Genetics and ECT Response: New International Study

Out on PubMed, from a consortium of international investigators, is this study:

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness.

Luykx JJ, Loef D, Lin B, van Diermen L, Nuninga JO, van Exel E, Oudega ML, Rhebergen D, Schouws SNTM, van Eijndhoven P, Verwijk E, Schrijvers D, Birkenhager TK, Ryan KM, Arts B, van Bronswijk SC, Kenis G, Schurgers G, Baune BT, Arns M, van Dellen EE, Somers M, Sommer IEC, Boks MP, Gülöksüz S, McLoughlin DM, Dols A, Rutten BPF.Biol Psychiatry. 2021 Oct 24:S0006-3223(21)01707-8. doi: 10.1016/j.biopsych.2021.10.013. Online ahead of print.PMID: 34955169

The abstract is copied below:

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness.

Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold is reported.

Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold.

Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.

Keywords: Depression; Electroconvulsive therapy (ECT); Polygenic liabilities; Schizophrenia.

The promise of genetics in psychiatry has yet to be realized, either for prognostication or treatment selection; this paper is a step in the direction of the latter.

This is a complex and sophisticated study with a cohort of depressed patients whose ECT outcome is correlated with their polygenic liability for schizophrenia; it is not about patients with schizophrenia. Genetic risk for psychosis across different psychiatric diagnoses is the underlying concept, as described in the "Discussion" above. 

 This is progress, but only as an adjunct to careful clinical diagnosis and symptom/history assessment. 

Of course, these findings are very preliminary, as the authors are careful to note.

I would be interested in comments from blog readers, including those with better familiarity with the genetic methods used in this study. A full read will be ~ 30 minutes.