title: Decreasing ADHD phenotypic heterogeneity: searching for neurobiological underpinnings of the restrictive inattentive phenotype.
abstract: During the process of developing the DSM-5, a new phenotype of ADHD was proposed-the ADHD restrictive inattentive presentation (ADHD-RI), describing subjects with high endorsement of inattentive symptoms and a low level of hyperactivity. However, this phenotype was not included in the DSM-5 because of the lack of robust neurobiological data. We aimed to assess the specific neurobiological underpinnings of individuals presenting ADHD-RI. We compared a sample of 301 subjects (101 ADHD-Combined; 50 ADHD-RI; 50 ADHD predominantly inattentive type and 100 typically developing subjects) aged 8-15 years, using a complete neuropsychological battery, molecular genetic data (DRD4 and DAT1 most studied polymorphisms) and functional MRI during a Go-No/Go task. Subjects with ADHD-RI had a significantly different neuropsychological profile compared with the other groups, including lower psychomotor speeds, longer reaction times and the worst overall performance in the global neurocognitive index. The proportion of subjects with the presence of DRD4-7 repeat allele was significantly higher in ADHD-RI. The fMRI data suggested that more attention-related posterior brain regions (especially temporo-occipital areas) are activated in ADHD-RI during both Go and No-Go cues compared to TD controls and ADHD predominantly inattentive type. ADHD-RI may represent a different phenotype than other types of ADHD. In addition, our results suggest that reducing the phenotypic heterogeneity may aid in the search for the neurobiological underpinnings of ADHD.
authors.affiliation: Child and Adolescent Psychiatry Department, Medical Faculty, Ege University, Izmir, Turkey. eyercan@hotmail.com.
authors.forename: Eyup Sabri
authors.initials: ES
authors.lastname: Ercan
authors.affiliation: Hospital for Psychiatry, Samsun, Turkey.
authors.forename: Serkan
authors.initials: S
authors.lastname: Suren
authors.affiliation: Children Hospital, Gaziantep, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Bacanlı
authors.affiliation: Child and Adolescent Psychiatry Department, Medical Faculty, Fırat University, Elazig, Turkey.
authors.forename: Kemal Utku
authors.initials: KU
authors.lastname: Yazici
authors.affiliation: Radiology Department, Medical Faculty, Ege University, Izmir, Turkey.
authors.forename: Cem
authors.initials: C
authors.lastname: Callı
authors.affiliation: Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Ozyurt
authors.affiliation: Medical Biology Department, Medical Faculty, Ege University, Izmir, Turkey.
authors.forename: Duygu
authors.initials: D
authors.lastname: Aygunes
authors.affiliation: Medical Biology Department, Medical Faculty, Ege University, Izmir, Turkey.
authors.forename: Buket
authors.initials: B
authors.lastname: Kosova
authors.affiliation: Brain Institute of Rio Grande do Sul (InsCer), PUCRS, Porto Alegre, Brazil.|School of Engineering, PUCRS, Porto Alegre, Brazil.
authors.forename: Alexandre Rosa
authors.initials: AR
authors.lastname: Franco
authors.affiliation: Department of Psychiatry, ADHD Outpatient Program, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.|National Institute of Developmental Psychiatry for Children and Adolescents, São Paulo, Brazil.
authors.forename: Luis Augusto
authors.initials: LA
authors.lastname: Rohde
mesh_terms: D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology; D001921:Brain / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D011930:Reaction Time
keywords: ADHD; Hyperactivity; Molecular genetics; Neuroimaging; Neuropsychology; Phenotype