A new study has discovered that close relatives of individuals with treatment-resistant depression (TRD) are nine times more likely to develop depression that does not respond to traditional treatment. TRD refers to a condition where standard treatments like psychiatric therapy and antidepressants prove ineffective in alleviating symptoms.

The research, conducted by senior author Dr. Cheng-Ta Li, a professor of medicine at the National Yang Ming Chiao Tung University in Taipei, Taiwan, is the first and largest study to employ an entire country's data to confirm the genetic transmission of TRD across families and its association with other major psychiatric disorders.

The study, published in the journal JAMA Psychiatry, analyzed national health insurance data in Taiwan over a 15-year period, examining inpatient and outpatient medical records and prescription information. Among over half a million Taiwanese individuals diagnosed with major depressive disorder during this period, over 21,000 went on to receive a diagnosis of treatment-resistant depression, which was defined as undergoing at least three separate courses of antidepressants without success within a two-year period.

The findings revealed that first-degree relatives of individuals with TRD, including parents, siblings, and children, were significantly more vulnerable to developing treatment-resistant depression, with a nine-fold increased risk compared to relatives of those without TRD. Additionally, these family members had a higher likelihood of developing other psychiatric conditions such as anxiety, bipolar disorder, obsessive-compulsive disorder, major depressive disorder, and attention deficit hyperactivity disorder. The study also noted that they were more susceptible to death by suicide.

Dr. Andrew McIntosh, a professor of psychiatry at the Centre for Clinical Brain Sciences at the University of Edinburgh in Scotland, who was not involved in the study, found the results to be the most convincing evidence to date that treatment-resistant depression tends to run in families. However, he also highlighted the possibility of shared life events, socioeconomic disadvantages, or other unidentified risk factors among family members.

Dr. Li suggests that alternative treatment options should be considered earlier for individuals with a family history of TRD if the initial antidepressant treatment fails. These alternative treatments may include the addition of lithium and other atypical antipsychotics, low-dose ketamine (esketamine), or repetitive transcranial magnetic stimulation, a form of shock therapy that does not require sedation and is not associated with cognitive adverse effects.

Furthermore, Dr. McIntosh praised the study for addressing the underrepresentation of Asian people in research and urged the scientific community to expand studies beyond individuals of European ancestries in Europe and North America.

The findings of this study provide valuable insights into the genetic factors contributing to treatment-resistant depression and the increased risk faced by family members. Further research is necessary to unravel the underlying causes and develop targeted interventions to better support individuals affected by TRD and their relatives.