Telomerase ECT Biomarker Study From Ireland: Negative results

 Out on PubMed, from colleagues in Ireland, is this study:

PBMC telomerase activity in depression and the response to electroconvulsive therapy.

Ryan KM, Finnegan M, Harkin A, McLoughlin DM.Eur Arch Psychiatry Clin Neurosci. 2021 Jul 15. doi: 10.1007/s00406-021-01294-4. Online ahead of print.PMID: 34268617

The abstract is copied below:

Telomerase, the DNA polymerase responsible for maintaining telomere length, has previously been implicated in depression and the response to antidepressant drugs. In this study, we aimed to compare telomerase activity in peripheral blood mononuclear cells between patients with severe depression recruited as part of the KEEP-WELL Trial (Ketamine for Depression Relapse Prevention Following ECT; NCT02414932) and age- and sex-matched healthy volunteers both at baseline/pre-ECT and at follow-up 1 month later for controls or in patients after a course of ECT. We found no differences in telomerase activity between patients with depression (n = 20) compared to healthy controls (n = 33) at baseline/pre-ECT, or between patients treated with ECT compared to controls at follow-up. In patients, telomerase activity was not associated with mood, as assessed by the 24-item Hamilton Rating Scale for Depression, or the duration of the current depressive episode. Additionally, we found no significant relationship between telomerase activity and exposure to recent or childhood adversity in either the patient or control groups. Overall, our results suggest that telomerase activity is not associated with depression, the therapeutic response to ECT, or exposure to adversity.

Keywords: Depression; Electroconvulsive therapy; HAM-D24; PBMC; Telomerase.

And from the text:

Electroconvulsive therapy (ECT) remains the most acutely effective treatment for severe, often life-threatening episodes of depression [23, 24]. However, its mechanism of action remains unclear [25]. To our knowledge, no study has yet examined telomerase activity in patients with depression undergoing treatment with ECT. Thus, here we examined telomerase activity in PBMCs collected from depressed patients pre- and post-treatment with ECT and from healthy controls at two time-points to approximate a course of ECT. We hypothesized that (1) telomerase activity would be lower in patients with depression compared to healthy controls and (2) telomerase activity would normalize in response to treatment with a course of ECT. We also explored whether there was any relationship between telomerase activity and depression severity or exposure to recent or early life adversity.

This is a well conducted study with a good rationale for its design. Limitations include the small sample size (20 patients, 33 healthy controls) and technical issues with sample collection. The findings are negative, with nary a signal that telomerase activity is a valid biomarker to pursue in ECT patients. The one possible exception was the trend for telomerase activity to be lower in patients who had experienced childhood adversity. The discussion comparing telomerase activity versus telomere length as biomarkers is excellent.

Students of the ECT biomarker/mechanism of action literature will want to read this paper in full, ~ 20 minutes.