Exploring mechanisms and contexts in a Peer Education Project to improve mental health literacy in schools in England: a qualitative realist evaluation.

Poor adolescent mental health calls for universal prevention. The Mental Health Foundation's 'Peer Education Project' equips older students ('peer educators') to teach younger students ('peer learners') about mental health. The peer-led lessons cover defining good and bad mental health, risk and protective factors, self-care, help-seeking and looking after one another. While previous pre-post evaluations have suggested effectiveness, the mechanisms through which the intervention improves mental health literacy remain unclear. We purposively recruited seven secondary schools across England from 2020 to 2022 and collected data through five observations, 12 staff interviews and 15 student focus groups (totalling 134 students; 46 peer educators aged 14-18 years and 88 peer learners aged 11-13 years). Our realist analysis adopted retroductive logic, intertwining deductive and inductive approaches to test the initial programme theory against insights arising from the data. We developed Context-Mechanisms-Outcome configurations related to four themes: (i) modelling behaviours and forming supportive relationships, (ii) relevant and appropriate content, (iii) peer educators feeling empowered and (iV) a school culture that prioritises mental health support. Our refined programme theory highlights key mechanisms, contexts conducive to achieving the outcomes and ways to improve training, recruitment and delivery to maximise effectiveness for similar peer-led initiatives.

Educating the next generation of cancer researchers: Evaluation of a cancer research partnership training program.

African American, American Indian and Alaska Native, Hispanic (or Latinx), Native Hawaiian, and other Pacific Islander groups are underrepresented in the biomedical workforce, which is one of the barriers to addressing cancer disparities among minority populations. The creation of a more inclusive biomedical workforce dedicated to reducing the burden of cancer health disparities requires structured, mentored research and cancer-related research exposure during the earlier stages of training. The Summer Cancer Research Institute (SCRI) is a multicomponent 8-week intensive summer program funded under the Partnership between a Minority Serving Institute and a National Institutes of Health-designated Comprehensive Cancer Center. In this survey study, we found that students who participated in the SCRI Program reported greater knowledge and interest in pursuing careers in cancer-related fields than their counterparts who did not participate in SCRI. Successes, challenges, and solutions in providing training in cancer and cancer health disparities research to improve diversity in the biomedical fields were also discussed.

Equal remission rates and reduced length of hospital stay with twice-daily repetitive transcranial magnetic stimulation (rTMS) for major depression - A large naturalistic retrospective cohort association study.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a level 1a evidence-based treatment for major depression, but high cost of care and limited effectiveness in naturalistic cohorts have been lingering criticisms. This naturalistic, retrospective cohort analysis compares the effect of once and twice daily treatment protocols of rTMS using quality assurance data collected at an Australian private psychiatric hospital. METHODS: A total of 210 inpatients self-selected into two groups receiving up to 30 sessions of either daily (n = 101) or twice daily (n = 109) 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC). The a priori primary outcome measure was remission rate as measured by pre and post treatment HAMD-17 scores. Length of hospital stay was a secondary post hoc outcome adopted due to the importance to cost of acute psychiatric care. RESULTS: Remission rates were similar across groups, with 44.9% and 45.4% for twice daily and daily rTMS groups respectively, although these may be confounded by patient expectations, other treatments and medication changes given the naturalistic setting. The length of hospital stay was 10.11 days and 18.44 days for twice daily and daily rTMS respectively - the twice daily rTMS length of hospital stay was 45.1% shorter 95% CI [38.7% - 51.56%]. Dropout rates were high; Twenty-seven (24.77%) twice daily participants dropped out before 20 sessions were completed, and 35 (34.65%) of daily participants. CONCLUSIONS: Twice daily 10 Hz left sided rTMS remission outcomes were similar to traditional once daily rTMS but required a shorter length of hospital stay. This finding has substantial cost of care implications. If these findings are independently replicated, twice daily rTMS may become the standard of care for inpatient rTMS.

Educating the Next Generation of Cancer Researchers: Evaluation of A Cancer Research Partnership Training Program.

