Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.

The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.

This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.

Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.

Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.

Recurrent laryngeal nerve injury leading to vocal cord paralysis is a known complication of cardiothoracic surgery. Its occurrence during interventional catheterisation procedures has been documented in case reports, but there have been no studies to determine an incidence.

To establish the incidence of left recurrent laryngeal nerve injury leading to vocal cord paralysis after left pulmonary artery stenting, patent ductus arteriosus device closure and the combination of the procedures either consecutively or simultaneously.

Members of the Congenital Cardiovascular Interventional Study Consortium were asked to perform a retrospective analysis to identify cases of recurrent laryngeal nerve injury after the aforementioned procedures. Twelve institutions participated in the analysis. They also contributed the total number of each procedure performed at their respective institutions for statistical purposes.

Of the 1337 patients who underwent left pulmonary artery stent placement, six patients (0.45%) had confirmed vocal cord paralysis. 4001 patients underwent patent ductus arteriosus device closure, and two patients (0.05%) developed left vocal cord paralysis. Patients who underwent both left pulmonary artery stent placement and patent ductus arteriosus device closure had the highest incidence of vocal cord paralysis which occurred in 4 of the 26 patients (15.4%). Overall, 92% of affected patients in our study population had resolution of symptoms.

Recurrent laryngeal nerve injury is a rare complication of left pulmonary artery stent placement or patent ductus arteriosus device closure. However, the incidence is highest in patients undergoing both procedures either consecutively or simultaneously. Additional research is necessary to determine contributing factors that might reduce the risk of recurrent laryngeal nerve injury.

Psychological interventions that are brief, acceptable, effective and can be delivered by non-specialists are especially necessary in low- and middle-income countries, where mental health systems are unable to address the high level of psychosocial needs. Problem Management Plus (PM+) is a five-session intervention designed for those impaired by psychological distress while living in communities affected by adversity. Individual PM+ has demonstrated effectiveness in reducing distress in Kenya and Pakistan, and a group version of PM+ (Group PM+) was effective for conflict-affected women in Pakistan. This paper describes a feasibility and acceptability trial of locally adapted Group PM+ for women and men in an earthquake-affected region of rural Nepal.

In this feasibility cluster randomised controlled trial, participants in the experimental arm were offered five sessions of Group PM+ and participants in the control arm received enhanced usual care (EUC), which entailed brief psycho-education and providing referral options to primary care services with health workers trained in the mental health Gap Action Programme Intervention Guide (mhGAP-IG). A mixed-methods design was used to assess the feasibility and acceptability of Group PM+. Feasibility was assessed with criteria including fidelity and retention of participants. Acceptability was assessed through in-depth interviews with participants, family members, programme staff and other stakeholders. The primary clinical outcome was depression symptoms assessed using the Patient Health Questionnaire (PHQ-9) administered at baseline and 8–8.5 weeks post-baseline (i.e. after completion of Group PM+ or EUC).

We recruited 121 participants (83% women and 17% men), with equal allocation to the Group PM+ and EUC arms (1:1). Group PM+ was delivered over five 2.5–3 hour sessions by trained and supervised gender-matched local non-specialists, with an average attendance of four out of five sessions. The quantitative and qualitative results demonstrated feasibility and acceptability for non-specialists to deliver Group PM+. Though the study was not powered to assess for effectiveness, for all five key outcome measures, including the primary clinical outcome, the estimated mean improvement was larger in the Group PM+ arm than the EUC arm.

The intervention and trial procedures were acceptable to participants, family members, and programme staff. The communities and participants found the intervention to be beneficial. Because feasibility and acceptability were established in this trial, a fully powered randomised controlled trial will be conducted for larger scale implementation to determine the effectiveness of the intervention in Nepal.

Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.

We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.

16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).

PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.

Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.

The IPS–WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS–WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS–WFM intervention (45 v. 26 weeks, p < 0.004).

The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.

Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.

To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.

Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.

A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).

The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.

Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.

This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).

Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.

Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

The effect of Hybrid stage 1 palliation for hypoplastic left heart syndrome on right ventricular function is unknown. We sought to compare right ventricular function in normal neonates and those with hypoplastic left heart syndrome before Hybrid palliation and to assess the effect of Hybrid palliation on right ventricular function, using the right ventricular myocardial performance index and the ratio of systolic and diastolic durations.

We carried out a retrospective review of echocardiographic data on 23 infants with hypoplastic left heart syndrome who underwent Hybrid palliation and 35 normal controls. Data were acquired before Hybrid and after Hybrid palliation – post 1, 0–4 days; post 2, 1 week; post 3, 2–3 weeks; post 4, 1–1.5 months following Hybrid palliation.

Myocardial performance index and ratio of systolic and diastolic durations were higher in the pre-Hybrid hypoplastic left heart syndrome group (n=23) – 0.47±0.16 versus 0.25±0.07, p<0.001; 1.59±0.44 versus 1.09±0.14, p<0.0001 – compared with controls (n=35). There was no significant change in the myocardial performance index at any of the post-Hybrid time points. Ratio of systolic and diastolic durations increased significantly 2 weeks after Hybrid – post 3: 2.08±0.62 and post 4: 2.21±0.45 versus pre: 1.59±0.44, p=0.043 and 0.003. There were no significant differences in parameters between sub-groups of infants who died (n=10) and survivors (n=13).

Right ventricular myocardial performance index and ratio of systolic and diastolic durations were significantly higher in infants with hypoplastic left heart syndrome before intervention compared with controls. The ratio of systolic and diastolic durations increased significantly 2 weeks after Hybrid palliation. Our data suggest that infants with hypoplastic left heart syndrome have right ventricular dysfunction before intervention, which worsens over 2 weeks after Hybrid palliation.