Trait-related changes in brain network topology in premenstrual dysphoric disorder

Rotem Dan, Inbal Reuveni, Laura Canetti, Marta Weinstock, Ronen Segman, Gadi Goelman*, Omer Bonne

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The female predominance in the prevalence of depression is partially accounted by reactivity to hormonal fluctuations. Premenstrual dysphoric disorder (PMDD) is a reproductive subtype of depression characterized by cyclic emotional and somatic symptoms that recur before menstruation. Despite the growing understanding that most psychiatric disorders arise from dysfunctions in distributed brain circuits, the brain's functional connectome and its network properties of segregation and integration were not investigated in PMDD. To this end, we examined the brain's functional network organization in PMDD using graph theoretical analysis. 24 drug naïve women with PMDD and 27 controls without premenstrual symptoms underwent 2 resting-state fMRI scans, during the mid-follicular and late-luteal menstrual cycle phases. Functional connectivity MRI, graph theory metrics, and levels of sex hormones were computed during each menstrual phase. Altered network topology was found in PMDD across symptomatic and remitted stages in major graph metrics (characteristic path length, clustering coefficient, transitivity, local and global efficiency, centrality), indicating decreased functional network segregation and increased functional network integration. In addition, PMDD patients exhibited hypoconnectivity of the anterior temporal lobe and hyperconnectivity of the basal ganglia and thalamus, across menstrual phases. Furthermore, the relationship between difficulties in emotion regulation and PMDD was mediated by specific patterns of functional connectivity, including connections of the striatum, thalamus, and prefrontal cortex. The shifts in the functional connectome and its topology in PMDD may suggest trait vulnerability markers of the disorder.

Original languageAmerican English
Article number104782
JournalHormones and Behavior
StatePublished - Aug 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.


  • Functional MRI
  • Functional connectivity
  • Graph theory
  • Menstrual cycle
  • PMDD
  • Premenstrual dysphoric disorder
  • Reproductive depression
  • Resting state
  • Sex hormones
  • fMRI


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