Brain Connectivity and Inflammatory Markers During Short-Term Psychotherapy for Treatment-Resistant Depression

Some adults continue to experience depression despite treatment with antidepressant medicines. This study aimed to explore relationships between depression symptoms, brain function, and blood markers of inflammation, and changes in these measures during a course of psychotherapy. Adults with treatment-resistant depression were assigned to receive 10 weekly sessions of individual short-term dynamic psychotherapy, a form of talking therapy, alongside their ongoing medication. Healthy adults served as a reference group and received no study treatment. Assessments were planned at the start of participation and at a 10-week follow-up. These included depression ratings, quality-of-life questionnaires, blood tests, and measurements of brain activity. The study aimed to compare initial measurements between participants with depression and healthy adults and to explore changes over time within each group.

Inclusion Criteria: All participants: * Aged 19 to 65 years. * All four grandparents are Korean. * Able to understand the study information and provide voluntary informed consent. Participants with treatment-resistant depression: * Persistent depressive symptoms despite treatment with at least two antidepressants for at least 6 weeks. * A 17-item Hamilton Depression Rating Scale (HAM-D) score of 17 or higher. * A history of at least two major depressive episodes. * First major depressive episode at age 14 years or older and before age 50 years. Healthy participants: \- No current or past psychiatric disorder. Exclusion Criteria: * History of bipolar disorder or psychosis. * History of alcohol or other substance dependence predating the onset of depression. * History of intellectual disability. * A parent or grandparent who is not Korean. * History of significant central nervous system disease, including traumatic brain injury, loss of consciousness, Parkinson's disease, epilepsy, Alzheimer's disease, or Huntington's disease. * Current infection, infection within the preceding 3 months, or an immunocompromised state. Immunocompromised states include congenital immune impairment and acquired conditions associated with immunosuppressive treatment, previous or current chemotherapy, or human immunodeficiency virus (HIV) infection. * Ongoing long-term use of oral corticosteroids or nonsteroidal anti-inflammatory drugs. * Pregnancy or breastfeeding. * Clinically significant suicide risk in the judgment of the treating psychiatrist or investigator. * Thoughts or intent to harm others. * Use of an unapproved drug within the preceding 30 days or current participation in a related clinical study. * Clinically significant abnormal screening findings in the judgment of the principal investigator. * An acute or chronic illness that makes participation unsuitable in the investigator's judgment. * Likely inability to follow study procedures and requirements. * Coronavirus disease 2019 (COVID-19) vaccination within the preceding month.