Evidence is needed for the integration of mental health into primary care advocated by the national health sector strategic investment plan in Uganda.

To describe the processes of developing a district mental healthcare plan (MHCP) in rural Uganda that facilitates integration of mental health into primary care.

Mixed methods using a situational analysis, qualitative studies, theory of change workshops and partial piloting of the plan at two levels informed the MHCP.

A MHCP was developed with packages of care to facilitate integration at the organisational, facility and community levels of the district health system, including a specified human resource mix. The partial embedding period supports its practical application. Key barriers to scaling up the plan were identified.

A real-world plan for the district was developed with involvement of stakeholders. Pilot testing demonstrated its feasibility and implications for future scaling up.

Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications.

To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain.

Searches in PubMed with the terms ‘oral ketamine’, ‘depression’, ‘chronic pain’, ‘neuropathic pain’, ‘intravenous ketamine’, ‘intranasal ketamine’ and ‘subcutaneous ketamine’ yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality.

Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects.

Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials.

Little is known about the service and system interventions required for successful integration of mental healthcare into primary care across diverse low- and middle-income countries (LMIC).

To examine the commonalities, variations and evidence gaps in district-level mental healthcare plans (MHCPs) developed in Ethiopia, India, Nepal, Uganda and South Africa for the PRogramme for Improving Mental health carE (PRIME).

A comparative analysis of MHCP components and human resource requirements.

A core set of MHCP goals was seen across all countries. The MHCPs components to achieve those goals varied, with most similarity in countries within the same resource bracket (low income v. middle income). Human resources for advanced psychosocial interventions were only available in the existing health service in the best-resourced PRIME country.

Application of a standardised methodological approach to MHCP across five LMIC allowed identification of core and site-specific interventions needed for implementation.

Transcranial direct current stimulation (tDCS) is a non-pharmacological intervention for depression. It has mixed results, possibly caused by study heterogeneity.

To assess tDCS efficacy and to explore individual response predictors.

Systematic review and individual patient data meta-analysis.

Data were gathered from six randomised sham-controlled trials, enrolling 289 patients. Active tDCS was significantly superior to sham for response (34% v. 19% respectively, odds ratio (OR) = 2.44, 95% CI 1.38–4.32, number needed to treat (NNT) = 7), remission (23.1% v. 12.7% respectively, OR = 2.38, 95% CI 1.22–4.64, NNT = 9) and depression improvement (B coefficient 0.35, 95% CI 0.12–0.57). Mixed-effects models showed that, after adjustment for other predictors and confounders, treatment-resistant depression and higher tDCS ‘doses' were, respectively, negatively and positively associated with tDCS efficacy.

The effect size of tDCS treatment was comparable with those reported for repetitive transcranial magnetic stimulation and antidepressant drug treatment in primary care. The most important parameters for optimisation in future trials are depression refractoriness and tDCS dose.

Cardiac vagal tone, indexed by heart rate variability (HRV), is a proxy for the functional integrity of feedback mechanisms integrating central and peripheral physiology.

To quantify differences in HRV in individuals with schizophrenia compared with healthy controls.

Databases were systematically searched for studies eligible for inclusion. Random effect meta-analyses of standardised mean differences were calculated for vagal activity indicated by high-frequency HRV and the root mean square of successive R–R interval differences (RMSSD).

Thirty-four studies were included. Significant main effects were found for high-frequency HRV (P = 0.0008; Hedges' g =–0.98, 95% CI −1.56 to −0.41, k = 29) and RMSSD (P<0.0001; g =–0.91, 95% CI −1.19 to −0.62, k = 24), indicating lower vagal activity in individuals with schizophrenia than in healthy controls. Considerable heterogeneity was evident but effects were robust in subsequent sensitivity analyses.

Given the association between low HRV, threat processing, emotion regulation and executive functioning, reduced vagal tone may be an endophenotype for the development of psychotic symptoms.

Reports linking the deinstitutionalisation of psychiatric care with homelessness and imprisonment have been published widely.

To identify cohort studies that followed up or traced back long-term psychiatric hospital residents who had been discharged as a consequence of deinstitutionalisation.

A broad search strategy was used and 9435 titles and abstracts were screened, 416 full articles reviewed and 171 articles from cohort studies of deinstitutionalised patients were examined in detail.

Twenty-three studies of unique populations assessed homelessness and imprisonment among patients discharged from long-term care. Homelessness and imprisonment occurred sporadically; in the majority of studies no single case of homelessness or imprisonment was reported.

Our results contradict the findings of ecological studies which indicated a strong correlation between the decreasing number of psychiatric beds and an increasing number of people with mental health problems who were homeless or in prison.

There is little practical guidance on how contextually relevant mental healthcare plans (MHCPs) can be developed in low-resource settings.

To describe how theory of change (ToC) was used to plan the development and evaluation of MHCPs as part of the PRogramme for Improving Mental health carE (PRIME).

ToC development occurred in three stages: (a) development of a cross-country ToC by 15 PRIME consortium members; (b) development of country-specific ToCs in 13 workshops with a median of 15 (interquartile range 13–22) stakeholders per workshop; and (c) review and refinement of the cross-country ToC by 18 PRIME consortium members.

One cross-country and five district ToCs were developed that outlined the steps required to improve outcomes for people with mental disorders in PRIME districts.

ToC is a valuable participatory method that can be used to develop MHCPs and plan their evaluation.

