Interactive Effects of Serum Leptin Levels and Physical Comorbidity on the Pharmacotherapeutic Response of Depressive Disorders

Abstract

Objective: To investigate individual and interactive associations of baseline serum leptin levels and physical comorbidity with short-and long-term treatment outcomes in outpatients with depressive disorders who received stepwise antidepressant treatment in a naturalistic prospective study design. Methods: Baseline serum leptin levels were measured, and the number of concurrent physical disorders ascertained from 1,094 patients. These patients received initial antidepressant monotherapy; then, for patients with an insufficient response or who experienced uncomfortable side effects, treatment was administered using alternative strategies every 3 weeks in the acute treatment phase (at 3, 6, 9, and 12 weeks) and every 3 months in the continuation treatment phase (at 6, 9, and 12 months). Then, 12-week and 12-month remission, defined as a Hamilton Depression Rating Scale score of ≤7, was estimated. Results: In multivariable logistic regression analyses, individual effects were found only between higher baseline serum leptin levels and 12-week non-remission. Significant interactive effects between higher leptin levels and fewer physical disorders (＜ 2 physical disorders) on 12-week non-remission were observed. However, neither individual nor interactive effects between leptin levels and physical comorbidity were associated with 12-month remission. Conclusion: The combination of serum leptin level and number of physical disorders may be a useful predictor of short-term treatment responses in patients with depressive disorders receiving pharmacotherapy.

Use of Serum Biomarkers to Aid Antidepressant Selection in Depressive Patients

“…Equivale findings have been re-ported regarding the predictive value of peripheral leptin levels in terms of the antidepressant response; lower levels were associated with a poor response in a study that did not stratify by antidepressants [24], and no significant association was reported elsewhere [25]. Based on previous findings of differential effects of leptin levels on the treatment response according to physical comorbidities [26], the significant association between low leptin levels and remission at 12 weeks seen in this study may have been mediated by other covariates, such as physical comorbidities. Therefore, further studies are needed on the association between leptin levels and treatment outcomes by antidepressant type considering these mediating factors.…”

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

“…Some studies showed lower plasma levels of leptin in these patients; however, in cases of major depression disorder, serum concentrations were higher than in control subjects [ 131 ]. In another study, leptin was analyzed in depressive patients with therapy, finding a relationship between the combination of serum leptin and number of behavior disorders, suggesting that leptin levels can be a predictor of treatment responses in these patients [ 132 ].…”

The Role of Glutamate Underlying Treatment-resistant Depression

“…Several studies using animal models of stress have shown that various forms of environmental stress have profound effects on the structure and morphology of the brain, resulting in dendritic remodeling, synaptic spine loss, glial loss, and volume loss [ 3 ]. It is noteworthy that functional (i.e., blood flow, metabolism) [ 4 ] and altered molecular function (i.e., gene expression, etc.) [ 5 ] as well as morphological changes in neurons and glia (cytoarchitectural) [ 3 ] are common in humans showing the depressive phenotypes.…”