, relative to those with depression or good mental health.

The cognitive process of worry, which keeps negative thoughts in mind and elaborates the content, contributes to the occurrence of many mental health disorders. Our principal aim was to develop a straightforward measure of general problematic worry suitable for research and clinical treatment. Our secondary aim was to develop a measure of problematic worry specifically concerning paranoid fears.

An item pool concerning worry in the past month was evaluated in 250 non-clinical individuals and 50 patients with psychosis in a worry treatment trial. Exploratory factor analysis and item response theory (IRT) informed the selection of scale items. IRT analyses were repeated with the scales administered to 273 non-clinical individuals, 79 patients with psychosis and 93 patients with social anxiety disorder. Other clinical measures were administered to assess concurrent validity. Test-retest reliability was assessed with 75 participants. Sensitivity to change was assessed with 43 patients with psychosis.

A 10-item general worry scale (Dunn Worry Questionnaire; DWQ) and a five-item paranoia worry scale (Paranoia Worries Questionnaire; PWQ) were developed. All items were highly discriminative (DWQ a = 1.98–5.03; PWQ a = 4.10–10.7), indicating small increases in latent worry lead to a high probability of item endorsement. The DWQ was highly informative across a wide range of the worry distribution, whilst the PWQ had greatest precision at clinical levels of paranoia worry. The scales demonstrated excellent internal reliability, test-retest reliability, concurrent validity and sensitivity to change.

The new measures of general problematic worry and worry about paranoid fears have excellent psychometric properties.

The 22q11.2 deletion syndrome (22q11DS) is caused by a deletion on chromosome 22 locus q11.2. This copy number variant results in haplo-insufficiency of the catechol-O-methyltransferase (COMT) gene, and is associated with a significant increase in the risk for developing cognitive impairments and psychosis. The COMT gene encodes an enzyme that primarily modulates clearance of dopamine (DA) from the synaptic cleft, especially in the prefrontal cortical areas. Consequently, extracellular DA levels may be increased in prefrontal brain areas in 22q11DS, which may underlie the well-documented susceptibility for cognitive impairments and psychosis in affected individuals. This study aims to examine DA D2/3 receptor binding in frontal brain regions in adults with 22q11DS, as a proxy of frontal DA levels.

The study was performed in 14 non-psychotic, relatively high functioning adults with 22q11DS and 16 age- and gender-matched healthy controls (HCs), who underwent DA D2/3 receptor [18F]fallypride PET imaging. Frontal binding potential (BPND) was used as the main outcome measure.

BPND was significantly lower in adults with 22q11DS compared with HCs in the prefrontal cortex and the anterior cingulate gyrus. After Bonferroni correction significance remained for the anterior cingulate gyrus. There were no between-group differences in BPND in the orbitofrontal cortex and anterior cingulate cortex.

This study is the first to demonstrate lower frontal D2/3 receptor binding in adults with 22q11DS. It suggests that a 22q11.2 deletion affects frontal dopaminergic neurotransmission.