African American, American Indian and Alaska Native, Hispanic (or Latinx), Native Hawaiian, and other Pacific Islander groups are underrepresented in the biomedical workforce, which is one of the barriers to addressing cancer disparities among minority populations. The creation of a more inclusive biomedical workforce dedicated to reducing the burden of cancer health disparities requires structured, mentored research and cancer-related research exposure during the earlier stages of training. The Summer Cancer Research Institute (SCRI), a multicomponent 8-week intensive summer program funded under the Partnership between a Minority Serving Institute and a National Institutes of Health-designated Comprehensive Cancer Center. This study assessed whether students who participated in the SCRI Program report greater knowledge and interest in pursuing careers in cancer-related fields than their counterparts who did not participate in SCRI. Successes, challenges, and solutions in providing training in cancer and cancer health disparities research to improve diversity in the biomedical fields were also discussed.

Interleukin-6 and total antioxidant capacity levels following N-acetylcysteine and a combination nutraceutical intervention in a randomised controlled trial for bipolar disorder.

OBJECTIVE: The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS). METHODS: This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers. RESULTS: In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023). CONCLUSION: Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.

ENACT: a protocol for a randomised placebo-controlled trial investigating the efficacy and mechanisms of action of adjunctive N-acetylcysteine for first-episode psychosis.

BACKGROUND: First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness; however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N-acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2 g/day for 26 weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups. METHODS/DESIGN: ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15-25 years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration. DISCUSSION: Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ID: ACTRN12618000413224. Registered on 21 March 2018.

EVALUATION OF A TRANSDISCIPLINARY CANCER RESEARCH TRAINING PROGRAM FOR UNDER-REPRESENTED MINORITY STUDENTS.

AIM/PURPOSE: This paper will describe the initial development of systems to evaluate research education activities of a U.S. academic Partnership to train minority students as cancer researchers and provide preliminary data from monitoring Partnership activities during the first six months. BACKGROUND: There is increased focus on multidisciplinary/transdisciplinary research training programs. However, few training programs have included detailed evaluations to assess their outcomes and effectiveness. METHODOLOGY: The Temple University/Fox Chase Cancer Center and Hunter College Regional Comprehensive Cancer Health Disparity Partnership (TUFCCC/HC Cancer Partnership, or the Partnership) is a recently-initiated center focused on training individuals from under-represented minorities (URMs) as cancer researchers. Evaluation of the training activities involves detailed specification of goals for each of the Partnership's Cores; objectives for addressing each goal; measures and indicators to determine progress towards each objective; and data sources to provide information for the measures/indicators. CONTRIBUTUION: This paper will provide important information for evaluation of training programs focused on students from URM populations and development of trans-disciplinary research education programs. FINDINGS: Goals, objectives, measures, and data sources for evaluation of the Partnership's Research Education Core (REC) were developed jointly by personnel from the REC and the Planning Evaluation Core (PEC) in an iterative process. These measures capture the training activities led by the REC (e.g., number of seminars and workshops), scientific output by trainees (e.g., papers and grants), and ability of the program to meet trainees' goals and expectations. RECOMMENDATIONS FOR PRACTITIONERS AND RESEARCHES: Evaluation plans for transdisciplinary training programs need to be developed prior to program initiation. Evaluation measures should be jointly specified by training and evaluation personnel, then reviewed and revised in an iterative process. IMPACT ON SOCIETY: This program is intended to enhance diversity among cancer researchers and increase studies to address disparities in cancer care. FUTURE RESEARCH: The PEC will oversee the evaluation of Partnership training activities over the five year period and assist Partnership leaders in ensuring successful outcomes.

Patient centric measures for a patient centric era: Agreement and convergent between ratings on The Patient Global Impression of Improvement (PGI-I) scale and the Clinical Global Impressions - Improvement (CGI-S) scale in bipolar and major depressive disorder.

