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

• Published in: Psychological medicine Vol. 51; no. 12; pp. 2117 - 2125
• Main Authors: Hough, Christina M., Bersani, F. Saverio, Mellon, Synthia H., Morford, Alexandra E., Lindqvist, Daniel, Reus, Victor I., Epel, Elissa S., Wolkowitz, Owen M.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.09.2021
• Subjects: Allostasis; Allostatic load; antidepressant response; Antidepressants; Antidepressive Agents - therapeutic use; Clinical Medicine; Clinical outcomes; Cross-Sectional Studies; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Depressive personality disorders; Enrollments; Health status; Humans; Hypothalamic-pituitary-adrenal axis; Hypothalamus; Illnesses; Klinisk medicin; major depressive disorder; Medical and Health Sciences; Medicin och hälsovetenskap; Mental depression; metabolic dysregulation; Metabolic syndrome; Metabolism; Original Article; Physiology; Pituitary; Post traumatic stress disorder; Psychiatry; Psychosis; Psychotherapy; Psykiatri; Selective Serotonin Reuptake Inhibitors - pharmacology; Selective Serotonin Reuptake Inhibitors - therapeutic use; Serotonin reuptake inhibitors; Serotonin uptake inhibitors; treatment prediction; treatment response; metabolic syndrome; metabolic dysregulation; major depressive disorder; treatment response; Allostatic load; antidepressant response; treatment prediction
• ISSN: 0033-2917; 1469-8978; 1469-8978
• DOI: 10.1017/S0033291720000896

Major 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. We 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. Pre-treatment AL and MetD scores significantly predicted continuous antidepressant response (i.e. absolute decreases in depression severity ratings) ( = 0.012 and 0.014, respectively), as well as post-treatment status as a Responder or Non-responder ( = 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 ( = 0.025 and 0.033, respectively) and Controls ( = 0.039 and 0.001, respectively). These 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.