Genetic Roots of Eight Major Psychiatric Disorders Shared

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Genetic Roots of Eight Major Psychiatric Disorders Shared

Revolutionary Treatment Targets Common Biological Pathways

February 2025 - In a discovery that could fundamentally change how we understand and treat mental illness, researchers at the University of North Carolina have identified the specific genetic mechanisms that underlie eight major psychiatric disorders, revealing why conditions like autism, ADHD, schizophrenia, and depression often occur together in the same individuals and families.

The groundbreaking study, published in Cell journal, analyzed nearly 18,000 genetic variants linked to autism spectrum disorder, attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorder, major depressive disorder, Tourette syndrome, obsessive-compulsive disorder, and anorexia nervosa. The research team, led by Dr. Hyejung Won and Dr. Patrick Sullivan from UNC's Department of Genetics, discovered that variants shared across multiple disorders operate differently from those specific to individual conditions.

"The proteins produced by these genes are also highly connected to other proteins," explains Dr. Won, associate professor in the Department of Genetics and the UNC Neuroscience Center. "Changes to these proteins in particular could ripple through the network, potentially causing widespread effects on the brain."

Understanding the 70% Overlap

The findings help explain a puzzling clinical observation: up to 70% of individuals diagnosed with autism or ADHD also have the other condition. Additionally, psychiatric disorders frequently cluster within families, suggesting a shared genetic foundation that researchers have now begun to map in detail.

Building on earlier research from 2019 that identified 109 genes linked to these eight disorders, the new study used advanced laboratory techniques to determine exactly how these genetic variants affect brain development. The team introduced genetic variants into precursor neurons to observe their impact during human brain development, identifying 683 genetic variants that significantly affected gene regulation.

The research revealed a crucial distinction between "pleiotropic" variants—those that affect multiple disorders—and "disorder-specific" variants that contribute to individual conditions. Pleiotropic variants were found to be more highly connected in protein networks, active across more types of brain cells, and involved in regulatory mechanisms that span multiple stages of brain development.

Transforming Treatment Approaches

The therapeutic implications could be revolutionary. Rather than developing separate treatments for each psychiatric disorder, researchers may now be able to target shared genetic pathways to address multiple conditions simultaneously.

"Pleiotropy was traditionally viewed as a challenge because it complicates the classification of psychiatric disorders," says Dr. Won. "However, if we can understand the genetic basis of pleiotropy, it might allow us to develop treatments targeting these shared genetic factors, which could then help treat multiple psychiatric disorders with a common therapy."

This approach could have enormous impact given that the World Health Organization estimates nearly 1 billion people worldwide live with some form of psychiatric condition. Current treatment often involves months or years of trial-and-error approaches, with many patients experiencing relapses and adverse effects.

The Promise of Precision Psychiatry

The research comes at a time of growing momentum in psychiatric genetics. Recent advances have enabled the development of polygenic risk scores (PRS) that estimate an individual's genetic susceptibility to various mental health conditions. However, experts note that current PRS tools are not yet ready for widespread clinical implementation.

A 2024 study of child and adolescent psychiatrists found that most clinicians believe PRS have limited clinical utility in their current form. Dr. Alexander Merner and colleagues interviewed 29 U.S.-based specialists, finding that "the majority indicated that PRS have limited clinical utility in their current form and are not ready for clinical implementation."

Despite these current limitations, researchers are optimistic about future applications. Recent research published in medRxiv demonstrated that patients with higher polygenic risk scores for psychiatric disorders may be more likely to experience suicidal thoughts when taking certain antidepressants, suggesting that genetic information could eventually guide treatment selection.

Breaking New Ground in Drug Development

The psychiatric drug development landscape is experiencing unprecedented activity. A systematic review published in December 2024 identified 89 pipeline drug trials in various phases, including treatments for schizophrenia, bipolar disorders, depression, anxiety, PTSD, and other conditions.

Notably, 2024 saw the FDA approval of Cobenfy, the first new schizophrenia medication in 30 years, which targets different brain chemical systems than previous treatments. The agency also approved Rejoyn, the first digital therapeutic for major depressive disorder, demonstrating the expanding toolkit available to mental health providers.

