International Consortium on the Genetics of Electroconvulsive Therapy and Severe Depressive Disorders (Gen-ECT-ic)

Abstract

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alli-ance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.

Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy

“…That SNP-based heritability is higher for severe MDD supports the extreme phenotype strategy, which has been successful for other traits [20], to elucidate the genetics of MDD. Indeed, an international consortium was recently formed to study the genomics of ECT-treated MDD [19]. We also compared the PREFECT and PGC MDD cohorts with respect to genetic correlations with other disorders and traits.…”

“…ECT is an effective treatment for severe major depressive episodes (MDE) [14,15], and is not prescribed for mild cases [16][17][18]. As described at length elsewhere [19], the rationale for focusing on individuals receiving ECT for MDE is threefold. First, clinical applicability is higher given that patients with mood disorders receiving ECT are among the most severely ill people seen in clinical psychiatry.…”

Elektrokonvulsionstherapie – eine Blackbox?

“…Diese ersten Einblicke in neurobiologische Mechanismen basieren jedoch nur auf kleinen Stichproben, und sollten zu weiteren Untersuchungen des Therapieansprechens auf EKT ermutigen. So wurde kürzlich das "Genetics of ECT International Consortium" (Gen-ECT-ic) gegründet, das die derzeit größte klinische Stichprobe zusammenstellt um bei 30.000 Patienten weltweit mittels Genom-weiter Assoziations-Studien (GWAS) genetische Befunde zum Therapieansprechen auf EKT bei schwerer depressiver Erkrankung zu untersuchen [10]. Da der Schweregrad von Depression mit dem genetischen Risiko assoziiert ist, könnte solch eine Studie wertvolle Ergebnisse zur Prädiktion des Verlaufs nach EKT Behandlung liefern und dazu beitragen, die Blackbox des neurobiologischen Hintergrunds dieser Therapiemethode zu erhellen.…”

Understanding the mechanisms of treatment response in depression, focus on electro-convulsive therapy

“…Identifying biomarkers to select those patients who will best respond to ECT could help clinicians to implement ECT earlier in the disease course. The topic of biomarkers in ECT is also the focus of two publications in this issue of the European Archives of Psychiatry and Clinical Neuroscience, namely Kranaster et al and Soda et al [6,7]. The two papers in this issue address these specific questions, i.e., identification biomarkers for ECT response but also whether such biomarkers can contribute to our understanding of the pathomechanisms of depression.…”

“…Soda et al [7] present another approach for understanding factors contributing to ECT response, namely genetic association studies. Like any other complex trait, response to ECT will be determined by polygenic factors, each with small effects, necessitating large sample sizes to detect meaningful and robust associations.…”