A New Study has Linked Treatment Resistant Depression to Body Mass Index

Individuals experiencing treatment-resistant depression (TRD) may not find relief with standard treatments like antidepressants or psychotherapy. Recent research highlights the significant role of genetic factors in TRD and its shared genetic overlap with conditions such as schizophrenia, attention deficit disorder, cognitive traits, alcohol and smoking behaviors, and body mass index (BMI). These findings suggest a common biological basis among these disorders, which could pave the way for new treatment approaches.

Depression: A Widespread Struggle Impacting 5% Globally

Depression, also known as depressive disorder, is a common mental disorder characterized by a persistent depressed mood or loss of interest in activities. It differs from regular mood changes and can impact all aspects of life, including relationships, school, and work. 

Individuals who have experienced abuse, severe losses, or stressful events are more likely to develop depression. According to recent statistics from the World Health Organization (WHO), women are about 50% more likely to experience depression than men. An estimated 3.8% of the global population has depression, including 5% of adults (4% of men and 6% of women) and 5.7% of those over 60 years old. Approximately 280 million people worldwide suffer from depression. More than 10% of pregnant women and new mothers experience depression. 

Each year, over 700,000 people die by suicide, making it the fourth leading cause of death among 15–29-year-olds. Despite effective treatments, over 75% of people in low- and middle-income countries receive no treatment due to factors such as inadequate mental health care investment, a shortage of trained providers, and social stigma. 

Treatment Resistant Depression is Prevalent Among 1/3 of Diagnosed Individuals 

Severe depression is experienced by nearly 20% of people in the United States, with approximately one-third not responding to antidepressant treatments and therapies, thus falling into the category of TRD. Despite its significant impact, TRD lacks a clear consensus in its definition, making active diagnosis and treatment challenging. Consequently, this patient population is often overlooked or misdiagnosed, leading to limited therapeutic options both in research and clinical practice.

Despite indications that treatment resistance may be inherited, the specific genetic makeup of this condition is not well understood. This is mainly due to the lack of a consistent and precise definition of what constitutes treatment resistance and the difficulty in recruiting a sufficient number of research subjects for study. Here is where the fact that TRD has a genetic basis becomes increasingly important. Through this genetic foundation, researchers are able to observe the significant overlap of TRD with the genetics of other conditions such as schizophrenia, attention deficit disorder, cognitive traits, alcohol use, smoking behaviors, and body mass index (BMI). This shared genetic foundation suggests that these conditions might have common biological pathways or mechanisms. Understanding these connections could lead to new approaches for treating TRD by targeting these shared biological factors.

TRD’s Genetic Loci Reveal Increased Risk Associated with Lower BMI

Researchers at Vanderbilt University Medical Center and Massachusetts General Hospital demonstrated the significant role of genetics in TRD, using electroconvulsive therapy (ECT) as a marker. They developed a machine learning model to predict ECT benefits based on patient health records, analyzing over 154,000 patients. Their study identified two genetic regions associated with TRD, linking them to body weight regulation and brain functions related to mood disorders such as bipolar disorder. One locus coincided with a region linked to body mass index (BMI), indicating that lower body weight correlates with higher treatment resistance, consistent with findings in anorexia nervosa patients. The other locus was associated with a gene highly expressed in brain regions regulating body weight and appetite, also implicated in bipolar disorder. These findings hold promise for advancing treatments for major depressive disorder.

Published in The American Journal of Psychiatry, the report sheds light on the genetics and biology of TRD, advocating for the use of clinical data in genomic research. It supports the use of clinical data for estimating disease probabilities in genomic research and “lays the groundwork for future efforts to apply genomic data for biomarker and drug development,” as highlighted by Douglas Ruderfer, Ph.D., associate professor. He maintains that “despite the large proportion of patients with TRD, the biology has remained poorly understood. Our work here provides genetic support for new biological directions to explore in addressing this gap,”

Further, Roy Perlis, MD, professor at Harvard Medical School, emphasizes the significance of these findings in diversifying treatment options for this common condition. “This work finally gives us some new leads, rather than reinventing the same antidepressants over and over again, for a condition that is extremely common.” 

If you are experiencing depression or suicidal thoughts or behaviors, it’s crucial to seek help immediately. This content is not a substitute for professional medical advice, diagnosis, or treatment. Please reach out to a trusted healthcare provider, counselor, or contact a mental health helpline for immediate support and assistance. You are not alone, and there are people who care about you and want to help you through this difficult time.Depression symptoms, depression treatment, signs of depression, types of depression, coping with depression, managing depression, depression therapy, depression support, understanding depression, depression help and resources, depression, depression symptoms, postpartum depression

Author

Bernice Lottering