Persistence and longitudinal development of attentiondeficit/hyperactivity disorder in consideration of family genetic determinants
Final Report Abstract
The main goal of SP1 (child and adolescent psychiatry) was the recruitment of child and adolescent ADHD patients and their parents in close collaboration with SP2 (recruitment of adult ADHD). SP1 thus referred participants to SP6-8 and provided biomaterial for SP3. The recruited sample is followed-up in an ongoing longitudinal study that furthermore harbors a katamnestic electrophysiological examination. Further spin-off investigations were performed on biomarkers of ADHD. Recruitment: Within the study period we have screened and assessed more than 1700 individuals of 454 patient families. Of these we thoroughly phenotyped and provided DNA from 965 individuals of 291 families with one or more affected siblings. Further 10 large multiplex families (226 individuals) with high density of ADHD across three or more generations were investigated in cooperation with SP 2. SP1 facilitated psychophysiological, electrophysiological, functional imaging and genetic investigations in the respective projects. We furthermore recruited 45 families (139 individuals) of children with Deletion syndrome 22q11.2, a natural genetic model of ADHD. Spin-off investigations on biomarkers in ADHD resulted in various publications. Longitudinal study: In an ongoing longitudinal study we have, to date, re-examined 69 patients (43 female, 83 male) with a diagnosis of childhood ADHD. The mean catamnestic period between measurements was 3.3 years, with participants aged 13.66 years at t1 and 17.0 y at t2. Remission rates were at 20%, with 15 patients changing subtype between the measurement points. In 79 % of cases, the diagnosis of ADHD could also be confirmed in the extended family, and 57 % had at least one sibling with the disorder. The most prevalent co-morbidities found in this sample were conduct disorders, oppositional-defiant disorder, affective and tic disorders. We further embedded a katamnestic electrophysiological investigation on those patients that were referred to SP8. A total of 80 patients (n=36, mean age 10.8 y, on stimulant medication; n=44, 9.7 y without medication) and 41 controls (10.7 y) were examined at two time points assessing response inhibition, working memory and sensory gating. Preliminary results from the first measurement indicate a reduced auditory gating capacity in unmedicated ADHD patients (p = 0.046) highlighting difficulties with the suppression of irrelevant environmental stimuli. A significantly increased general response time variability in those patients without medication points to deficits in state control. Biomarkers: Investigations on biomarkers in ADHD pertained to structural and functional imaging studies, olfactory function and peripheral gene expression analyses resulting in several high-ranking publications. Future studies further investigating the potential of multivariate biomarkers are warranted.
Publications
- (2007) Does methylphenidate cause a cytogenetic effect in children with attention deficit hyperactivity disorder? Environ Health Perspect 115: 936-940
Walitza S, Werner B, Romanos M, Warnke A, Gerlach M, Stopper H
(See online at https://doi.org/10.1289/ehp.9866) - (2008) Improved odor sensitivity in attentiondeficit/hyperactivity disorder. Biol Psychiatry 64: 938-940
Romanos M, Renner TJ, Schecklmann M, Hummel B, Roos M, von Mering C, Pauli P, Reichmann H, Warnke A, Gerlach M
(See online at https://doi.org/10.1016/j.biopsych.2008.08.013) - (2009) No elevated genomic damage in children and adolescents with attention deficit/hyperactivity disorder after methylphenidate therapy. Toxicol Lett 184: 38-43
Walitza S, Kampf K, Artamonov N, Romanos M, Gnana Oli R, Wirth S, Warnke A, Gerlach M, Stopper H
(See online at https://doi.org/10.1016/j.toxlet.2008.10.011) - (2010) Association of attention-deficit/hyperactivity disorder and atopic eczema modified by sleep disturbance in a large population-based sample. J Epidemiol Community Health 64: 269-273
Romanos M, Gerlach M, Warnke A, Schmitt J
(See online at https://dx.doi.org/10.1136/jech.2009.093534) - (2010) Prefrontal oxygenation during working memory in ADHD. J Psychiatr Res 44: 621-628
Schecklmann M, Romanos M, Bretscher F, Plichta MM, Warnke A, Fallgatter AJ
(See online at https://doi.org/10.1016/j.jpsychires.2009.11.018) - (2010) Structural abnormality of the substantia nigra in children with attentiondeficit hyperactivity disorder. J Psychiatry Neurosci 35: 55-58
Romanos M, Weise D, Schliesser M, Schecklmann M, Loffler J, Warnke A, Gerlach M, Classen J, Mehler-Wex C
(See online at https://dx.doi.org/10.1503%2Fjpn.090044) - (2011) Altered frontal and temporal brain function during olfactory stimulation in adult attention-deficit/hyperactivity disorder. Neuropsychobiology 63: 66-76
Schecklmann M, Schenk E, Maisch A, Kreiker S, Jacob C, Warnke A, Gerlach M, Fallgatter AJ, Romanos M
(See online at https://doi.org/10.1159/000323448) - (2011) Effects of methylphenidate on olfaction and frontal and temporal brain oxygenation in children with ADHD. J Psychiatr Res 45: 1463-1470
Schecklmann M, Schaldecker M, Aucktor S, Brast J, Kirchgassner K, Muhlberger A, Warnke A, Gerlach M, Fallgatter AJ, Romanos M
(See online at https://doi.org/10.1016/j.jpsychires.2011.05.011) - (2011) Olfactory deficits in deletion syndrome 22q11.2. Schizophr Res 129: 220-221
Romanos M, Schecklmann M, Kraus K, Fallgatter AJ, Warnke A, Lesch KP, Gerlach M
(See online at https://psycnet.apa.org/doi/10.1016/j.schres.2010.12.015)
