Suicide associated with COVID-19 infection: an immunological point of view.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. RESULTS: Patients infected with COVID-19 have high amounts of IL-1ß, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.

Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimer's disease: an umbrella review and re-analysis of data from meta-analyses.

OBJECTIVE: Alzheimer's disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger's test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.

Comparative efficacy and acceptability of psychological interventions for the treatment of adult outpatients with anorexia nervosa: a systematic review and network meta-analysis.

BACKGROUND: No consistent first-option psychological interventions for adult outpatients with anorexia nervosa emerges from guidelines. We aimed to compare stand-alone psychological interventions for adult outpatients with anorexia nervosa with a specific focus on body-mass index, eating disorder symptoms, and all-cause dropout rate. METHODS: In this systematic review and network meta-analysis, we assessed randomised controlled trials about stand-alone pharmacological or non-pharmacological treatments of adult outpatients with anorexia nervosa, defined according to standardised criteria, with data for at least two timepoints relating to either body-mass index or global eating disorder psychopathology. We searched Cochrane CENTRAL, CINAHL, MEDLINE, and PsychINFO for published and unpublished literature from inception until March 20, 2020. The primary outcomes were the change in body mass index and clinical symptoms, and the secondary outcome was all-cause dropout rate, which were all assessed for treatment as usual, cognitive behavioural therapy (CBT), Maudsley anorexia treatment for adults, family-based treatment, psychodynamic-oriented psychotherapies, a form of CBT targeting compulsive exercise, and cognitive remediation therapy followed by CBT. Global and local inconsistencies for the network meta-analysis were measured, and CINeMA was used to assess the confidence in evidence for primary outcomes. The protocol is registered in PROSPERO (CRD42017064429). FINDINGS: Of 14 003 studies assessed for their title and abstract, 16 (0·1%) randomised controlled trials for psychological treatments were included in the systematic review, of which 13 (0·1%) contributed to the network meta-analysis, with 1047 patients in total (of whom 1020 [97·4%] were female). None of the interventions outperformed treatment as usual in our primary outcomes, but the all-cause dropout rate was lower for CBT than for psychodynamic-oriented psychotherapies (OR 0·54, 95% CI 0·31-0·93). Heterogeneity or inconsistency emerged only for a few comparisons. Confidence in the evidence was low to very low. INTERPRETATION: Compared with treatment as usual, specific psychological treatments for adult outpatients with anorexia nervosa can be associated with modest improvements in terms of clinical course and quality of life, but no reliable evidence supports clear superiority or inferiority of the specific treatments that are recommended by clinical guidelines internationally. Our analysis is based on the best data from existing clinical studies, but these findings should not be seen as definitive or universally applicable. There is an urgent need to fund new research to develop and improve therapies for adults with anorexia nervosa. Meanwhile, to better understand the effects of available treatments, participant-level data should be made freely accessible to researchers to eventually identify whether specific subgroups of patients are more likely to respond to specific treatments. FUNDING: Flinders University, National Institute for Health Research Oxford Health Biomedical Research Centre.

Antipsychotic use and risk of life-threatening medical events: umbrella review of observational studies.

OBJECTIVE: To quantify the risk of hip fracture, thromboembolism, stroke, myocardial infarction, pneumonia and sudden cardiac death associated with exposure to antipsychotics. METHODS: Systematic searches were conducted in Medline, Embase and PsycINFO from inception until 30/07/2018 for systematic reviews of observational studies. AMSTAR-2 was used for the quality assessment of systematic reviews, while the strength of associations was measured using GRADE and quantitative umbrella review criteria (URC). RESULTS: Sixty-eight observational studies from six systematic reviews were included. The association between antipsychotic exposure and pneumonia was the strongest [URC = class I; GRADE = low quality; odds ratio (OR) = 1.84, 95% confidence interval (CI) = 1.62-2.09; participants = 28 726; age = 76.2 ± 12.3 years], followed by the association with hip fracture (URC = class II; GRADE = low quality; OR = 1.57, 95% CI = 1.42-1.74; participants = 5 288 118; age = 55.4 ± 12.5 years), and thromboembolism (URC = class II; GRADE = very low quality; OR = 1.55, 95% CI = 1.31-1.83; participants = 31 417 175; age = 55.5 ± 3.2 years). The association was weak for stroke (URC = class III; GRADE = very low quality; OR = 1.45, 95% CI = 1.24-1.70; participants = 65 700; age = 68.7 ± 13.8 years), sudden cardiac death (URC = class III; GRADE = very low quality; OR = 2.24, 95% CI = 1.45-3.46; participants = 77 488; age = 52.2 ± 6.2 years) and myocardial infarction (URC = class III; GRADE = very low quality; OR = 2.21, 95% CI = 1.41-3.46; participants = 399 868; age = 74.1 ± 9.3 years). CONCLUSION: The most robust results were found for the risk of pneumonia, followed by the risk of hip fracture and thromboembolism. For stroke, sudden cardiac death and myocardial infarction, the strength of association was weak. The observational nature of the primary studies may represent a source of bias.