BACKGROUND: Concordant with an increased emphasis on consumer engagement, the Patient Global Impression Scale of Improvement (PGI-I) is commonly used as an outcome measure in studies evaluating the efficacy of treatments in medical and psychiatric conditions with subjective symptom domains. The current study evaluated the agreement between PGI-I and Clinician Global Impression Scale of Improvement (CGI-I) ratings and convergent validity of PGI-I among individuals with bipolar or major depressive disorders. METHOD: Data were derived from three double-blind, placebo-controlled, multicentre studies conducted from 2007 to 2015 among adult individuals (N = 472). Clinicians were asked to rate participants symptoms using the CGI-I as well as severity of depression by the Montgomery-Åsberg Depression (MADRS), quality of life (Q-LES-Q), social and occupational functioning (SOFAS), and functional impairment (LIFE-RIFT). Participants were asked to assess their symptom improvement with the PGI-I. Bland-Altman agreement plots and Intra-class correlations were used to evaluate agreement, and Spearman correlation coefficients were implemented to examine convergent validity. Sub-group analyses for disorder type (bipolar and major depression) were performed. RESULTS: There was high agreement between the PGI-I and CGI-I ratings across follow-up time points (weeks 2, 4, 6, 8, 12, 16, 20, 24, and 28). Similar results were observed in male only and female only data and after adjustment for age and gender. Both PGI-I and CGI-I ratings were robustly positively correlated with MADRS, and LIFE-RIFT and negatively correlated with SOFAS and Q-LES-Q, supporting the convergent validity of the PGI-I. Sub-group analyses for bipolar and major depressive disorder showed similar findings. CONCLUSION: Our findings support the utility of the PGI-I as a participant rated measure of global improvement among individuals with bipolar or major depressive disorders.

Transverse relaxation of cerebrospinal fluid depends on glucose concentration.

PURPOSE: To evaluate the biophysical processes that generate specific T2 values and their relationship to specific cerebrospinal fluid (CSF) content. MATERIALS AND METHODS: CSF T2s were measured ex vivo (14.1T) from isolated CSF collected from human, rat and non-human primate. CSF T2s were also measured in vivo at different field strength in human (3 and 7T) and rodent (1, 4.7, 9,4 and 11.7T) using different pulse sequences. Then, relaxivities of CSF constituents were measured, in vitro, to determine the major molecule responsible for shortening CSF T2 (2s) compared to saline T2 (3s). The impact of this major molecule on CSF T2 was then validated in rodent, in vivo, by the simultaneous measurement of the major molecule concentration and CSF T2. RESULTS: Ex vivo CSF T2 was about 2.0s at 14.1T for all species. In vivo human CSF T2 approached ex vivo values at 3T (2.0s) but was significantly shorter at 7T (0.9s). In vivo rodent CSF T2 decreased with increasing magnetic field and T2 values similar to the in vitro ones were reached at 1T (1.6s). Glucose had the largest contribution of shortening CSF T2in vitro. This result was validated in rodent in vivo, showing that an acute change in CSF glucose by infusion of glucose into the blood, can be monitored via changes in CSF T2 values. CONCLUSION: This study opens the possibility of monitoring glucose regulation of CSF at the resolution of MRI by quantitating T2.

Solar insolation in springtime influences age of onset of bipolar I disorder.

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

Reviving a Positive Discourse on Sexuality within Social Work.

Sexuality is not an invisible dimension within social work. Social workers are constantly engaged with aspects of sexuality across virtually all practice domains. Indeed, some of the most fundamental and frequent concerns of social workers involve sexual abuse, sexual violence, and HIV and other sexually transmitted infections. However, conversations about healthy sexuality, positive sexuality, or sexual well-being that are well ensconced in many disciplines are all but absent from current social work literature, education, and practice. In this academic silence, social work is missing a significant opportunity to contribute to the larger conversation around healthy sexuality in a way that illuminates a more holistic perspective and that acknowledges desire and sexual satisfaction across the spectrum, including among marginalized and oppressed groups. In this article, authors make the case for shifting away from a pervasive focus on sexuality as solely risk based to one of balance, incorporating the normative nature and importance of sexuality, intimacy, pleasure, and desire within social work curricula, practice, and dialogue in general. They encourage social workers to recognize sexuality as a critical site of intersectionality and argue for the integration of a multidimensional approach to sexuality within social work education, practice, and research.

Homocysteine as a peripheral biomarker in bipolar disorder: A meta-analysis.

