When used as an adjunctive with antipsychotics, certain vitamins and minerals may be effective for improving symptomatic outcomes of schizophrenia, by restoring nutritional deficits, reducing oxidative stress, or modulating neurological pathways.

We conducted a systematic review of all randomized controlled trials (RCTs) reporting effects of vitamin and/or mineral supplements on psychiatric symptoms in people with schizophrenia. Random-effects meta-analyses were used to calculate the standardized mean difference between nutrient and placebo treatments.

An electronic database search in July 2016 identified 18 eligible RCTs, with outcome data for 832 patients. Pooled effects showed that vitamin B supplementation (including B6, B8 and B12) reduced psychiatric symptoms significantly more than control conditions [g = 0.508, 95% confidence interval (CI) 0.01–1.01, p = 0.047, I 2 = 72.3%]. Similar effects were observed among vitamin B RCTs which used intention-to-treat analyses (g = 0.734, 95% CI 0.00–1.49, p = 0.051). However, no effects of B vitamins were observed in individual domains of positive and negative symptoms (both p > 0.1). Meta-regression analyses showed that shorter illness duration was associated with greater vitamin B effectiveness (p = 0.001). There were no overall effects from antioxidant vitamins, inositol or dietary minerals on psychiatric symptoms.

There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia. Further research is needed to examine how the benefits of supplementation relate to nutrient deficits and the impact upon underlying neurobiological pathways, in order to establish optimal nutrient formulations for improving clinical outcomes in this population. Future studies should also explore the effects of combining beneficial nutrients within multi-nutrient formulas.

Substance use may increase the risk of non-adherence to antipsychotics, resulting in negative outcomes in patients with psychosis.

We aimed to quantitatively summarize evidence regarding the effect of cannabis use, the most commonly used illicit drug amongst those with psychosis, on adherence to antipsychotic medication. Studies were identified through a systematic database search. Adopting random-effects models, pooled odds ratios (OR) for risk of non-adherence to antipsychotic medications were calculated comparing: cannabis-users at baseline v. non-users at baseline; non users v. continued cannabis users at follow-up; non-users v. former users at follow-up; former users v. current users.

Fifteen observational studies (n = 3678) were included. Increased risk of non-adherence was observed for cannabis users compared to non-users (OR 2.46, n = 3055). At follow-up, increased risk of non-adherence was observed for current users compared to non-users (OR 5.79, n = 175) and former users (OR 5.5, n = 192), while there was no difference between former users and non-users (OR 1.12, n = 187).

Cannabis use increases the risk of non-adherence and quitting cannabis use may help adherence to antipsychotics. Thus, cannabis use may represent a potential target for intervention to improve medication adherence in those with psychosis.

To enhance indicated prevention in patients with a clinical high risk (CHR) for psychosis, recent research efforts have been increasingly directed towards estimating the risk of developing psychosis on an individual level using multivariable clinical prediction models. The aim of this study was to systematically review the methodological quality and reporting of studies developing or validating such models.

A systematic literature search was carried out (up to 14 March 2016) to find all studies that developed or validated a clinical prediction model predicting the transition to psychosis in CHR patients. Data were extracted using a comprehensive item list which was based on current methodological recommendations.

A total of 91 studies met the inclusion criteria. None of the retrieved studies performed a true external validation of an existing model. Only three studies (3.5%) had an event per variable ratio of at least 10, which is the recommended minimum to avoid overfitting. Internal validation was performed in only 14 studies (15%) and seven of these used biased internal validation strategies. Other frequently observed modeling approaches not recommended by methodologists included univariable screening of candidate predictors, stepwise variable selection, categorization of continuous variables, and poor handling and reporting of missing data.

Our systematic review revealed that poor methods and reporting are widespread in prediction of psychosis research. Since most studies relied on small sample sizes, did not perform internal or external cross-validation, and used poor model development strategies, most published models are probably overfitted and their reported predictive accuracy is likely to be overoptimistic.

The efficient organization and communication of brain networks underlie cognitive processing and their disruption can lead to pathological behaviours. Few studies have focused on whole-brain networks in obesity and binge eating disorder (BED). Here we used multi-echo resting-state functional magnetic resonance imaging (rsfMRI) along with a data-driven graph theory approach to assess brain network characteristics in obesity and BED.

Multi-echo rsfMRI scans were collected from 40 obese subjects (including 20 BED patients) and 40 healthy controls and denoised using multi-echo independent component analysis (ME-ICA). We constructed a whole-brain functional connectivity matrix with normalized correlation coefficients between regional mean blood oxygenation level-dependent (BOLD) signals from 90 brain regions in the Automated Anatomical Labeling atlas. We computed global and regional network properties in the binarized connectivity matrices with an edge density of 5%–25%. We also verified our findings using a separate parcellation, the Harvard–Oxford atlas parcellated into 470 regions.