Addressing Global Mental Health Challenges

The timing of these scientific advances is crucial. According to 2024 data from the Centers for Disease Control and Prevention, nearly 25% of U.S. adults have a mental health condition, with almost 5% experiencing serious conditions that interfere with daily life. Among children under 17, approximately 1 in 7 has a mental or behavioral health condition.

Cost remains a significant barrier to care, with 10% of adults with mental illness being uninsured. Even among those with insurance, around 10% of adults and more than 8% of children have plans that don't cover mental health services. The shortage of mental health providers compounds these challenges, with an estimated 340 people for every mental health care provider in the United States.

The Road Ahead

While the UNC research represents a major breakthrough in understanding the genetic architecture of psychiatric disorders, translating these findings into clinical applications will require continued investment and research. The study's identification of shared genetic pathways opens new avenues for drug development, but researchers caution that the journey from discovery to treatment typically takes years or decades.

The research also highlights the complex interplay between genetics and environment in mental health. While genetic factors contribute significantly to psychiatric disorders, environmental influences and epigenetic mechanisms also play crucial roles, emphasizing the multifaceted nature of mental illness.

As the field moves forward, the integration of genetic insights with other biomarkers, environmental factors, and clinical observations may finally enable the precision medicine approach that has long been promised for psychiatry. The hope is that individuals suffering from mental health conditions will soon benefit from treatments that are not only more effective but also more precisely targeted to their specific biological profiles.

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SIDEBAR: A Parent's Guide to Early Recognition and Non-Drug Interventions

What Parents Should Watch For

If psychiatric conditions run in your family, research shows that genetics play a significant role in autism and ADHD risk. If you already have one child with autism spectrum disorder, you have a 20% chance of your next child developing autism. If you have more than one child with ASD, the odds are even higher.

Early Warning Signs to Monitor (Ages 0-3):

For Autism Spectrum Disorder:

• Delayed or absent speech development by 12-18 months
• Limited eye contact or social smiling
• Repetitive behaviors (hand flapping, rocking)
• Difficulty with changes in routine
• Unusual responses to sensory input (sound, touch, light)
• Lack of pretend play or pointing to show interest

For ADHD (symptoms typically emerge by age 4-7):

• Extreme difficulty sitting still or remaining calm
• Impulsive behavior that seems inappropriate for age
• Trouble focusing on tasks or play activities
• Excessive talking or interrupting others
• Difficulty waiting turns or following instructions

Important Note: According to scientific literature, 50% to 70% of children with autism also have ADHD, and mothers with ADHD have a two-and-a-half-times greater chance of having a child with autism.

Early Diagnostic Tools Available

Primary Screening Tests:

• M-CHAT-R/F (Modified Checklist for Autism in Toddlers, Revised): A 20-question screening tool for children 16-30 months that can be completed by parents and provides immediate results. This is the most recommended screening test
• Ages & Stages Questionnaire (ASQ-3): Developmental screening for children birth to 5½ years
• Vanderbilt ADHD Assessment Scales: For attention-deficit hyperactivity disorder screening

When to Screen: The American Academy of Pediatrics recommends developmental screening at 9, 18, and 24-month well-child visits, with specific autism screening at 18 and 24 months.

Professional Evaluations:

• ADOS-2 (Autism Diagnostic Observation Schedule): Gold standard diagnostic tool administered by specialists
• CARS (Childhood Autism Rating Scale): For comprehensive autism diagnosis
• Comprehensive psychological and developmental evaluations

Evidence-Based Non-Drug Treatments

For Children on the Autism Spectrum:

Applied Behavior Analysis (ABA): ABA is considered the most effective treatment with the strongest evidence base. It uses rewards to reinforce positive behaviors and teaches new skills through breaking complex behaviors into smaller tasks. Types include:

• Discrete Trial Training (DTT)
• Pivotal Response Training (PRT)
• Early Intensive Behavioral Intervention (EIBI)

Speech and Language Therapy: Helps improve understanding and use of speech and language. For non-verbal children, therapists use gestures, sign language, pictures, or electronic communication devices.

Occupational Therapy: Teaches skills for independent living including dressing, eating, bathing, and social interaction. Can include sensory integration therapy to help with overwhelming sensory input.

