Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric disorder

Abstract

Background: Premenstrual dysphoric disorder (PMDD) is a debilitating cyclic disorder that is characterized by affective symptoms, including irritability, depression, and anxiety, which arise in the luteal phase of the menstrual cycle and resolve soon after the onset of menses. Despite a prevalence of up to 8% in women of reproductive age, few studies have investigated the brain mechanisms that underlie this disorder.

Methods: We used positron emission tomography with [(18)F] fluorodeoxyglucose and self-report questionnaires to assess cerebral glucose metabolism and mood in 12 women with PMDD and 12 healthy comparison subjects in the follicular and late luteal phases of the menstrual cycle. The primary biological end point was incorporated regional cerebral radioactivity (scaled to the global mean) as an index of glucose metabolism. Relationships between regional brain activity and mood ratings were assessed. Blood samples were taken before each session for assay of plasma estradiol and progesterone concentrations.

Results: There were no group differences in hormone levels in either the follicular or late luteal phase, but the groups differed in the effect of menstrual phase on cerebellar activity. Women with PMDD but not comparison subjects showed an increase in cerebellar activity (particularly in the right cerebellar vermis) from the follicular phase to the late luteal phase (p = .003). In the PMDD group, this increase in cerebellar activity was correlated with worsening of mood (p = .018).

Conclusions: These findings suggest that the midline cerebellar nuclei, which have been implicated in other mood disorders, also contribute to negative mood in PMDD.

Figure 1

Effect of premenstrual dysphoric disorder (PMDD), menstrual phase and mood on cerebellar activity. The gray-scale images (neurological orientation) depict slices through a T1 structural MR image in standard space (Montreal Neurological Institute), where positive values of the x, y, and z coordinates approximately represent mm to the right, anterior and superior relative to the origin (the sagittal midpoint of the anterior commissure). The sagittal slices (left column) are 8 mm to the right, the coronal slices (middle column) are 60 mm posterior and the axial slices (right column) are 24 mm inferior, relative to the origin. The color bars indicate t-values exceeding 2.82 (p<0.005) in clusters containing >100 contiguous voxels. Right side of image represents right side of brain. Top row: clusters where Group (PMDD, Control) interacted with Menstrual Phase (Follicular, Late Luteal). Middle row: clusters where activity was greater during the late luteal than the follicular phase in PMDD patients. Bottom row: clusters where activity was greater to the extent that mood score was worse across the two menstrual phases in PMDD patients.