The role of meta-analyses and umbrella reviews in assessing the harms of psychotropic medications: beyond qualitative synthesis.

á½ φελέειν, á¼¢ µá½´ ßλάπτειν (Primum non nocere) - Hιppocrates' principle should still guide daily medical prescribing. Therefore, assessing evidence of psychopharmacologic agents' safety and harms is essential. Randomised controlled trials (RCTs) and observational studies may provide complementary information about harms of psychopharmacologic medications from both experimental and real-world settings. It is considered that RCTs provide a better control of confounding variables, while observational studies provide evidence from larger samples, longer follow-ups, in more representative samples, which may be more reflective of real-life clinical scenarios. However, this may not always hold true. Moreover, in observational studies, safety data are poorly or inconsistently reported, precluding reliable quantitative synthesis in meta-analyses. Beyond individual studies, meta-analyses, which represent the highest level of 'evidence', can be misleading, redundant and of low methodological quality. Overlapping meta-analyses sometimes even reach different conclusions on the same topic. Meta-analyses should be assessed systematically. Descriptive reviews of reviews can be poorly informative. Conversely, 'umbrella reviews' can use a quantitative approach to grade evidence. In this editorial, we present the main factors involved in the assessment of psychopharmacologic agents' harms from individual studies, meta-analyses and umbrella reviews. Study design features, sample size, number of the events of interest, summary effect sizes, p-values, heterogeneity, 95% prediction intervals, confounding factor adjustment and tests of bias (e.g., small-study effects and excess significance) can be combined with other assessment tools, such as AMSTAR and GRADE to create a framework for assessing the credibility of evidence.

Osteoarthristis Increases the Risk of Cardiovascular Disease: Data from the Osteoarthritis Initiative.

OBJECTIVES: Although osteoarthritis (OA) is a common condition in older adults, the role of OA in increasing cardiovascular disease (CVD) incidence is still debated. The aim of this study was to investigate the association between OA and the onset of CVD in a large database of American adults. DESIGN: Longitudinal. SETTING: Community-dwelling. PARTICIPANTS: People with OA or at high risk of OA. MEASUREMENTS: Osteoarthritis was defined as the presence of OA of the hand, knee, hip, back/neck or of other sites. CVD was defined as self-reported presence of heart attack, heart failure, stroke and other cerebral atherosclerotic conditions, and peripheral artery disease. RESULTS: A total 4,265 persons without CVD (mean age=60.8 years, females=59.2%) at baseline were analyzed (1,775 with OA versus 2,490 without). Over a mean of 8.2 years, according to an adjusted Cox's regression analysis for 11 potential baseline confounders, study participants with OA of any joint had a significantly higher risk of developing CVD compared to those without OA (Hazard ratio (HR): =1.27; 95% CI: 1.03-1.56). The presence of hand OA was associated with a higher risk of developing CVD (HR=1.31; 95%CI: 1.01-1.68) with respect to those who had no OA. Knee, hip and back/neck OA did not, instead, increase the risk of developing CVD. The association between OA and CVD was significant in the women, but not in the men. CONCLUSIONS: OA, in particular, when it affects the hand and in women, was associated with a higher risk of developing CVD.

High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies.

