These highdimensional approaches are somewhat technically cumbersome when the aim is to explore the phenotype of biological clocks. However, this will probably be a necessary step in the understanding of several disorders in psychiatry Indeed, several psychiatric disorders show more or less regular periodicity in their clinical manifestation, and they could be seen as dynamic diseases, in the sense given to this term by Glass and Mackey,173 ie, diseases characterized Inhibitors,research,lifescience,medical by abnormal temporal organization of bodily systems. Selected abbreviations and acronyms BRAC basic rest-activity cycle EEG electroencephalogram

GnRH gonadotrophin-releasing hormone LH luteinizing hormone PMDD premestrual dysphoric disorder REM rapid eye movement RNA ribonucleic acid SAD seasonal affective disorder Inhibitors,research,lifescience,medical SCN suprachiasmatic nuclei TSH thyroid-stimulating hormone Notes The studies by the author were supported by grants 3.599.084 and 3.968.085 from the Swiss Fonds National de la Recherche.
Winter seasonal affective disorder

(SAD) Is a mood disorder characterized Inhibitors,research,lifescience,medical by the predictable onset of depression in the fall/winter months, with spontaneous remissions in the spring/summer period.1 The typical patient with SAD is a premenopausal woman who experiences carbohydrate craving, hypersomnia, and prominent fatigue during winter depressive episodes.1 Many adults experience similar but milder vegetative symptoms in the fall/winter months,2,3 often referred to as “subsyndromal SAD.” This suggests that seasonality may be a dimensional process rather than a discrete syndrome. Based on the energy-conserving nature Inhibitors,research,lifescience,medical of the core symptoms of SAD, various evolutionary theories of SAD and seasonality have been proposed.4-8 The possibility

that obesity in the context Inhibitors,research,lifescience,medical of SAD might reflect a ”seasonal thrifty phenotype“ has also been suggested.9 To date, research on the biology of SAD has had two major foci. One major body of work has attempted to delineate one or more chronobiological factors contributing to SAD and seasonality, with an emphasis on circadian rhythms, melatonin, and photoperiodic mechanisms. The second major body of work has used a variety Dacomitinib of approaches to examine other brain processes that might play a role in SAD, with a primary focus on major brain neurotransmitters such as serotonin, norepinephrine, and dopamine. Ultimately, as with other psychiatric illnesses, it might be best to consider SAD as a complex disorder that results from the interaction of several vulnerability factors acting at different levels, and the various Glioma genetic mechanisms that underlie them (Figure 1). The following paragraphs will summarize work to date on the chronobiology /neurobiology of SAD, and are followed by a general discussion and directions for future work. Figure 1.