BACKGROUND: Bipolar disorder (BD) is a psychiatric disorder with an uncertain aetiology. Recently, special attention has been given to homocysteine (Hcy), as it has been suggested that alterations in 1-carbon metabolism might be implicated in diverse psychiatric disorders. However, there is uncertainty regarding possible alterations in peripheral Hcy levels in BD. METHODS: This study comprises a meta-analysis comparing serum and plasma Hcy levels in persons with BD and healthy controls. We conducted a systematic search for all eligible English and non-English peer-reviewed articles. RESULTS: Nine cross-sectional studies were included in the meta-analyses, providing data on 1547 participants. Random-effects meta-analysis showed that serum and plasma levels of Hcy were increased in subjects with BD in either mania or euthymia when compared to healthy controls, with a large effect size in the mania group (g=0.98, 95% CI: 0.8-1.17, P<0.001, n=495) and a small effect in the euthymia group (g=0.3, 95% CI: 0.11-0.48, P=0.002, n=1052). CONCLUSIONS: Our meta-analysis provides evidence that Hcy levels are elevated in persons with BD during mania and euthymia. Peripheral Hcy could be considered as a potential biomarker in BD, both of trait (since it is increased in euthymia), and also of state (since its increase is more accentuated in mania). Longitudinal studies are needed to clarify the relationship between bipolar disorder and Hcy, as well as the usefulness of peripheral Hcy as both a trait and state biomarker in BD.

Progressing MoodSwings. The upgrade and evaluation of MoodSwings 2.0: An online intervention for bipolar disorder.

MoodSwings 2.0 is a self-guided online intervention for bipolar disorder. The intervention incorporates technological improvements on an earlier validated version of the intervention (MoodSwings 1.0). The previous MoodSwings trial provides this study with a unique opportunity to progress previous work, whilst being able to take into consideration lesson learnt, and technological enhancements. The structure and technology of MoodSwings 2.0 are described and the relevance to other online health interventions is highlighted. An international team from Australia and the US updated and improved the programs content pursuant to changes in DSM-5, added multimedia components and included larger numbers of participants in the group discussion boards. Greater methodological rigour in this trial includes an attention control condition, quarterly telephone assessments, and red flag alerts for significant clinical change. This paper outlines these improvements, including additional security and safety measures. A 3 arm RCT is currently evaluating the enhanced program to assess the efficacy of MS 2.0; the primary outcome is change in depressive and manic symptoms. To our knowledge this is the first randomized controlled online bipolar study with a discussion board attention control and meets the key methodological criteria for online interventions.

Investigation of outbreaks of Pneumocystis jirovecii pneumonia in two Scottish renal units.

Pneumocystis jirovecii is recognized as an opportunistic pathogen. In recent years, human-to-human transmission of P. jirovecii has been demonstrated. However, outbreaks of P. jirovecii infections are not well defined because the epidemiological setting that facilitates transmission is not fully understood. This article describes two outbreaks of P. jirovecii pneumonia (PCP) in renal transplant patients in the West of Scotland. In total, 25 patients in two geographically contiguous locations were affected. Allele B was identified as the dominant type, along with allele A3. It was not possible to determine the exact reason for clustering of cases, although the outpatient clinic setting featured in one of the outbreaks. The outbreaks ceased with the use of trimethoprim-sulphamethoxazole prophylaxis; the target populations that received prophylaxis were different in the two outbreaks. Infection control teams should be alert to the possibility of outbreaks of PCP.

Investigating lipids as a source of chemical exchange-induced MRI frequency shifts.

While magnetic susceptibility is a major contributor to NMR resonance frequency variations in the human brain, a substantial contribution may come from the chemical exchange of protons between water and other molecules. Exchange-induced frequency shifts fe have been measured in tissue and protein solutions, but relatively lipid-rich white matter (WM) has a larger fe than gray matter, suggesting that lipids could contribute. Galactocerebrosides (GC) are a prime candidate as they are abundant in WM and susceptible to exchange. To investigate this, fe was measured in a model of WM lipid membranes in the form of multilamellar vesicles (MLVs), consisting of a 1:2 molar ratio of GC and phospholipids (POPC), and in MLVs with POPC only. Chemical shift imaging with 15% volume fraction of dioxane, an internal reference whose protons are assumed not to undergo chemical exchange, was used to remove susceptibility-induced frequency shifts in an attempt to measure fe in MLVs at several lipid concentrations. Initial analysis of these measurements indicated a necessity to correct for small unexpected variations in dioxane concentration due to its effect on the water frequency shift. To achieve this, the actual dioxane concentration was inferred from spectral analysis and its additional contribution to fe was removed through separate experiments which showed that the water-dioxane frequency shift depended linearly on the dioxane concentration at low concentrations with a proportionality constant of -0.021 ± 0.002 ppb/mM in agreement with published experiments. Contrary to expectations and uncorrected results, for GC + POPC vesicles, the dependence of the corrected fe on GC concentration was insignificant (0.023 ± 0.037 ppb/mM; r2 = 0.085, p > 0.57), whereas for the POPC-only vesicles a small but significant linear increase with POPC concentration was found: 0.044 ± 0.008 ppb/mM (r2 = 0.877, p < 0.01). These findings suggest that the exchange-induced contribution of lipids to frequency contrast in WM may be small. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Why so GLUMM? Detecting depression clusters through graphing lifestyle-environs using machine-learning methods (GLUMM).