Stressful life events (SLEs) are associated with psychotic experiences. SLEs might act as an environmental risk factor, but may also share a genetic propensity with psychotic experiences.

To estimate the extent to which genetic and environmental factors influence the relationship between SLEs and psychotic experiences.

Self- and parent reports from a community-based twin sample (4830 16-year-old pairs) were analysed using structural equation model fitting.

SLEs correlated with positive psychotic experiences (r = 0.12–0.14, all P<0.001). Modest heritability was shown for psychotic experiences (25–57%) and dependent SLEs (32%). Genetic influences explained the majority of the modest covariation between dependent SLEs and paranoia and cognitive disorganisation (bivariate heritabilities 74–86%). The relationship between SLEs and hallucinations and grandiosity was explained by both genetic and common environmental effects.

Further to dependent SLEs being an environmental risk factor, individuals may have an underlying genetic propensity increasing their risk of dependent SLEs and positive psychotic experiences.

Anxiety has been associated with new-onset cardiovascular disease (CVD), but the quality of this relationship is unclear. Only if anxiety is a causal, independent cardiovascular risk factor might it be a target for CVD prevention.

To determine and examine the independent association and causality between anxiety and incident CVD.

PubMed, EMBASE and PsycINFO databases were searched up to October 2013. A review of Hill's criteria for causality and random effects meta-analysis were conducted of prospective, population-based studies examining anxiety and incident CVD in people free from CVD at baseline.

The meta-analysis comprised 37 papers (n = 1 565 699). The follow-up ranged from 1 to 24 years. Anxiety was associated with a 52% increased incidence of CVD (hazard ratio = 1.52, 95% CI 1.36–1.71). The risk seemed independent of traditional risk factors and depression. The evaluation of Hill's criteria largely argued in favour of causality.

Anxiety may be of interest for CVD prevention. Future research should examine biological and behavioural underpinnings of the association in order to identify targets for intervention.

It has been suggested that the efficacy of antidepressants has been overestimated in clinical trials owing to unblinding of drug treatments by adverse events.

To investigate the association between adverse events and the efficacy of selective serotonin reuptake inhibitors (SSRIs).

The literature was searched to identify randomised, double-blind, placebo-controlled trials of SSRIs in the treatment of major depression. Efficacy outcomes were response to treatment and change in depressive symptoms. Reporting of adverse events was used as an indicator of tolerability. Random effects meta-analyses were used to calculate pooled estimates. Meta-regression analyses were performed to investigate the association between adverse events and efficacy. Potential mediation was investigated with the Baron & Kenny approach.

A total of 68 trials (n = 17 646) were included in the analyses. In meta-analysis SSRIs were superior to placebo in terms of efficacy (odds ratio, OR = 1.62, 95% CI 1.51–1.72). More patients allocated to SSRIs reported adverse events than did patients receiving placebo (OR = 1.73, 95% CI 1.58–1.89). Meta-regression analyses did not find an association between adverse events and efficacy (P = 0.439). There was no indication of adverse events mediating the effect of SSRI treatment.

Our results do not support, but also do not unequivocally disprove, the hypothesis that adverse events lead to an overestimation of the effect of SSRIs over placebo.

Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder.

To quantify the shared genetic variability between bipolar disorder and cognitive measures.

Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder.

Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (r g = |0.23|–|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (r g = |0.51|–|1.00|), which remained significant after covarying for affective symptoms.

Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder.

Few studies have evaluated the implementation and impact of real-world mental health programmes delivered at scale in low-resource settings.

To describe the cross-country research methods used to evaluate district-level mental healthcare plans (MHCPs) in Ethiopia, India, Nepal, South Africa and Uganda.

Multidisciplinary methods conducted at community, health facility and district levels, embedded within a theory of change.

The following designs are employed to evaluate the MHCPs: (a) repeat community-based cross-sectional surveys to measure change in population-level contact coverage; (b) repeat facility-based surveys to assess change in detection of disorders; (c) disorder-specific cohorts to assess the effect on patient outcomes; and (d) multilevel case studies to evaluate the process of implementation.

To evaluate whether and how a health-system-level intervention is effective, multidisciplinary research methods are required at different population levels. Although challenging, such methods may be replicated across diverse settings.

There is inconsistent evidence regarding the influence of general cognitive abilities on the long-term course of depression.

To investigate the association between general childhood cognitive abilities and adult depression outcomes.

We conducted a cohort study using data from 633 participants in the New England Family Study with lifetime depression. Cognitive abilities at age 7 were measured using the Wechsler Intelligence Scale for Children. Depression outcomes were assessed using structured diagnostic interviews administered up to four times in adulthood between ages 17 and 49.

In analyses adjusting for demographic factors and parental psychiatric illness, low general cognitive ability (i.e. IQ<85 v. IQ>115) was associated with recurrent depressive episodes (odds ratio (OR) = 2.19, 95% CI 1.20–4.00), longer episode duration (rate ratio 4.21, 95% CI 2.24–7.94), admission to hospital for depression (OR = 3.65, 95% CI 1.34–9.93) and suicide ideation (OR = 3.79, 95% CI 1.79–8.02) and attempt (OR = 4.94, 95% CI 1.67–14.55).

Variation in cognitive abilities, predominantly within the normal range and established early in childhood, may confer long-term vulnerability for prolonged and severe depression. The mechanisms underlying this vulnerability need to be established to improve the prognosis of depression among individuals with lower cognitive abilities.