Erectile dysfunction may be common among men with diabetes, but its prevalence is still debated. We aimed to assess the relative prevalence of erectile dysfunction in diabetes searching major databases from inception to November 2016 for studies reporting erectile dysfunction in men with Type 1 and Type 2 diabetes mellitus. We conducted a meta-analysis of the prevalence [and 95% confidence intervals (95% CIs)] of erectile dysfunction in diabetes compared with healthy controls, calculating the relative odds ratios (ORs) and 95% CIs. A random effect model was applied. From 3747 initial hits, 145 studies were included representing 88 577 men (age: 55.8 ± 7.9 years). The prevalence of erectile dysfunction in diabetes overall was 52.5% (95% CI, 48.8 to 56.2) after adjusting for publication bias, and 37.5%, 66.3% and 57.7% in Type 1, Type 2 and both types of diabetes, respectively (P for interaction < 0.0001). The prevalence of erectile dysfunction was highest in studies using the Sexual Health Inventory for Men (82.2%, 17 studies, P for interaction < 0.0001). Studies with a higher percentage of people with hypertension moderated our results (beta = 0.03; 95% CI, 0.008 to 0.040; P = 0.003; R2  = 0.00). Compared to healthy controls (n = 5385) men with diabetes (n = 863) were at increased odds of having erectile dysfunction (OR 3.62; 95% CI, 2.53 to 5.16; P < 0.0001; I2  = 67%, k = 8). Erectile dysfunction is common in diabetes, affecting more than half of men with the condition and with a prevalence odds of approximately 3.5 times more than controls. Our findings suggest that screening and appropriate intervention for men with erectile dysfunction is warranted.

Depression and pain: primary data and meta-analysis among 237 952 people across 47 low- and middle-income countries.

BACKGROUND: Depression and pain are leading causes of global disability. However, there is a paucity of multinational population data assessing the association between depression and pain, particularly among low- and middle-income countries (LMICs) where both are common. Therefore, we investigated this association across 47 LMICs. METHODS: Community-based data on 273 952 individuals from 47 LMICs were analysed. Multivariable logistic and linear regression analyses were performed to assess the association between the International Classification of Diseases, 10th Revision depression/depression subtypes (over the past 12 months) and pain in the previous 30 days based on self-reported data. Country-wide meta-analysis adjusting for age and sex was also conducted. RESULTS: The prevalence of severe pain was 8.0, 28.2, 20.2, and 34.0% for no depression, subsyndromal depression, brief depressive episode, and depressive episode, respectively. Logistic regression adjusted for socio-demographic variables, anxiety and chronic medical conditions (arthritis, diabetes, angina, asthma) demonstrated that compared with no depression, subsyndromal depression, brief depressive episode, and depressive episode were associated with a 2.16 [95% confidence interval (CI) 1.83-2.55], 1.45 (95% CI 1.22-1.73), and 2.11 (95% CI 1.87-2.39) increase in odds of severe pain, respectively. Similar results were obtained when a continuous pain scale was used as the outcome. Depression was significantly associated with severe pain in 44/47 countries with a pooled odds ratio of 3.93 (95% CI 3.54-4.37). CONCLUSION: Depression and severe pain are highly comorbid across LMICs, independent of anxiety and chronic medical conditions. Whether depression treatment or pain management in patients with comorbid pain and depression leads to better clinical outcome is an area for future research.

Depression and physical health multimorbidity: primary data and country-wide meta-analysis of population data from 190 593 people across 43 low- and middle-income countries.

BACKGROUND: Despite the known heightened risk and burden of various somatic diseases in people with depression, very little is known about physical health multimorbidity (i.e. two or more physical health co-morbidities) in individuals with depression. This study explored physical health multimorbidity in people with clinical depression, subsyndromal depression and brief depressive episode across 43 low- and middle-income countries (LMICs). METHOD: Cross-sectional, community-based data on 190 593 individuals from 43 LMICs recruited via the World Health Survey were analysed. Multivariable logistic regression analysis was done to assess the association between depression and physical multimorbidity. RESULTS: Overall, two, three and four or more physical health conditions were present in 7.4, 2.4 and 0.9% of non-depressive individuals compared with 17.7, 9.1 and 4.9% among people with any depressive episode, respectively. Compared with those with no depression, subsyndromal depression, brief depressive episode and depressive episode were significantly associated with 2.62, 2.14 and 3.44 times higher odds for multimorbidity, respectively. A significant positive association between multimorbidity and any depression was observed across 42 of the 43 countries, with particularly high odds ratios (ORs) in China (OR 8.84), Laos (OR 5.08), Ethiopia (OR 4.99), the Philippines (OR 4.81) and Malaysia (OR 4.58). The pooled OR for multimorbidity and depression estimated by meta-analysis across 43 countries was 3.26 (95% confident interval 2.98-3.57). CONCLUSIONS: Our large multinational study demonstrates that physical health multimorbidity is increased across the depression spectrum. Public health interventions are required to address this global health problem.

Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies.

OBJECTIVE: To conduct a systematic review and meta-analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs). METHOD: The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random-effects models. RESULT: Eighty-two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria. Peripheral levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs, whereas interferon-gamma levels were lower in MDD (Hedge's g = -0.477, P = 0.043). Levels of IL-1ß, IL-2, IL-4, IL-8, the soluble IL-6 receptor (sIL-6R), IL-5, CCL-3, IL-17, and transforming growth factor-beta 1 were not significantly altered in individuals with MDD compared to HCs. Heterogeneity was large (I2 : 51.6-97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index). CONCLUSION: Our results further characterize a cytokine/chemokine profile associated with MDD. Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.

Physical activity and depression: a large cross-sectional, population-based study across 36 low- and middle-income countries.

OBJECTIVE: Physical activity (PA) is good for health, yet several small-scale studies have suggested that depression is associated with low PA. A paucity of nationally representative studies investigating this relationship exists, particularly in low- and middle-income countries (LMICs). This study explored the global association of PA with depression and its mediating factors. METHOD: Participants from 36 LMICs from the World Health Survey were included. Multivariable logistic regression analyses were undertaken exploring the relationship between PA and depression. RESULTS: Across 178 867 people (mean ± SD age = 36.2 ± 13.5 years; 49.9% male), the prevalence of depression and the prevalence of low PA were 6.6% and 16.8% respectively. The prevalence of low PA was significantly higher among those with depression vs. no depression (26.0% vs. 15.8%, P < 0.0001). In the adjusted model, depression was associated with higher odds for low PA (OR = 1.42; 95% CI = 1.24-1.63). Mediation analyses demonstrated that low PA among people with depression was explained by mobility limitations (40.3%), pain and discomfort (35.8%), disruptions in sleep and energy (25.2%), cognition (19.4%) and vision (10.9%). CONCLUSION: Individuals with depression engage in lower levels of PA in LMICs. Future longitudinal research is warranted to better understand the relationships observed.

Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials.

Although higher dietary intakes of magnesium (Mg) seem to correspond to lower diabetes incidence, research concerning Mg supplementation in people with or at risk of diabetes is limited. Thus, we aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes compared with placebo. A literature search in PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials and Clinicaltrials.gov without language restriction, was undertaken. Eligible studies were randomized controlled trials (RCTs) investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or at high risk of diabetes. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were used for summarizing outcomes with at least two studies; other outcomes were summarized descriptively. Eighteen RCTs (12 in people with diabetes and 6 in people at high risk of diabetes) were included. Compared with placebo (n=334), Mg treatment (n=336) reduced fasting plasma glucose (studies=9; SMD=-0.40; 95% CI: -0.80 to -0.00; I2=77%) in people with diabetes. In conditions in people at high risk of diabetes (Mg: 226; placebo=227 participants), Mg supplementation significantly improved plasma glucose levels after a 2 h oral glucose tolerance test (three studies; SMD=-0.35; 95% CI: -0.62 to -0.07; I2=0%) and demonstrated trend level reductions in HOMA-IR (homeostatic model assessment-insulin resistance; five studies; SMD=-0.57; 95% CI: -1.17 to 0.03; I2=88%). Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes and also improves insulin-sensitivity parameters in those at high risk of diabetes.

Nephrolithiasis, bone mineral density, osteoporosis, and fractures: a systematic review and comparative meta-analysis.

