Wong et a!126 demonstrated in a small number of subjects that dopamine receptor density in the caudate (measured by positron emission tomography [PET]) varied as a function of the menstrual cycle (lower in the follicular phase). Further, in two recent studies using paired-pulse transcranial magnetic stimulation, Smith et al127,128 showed that cortical facilitation was enhanced in the late follicular phase, while cortical inhibition was enhanced during the luteal

phase, consistent with putative central excitatory effects of estradiol and inhibitory effects of progesterone metabolites. Despite gender-related and reproductive steroid-related differences in brain physiology, it is the investigation of mood disorders Inhibitors,research,lifescience,medical linked to reproductive endocrine change that offers the greatest Inhibitors,research,lifescience,medical potential

insight into the role of reproductive steroids in the regulation and dysregulation of affect. Reproductive endocrine-related mood disorders Premenstrual syndrome While .Frank is credited with the first description of “premenstrual tension” in 1931, reports of mood and behavioral disturbances confined to the luteal phase of the menstrual cycle appeared earlier in the medical literature of the 19th century. For DAPT secretase purchase example, in 1847, Dr Ernst G. Von Feuchtersleben stated that “the menses in sensitive women is almost always attended by mental uneasiness, irritability or sadness.”129 Inhibitors,research,lifescience,medical As the symptoms of PMS occurred in a menstrual cycle phase-specific fashion (ie, only in the luteal phase), it was presumed that abnormalities in the hormonal constituents of the menstrual cycle

(eg, estradiol, progesterone) Inhibitors,research,lifescience,medical must underlie PMS. Despite the appeal of this hormone excess or deficiency hypothesis, however, early studies of the putative hormonal etiologies of PMS were inconsistent in their conclusions. A major source of study inconsistency was identified in the 1980s,130 namely that samples of women with PMS were selected (diagnosed) with highly unreliable techniques (ie, unconfirmed history). Without prospective demonstration of luteal phase-restricted symptom expression, samples selected Inhibitors,research,lifescience,medical were certain to contain a large number of false positives, thus rendering the data obtained ungeneralizable to the population with PMS.131 This requirement for prospective confirmation of luteal phase selleck chem Ruxolitinib symptomatology was ultimately incorporated into diagnostic criteria for PMS132 and late luteal phase dysphoric Dacomitinib disorder (LLPDD)/premenstrual dysphoric disorder (PMDD).133 While the use of these diagnostic criteria/guidelines has permitted greater homogeneity of samples across studies – a requirement for comparison and generalization of results obtained – data subsequently generated have provided little if any evidence for hormonal excess or deficiency as etiologically relevant in PMS. Indeed, more recent studies have, if anything, largely preserved the formerly observed inconsistency.