Abstract
The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.
Highlights
Premenstrual dysphoric disorder (PMDD) affects 2%‒5% of women in their reproductive years, and is characterized by affective, behavioral and somatic symptoms that recur monthly in the luteal phase of the menstrual cycle and resolve during menstruation
The menstrual cycle-related decrease in temporal cortex blood flow in symptomatic premenstrual syndrome (PMS) patients, which was the main finding of that study [37], was not well supported by the other two studies, one of them found small clusters within the temporal lobes that accounted for 1% of the voxels showing greater Positron emission tomography (PET) activation in PMDD summed across symptomatic and asymptomatic conditions and 2% of the voxels where activation was correlated with psychosocial/somatic impairment [47]
Because cognitive complaints are common in PMDD, but have been difficult to quantify, we suggested that most women with PMDD exert greater effort, or other compensatory mechanisms that increase cerebellar activity, in order to maintain cognitive functioning during symptomatic periods, which can total over 3000 days over the lifetime [49]
Summary
Premenstrual dysphoric disorder (PMDD) affects 2%‒5% of women in their reproductive years, and is characterized by affective, behavioral and somatic symptoms that recur monthly in the luteal phase of the menstrual cycle and resolve during menstruation. The affective symptoms, which are the most debilitating in the syndrome, include marked irritability or anger, depressed mood, anxiety, tension, mood lability, difficulty concentrating, and feeling overwhelmed or out of control [1,2]. Behavioral and somatic symptoms contribute to impairment, and can include decreased interest, sleep and appetite disturbances, fatigue, lethargy, poor concentration, swelling, and pain [1]. Preceding the classification of PMDD in the Diagnostic and Statistical Manual of Mental Disorders [1], a syndrome characterized by the occurrence of these symptoms was classified as severe premenstrual syndrome (PMS). A link between menstruation and cyclical dysphoria had been recognized since the time of Hippocrates [4], the connection has only recently been explored from the perspective of neuroscience [2]
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