Why does depression respond readily to treatment in some patients and resist everything in others? A Karolinska Institutet twin study published in JAMA Network Open, Adverse Childhood Experiences and Treatment-Resistant Depression, points to events decades before diagnosis. Drawing on the Swedish Twin Registry, the researchers identified more than 21,000 twins and included about 17,800 in the main analysis, combining questionnaire data on childhood adversity such as neglect and abuse with national register data on depression diagnoses and medication.
The risk of treatment-resistant depression climbed with each additional adverse childhood experience, and the gradient held even when comparing twins raised in the same family, a design that strips out much genetic and shared environmental confounding. Among people reporting three or more adverse experiences, about 5 per cent developed treatment-resistant depression, compared with 0.7 per cent of those reporting none, a sevenfold difference in absolute terms.
First author Ying Xiong, a postdoctoral researcher at Karolinska's Department of Medical Epidemiology and Biostatistics, notes that the findings could help clinicians identify patients at higher risk of poor treatment response earlier, though the observational design limits causal conclusions. The study was funded by bodies including the Swedish Research Council, the EU Horizon 2020 programme and the US National Institute of Mental Health.