Physical Therapy: Used to improve gross motor skills and handle sensory integration issues, teaching skills like walking, sitting, coordination, and balance.

For Children with ADHD:

Behavioral Therapy:

• Parent training programs
• Social skills training
• Cognitive Behavioral Therapy (CBT) for older children
• Classroom behavior management strategies

Environmental Modifications:

• Structured routines and clear expectations
• Minimizing distractions in study areas
• Breaking tasks into smaller, manageable steps
• Regular exercise and outdoor time

Combined Approaches for Children with Both Conditions:

Developmental Approaches: DIR/Floortime model follows the child's interests to expand communication opportunities. Relationship Development Intervention (RDI) focuses on shared social interactions.

Social Skills Training:

• Social Stories that describe what to expect in social situations
• Structured social skills groups
• Peer interaction programs

Family-Centered Interventions:

• Parent training in behavioral techniques
• Family therapy to develop coping strategies
• Support groups for parents and siblings

Important Considerations

Early Intervention is Key: Research shows that early diagnosis and interventions, particularly during preschool years or before, are more likely to have major positive effects on symptoms and later skills.

Individual Treatment Plans: Because children with ASD and ADHD show different symptoms, treatment plans need to be personalized based on each child's specific needs, strengths, and challenges.

Insurance Coverage: Many insurance plans, including Medicaid, cover occupational therapy, speech therapy, and other evidence-based treatments for autism. Schools are also required by law to provide certain therapeutic services.

What to Avoid: Be cautious of non-evidence-based therapies including high-dose vitamins, electromagnetic therapy, or specialized diets that claim to "cure" autism. While some complementary therapies may be harmless, always discuss them with your healthcare provider first.

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Sources and Citations

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Additional Sources for Sidebar:

21. Cleveland Clinic. (2023, April 28). Does Autism Run in Families? Available at: https://health.clevelandclinic.org/are-siblings-at-greater-risk-of-autism

22. Abacus Therapies. (2025, January 14). Autism and Genetics: Which Parent Carries Autism Gene? Available at: https://abacustherapies.com/which-parent-carries-autism-gene/

23. Centers for Disease Control and Prevention. (2025, April 15). Screening for Autism Spectrum Disorder. Available at: https://www.cdc.gov/autism/diagnosis/index.html

24. Centers for Disease Control and Prevention. (2024, July 18). Treatment and Intervention for Autism Spectrum Disorder. Available at: https://www.cdc.gov/autism/treatment/index.html

25. UCLA Health. (2023, July 30). New genetic clues uncovered in largest study of families with multiple children with autism. Available at: https://www.uclahealth.org/news/release/new-genetic-clues-uncovered-largest-study-families-with

26. dos Santos, C.L., et al. (2024). Screening and diagnostic tools for autism spectrum disorder: Systematic review and meta-analysis. Clinics, 79, 100323. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC10951453/

27. Autism Speaks. M-CHAT-R Autism Screening Tool. Available at: https://www.autismspeaks.org/screen-your-child

28. WebMD. (2023, September 4). Therapies That Help With Autism. Available at: https://www.webmd.com/brain/autism/therapies-to-help-with-autism

29. HelpGuide. (2024, February 5). Autism Treatments, Interventions, and Therapy Options. Available at: https://www.helpguide.org/mental-health/autism/autism-treatments-therapies-interventions

30. Children's Hospital of Philadelphia. Evidence-based Treatment Options for Autism. Available at: https://www.chop.edu/news/evidence-based-treatment-options-autism

31. Effective Health Care Program. Therapies for Children With Autism Spectrum Disorder. Available at: https://effectivehealthcare.ahrq.gov/products/autism-update/consumer

32. Autism Science Foundation. (2023, June 7). Treatment Options. Available at: https://autismsciencefoundation.org/treatment-options/

33. Faraone, S.V., & Larsson, H. (2019). Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry, 26, 562-575. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6477889/

34. Marlow, M., et al. (2019). A review of screening tools for the identification of autism spectrum disorders and developmental delay in infants and young children. Autism Research, 12(2), 176-199. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/aur.2033