Depression and Disturbed Bone Metabolism: A Narrative Review of the Epidemiological Findings and Postulated Mechanisms.

Major depressive disorder (MDD) is a pervasive chronic condition that contributes substantially to the global burden of disease and disability. Adding to the complexity of this disorder are numerous associated medical comorbidities with a bidirectional impact on morbidity and mortality. In recent years, osteoporosis has been increasingly identified as a significant comorbidity of MDD. This narrative review examines the literature to summarize key epidemiological studies and discuss postulated mechanisms of interaction. Epidemiological studies have repeatedly shown an increased co-prevalence of fractures and decreased bone mineral density (BMD) in MDD. The pathophysiological mechanism underlying this interaction is undoubtedly complex and multifactorial, and proposed pathways have varying levels of evidence from preclinical and clinical models. Conceptually, the mechanisms by which depression might influence bone metabolism can be categorized into biological, behavioral, iatrogenic, and comorbidity-related factors. Biological factors include the inflammatory-mood pathway, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, metabolic dysfunction, and serotonin's direct and indirect effects on bone cells. Behavioral factors incorporate lifestyle choices typical in depressed patients, such as increased tobacco use or limited exercise. The prominent iatrogenic factor is the independent effects of anti-depressants on bone metabolism. Psychiatric and medical comorbidities common to both osteoporosis and MDD are also important to consider. Physical activity promotion, vitamin D supplementation, and routine BMD screening of MDD patients are simple interventions that might lead to improved outcomes for both conditions. An improved understanding of the underlying mechanisms may yield insights into novel prevention and treatment strategies to target osteoporosis and fractures in the MDD population.

Prevalence of fibromyalgia and co-morbid bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Fibromyalgia (FM) is a chronic disorder with high morbidity and significant health service utilization costs. Few studies have reported on the phenotypic overlap of FM and bipolar disorder (BD). The aim of this review is to qualitatively and quantitatively summarize the results and clinical implications of the extant literature on the co-occurrence of FM and BD. METHODS: A systematic search of PubMed/Medline, Cochrane, PsycINFO, CINAHL and Embase was conducted to search for relevant articles. Articles were included if incidence and/or prevalence of BD was determined in the FM sample. Results of prevalence were pooled from all studies. Pooled odds ratio (OR) was calculated based on case-control studies using standard meta-analytic methods. RESULTS: A total of nine studies were included. The pooled rate of BD comorbidity in samples of FM patients was 21% (n=678); however, results varied greatly as a function of study methodology. Case-controlled studies revealed a pooled OR of 7.55 of BD co-morbidity in samples of FM patients [95% Confidence Interval (CI)=3.9-14.62, FM n=268, controls n=413] with low heterogeneity (I(2)=0%). LIMITATIONS: The current study was limited by the low number of available studies and heterogeneity of study methods and results. CONCLUSIONS: These data strongly suggest an association between BD and FM. Future studies employing a validated diagnostic screen are needed in order to more accurately determine the prevalence of BD in FM. An adequate psychiatric assessment is recommended in FM patients with suspected symptoms consistent with BD prior to administration of antidepressants in the treatment of FM.

Are medical comorbid conditions of bipolar disorder due to immune dysfunction?

OBJECTIVE: Epidemiological data have shown a clear association between bipolar disorder (BD) and medical comorbidities. The aim of this article was to assess the evidence of immune dysfunction as a key mediator of this observed association. METHOD: For this narrative clinical overview, the MEDLINE/PubMed, EMBASE, Google Scholar, and ClinicalTrials.gov databases were searched for relevant articles. RESULTS: Bipolar disorder has been shown to have an increased prevalence in patients with autoimmune disorders, cardiovascular disease, and metabolic dysfunction. Further, an elevation in proinflammatory cytokines in BD has been repeatedly demonstrated. Several mechanisms have been proposed to explain the effect of immune dysfunction on mood and cognition. Anti-inflammatory agents including TNF-α inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), minocycline and omega-3 polyunsaturated fatty acids (O3PUFA) are being investigated for their use as novel treatment of BD in patients with immune dysfunction. CONCLUSION: Immune dysfunction appears to be an important mediator of the association observed between BD and medical comorbidities. It therefore serves as a potential novel target for treatment of BD. Further, the observed bidirectional interaction merits screening for psychiatric disorders in patients with immune dysfunction and vice versa to allow for early detection and treatment of this at risk population.