Obese subjects exhibited significantly reduced global and local network efficiency as well as decreased modularity compared with healthy controls, showing disruption in small-world and modular network structures. In regional metrics, the putamen, pallidum and thalamus exhibited significantly decreased nodal degree and efficiency in obese subjects. Obese subjects also showed decreased connectivity of cortico-striatal/cortico-thalamic networks associated with putaminal and cortical motor regions. These findings were significant with ME-ICA with limited group differences observed with conventional denoising or single-echo analysis.

Using this data-driven analysis of multi-echo rsfMRI data, we found disruption in global network properties and motor cortico-striatal networks in obesity consistent with habit formation theories. Our findings highlight the role of network properties in pathological food misuse as possible biomarkers and therapeutic targets.

Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.

Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.

Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).

Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

Stigma associated with mental illness can delay or prevent help-seeking and service contact. Stigma-related influences on pathways to care in the early stages of psychotic disorders have not been systematically examined.

This review systematically assessed findings from qualitative, quantitative and mixed-methods research studies on the relationship between stigma and pathways to care (i.e. processes associated with help-seeking and health service contact) among people experiencing first-episode psychosis or at clinically defined increased risk of developing psychotic disorder. Forty studies were identified through searches of electronic databases (CINAHL, EMBASE, Medline, PsycINFO, Sociological Abstracts) from 1996 to 2016, supplemented by reference searches and expert consultations. Data synthesis involved thematic analysis of qualitative findings, narrative synthesis of quantitative findings, and a meta-synthesis combining these results.

The meta-synthesis identified six themes in relation to stigma on pathways to care among the target population: ‘sense of difference’, ‘characterizing difference negatively’, ‘negative reactions (anticipated and experienced)’, ‘strategies’, ‘lack of knowledge and understanding’, and ‘service-related factors’. This synthesis constitutes a comprehensive overview of the current evidence regarding stigma and pathways to care at early stages of psychotic disorders, and illustrates the complex manner in which stigma-related processes can influence help-seeking and service contact among first-episode psychosis and at-risk groups.

Our findings can serve as a foundation for future research in the area, and inform early intervention efforts and approaches to mitigate stigma-related concerns that currently influence recognition of early difficulties and contribute to delayed help-seeking and access to care.

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.

Some evidence suggests that heart rate variability (HRV) biofeedback might be an effective way to treat anxiety and stress symptoms. To examine the effect of HRV biofeedback on symptoms of anxiety and stress, we conducted a meta-analysis of studies extracted from PubMed, PsycINFO and the Cochrane Library.

The search identified 24 studies totaling 484 participants who received HRV biofeedback training for stress and anxiety. We conducted a random-effects meta-analysis.

The pre-post within-group effect size (Hedges' g) was 0.81. The between-groups analysis comparing biofeedback to a control condition yielded Hedges' g = 0.83. Moderator analyses revealed that treatment efficacy was not moderated by study year, risk of study bias, percentage of females, number of sessions, or presence of an anxiety disorder.

HRV biofeedback training is associated with a large reduction in self-reported stress and anxiety. Although more well-controlled studies are needed, this intervention offers a promising approach for treating stress and anxiety with wearable devices.

Individuals with anxiety disorders exhibit a ‘vigilance-avoidance’ pattern of attention to threatening stimuli when threatening and neutral stimuli are presented simultaneously, a phenomenon referred to as ‘threat bias’. Modifying threat bias through cognitive retraining during adolescence reduces symptoms of anxiety, and so elucidating neural mechanisms of threat bias during adolescence is of high importance. We explored neural mechanisms by testing whether threat bias in adolescents is associated with generalized or threat-specific differences in the neural processing of faces.

Subjects were categorized into those with (n = 25) and without (n = 27) threat avoidance based on a dot-probe task at average age 12.9 years. Threat avoidance in this cohort has previously been shown to index threat bias. Brain response to individually presented angry and neutral faces was assessed in a separate session using functional magnetic resonance imaging.

Adolescents with threat avoidance exhibited lower activity for both angry and neutral faces relative to controls in several regions in the occipital, parietal, and temporal lobes involved in early visual and facial processing. Results generalized to happy, sad, and fearful faces. Adolescents with a prior history of depression and/or an anxiety disorder had lower activity for all faces in these same regions. A subset of results replicated in an independent dataset.

Threat bias is associated with generalized, rather than threat-specific, differences in the neural processing of faces in adolescents. Findings may aid in the development of novel treatments for anxiety disorders that use attention training to modify threat bias.

Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis.

A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1–3, posterior CA1–3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability.

Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans.

This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.