Pre-treatment Aallostatic load and metabolic dysregulation predict antidepressant response in major depressive disorder

Background Major depressive disorder (MDD) is associated with significant health risks, including increased rate of cardiovascular disease, stroke, and diabetes. Allostatic load (AL), a biological measure of cumulative stress, and metabolic dysregulation (MetD), a summary score of metabolic syndrome risk factors, are associated with increased disease burden and mortality risk. Though increased AL and MetD are well-established in MDD, no prior study has prospectively examined their relationship with antidepressant response. Methods We determined baseline AL and MetD summary scores in 34 medically-healthy, medication-free individuals with MDD, before they completed eight-weeks of open-label selective serotonin reuptake inhibitor (SSRI) treatment, and in 67 healthy controls. Baseline AL and MetD scores of “Responders” (≥50% improvement in depression severity ratings after treatment), “Non-responders” (<50% improvement in depression severity), and controls were compared. Results Baseline depression severity did not differ between Responders and Non-responders. Baseline AL and MetD scores were significantly higher in Non-responders compared to Responders (p=0.025 and 0.026, respectively) and controls (p=0.039 and 0.001, respectively), but did not significantly differ between Responders and controls (p=0.512 and 0.748, respectively). Further, higher baseline AL and MetD were significantly associated with less absolute improvement in depression severity (p=0.010 and 0.011, respectively). Correcting for sex and age did not alter these findings. Conclusions Increased pre-treatment AL and MetD predicted poorer SSRI-response in MDD. This suggests that greater biological dysfunction (i.e. AL and MetD) may not only be associated with MDD, but may also relate to the capacity for clinical response to SSRI-treatment. Potential mechanisms of this relationship are discussed.