[Metabolic syndrome and bipolar disorder: Is sleep the missing link?]

OBJECTIVE: To examine the pathophysiologic mechanisms that may link circadian disorder and metabolic syndrome in bipolar disorder (BP).

METHOD: A systematic review of the literature was conducted from January 2013 to January 2015, using the Medline and Cochrane databases, using the keywords "metabolic syndrome", "obesity", "leptin" and "circadian disorders", "sleeping disorders" and cross-referencing them with "bipolar disorder". The following types of publications were candidates for review: (i) clinical trials; (ii) studies involving patients diagnosed with bipolar disorder; (iii) studies involving patients with sleeping disorder; or (iv) data about metabolic syndrome.

RESULTS: Forty articles were selected. The prevalence of metabolic syndrome in BP was significantly higher compared to the general population (from 36 to 49% in the USA [Vancampfort, 2013]), and could be explained by several factors including reduced exercise and poor diet, genetic vulnerability, frequent depressive episodes, psychiatric comorbidity and psychotropic treatment. This high frequency of metabolic syndrome worsens the prognosis of these patients, increasing morbidity and mortality. Secondly, patients with BP experienced circadian and sleep disturbance, including modification in melatonin secretion. These perturbations are known to persist in periods of mood stabilization and are found in patients' relatives. Circadian disturbances are factors of relapse in bipolar patients, and they may also have a role in the metabolic comorbidities of these patients. Recent studies show that in populations of patients with bipolar disorder, a correlation between circadian disturbance and metabolic parameters are found. To identify the pathophysiological pathway connecting both could lead to a better comprehension of the disease and new therapeutics. In the overall population, mechanisms have been identified linking circadian and metabolic disorder involving hormones like leptin and ghrelin. These hormones are keys to regulation of energy balance in the organism, via their action on the hypothalamus, and are also regulated by sleep. We have hypothesized that these pathways could be implicated in the vulnerability of bipolar patients to metabolic syndrome. This hypothesis is supported by several studies showing dysregulation in leptin and ghrelin secretion in multiple psychiatric disorders, including bipolar disorder, as well as genetic variations of leptin and ghrelin genes in these diseases. We also assume that other mechanisms may be at stake to explain this link, such as melatonin dysregulation and inflammation.

CONCLUSIONS: Circadian and sleeping disorder may have a role in the prevalence of metabolic syndrome in BP. Hormones like leptin and ghrelin could be the link between these perturbations. Prevention and treatment of circadian disorder in BP may greatly reduce the occurrence of MetS in these patients. Being aware of this statement and taking care of these troubles should be a big step forward for treatment of BP.