Abstract
Objective: The past decades have seen a surge in stimulant prescriptions for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulants acutely alleviate symptoms and cognitive deficits associated with ADHD by modulating striatal dopamine neurotransmission and induce therapeutic changes in brain activation patterns. Long-term functional changes after treatment are unknown, as long-term studies are scarce and have focused on brain structure. In this observational study (2009-2012), we investigated associations between lifetime stimulant treatment history and neural activity during reward processing. Methods: Participants fulfilling DSM-5 criteria for ADHD (N = 269) were classified according to stimulant treatment trajectory. Of those, 124 performed a monetary incentive delay task during magnetic resonance imaging, all in their nonmedicated state (nEARLY&INTENSE = 51; nLATE&MODERATE = 49; nEARLY&MODERATE = 9; nNAIVE = 15; mean age = 17.4 years; range, 10-26 years). Whole-brain analyses were performed with additional focus on the striatum, concentrating on the 2 largest treatment groups. Results: Compared to the late-and-moderate treatment group, the early-and-intense treatment group showed more activation in the supplementary motor area and dorsal anterior cingulate cortex (SMA/dACC) during reward outcome (cluster size = 8,696 mm3; PCLUSTER <.001). SMA/dACC activation of the control group fell in between the 2 treatment groups. Treatment history was not associated with striatal activation during reward processing. Conclusions: Our findings are compatible with previous reports of acute increases of SMA/dACC activity in individuals with ADHD after stimulant administration. Higher SMA/dACC activity may indicate that patients with a history of intensive stimulant treatment, but currently off medication, recruit brain regions for cognitive control and/or decisionmaking upon being rewarded. No striatal or structural changes were found.
| Original language | English |
|---|---|
| Pages (from-to) | e790-e796 |
| Number of pages | 7 |
| Journal | Journal of Clinical Psychiatry |
| Volume | 78 |
| Issue number | 7 |
| Early online date | 23 Aug 2017 |
| DOIs | |
| Publication status | Published - 2017 |
Funding
and Vrije Universiteit Amsterdam. Dr Franke 2009;48(5):484\u2013500.PubMed doi:10.1097/CHI.0b013e31819c23d0 is supported by a Vici personal grant from the 5. Frodl T, Skokauskas N. Meta-analysis of Netherlands Organization for Scientific Research structural MRI studies in children and adults (NWO, 016-130-669). The research of Drs Franke and with attention deficit hyperactivity disorder BuitelaaralsoreceivesfundingfromtheEuropean indicatestreatmenteffects.ActaPsychiatr Community\u2019s Seventh Framework Programme Scand. 2012;125(2):114\u2013126.PubMed doi:10.1111/j.1600-0447.2011.01786.x (FP7/2007\u20132013) under grant agreement no. 278948 Nakao T, Radua J, Rubia K, et al. Gray matter (TACTICS) and no. 602450 (IMAGEMEND). volume abnormalities in ADHD: voxel-based Role of the sponsor: Sponsors were not involved meta-analysis exploring the effects of age and in the design of the study; data collection, stimulant medication. Am J Psychiatry. management, analysis, or interpretation; or 2011;168(11):1154\u20131163.PubMed doi:10.1176/appi.ajp.2011.11020281 preparation, review, or approval of the manuscript. Shaw P, De Rossi P, Watson B, et al. Mapping Supplementarymaterial:Seeaccompanying the development of the basal ganglia in pages. children with attention-deficit/hyperactivity disorder. J\u00A0Am Acad Child Adolesc Psychiatry. Submitted: December 31, 2015; accepted November 3, 2016. Published online: June 20, 2017. Potential conflicts of interest: Dr Faraone received income, travel expenses, and/or research support from Arbor, Pfizer, Ironshore, Shire, Akili Interactive Laboratories, CogCubed, Alcobra, VAYA Pharma, Neurovance, Impax, and NeuroLifeSciences in the past year. With his institution, he has US patent US20130217707A1 (sodium-hydrogen exchange inhibitors in the treatment of ADHD). Dr Franke has received an educational speaking fee from Merz. Dr Buitelaar has in the past 3 years been a consultant to, member of advisory board of, and/or speaker for Janssen Cilag BV, Eli Lilly, Shire, Novartis, Lundbeck, and Servier. He is not an employee/stockholder of any of these companies and has no other financial or material support, including expert testimony, patents, or royalties. Dr Oosterlaan has received an unrestricted investigator grant from Shire. Dr Hoekstra has been a paid consultant to Shire and Eli Lilly. Drs Schweren, Groenman, von Rhein, Weeda, Luman, van Ewijk, Heslenfeld, and Hartman report no potential conflicts of interest. Funding/support: This work was supported by National Institutes of Health grant R01MH62873 (to Dr Faraone); Netherlands Organization for Scientific Research (NWO) Large Investment Grant 1750102007010, ZonMW Priority Medicines for Children Grant 113202005, ZonMW grant 60-60600-97-193, Brain & Cognition grants 433-09-242 and 056-13-015 (to Dr Buitelaar); and grants from Radboud University Nijmegen Medical Center, University Medical Center Groningen and Accare,
| Funders | Funder number |
|---|---|
| FP7/2007 | 168, 11):1154–1163, 602450, :10.1176/appi.ajp.2011.11020281, 278948 |
| National Institutes of Health | R01MH62873 |
| National Institutes of Health | |
| Eli Lilly and Company | |
| Pfizer | |
| Novartis | |
| M & T Bank | 433-09-242, 056-13-015 |
| M & T Bank | |
| Janssen Biotech | |
| Pharmavite | US20130217707A1 |
| Pharmavite | |
| Shire | |
| British Veterinary Association | |
| Seventh Framework Programme | 11, :114, 125, 126, :10.1111/j.1600-0447.2011.01786.x |
| Seventh Framework Programme | |
| Netherlands Organization for International Cooperation in Higher Education | |
| ZonMw | |
| Vrije Universiteit Amsterdam | 2, 500, :484, :10.1097/CHI.0b013e31819c23d0 |
| Vrije Universiteit Amsterdam | |
| Nederlandse Organisatie voor Wetenschappelijk Onderzoek | 016-130-669, 1750102007010 |
| Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
| Accare | |
| ArboraNano | |
| Lundbeckfonden | |
| Medicines for Malaria Venture | 60-60600-97-193, 113202005 |
| Medicines for Malaria Venture | |
| Universitair Medisch Centrum Groningen | |
| Radboud Universitair Medisch Centrum |
