Background
Research suggests that how people respond to treatment for major depressive disorder (MDD), including resistance to treatment, may be influenced by genetics. However, defining treatment resistance is complex, making it difficult to fully understand its genetic basis.
This study aimed to establish a clear definition of treatment-resistant depression (TRD) and explore the genetic links between treatment response and resistance. Researchers used Swedish electronic medical records to analyze antidepressant and electroconvulsive therapy (ECT) usage in 4,500 individuals with MDD across three Swedish cohorts.
Results
Among 1,778 individuals who received ECT, nearly all (94%) had previously used antidepressants, and most had tried at least one (84%) or two (61%) antidepressants for a sufficient period, confirming that they were resistant to these treatments.
To investigate the genetic links, researchers analyzed polygenic risk scores (PRS)—a measure of genetic likelihood for responding to antidepressants and lithium. They found no significant difference in the genetic likelihood of antidepressant response between TRD and non-TRD groups. However, individuals with TRD had a higher genetic likelihood of responding to lithium compared to those without TRD.
Conclusions
These findings suggest that treatment resistance in depression has a genetic component and that individuals with TRD may have a genetic predisposition to respond better to lithium. This provides further support for the effectiveness of lithium in treating TRD and offers a genetic explanation for why it works in these cases. Understanding these genetic factors could help guide more personalized treatment strategies for people with severe depression.
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