Lipid profile and suicide attempt in bipolar disorder: A meta-analysis of published and unpublished data

https://doi.org/10.1016/j.pnpbp.2017.06.008Get rights and content

Highlights

  • The identification of suicide biomarkers in bipolar disorder is crucial.

  • This meta-analysis explores the association between lipid levels and suicidality.

  • No differences in lipid profiles between attempters and non-attempters were found.

Abstract

Evidence suggests an association between low lipid levels and suicidality in subjects with severe mental disorders. This is the first systematic review and meta-analysis aimed at exploring differences in lipid profile between suicide attempters and non-attempters with bipolar disorder. We included observational studies providing comparative cross-sectional data on total cholesterol, LDL-cholesterol and triglycerides levels. We searched main Electronic Databases, identifying 11 studies that met our inclusion criteria, including also unpublished data. Meta-analyses based on random-effects models were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity among studies was estimated using the I2 index. The meta-analyses included data on lipid profile from 11 studies based on 288 subjects with and 754 without suicide attempt, respectively. No differences in total cholesterol (SMD: − 0.10; 95%CI: − 0.30 to 0.10; p = 0.34), LDL-cholesterol (SMD: − 0.26; 95%CI: − 0.65 to 0.13; p = 0.19), and triglycerides (SMD: − 0.06; 95%CI: − 0.31 to 0.19; p = 0.63) were detected. Heterogeneity across studies was low-moderate and no risk of publication bias was found. Subgroup analyses showed no differences on effect size across different study characteristics, including different time-frames of suicide attempt, except for small sample size. Therefore, the evidence for an association between serum lipid profile and suicidality in bipolar disorder cannot be claimed. More research is needed to better understand the mechanisms underlying suicidal behaviours in bipolar patients, exploring further peripheral biomarkers as this may help clinicians screen and prevent suicidality.

Introduction

World Health Organization data report that over 800,000 subjects die due to suicide every year, with many more attempting suicide (WHO, 2017). Suicide represents the 15th leading cause of mortality, accounting for about 1–2% of global deaths (WHO, 2017). Due to its epidemiological burden, an increasing body of research aimed at identifying peripheral biomarkers of suicide, even if little is known about related neurobiological mechanisms (Pandey, 2013). In particular, during the last 25 years, the role of lipid parameters has attracted growing interest (Engelberg, 1992), with several studies exploring the relationship between low total cholesterol levels and suicide attempts (e.g., Golier et al., 1995, Fiedorowicz and Coryell, 2007, Perez-Rodriguez et al., 2008, Bartoli et al., 2017a). The main neurochemical hypothesis suggests that low peripheral lipid levels may be correlated to a decrease of cholesterol in the lipid rafts of synaptic membranes leading to a reduced serotonergic activity (Cantarelli et al., 2014, De Berardis et al., 2012). The hypoactivity of serotonergic signalling may, in turn, increase impulsivity and the risk of suicidal behaviours (Cantarelli et al., 2014). In addition, the potential role of polyunsaturated fatty acids in the pathogenesis of bipolar disorder and unipolar depression should be considered (Pompili et al., 2017). Previous studies reported an association between fatty acid depletion and suicidal behaviours, involving changes in membrane viscosity and modulation of gene expression (Pompili et al., 2017). A recent systematic review and meta-analysis, based on 65 studies accounting for 510,392 participants, pointed out that subjects who attempted suicide had significantly lower levels of serum total cholesterol, LDL cholesterol, and triglycerides, as compared with their non-suicidal counterpart (Wu et al., 2016). Subgroups analyses showed an association between lipid profile and suicidal behaviours in both major depressive disorders and schizophrenia (Wu et al., 2016). However, despite the body of evidence accumulated in the last few years (e.g., D'Ambrosio et al., 2012, Ahmadpanah et al., 2015, Shakeri et al., 2015) and the considerable contribution of bipolar disorder to suicidal behaviours (Novick et al., 2010), there are no studies that systematically pooled data on the association between lipid profile and suicidality in subjects with bipolar disorder. In order to fill previous research gaps, we conducted a MOOSE guidelines-based systematic review and meta-analysis (Stroup et al., 2000) of both published and unpublished data, testing if among subjects with bipolar disorder suicide attempters would have levels of total cholesterol and other lipid parameters (LDL cholesterol and triglycerides) lower than those without suicide attempts.

Section snippets

Search strategy and selection of studies

We searched, via Ovid, Medline, PsycINFO and Embase electronic databases for articles published up to March 2017. We combined the following index terms: ‘bipolar’ and ‘suicide’ and (‘cholesterol’ or ‘triglycerides’). We also checked the reference list of a recent review exploring a similar topic (Wu et al., 2016). Two authors (FB and CDB) independently completed the preliminary screening based on titles and abstracts, and evaluated full texts for final eligibility. Differences in suitability

Study selection and characteristics

Our search generated 200 records and, after removing duplicates, we identified 141 research articles. The preliminary evaluation by title and abstract identified 15 potentially eligible studies for further full text screening. The final assessment included also additional, unpublished information obtained by corresponding authors (Ainiyet and Rybakowski, 2014, Bocchetta et al., 2001, Fiedorowicz and Coryell, 2007, Pompili et al., 2010, Shakeri et al., 2015) and data from a recent study we

Summary of findings

To the best of our knowledge, this is the first meta-analysis exploring lipid profile in subjects suffering from bipolar disorder who attempted suicide as compared with those who did not. We included 11 observational studies with comparative, cross-sectional data, involving 288 attempters and 754 non-attempters with bipolar disorder. The current systematic review and meta-analysis estimated no relevant differences in total cholesterol, LDL cholesterol, and triglycerides levels, thus we could

Conclusions

Suicide is one of the most important cause of death in subjects with bipolar disorder (Chesney et al., 2014). Our meta-analysis did not uncover any differences in lipid levels between suicide attempters and non-attempters. Therefore, it seems inappropriate considering cholesterol and triglycerides levels as valid and reliable markers for suicidality in individuals with bipolar disorder, based on the available literature. More research is needed to better understand the mechanisms underlying

Contributors

Francesco Bartoli and Cristina Crocamo had full access to the dataset of this study and take responsibility for the integrity of data and the accuracy of data analysis.

All authors made substantial contributions to the intellectual content of the paper.

Conception and design: Francesco Bartoli, Giuseppe Carrà, Massimo Clerici.

Literature screening: Francesco Bartoli, Carmen Di Brita.

Study Protocol: Francesco Bartoli, Carmen Di Brita.

Data collection and dataset management: Francesco Bartoli, Carmen

Role of funding source

The authors report no financial or other relationship relevant to the subject of this article.

Conflict of interest

None.

Acknowledgments

We thank all the authors of the studies included in our meta-analysis, especially Alberto Bocchetta, Serge Brand, Jess Fiedorowicz, Maurizio Pompili, Janusz Rybakowski, who provided additional data on their articles.

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