Childhood trauma linked to treatment resistant depression
People who have experienced adverse childhood experiences are at increased risk of developing depression later in life that is difficult to treat. This is shown in a new twin study from Karolinska Institutet based on Swedish twin data, published in the journal JAMA Network Open.
Depression is one of the most common mental disorders, but not everyone responds to standard treatments. In some cases, the condition develops into a treatment‑resistant form. In the new study, researchers investigated whether adverse childhood experiences, such as neglect or abuse, are associated with an increased risk of treatment‑resistant depression.
The researchers analysed data from more than 21,000 Swedish twins, of whom around 17,800 were included in the main analysis. Questionnaire data on childhood experiences were combined with information on depression diagnosis and medications from national health registers. The results show that the risk of treatment‑resistant depression increased with each adverse childhood experience, even when comparing twins who grew up in the same family.
Higher risk after multiple negative experiences
Among individuals who reported three or more adverse childhood experiences, around five per cent had treatment‑resistant depression, compared with 0.7 per cent among those without such experiences.
“Knowledge of difficult childhood experiences may be important for the early identification of patients at increased risk of treatment-resistant depression and could help clinicians better understand individual patients when they assess them,” says first author Ying Xiong, postdoctoral researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
The researchers emphasise that the findings provide support for a possible causal link. However, the study is observational, and further studies are needed to confirm the results before firm conclusions can be drawn.
The study is based on data from the Swedish Twin Registry and was funded by, among others, the Swedish Research Council, the EU’s Horizon 2020 programme, and the US National Institute of Mental Health. No conflicts of interest are reported.
Publication
"Adverse Childhood Experiences and Treatment-Resistant Depression", Xiong Y, Lindersten P, Gong T, Magnusson PKE, Liu S, Lu Y, JAMA Netw Open, online 9 mars 2026.