BACKGROUND: Key lifestyle-environ risk factors are operative for depression, but it is unclear how risk factors cluster. Machine-learning (ML) algorithms exist that learn, extract, identify and map underlying patterns to identify groupings of depressed individuals without constraints. The aim of this research was to use a large epidemiological study to identify and characterise depression clusters through "Graphing lifestyle-environs using machine-learning methods" (GLUMM). METHODS: Two ML algorithms were implemented: unsupervised Self-organised mapping (SOM) to create GLUMM clusters and a supervised boosted regression algorithm to describe clusters. Ninety-six "lifestyle-environ" variables were used from the National health and nutrition examination study (2009-2010). Multivariate logistic regression validated clusters and controlled for possible sociodemographic confounders. RESULTS: The SOM identified two GLUMM cluster solutions. These solutions contained one dominant depressed cluster (GLUMM5-1, GLUMM7-1). Equal proportions of members in each cluster rated as highly depressed (17%). Alcohol consumption and demographics validated clusters. Boosted regression identified GLUMM5-1 as more informative than GLUMM7-1. Members were more likely to: have problems sleeping; unhealthy eating; ≤2 years in their home; an old home; perceive themselves underweight; exposed to work fumes; experienced sex at ≤14 years; not perform moderate recreational activities. A positive relationship between GLUMM5-1 (OR: 7.50, P<0.001) and GLUMM7-1 (OR: 7.88, P<0.001) with depression was found, with significant interactions with those married/living with partner (P=0.001). CONCLUSION: Using ML based GLUMM to form ordered depressive clusters from multitudinous lifestyle-environ variables enabled a deeper exploration of the heterogeneous data to uncover better understandings into relationships between the complex mental health factors.

Cognitive effects of adjunctive N-acetyl cysteine in psychosis.

BACKGROUND: Cognitive deficits are predictors of functional outcome in patients with psychosis. While conventional antipsychotics are relatively effective on positive symptoms, their impact on negative and cognitive symptoms is limited. Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis. N-acetylcysteine (NAC), a glutathione precursor with glutamatergic properties, has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder, respectively. However, there are few evidence-based approaches for managing cognitive impairment in psychosis. The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder. METHOD: A sample of 58 participants were randomized in a double fashion to receive 2 g/day of NAC (n = 27) or placebo (n = 31) for 24 weeks. Attention, working memory and executive function domains were assessed. Differences between cognitive performance at baseline and end point were examined using Wilcoxon's test. The Mann-Whitney test was used to examine the differences between the NAC and placebo groups at the end point. RESULTS: Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo (U = 98.5, p = 0.027). CONCLUSIONS: NAC may have an impact on cognitive performance in psychosis, as a significant improvement in working memory was observed in the NAC-treated group compared with placebo; however, these preliminary data require replication. Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis.

Leptin in bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD. METHODS: This study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges' adjusted g using random effects. RESULTS: Eleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania (g=-0.99, 95% CI -2.43 to 0.43, P=0.171), in depression (g=0.17, 95% CI -0.45 to 0.79, P=0.584), or in euthymia (g=0.03, 95% CI -0.39 to 0.46, P=0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the individuals, the greater the difference in leptin levels between BD and controls; and the higher the BMI, the greater the difference in leptin levels between BD and controls. CONCLUSIONS: Our meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications.

The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P<0.001, 24 between-group comparisons, n=82 962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8 within-group comparisons, n=713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.