Effects of gonadal steroids on reward circuitry function and anhedonia in women with a history of postpartum depression.

BACKGROUND: Reward system dysfunction is evident across neuropsychiatric conditions. Here we present data from a double-blinded pharmaco-fMRI study investigating the triggering of anhedonia and reward circuit activity in women. METHODS: The hormonal states of pregnancy and parturition were simulated in euthymic women with a history of postpartum depression (PPD+; n = 15) and those without such a history (PPD-; n = 15) by inducing hypogonadism, adding back estradiol and progesterone for 8 weeks ("addback"), and then withdrawing both steroids ("withdrawal"). Anhedonia was assessed using the Inventory of Depression and Anxiety Symptoms (IDAS) during each hormone phase. Those who reported a 30 % or greater increase in IDAS anhedonia, dysphoria, or ill temper during addback or withdrawal, compared with pre-treatment, were identified as hormone sensitive (HS+) and all others were identified as non-hormone sensitive (HS-). The monetary incentive delay (MID) task was administered during fMRI sessions at pre-treatment and during hormone withdrawal to assess brain activation during reward anticipation and feedback. RESULTS: On average, anhedonia increased during addback and withdrawal in PPD+ but not PPD-. During reward feedback, both HS+ (n = 10) and HS- (n = 18) showed decreased activation in clusters in the right putamen (p < .031, FWE-corrected) and left postcentral and supramarginal gyri (p < .014, FWE-corrected) at the withdrawal scans, relative to pre-treatment scans. LIMITATIONS: A modest sample size, stringent exclusion criteria, and relative lack of diversity in study participants limit the generalizability of results. CONCLUSION: Although results do not explain differential hormone sensitivity in depression, they demonstrate significant effects of reproductive hormones on reward-related brain function in women.

Predictors of premenstrual impairment among women undergoing prospective assessment for premenstrual dysphoric disorder: a cycle-level analysis.

BACKGROUND: Women who experience significant premenstrual symptoms differ in the extent to which these symptoms cause cyclical impairment. This study clarifies the type and number of symptoms that best predict premenstrual impairment in a sample of women undergoing prospective assessment for premenstrual dysphoric disorder (PMDD) in a research setting. Central research goals were to determine (1) which emotional, psychological, and physical symptoms of PMDD are uniquely associated with premenstrual impairment, and (2) how many cyclical symptoms optimally predict the presence of a clinically significant premenstrual elevation of impairment. METHOD: A total of 267 naturally cycling women recruited for retrospective report of premenstrual emotional symptoms completed daily symptom reports using the Daily Record of Severity of Problems (DRSP) and occupational, recreational, and relational impairment for 1-4 menstrual cycles (N = 563 cycles). RESULTS: Multilevel regression revealed that emotional, psychological, and physical symptoms differ in their associations with impairment. The core emotional symptoms of PMDD were predictors of impairment, but not after accounting for secondary psychological symptoms, which were the most robust predictors. The optimal number of premenstrual symptoms for predicting clinically significant premenstrual impairment was four. CONCLUSION: Results enhance our understanding of the type and number of premenstrual symptoms associated with premenstrual impairment among women being evaluated for PMDD in research contexts. Additional work is needed to determine whether cognitive symptoms should receive greater attention in the study of PMDD, and to revisit the usefulness of the five-symptom diagnostic threshold.