Mind and Body in ADHD: somatic comorbidity
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1 Mind and Body in ADHD: somatic comorbidity Jan Haavik K.G. Jebsen Centre for Research on Neuropsychiatric Disorders Department of Biomedicine Haukeland University Hospital University of Bergen, Norway & UMC St. Radboud, Nijmegen, NL UKAAN conference Mermaid Conference and Events Centre 1 IMPACT Sept
2 Agenda Background and terminology; Comorbid" can be medical conditions existing simultaneously but independently; or can indicate related conditions ADHD symptoms are not specific: are observed in several somatic & psychiatric conditions: ADHD considered an exclusion diagnosis misdiagnosis or missed diagnoses? Evidence from Clinical studies Epidemiology Animal models (e.g. SHR rats) Biomarkers, including DNA variants Shared mechanisms? Implications for diagnosis or treatment
3 Literature data (Pubmed: August 2014) ADHD and (somatic) comorbidity 3357 references (40 adult, 11 reviews.) (Adult) ADHD and endocrine disorders ADHD and obesity: 287 ADHD and thyroid: 128 ADHD and corticoid: 113 (Adult) ADHD and neurological disorders (Sleep disorders: )852 Epilepsy: 678 Migraine: 82 (Adult) ADHD and other disorders Birth defects: 1339 Asthma: 239 Hypertension: 157 Autoimmunity: 61 Rheumatoid arthritis: 15
4 Literature data (Adult) ADHD and endocrine disorders ADHD and obesity ADHD and thyroid ADHD and corticoid (Adult) ADHD and neurological disorders Sleep disorders: Strong evidence, causality? Epilepsy: Migraine: Strong associations also reported for bipolar disorders (Adult) ADHD and other disorders Birth defects: Strong evidence, causality? Asthma: Some evidence, confounders? Hypertension: Autoimmunity: Some evidence, confounders? Rheumatoid arthritis: Some evidence, confounders?
5
6 Checklists / systematic interviews, examinations and laboratory tests to determine: Are symptoms better explained by other psychiatric or somatic conditions? Does the patient suffer from concurrent medical conditions (psychiatric or somatic comorbidity)? Causally related to ADHD or unrelated? What are the implications of these conditions for future management/ treatment? Cardiovascular diseases Endocrine diseases Neurological diseases
7 Norwegian clinical sample (572 adult ADHD patients): O.R.:
8 Selected Norwegian health registries Central health registries 8 Since Responsible 1. The Norwegian Cause of DEATH Registry 1951 NIPH 2. The Medical BIRTH Registry of Norway 1967 NIPH 3. The Norw. CARDIOVASCULAR Registry 2010 NIPH 4. The Norw. Surveill. Syst.for COMMUNICABLE DISEASES 1977 NIPH 5. The TUBERCULOSIS Registry 1962 NIPH 6. The Childhood VACCINATION Registry 1998 NIPH 9. The Norwegian PRESCRIPTION Database 2004 NIPH 11. The Norwegian CANCER Registry 1952 Helse Sør-Øst 12. The Norwegian PATIENT Registry 2007 Health dir 15. The Health Registry of the Nor. Off.of DEFENCE 2005 Defence ministry
9 Norwegian registry data: ADHD cases O.R.:
10
11 Norwegian clinical sample: 594 ADHD patients O.R.:
12 Prevalence of asthma Control group (n = 719) Males Females 9.2 % 12.7 % ADHD group (n = 594) Males Females 18.2 % 30.9 % 12
13 ADHD and self-reported asthma Clinical study logistic regression (OR) Unadjusted : Adjusted for : + + age gender education 2.55 anxiety/depression bipolar disorder Possible confounders: Smoking, other co-occurring conditions. Ongoing follow-up studies: Adjusting for serum cotinine levels. 13
14 Norwegian registry data: (population of 4. 6 million) O.R.:
15 Drug treatment females males 15
16 Age groups 16
17 Sleep disturbances frequently reported by children and adults with ADHD Hyposomnia, hypersomina, parasomnias May be causally related to ADHD symptoms, endocrine disturbances, obesity, hypertension etc. Implications for treatment Bergen study: Detailed sleep data from ~500 adult ADHD patients and controls, 18 questions, based on Pittsburgh Sleep Quality Index Bergen Insomnia Scale (ms. in prep.) Self-reported hours of sleep
18 Ongoing studies: Maternal health, ADHD risk & comorbid disorders:
19 ADHD cases Norwegians born : N = 48,396 dispensed central stimulants (CS) or atomoxetine , age 4 years excluded if narcolepsy 4 17 years (children); N = 27, years (adults); N = 21,038 Controls All remaining individuals in the MBRN born and surviving 4 first years N = 2,326,420 Young control group: Born > 1985 Adult control group: Born < 1995
20 Gestational age and birth weight (Instanes, Halmøy, Haavik & Klungsøyr, in prep.) Gestational age distribution (%) ADHD cases and control population 30 Birth weight distribution (%) ADHD cases and control population ADHD Ktr
21 Biomarkers can reveal shared risk factors and mechanisms: Genomics Polygenic risk scores Metabolomics Proteomics Cross-Disorder Group of the PGC. Nature genetics Genome wide studies: Shared polygenic contributions for many psychiatric and somatic disorders/diseases Some serum biomarkers, including immunological markers have indicated autoimmune mechanisms in ADHD
22 Haavik et al.,
23 Conclusions & Implications for diagnosis and treatment: Detailed psychiatric & somatic assessments needed for differential diagnosis to reveal comorbid conditions Biomarkers can reveal shared etiopathogenic pathways Overlapping polygenic contributions to many psychiatric and somatic disorders/diseases Some serum biomarkers, including immunological markers have indicted autoimmune mechanisms in ADHD Repositioning of previously drugs therapies are being investigated in ADHD More translational / cross disciplinary research is needed
24 K.G. Jebsen Centre for Research on Neuropsychiatric Disorders Patient recruitment and clinical studies Biostatistics & epidemiology Norwegian medical birth registry von Plessen) Families Fasmer/Ødegaard/ Haavik Knappskog/Johansson (2.3 million records): Klungsøyr Children (Lundervold/ Molecular genetics BioBanks: Norwegian ADHD Patient Registry & Biobank+others: 5000 clinical records 2000 DNA samples 1000 serum samples Functional and Molecular studies of Candidate genes Bramham/Martinez/Haavik Brain imaging Plessen/Hugdahl/Eichele Neuropsychology Lundervold Adults Fasmer/Ødegaard/ Haavik National and international collaboration: HUNT study & biobank, IMpACT, International ADHD molecular genetics network Toxicology/ pharmacological chaperones Martinez/Haavik
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