Investigating the Role of Leukocyte Telomere Length in Treatment-Resistant Depression and in Response to Electroconvulsive Therapy.

Claudia Pisanu,Giovanni Severino,Alessandra Minelli,Alessio Squassina,Raffaella Ardau,Erika Vitali,Marco Bortolomasi,Massimo Gennarelli,Luigi Trabucchi,Anna Meloni,Donatella Congiu,Caterina Chillotti

doi:10.3390/jpm11111100

Abstract

Psychiatric disorders seem to be characterized by premature cell senescence. However, controversial results have also been reported. In addition, the relationship between accelerated aging and treatment-resistance has scarcely been investigated. In the current study, we measured leukocyte telomere length (LTL) in 148 patients with treatment-resistant depression (TRD, 125 with major depressive disorder, MDD, and 23 with bipolar disorder, BD) treated with electroconvulsive therapy (ECT) and analyzed whether LTL was associated with different response profiles. We also compared LTL between patients with TRD and 335 non-psychiatric controls. For 107 patients for which genome-wide association data were available, we evaluated whether a significant overlap among genetic variants or genes associated with LTL and with response to ECT could be observed. LTL was negatively correlated with age (Spearman’s correlation coefficient = −0.25, p < 0.0001) and significantly shorter in patients with treatment-resistant MDD (Quade’s F = 35.18, p < 0.0001) or BD (Quade’s F = 20.84, p < 0.0001) compared to controls. Conversely, baseline LTL was not associated with response to ECT or remission. We did not detect any significant overlap between genetic variants or genes associated with LTL and response to ECT. Our results support previous findings suggesting premature cell senescence in patients with severe psychiatric disorders and suggest that LTL could not be a predictive biomarker of response to ECT.

Highlights

IntroductionMood disorders affect 5.4% of the general population representing a substantial socioeconomic burden and significantly impacting the patients’ quality of life [1,2,3]
In the present study we showed no difference in leukocyte telomere length (LTL) based on response to electroconvulsive therapy (ECT) in patients with treatment-resistant depression (TRD)
This result is in accordance with the only available previous study that reported no association between whole blood Telomere length (TL) and response to ECT, remission or cognitive side effects in a sample of 100 patients with severe depression in which improvement was assessed using the Hamilton rating scale for depression-24 [79]

Summary

Introduction

Mood disorders affect 5.4% of the general population representing a substantial socioeconomic burden and significantly impacting the patients’ quality of life [1,2,3]. Mood disorders are associated with a reduced life expectancy compared to the general population (up to 20 years), and this is largely accounted for by a higher incidence of cardiovascular and metabolic disorders [6,7] and suicide [8,9,10]. In both disorders, pharmacological treatments represent the main approach. The treatment of bipolar depression is a big challenge because there are few drugs with proven efficacy and the use of antidepressants is controversial [12,13,14], due to the risk for manic switch [15]

Methods

Results

Conclusion