Polygenic Risk Scores and ECT Outcome: New Study inThe American Journal of Psychiatry

Out on Pubmed, from investigators in Sweden, Canada and the USA, is this study:

Association Between Polygenic Risk Scores and Outcome of ECT.

Sigström R, Kowalec K, Jonsson L, Clements CC, Karlsson R, Nordenskjöld A, Pålsson E, Sullivan PF, Landén M.Am J Psychiatry. 2022 Sep 7:appiajp22010045. doi: 10.1176/appi.ajp.22010045. Online ahead of print.PMID: 36069021

The abstract is copied below:

Objective: Identifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode.

Methods: Between 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping. The present study included 2,320 participants (median age, 51 years; 62.8% women) who had received an ECT series for a major depressive episode (77.1% unipolar depression), who had a registered treatment outcome, and whose polygenic risk scores (PRSs) could be calculated. Ordinal logistic regression was used to estimate the effect of PRS on Clinical Global Impressions improvement scale (CGI-I) score after each ECT series.

Results: Greater PRS for major depressive disorder was significantly associated with less improvement on the CGI-I (odds ratio per standard deviation, 0.89, 95% CI=0.82, 0.96; R2=0.004), and greater PRS for bipolar disorder was associated with greater improvement on the CGI-I (odds ratio per standard deviation, 1.14, 95% CI=1.05, 1.23; R2=0.005) after ECT. PRS for schizophrenia was not associated with improvement. In an overlapping sample (N=1,207) with data on response and remission derived from the self-rated version of the Montgomery-Åsberg Depression Rating Scale, results were similar except that schizophrenia PRS was also associated with remission.

Conclusions: Improvement after ECT is associated with polygenic liability for major depressive disorder and bipolar disorder, providing evidence of a genetic component for ECT clinical response. These liabilities may be considered along with clinical predictors in future prediction models of ECT outcomes.

Keywords: Bipolar and Related Disorders; Depressive Disorders; Electroconvulsive Therapy (ECT); Genetics/Genomics.

The article is here.

And from the text:

Here is yet another fascinating, sophisticated, and well carried out registry study from Sweden. The big picture finding, that there is an association between genetic risk for psychiatric illness and ECT outcome is intuitively satisfying.

The detailed finding about depression is counterintuitive (goes in the "wrong" direction); the one about bipolar disorder is expected. 

The depression finding remains unexplained, and the authors eruditely discuss some possibilities; seems to me it may also have something to do with the fuzziness of the diagnosis of depression compared to that of bipolar disorder. Bipolar disorder is a strange phenomenon in nature and much less likely to be as heterogeneous as "depression."

Another overarching conclusion is that genetic studies in psychiatry have, to date, been quite limited in the power, scope and utility of their findings. But kudos to these authors for putting ECT front and center in the mix; as the most powerful treatment in psychiatry, it is a very good paradigm with which to look for biological and genetic effects.