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

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.

A healthy lifestyle is positively associated with mental health and well-being and core markers in ageing

“…As for TL, we did not find an association with any of the mental health and well-being outcomes. Previous studies in adults showed a lower TL in association with current but not remitted anxiety disorder [ 81 ], depressive [ 82 ] and major depressive disorder [ 73 , 83 ], childhood trauma [ 84 ] suicide [ 77 , 85 ], depressive symptoms in younger adults [ 86 ] and acculturative stress and postpartum depression in Latinx women [ 87 ]. Also, in a meta-analysis, psychiatric disorders overall were associated with a shorter leucocyte TL [ 88 ].…”

Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome

“… 48 Also, a recent study 49 reported a substantial association between the severity of the depressive episode in LLD and shorter leukocyte telomere length. A few small clinical trials 50 , 51 , 52 evaluated whether leukocyte telomere length was associated with treatment response or remission in MDD, with mixed results. None of these studies included older adults with LLD, a population more vulnerable to age-related biological abnormalities.…”