Does PMDD affect how the brain handles motivation when facing difficult choices?

Introduction: Motivation drives goal-directed behavior, often requiring individuals to approach rewards while facing potential punishment (i.e., goal-conflict). Premenstrual dysphoric disorder (PMDD) is marked by emotional and cognitive impairments that may affect motivational functioning. While emotional deficits in PMDD are well-known, their impact on motivation under goal-conflict remains unclear. This study examined neurobehavioral indications for motivational deficits in PMDD during naturalistic goal-conflict and their relation to symptom severity. Methods: Fifty-one women with regular menstrual cycles (28 with PMDD, 23 healthy controls) completed a computer-based approach-avoidance task during fMRI scanning in the luteal phase. The task included high and low goal-conflict (HiGC or LoGC) conditions, where rewards were threatened by punishment. Neural activity in mesostriatal reward-related regions - the ventral striatum (VS) and ventral tegmental area (VTA) - was analyzed using general linear models. Symptom severity was assessed using the Premenstrual Tension Syndrome Observer Rating Scale (PMTS-OR). Results: Compared with healthy controls, participants with PMDD were less able to increase approach behavior as conflict decreased, resulting in fewer approach events under LoGC condition, while no group differences were observed under HiGC. Additionally, within the PMDD group, greater symptom severity (depression and anxiety) was associated with lower approach behavior under HiGC conditions. fMRI analyses revealed diminished activation in the VS and VTA under HiGC in the PMDD group, suggesting reduced conflict-related engagement of reward-related circuitry. Conclusion: PMDD is associated with impaired motivational adaptation across conflict levels, reflected in a blunted increase in approach behavior under conditions of lower risk. Diminished conflict-related activity in reward-related mesostriatal regions (VS, VTA) may underlie this deficit. These findings highlight the potential role of mesolimbic circuitry dysfunction in PMDD and point toward reward processing pathways as candidate therapeutic targets. Trial registration number: NCT02448836, ClinicalTrials.gov.

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