In this way, circadian clocks exert regulatory control over almost every aspect of physiology, with disruptions leading to disease states, and their understanding lending opportunities for the analysis of novel mechanisms of diagnosis and 17-AAG research buy treatment. An aspect of the circadian regulation of genetic, metabolic and cytosolic clocks that has received relatively little attention is how these processes might be affected by sex differences. Also, sex differences may confound the results of studies in which the sex of the animal or cell is not taken

into account. Within the brain, widespread sex differences in gene expression and splicing have been detected in all major brain regions and involve 2.5% of all expressed genes (Trabzuni et al., 2013). Furthermore, a diffusion tensor imaging study indicates widespread sex differences in regional and global network characteristics of the brains of youths (Ingalhalikar et al., 2014). The sparsity of circadian studies may be attributed in part to the expense and work load associated with undertaking studies of both males and females, especially when buy PS-341 ovulatory cycle-associated changes must also be taken into account (Morin et al.,

1977). That said, there are tremendous sex differences in the circadian timing system (reviewed in Bailey & Silver, 2013). A salient example is seen in sleep regulation. Women go to sleep later and later until the age of around 19.5 years, whereas men continue to delay their sleep until around the age of 21 years (Roenneberg et al., 2007). Furthermore, throughout adulthood, men tend to go to sleep later than women. This sex difference disappears at around the age of 50, at around the time of menopause. A key symptom of major depressive disorder is the disruption of circadian patterns. In a study applying time-of-death analysis to gene expression Methocarbamol data from postmortem brains, cyclic patterns

of gene expression were much weaker in the brains of patients with major depressive disorders due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes (Li et al., 2013). As noted above, sleep disturbance is associated with major depressive disorders. Turning to the question of sex differences, Plante et al. (2012) found that women, but not men, with major depressive disorders demonstrate significant increases in slow wave activity in multiple cortical areas relative to control subjects. In conclusion, sex differences become important when they can provide clues to the mechanisms conferring protection to one sex or susceptibility to the other, and in those research areas where sex differences are salient, attention to the underlying mechanisms is especially warranted.