Pre-treatment allostatic load and metabolic dysregulation predict SSRI response in major depressive disorder: A preliminary report

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BackgroundMajor depressive disorder (MDD) is associated with increased allostatic load (AL; a measure of physiological costs of repeated/chronic stress-responding) and metabolic dysregulation (MetD; a measure of metabolic health and precursor to many medical illnesses). Though AL and MetD are associated with poor somatic health outcomes, little is known regarding their relationship with antidepressant-treatment outcomes.MethodsWe determined pre-treatment AL and MetD in 67 healthy controls and 34 unmedicated, medically healthy MDD subjects. Following this, MDD subjects completed 8-weeks of open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment and were categorized as 'Responders' (≥50% improvement in depression severity ratings) or 'Non-responders' (<50% improvement). Logistic and linear regressions were performed to determine if pre-treatment AL or MetD scores predicted SSRI-response. Secondary analyses examined cross-sectional differences between MDD and control groups.ResultsPre-treatment AL and MetD scores significantly predicted continuous antidepressant response (i.e. absolute decreases in depression severity ratings) (p = 0.012 and 0.014, respectively), as well as post-treatment status as a Responder or Non-responder (p = 0.022 and 0.040, respectively), such that higher pre-treatment AL and MetD were associated with poorer SSRI-treatment outcomes. Pre-treatment AL and MetD of Responders were similar to Controls, while those of Non-responders were significantly higher than both Responders (p = 0.025 and 0.033, respectively) and Controls (p = 0.039 and 0.001, respectively).ConclusionsThese preliminary findings suggest that indices of metabolic and hypothalamic-pituitary-adrenal-axis dysregulation are associated with poorer SSRI-treatment response. To our knowledge, this is the first study to demonstrate that these markers of medical disease risk also predict poorer antidepressant outcomes.


  • Christina M. Hough
  • F. Saverio Bersani
  • Synthia H. Mellon
  • Alexandra E. Morford
  • Daniel Lindqvist
  • Victor I. Reus
  • Elissa S. Epel
  • Owen M. Wolkowitz
Enheter & grupper
Externa organisationer
  • University of California, San Francisco
  • University of California, Los Angeles
  • Sapienza University of Rome
  • Northwestern University

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Psykiatri


TidskriftPsychological Medicine
StatusE-pub ahead of print - 2020 maj 22
Peer review utfördJa