Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome that is characterized predominantly by mood symptoms.[31] DSM-IV includes PMDD under the category of “depressive disorders not otherwise specified.” Approximately 3% to 9% of premenopausal women experience PMDD.[32,33] Onset typically occurs during the teens to late twenties, and symptoms usually peak in one’s thirties and early forties. Past episodes and a family history of mood disorder appear to be common in women with PMDD, and these women are also at high risk for eventually developing a major depressive episode.

The course of PMDD parallels that of a recurrent major mood disorder in that it becomes more severe, extends in duration, and becomes more refractory to treatment over time.[34] The lifetime comorbidity rate ranges from 30% to 70% in PMDD patients with a history of a major depressive episode.[31] The symptoms of PMDD, as described in the DSM-IV, are shown in Table 4. There is some overlap between symptoms of a major depressive episode and PMDD, with PMDD typically mimicking an atypical form of MD. DSM-IV specifies that the diagnosis of PMDD applies only to women who have symptoms that emerge during the luteal phase (1 to 2 weeks before menstrual flow) and subside shortly after menses.

Additionally, the symptoms must cause functional impairment at work or of interpersonal relationships.[7] The etiology of PMDD is unknown, but may be related to the effects of changes in reproductive hormones during the luteal phase of the menstrual cycle on neurotransmitter, neuroendocrine, or circadian systems.[34] More specifically, changes in adrenergic-receptor binding through a precipitous decline or fluctuation in ß-endorphin levels have been correlated with symptoms of PMDD. Decreases in gamma-aminobutyric acid levels, serotonin uptake in platelets of women with premenstrual changes, and imipramine receptor binding have also been found in PMDD. Changes in these markers are also found in MD in women, which may explain the similarity of depressive symptoms between MD and PMDD.

Validated and standardized instruments to assess and diagnose PMDD include the Structured Clinical Interview for DSM-IV Depressive Disorders and the Structured Interview Guide for the Hamilton Depression Rating Scale (inclusive of items pertaining to atypical depression), the Menstrual Distress Questionnaire, the Premenstrual Affective Form, and the Calendar of Premenstrual Experiences. To confirm the diagnosis, clinicians should use patients’ self-rated symptoms of PMDD, using daily mood visual analogue scales, for two consecutive menstrual cycles. Other components of the evaluation include a physical and gynecologic examination, a thyroid function test, and measurement of the serum luteal progesterone level or urine luteal hormone surge to document ovulation.

Clinical and demographic data for all three groups are presented in Table 1. All subjects were Caucasian, and the groups were well matched in aggregate for age, gender, premorbid IQ (National Adult Reading Test; Nelson, 1982) and handedness. Healthy volunteers were clearly less fatigued than the patient groups. Median Hamilton Depression scores were highest for the depressed patients, significantly lower in the CFS patients, and lowest in healthy volunteers. Table 2 lists the peak differences in perfusion between the three diagnostic groups using SPM.

Figure 1 illustrates perfusion differences between patient groups and healthy volunteers in a slice 40 mm above the orbitomeatal line. Uptake was greater, mainly in the right thalamus (as well as pallidum and putamen), both in subjects with CFS and those with depression, than in healthy controls. CFS patients also showed increased perfusion in the left thalamus. In comparison with the CFS group, in the patients with depression perfusion was decreased in the left prefrontal cortex. The remaining foci in Fig. 1 did not achieve statistical significance at the cluster (volume) level. Table 2 Effect of diagnosis on cerebral perfusion (statistical parametric mapping analysis).

All areas containing voxels with uncorrected P < 0.001 are listed Fig. 1 Voxels with increased perfusion in patient groups, compared with healthy volunteers and with each other. The cross-point marks the peak difference: (a) chronic fatigue syndrome v. healthy volunteers; (b) depression v. healthy volunteers; (c) depression v. chronic fatigue syndrome. The results of the ROI analysis are shown in Table 3.

The pattern of results in the thalamus and putamen is similar to the patterns obtained with SPM, although the differences are non-significant, apart from in the left thalamus and right caudate and putamen in unmedicated CFS patients. The significant ROI differences in caudate nuclei could be due to the cortical rim fitting of the template, which can result in partial volume effects between central structures and ventricular cerebrospinal fluid.