Genome-wide analysis of emotional lability in adult attention deficit hyperactivity disorder (ADHD) |
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| Affiliation: | 1. Department of Psychiatry, Hospital Universitari Vall d''Hebron, Barcelona, Spain;2. Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain;3. Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain;4. Psychiatric Genetics Unit, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain;5. Grup de Coagulopaties Congènites, Banc de Sang i Teixits, Barcelona, Catalonia, Spain;1. PEPP-Montréal, Douglas Mental Health University Institute, Montréal, QC H4H 1R3, Canada;2. Psychiatry Department, Bellvitge University Hospital-IDIBELL, Barcelona, Spain;3. Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain;4. CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Madrid, Spain;5. Department of Psychiatry, McGill University, Montréal, Canada;7. Department of Biological and Biomedical Engineering, McGill University, Montréal, Canada;8. Brain Imaging Center, Douglas Mental Health University Institute, Montréal, Canada;1. Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Japan;2. Department of Medical Chemistry, Graduate School of Pharmacy, Meijo University, Nagoya, Japan;3. Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, Nagoya, Japan;4. Laboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan;5. Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan;1. Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China;2. Medical Psychological Institute of Central South University, Changsha, Hunan, PR China;3. China National Clinical Research Center on Mental Disorders (Xiangya), Changsha, Hunan, PR China;4. Department of Psychiatry, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China;1. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;2. Department of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;1. Department of Psychiatry, Stony Brook University, Stony Brook, NY, United States;2. Department of Radiology, Stony Brook University, Stony Brook, NY, United States;3. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States;4. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, United States;5. Department of Family, Population, & Preventive Medicine, Stony Brook University, Stony Brook, NY, United States;6. Department of Psychiatry, University of Texas Southwestern Medical Center, United States;7. Department of Psychiatry, College of Physicians and Surgeons, Columbia University and the New York Psychiatric Institute, United States;8. Department of Psychiatry, Harvard Medical School, United States;9. Department of Psychiatry, University of Michigan, United States;10. Department of Psychiatry, University of Pennsylvania, United States;11. Department of Psychiatry, Molecular Imaging and Neuropathology Division, Columbia University, New York, NY, United States;1. National Center for PTSD, VA Boston Healthcare System, Boston, MA, United States;2. Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States;3. Biomedical Genetics, Boston University School of Medicine, Boston, MA, United States;4. Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States;5. Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, United States;6. Department of Psychiatry, Harvard Medical School, Boston, MA, United States;7. Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, United States;8. Anthinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States;9. Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, AK, United States |
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| Abstract: | Emotional lability is strongly associated with Attention Deficit Hyperactivity Disorder (ADHD), represents a major source of impairment and predicts poor clinical outcome in ADHD. Given that no specific genes with a role in the co-occurrence of both conditions have been described, we conducted a GWAS of emotional lability in 563 adults with ADHD. Despite not reaching genome-wide significance, the results highlighted genes related with neurotransmission, cognitive function and a wide range of psychiatric disorders that have emotional lability as common clinical feature. By constructing polygenic risk scores on mood instability in the UK Biobank sample and assessing their association with emotional lability in our clinical dataset, we found suggestive evidence of common genetic variation contributing to emotional lability in general population and in clinically diagnosed ADHD. Although not conclusive, these tentative results are in agreement with previous studies that suggest emotion dysregulation as a transdiagnostic construct and highlight the need for further investigation to disentangle the genetic basis of mood instability in ADHD and co-occurring psychiatric disorders. |
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