ECT As Surrogate For TRD: GWAS Study in AM J Psych

 Out on PubMed,  in AM J Psych, is this article:


Genome-Wide Association Study of Treatment-Resistant Depression: Shared Biology With Metabolic Traits.

Kang J, Castro VM, Ripperger M, Venkatesh S, Burstein D, Linnér RK, Rocha DB, Hu Y, Wilimitis D, Morley T, Han L, Kim RY, Feng YA, Ge T, Heckers S, Voloudakis G, Chabris C, Roussos P, McCoy TH, Walsh CG, Perlis RH, Ruderfer DM.Am J Psychiatry. 2024 May 15:appiajp20230247. doi: 10.1176/appi.ajp.20230247. Online ahead of print.PMID: 38745458

The abstract is copied below:
Objective: Treatment-resistant depression (TRD) occurs in roughly one-third of all individuals with major depressive disorder (MDD). Although research has suggested a significant common variant genetic component of liability to TRD, with heritability estimated at 8% when compared with non-treatment-resistant MDD, no replicated genetic loci have been identified, and the genetic architecture of TRD remains unclear. A key barrier to this work has been the paucity of adequately powered cohorts for investigation, largely because of the challenge in prospectively investigating this phenotype. The objective of this study was to perform a well-powered genetic study of TRD.


Methods: Using receipt of electroconvulsive therapy (ECT) as a surrogate for TRD, the authors applied standard machine learning methods to electronic health record data to derive predicted probabilities of receiving ECT. These probabilities were then applied as a quantitative trait in a genome-wide association study of 154,433 genotyped patients across four large biobanks.

Results: Heritability estimates ranged from 2% to 4.2%, and significant genetic overlap was observed with cognition, attention deficit hyperactivity disorder, schizophrenia, alcohol and smoking traits, and body mass index. Two genome-wide significant loci were identified, both previously implicated in metabolic traits, suggesting shared biology and potential pharmacological implications.

Conclusions: This work provides support for the utility of estimation of disease probability for genomic investigation and provides insights into the genetic architecture and biology of TRD.

Keywords: Depressive Disorders; Electroconvulsive Therapy (ECT); Genetics/Genomics; Major Depressive Disorder; Treatment-Resistant Depression.

The article is here.
And from the text:






This article is of interest mostly for the study's use of ECT as a proxy for TRD, and what the text (above, highlighted) says about ECT. The genetic results, while somewhat interesting, are unspectacular.
Whether ECT use is a marker of "TRD" or something similar, like severity or urgency of depressive episode symptoms, is debatable.
The text notes ECT as the "gold standard" antidepressant, but also its use in <1% of MDD patients.





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