title: Distinct effects of childhood ADHD and cannabis use on brain functional architecture in young adults.
abstract: One of the most salient long-term implications of a childhood diagnosis of ADHD is an increased risk for substance use, abuse, or dependence in adolescence and adulthood. The extent to which cannabis use affects ADHD-related alterations in brain functional organization is unknown, however. To address this research gap, we recruited a sample of 75 individuals aged 21-25 years with and without a childhood diagnosis of ADHD Combined Type, who were either frequent users or non-users of cannabis. These participants have been followed longitudinally since age 7-9.9 years as part of a large multi-site longitudinal study of ADHD, the Multimodal Treatment Study of Children with ADHD (MTA). We examined task-independent intrinsic functional connectivity (iFC) within 9 functional networks using a 2 × 2 design, which compared four groups of participants: (1) individuals with a childhood diagnosis of ADHD who currently use cannabis (n= 23); (2) individuals with ADHD who do not currently use cannabis (n= 22); (3) comparisons who currently use cannabis (n= 15); and (4) comparisons who do not currently use cannabis (n= 15). The main effects of childhood ADHD were primarily weakened iFC in networks supporting executive function and somatomotor control. Contrary to expectations, effects of cannabis use were distinct from those of diagnostic group and no interactions were observed. Exploratory brain-behavior analyses suggested that ADHD-related effects were primarily linked with poorer neurocognitive performance. Deficits in the integrity of functional networks supporting executive function and somatomotor control are consistent with the phenotypic and neurocognitive features of ADHD. Our data suggest that cannabis use does not exacerbate ADHD-related alterations, but this finding awaits replication in a larger sample. Longitudinal neuroimaging studies are urgently required to delineate the neurodevelopmental cascade that culminates in positive and negative outcomes for those diagnosed with ADHD in childhood.
authors.affiliation: School of Psychology, Trinity College Dublin, Dublin, Ireland; Department of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Center for Neurodevelopmental Disorders, Child Study Center, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Clare
authors.initials: C
authors.lastname: Kelly
authors.affiliation: Center for Neurodevelopmental Disorders, Child Study Center, New York University Langone Medical Center, New York, NY, USA; Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Castellanos
authors.affiliation: Center for Neurodevelopmental Disorders, Child Study Center, New York University Langone Medical Center, New York, NY, USA; National Adoption & Fostering Team, Michael Rutter Center, Maudsley Hospital, London, UK.
authors.forename: Olivia
authors.initials: O
authors.lastname: Tomaselli
authors.affiliation: University of Wisconsin-Milwaukee, Psychology Department, 2441 E. Hartford Ave, Milwaukee, WI, USA.
authors.forename: Krista
authors.initials: K
authors.lastname: Lisdahl
authors.affiliation: Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML10006 Cincinnati, OH, USA.
authors.forename: Leanne
authors.initials: L
authors.lastname: Tamm
authors.affiliation: Center for Human Development, University of California, San Diego, La Jolla, CA, USA; Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Jernigan
authors.affiliation: Center for Human Development, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Newman
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Jeffery N
authors.initials: JN
authors.lastname: Epstein
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Brooke S G
authors.initials: BS
authors.lastname: Molina
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Laurence L
authors.initials: LL
authors.lastname: Greenhill
authors.affiliation: Department of Psychiatry and Human Behavior, School of Medicine, University of California Irvine, Irvine, CA, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.affiliation: Department of Psychology, University of California-Berkeley, Berkeley, CA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hinshaw
authors.affiliation: Child Development Center, University of California, Irvine, Irvine, CA, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Swanson
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D002188:Cannabis / Q000009:adverse effects; D063132:Connectome / Q000379:methods*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D011597:Psychomotor Performance / Q000502:physiology*; D055815:Young Adult
keywords: ADHD; Cannabis; Functional connectivity; Marijuana; Neurocognitive; fMRI