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No published epidemiologic study has examined premenstrual exacerbation of depressive disorders (PME-DD) in a representative sample. Knowledge gained should indicate the burden of illness, suggest whom to monitor, and facilitate diagnosis. The objectives were to 1) ascertain the prevalence and predictors of PME-DD; and 2) test competing hypotheses that PME-DD is related to a) severity or history of depression, b) menstrual cyclicity in females in general, or c) a methodological artifact.Menstruating females (N = 900) from ages 13 to 53 living in urban or rural Illinois completed semi-structured psychiatric diagnostic interviews and rated symptoms of depression daily for two menstrual cycles; 58 had major depressive, dysthymic, or subclinical depressive disorders, and the remaining 842 were the non-depressed portion of the representative sample.Depressed females had 1.34 (95% confidence interval, 1.02 - 1.66) symptoms exacerbated premenstrually. The best model for predicting exacerbation contained only age. Older women more often had symptoms worsen. Symptoms during the follicular phase were most severe for clinically depressed, intermediate for subclinically depressed, and least severe for non-depressed participants, ps < 0.001. Consistent with the hypothesis that exacerbation is related to cyclicity in all females, the number of symptoms that became worse did not differ between groups, ps < 0.46. Given no symptoms in one cycle, the odds of having symptoms in the next cycle were 0.91. Only 56% of non-depressed females taking antidepressants were asymptomatic all month long; the remaining 44% still had symptoms premenstrually.Premenstrual exacerbation of depressive disorders is associated with deteriorated functioning over and above that already experienced by depressed females. Patients may be susceptible regardless of severity of depression, number of episodes, or remission status.ANOVA = analyses of variance; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; DSMQ = Daily Symptom Mood Questionnaire; K-SADS-E = Schedule for Affective Disorders and Schizophrenia for School Age Children Epidemiological Version-5 Kiddie SADS-E; MDD = major depressive disorder; PME-DD = premenstrual exacerbation of depressive disorders; PMDD = premenstrual dysphoric disorder; RDC = research diagnostic criteria; SCID-I/NP = Structured Clinical Interview for DSM-IV Axis I Disorders - Non-Patient Edition; SSRI = selective serotonin reuptake inhibitor.