Our meta-analysis demonstrates that people with nephrolithiasis have decreased bone mineral density, an increased odds of osteoporosis, and potentially an elevated risk of fractures. INTRODUCTION: People with nephrolithiasis might be at risk of reduced bone mineral density (BMD) and fractures, but the data is equivocal. We conducted a meta-analysis to investigate if patients with nephrolithiasis have worse bone health outcomes (BMD), osteoporosis, and fractures versus healthy controls (HCs). METHODS: Two investigators searched major databases for articles reporting BMD (expressed as g/cm2 or a T- or Z-score), osteoporosis or fractures in a sample of people with nephrolithiasis, and HCs. Standardized mean differences (SMDs), 95 % confidence intervals (CIs) were calculated for BMD parameters; in addition odds (ORs) for case-control and adjusted hazard ratios (HRs) in longitudinal studies for categorical variables were calculated. RESULTS: From 1816 initial hits, 28 studies were included. A meta-analysis of case-control studies including 1595 patients with nephrolithiasis (mean age 41.1 years) versus 3402 HCs (mean age 40.2 years) was conducted. Patients with nephrolithiasis showed significant lower T-scores values for the spine (seven studies; SMD = -0.69; 95 % CI = -0.86 to -0.52; I 2 = 0 %), total hip (seven studies; SMD = -0.82; 95 % CI = -1.11 to -0.52; I 2 = 72 %), and femoral neck (six studies; SMD = -0.67; 95 % CI = --1.00 to -0.34; I 2 = 69 %). A meta-analysis of the case-controlled studies suggests that people with nephrolithiasis are at increased risk of fractures (OR = 1.15, 95 % CI = 1.12-1.17, p < 0.0001, studies = 4), while the risk of fractures in two longitudinal studies demonstrated trend level significance (HR = 1.31, 95 % CI = 0.95-1.62). People with nephrolithiasis were four times more likely to have osteoporosis than HCs (OR = 4.12, p < 0.0001). CONCLUSIONS: Nephrolithiasis is associated with lower BMD, an increased risk of osteoporosis, and possibly, fractures. Future screening/preventative interventions targeting bone health might be indicated.

Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis.

Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging.

Serotonin transporter gene polymorphism in eating disorders: Data from a new biobank and META-analysis of previous studies.

UNLABELLED: Objectives Growing interest focuses on the association between 5-HTTLPR polymorphism and eating disorders (ED), but published findings have been conflicting. Methods The Italian BIO.VE.D.A. biobank provided 976 samples (735 ED patients and 241 controls) for genotyping. We conducted a literature search of studies published up to 1 April 2015, including studies reporting on 5HTTLPR genotype and allele frequencies in obesity and/or ED. We ran a meta-analysis, including data from BIO.VE.D.A. - comparing low and high-functioning genotype and allele frequencies in ED vs. CONTROLS: Results Data from 21 studies, plus BIO.VE.D.A., were extracted providing information from 3,736 patients and 2,707 controls. Neither low- nor high-functioning genotype frequencies in ED patients, with both bi- and tri-allelic models, differed from controls. Furthermore, neither low- nor high-functioning allele frequencies in ED or in BN, in both bi- and triallelic models, differed from control groups. After sensitivity analysis, results were the same in AN vs. CONTROLS: Results remained unaltered when investigating recessive and dominant models. Conclusions 5HTTLPR does not seem to be associated with ED in general, or with AN or BN in particular. Future studies in ED should explore the role of ethnicity and psychiatric comorbidity as a possible source of bias.

The prevalence and predictors of bipolar and borderline personality disorders comorbidity: Systematic review and meta-analysis.

INTRODUCTION: Data about the prevalence of borderline personality (BPD) and bipolar (BD) disorders comorbidity are scarce and the boundaries remain controversial. We conducted a systematic review and meta-analysis investigating the prevalence of BPD in BD and BD in people with BPD. METHODS: Two independent authors searched MEDLINE, Embase, PsycINFO and the Cochrane Library from inception till November 4, 2015. Articles reporting the prevalence of BPD and BD were included. A random effects meta-analysis and meta-regression were conducted. RESULTS: Overall, 42 papers were included: 28 considering BPD in BD and 14 considering BD in BPD. The trim and fill adjusted analysis demonstrated the prevalence of BPD among 5273 people with BD (39.94 ± 11.78 years, 44% males) was 21.6% (95% CI 17.0-27.1). Higher comorbid BPD in BD were noted in BD II participants (37.7%, 95% CI 21.9-56.6, studies=6) and North American studies (26.2%, 95% CI 18.7-35.3, studies=11). Meta regression established that a higher percentage of males and higher mean age significantly (p<0.05) predicted a lower prevalence of comorbid BPD in BD participants. The trim and fill adjusted prevalence of BD among 1814 people with BPD (32.22 ± 7.35 years, 21.5% male) was 18.5% (95% CI 12.7-26.1). LIMITATIONS: Paucity of longitudinal/control group studies and accurate treatment records. CONCLUSIONS: BPD-BD comorbidity is common, with approximately one in five people experiencing a comorbid diagnosis. Based on current diagnostic constructs, and a critical interpretation of results, both qualitative and quantitative syntheses of the evidence prompt out the relevance of differences rather similarities between BD and BPD.