Supplementary Material for: Are there connections between the neuroendocrine and dopamine systems in bipolar disorder?

Background: Bipolar disorder (BPD) represents a frequent and disabling disease, characterized by the occurrence of extreme mood swings leading to episodes of depression or mania. Although dysfunctions in dopamine (DA) neurotransmission are increasingly recognized as key determinants of BPD, little attention has been given to the biological factors which may shape such a cyclicity of mania and depression. Summary: We propose that BPD may result, at least in part, from skewed connections between the neuroendocrine system, the DA system and the hypothalamic clock center. First, we provide a brief description of the hypothalamic-pituitary complex i.e the core anatomical structure of the neuroendocrine system. We then review clinical data demonstrating the frequent onset of BPD at menopause, during postpartum or in peri-pubertal periods, suggesting that hormonal changes, under neuroendocrine regulation, may favor the clinical expression of BPD. Finally, we revisit the DA hypothesis of BPD and propose that both the hypothalamic clock center and the hypothalamic-pituitary axis exert rheostat effects on the regulation of mood by DA. Thus, in individuals with a genetically-determined predisposition to BPD, an alteration of such rheostat functions may translate into a hyper- or hypo-activity of the DA system. Potential therapeutic implications and future research directions are discussed. Key messages: BPD may be related to altered connections between the DA system, the neuroendocrine system and the hypothalamic clock center. We hope this paper will provide a basis for future interactions between endocrinologists, neurobiologists and psychiatrists.