Findings Published in JAMA Psychiatry Highlight the Role of Genetic Traits in Treatment Resistance
A groundbreaking study published in JAMA Psychiatry sheds new light on the genetic factors contributing to treatment-resistant depression (TRD), a severe form of major depressive disorder that does not respond to standard treatments. Researchers from the Laureate Institute for Brain Research and collaborating institutions analyzed data from nearly 300,000 participants in the All of Us Research Program to identify genetic traits associated with TRD.

Key Findings:

• Genetic Risk Factors for TRD: Individuals with a genetic predisposition for neuroticism, insomnia, and negative emotional temperament were more likely to develop TRD.
• Protective Genetic Traits: Higher genetic scores for educational attainment and cognitive function were linked to a lower likelihood of developing TRD.
• Consistent Across Populations: The results were replicated across different groups, reinforcing the role of these genetic factors in depression treatment outcomes.
• Potential for Improved Treatments: These insights highlight the need to integrate genetic and psychological factors into personalized treatment strategies for depression.

Why This Matters
TRD affects millions of people worldwide, leading to prolonged suffering, increased healthcare costs, and higher suicide risk. While depression treatments work for many, about one-third of patients experience TRD, making it crucial to understand why some individuals do not respond to standard therapies. This study suggests that genetic predispositions influence treatment resistance, paving the way for more targeted interventions.

Expert Quotes
"Our findings emphasize that TRD is not just an extension of major depressive disorder but may have distinct biological underpinnings," said Dr. Chun Chieh Fan, the study’s senior author. "Recognizing the role of genetic factors could help refine treatment approaches and improve outcomes for those who struggle with depression."

What’s Next?
The researchers hope that these findings will inspire further studies on integrating genetics with clinical and environmental factors to develop personalized treatment plans for individuals with depression. Future research may also explore how interventions targeting neuroticism and sleep patterns could help prevent or mitigate TRD.

About the Study
The study analyzed 292,663 participants from the All of Us Research Program, a nationwide initiative collecting diverse health and genetic data. The researchers examined 61 genetic traits across various domains, including personality, cognition, sleep, and psychiatric conditions, to identify their associations with TRD.
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For more information, access the full study in JAMA Psychiatry  here. 

Dr. Nicolas Crossley - March 4, 2025

"Psychosis, Social Determinants, and Neural Correlates:  Bridging Mental Health, Society, and the Brain"

William K. Warren, Jr.  Frontiers in Neuroscience Lecture 
12:00 pm - 1:00 pm     Program in the LPCH auditorium  

Dr. Crossley is an academic psychiatrist with an interest in understanding brain function in health and disease through neuroimaging, particularly in psychotic disorders. After completing his training in the UK, he returned to his native Chile in 2016 where he continues his imaging research, including on treatment resistance and the 22q11 deletion syndrome. In 2017 he established the ANDES network, a collaboration of Latin American researchers in psychosis, comprising members from six Latin American countries. The focus of this network has been the impact of the social determinants of health—such as poverty, violence, and gender inequality—on the clinical trajectories of psychosis and brain structure and function, issues that are particularly pertinent to the Global South.

Learning objectives:  

1. Identify the importance of specific social determinants of health in the trajectories of psychosis.
2. Identify the impact of specific social determinants of health in brain anatomy.
3. Identify the importance of including the social determinants in studies developing brain biomarkers in psychosis.

For Physicians: Saint Francis Health System is accredited by the Oklahoma State Medical Association to provide continuing medical education for physicians.
Saint Francis Health System designates this live activity for a maximum of 1 AMA PRA Category 1 Credit(s)™.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.
 
For Psychologists: The Oklahoma State Board of Examiners of Psychologists, the American Psychological Association and the Oklahoma Psychological Association recognize AMA PRA Category 1  credit™. Saint Francis Health System is accredited by the OSMA
 
For Social Workers: The Oklahoma State Board of Licensed Social Workers has approved this event for 1 hour Category 1 Clinical. (20250007)

For CADCs and LADCs Saint Francis Health System is accredited as a provider of continuing education programs for CADCs and LADCs through the Oklahoma Board of Licensed Alcohol and Drug Counselors.      (1 hour)
 
The LPC/LMFT This event as been approved by the State Board of Behavioral Health Licensure (BBHL) for 1 hour of CE.  

For questions , email:  Ally Deatherage at [email protected]