De nombreuses études montrent que la prévalence du syndrome métabolique est plus élevée chez les patients bipolaires que dans la population générale. En effet, entre 36 et 49 % de ces patients présentent des troubles métaboliques (Vancampfort, 2013), ce qui aggrave leur pronostic. La présence de troubles métaboliques chez ces patients peut être expliquée par de nombreux facteurs comme une hygiène de vie à risque, une vulnérabilité génétique, la fréquence des épisodes dépressifs ou les comorbidités psychiatriques, et les traitements psychotropes. D’autre part, ces patients présentent des perturbations de leurs rythmes circadiens, même lors des périodes normothymiques. Plusieurs études récentes ont montré une corrélation entre des perturbations circadiennes et des marqueurs métaboliques chez des patients bipolaires. L’objectif de cette revue est de mettre en évidence un lien possible entre troubles circadiens et du sommeil et anomalies métaboliques chez les patients bipolaires, et les voies physiopathologiques possiblement impliquées. Dans la population générale, des voies de régulation ont été mises en évidence pour expliquer de tels liens, via des hormones comme la leptine et la ghréline. Une de nos hypothèses est l’implication de ces voies dans la vulnérabilité des patients bipolaires aux troubles métaboliques. Cette hypothèse est appuyée par des données de la littérature récente sur des perturbations de ces hormones dans des maladies psychiatriques dont le trouble bipolaire. D’autres mécanismes semblent également en jeu, impliquant une dérégulation de la sécrétion de mélatonine et des mécanismes inflammatoires.

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

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.

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.

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.