Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder

Anouk Schrantee, C. Bouziane, E. E. Bron, S. Klein, M. A. Bottelier, J. J. S. Kooij, S. A. R. B. Rombouts, L. Reneman

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We here assessed the long-term modifying effects of age-of-first-stimulant treatment on the human brain and behavior. 81 male adult ADHD patients were stratified into three groups: 1) early stimulant treatment (EST; <16 years of age) 2) late stimulant treatment (LST: ≥23 years of age) and 3) stimulant treatment naive (STN; no history of stimulant treatment). We used pharmacological magnetic resonance imaging (phMRI) to assess the cerebral blood flow (CBF) response to an oral methylphenidate challenge (MPH, 0.5 mg/kg), as an indirect measure of dopamine function in fronto-striatal areas. In addition, mood and anxiety scores, and recreational drug use were assessed. Baseline ACC CBF was lower in the EST than the STN group (p = 0.03), although CBF response to MPH was similar between the three groups (p = 0.23). ADHD symptom severity was higher in the STN group compared to the other groups (p < 0.01). In addition, the EST group reported more depressive symptoms (p = 0.04), but not anxiety (p = 0.26), and less recreational drug use (p = 0.04). In line with extensive pre-clinical data, our data suggest that early, but not late, stimulant treatment long-lastingly affects the human brain and behavior, possibly indicating fundamental changes in the dopamine system.
Original languageEnglish
Pages (from-to)402-410
JournalBrain Imaging and Behavior
Volume12
Issue number2
DOIs
Publication statusPublished - 2018
Externally publishedYes

Cite this

Schrantee, Anouk ; Bouziane, C. ; Bron, E. E. ; Klein, S. ; Bottelier, M. A. ; Kooij, J. J. S. ; Rombouts, S. A. R. B. ; Reneman, L. / Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder. In: Brain Imaging and Behavior. 2018 ; Vol. 12, No. 2. pp. 402-410.
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abstract = "Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We here assessed the long-term modifying effects of age-of-first-stimulant treatment on the human brain and behavior. 81 male adult ADHD patients were stratified into three groups: 1) early stimulant treatment (EST; <16 years of age) 2) late stimulant treatment (LST: ≥23 years of age) and 3) stimulant treatment naive (STN; no history of stimulant treatment). We used pharmacological magnetic resonance imaging (phMRI) to assess the cerebral blood flow (CBF) response to an oral methylphenidate challenge (MPH, 0.5 mg/kg), as an indirect measure of dopamine function in fronto-striatal areas. In addition, mood and anxiety scores, and recreational drug use were assessed. Baseline ACC CBF was lower in the EST than the STN group (p = 0.03), although CBF response to MPH was similar between the three groups (p = 0.23). ADHD symptom severity was higher in the STN group compared to the other groups (p < 0.01). In addition, the EST group reported more depressive symptoms (p = 0.04), but not anxiety (p = 0.26), and less recreational drug use (p = 0.04). In line with extensive pre-clinical data, our data suggest that early, but not late, stimulant treatment long-lastingly affects the human brain and behavior, possibly indicating fundamental changes in the dopamine system.",
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Schrantee, A, Bouziane, C, Bron, EE, Klein, S, Bottelier, MA, Kooij, JJS, Rombouts, SARB & Reneman, L 2018, 'Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder' Brain Imaging and Behavior, vol. 12, no. 2, pp. 402-410. https://doi.org/10.1007/s11682-017-9707-x

Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder. / Schrantee, Anouk; Bouziane, C.; Bron, E. E.; Klein, S.; Bottelier, M. A.; Kooij, J. J. S.; Rombouts, S. A. R. B.; Reneman, L.

In: Brain Imaging and Behavior, Vol. 12, No. 2, 2018, p. 402-410.

Research output: Contribution to journal › Article › Academic › peer-review

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T1 - Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder

AU - Schrantee, Anouk

AU - Bouziane, C.

AU - Bron, E. E.

AU - Klein, S.

AU - Bottelier, M. A.

AU - Kooij, J. J. S.

AU - Rombouts, S. A. R. B.

AU - Reneman, L.

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N2 - Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We here assessed the long-term modifying effects of age-of-first-stimulant treatment on the human brain and behavior. 81 male adult ADHD patients were stratified into three groups: 1) early stimulant treatment (EST; <16 years of age) 2) late stimulant treatment (LST: ≥23 years of age) and 3) stimulant treatment naive (STN; no history of stimulant treatment). We used pharmacological magnetic resonance imaging (phMRI) to assess the cerebral blood flow (CBF) response to an oral methylphenidate challenge (MPH, 0.5 mg/kg), as an indirect measure of dopamine function in fronto-striatal areas. In addition, mood and anxiety scores, and recreational drug use were assessed. Baseline ACC CBF was lower in the EST than the STN group (p = 0.03), although CBF response to MPH was similar between the three groups (p = 0.23). ADHD symptom severity was higher in the STN group compared to the other groups (p < 0.01). In addition, the EST group reported more depressive symptoms (p = 0.04), but not anxiety (p = 0.26), and less recreational drug use (p = 0.04). In line with extensive pre-clinical data, our data suggest that early, but not late, stimulant treatment long-lastingly affects the human brain and behavior, possibly indicating fundamental changes in the dopamine system.

AB - Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We here assessed the long-term modifying effects of age-of-first-stimulant treatment on the human brain and behavior. 81 male adult ADHD patients were stratified into three groups: 1) early stimulant treatment (EST; <16 years of age) 2) late stimulant treatment (LST: ≥23 years of age) and 3) stimulant treatment naive (STN; no history of stimulant treatment). We used pharmacological magnetic resonance imaging (phMRI) to assess the cerebral blood flow (CBF) response to an oral methylphenidate challenge (MPH, 0.5 mg/kg), as an indirect measure of dopamine function in fronto-striatal areas. In addition, mood and anxiety scores, and recreational drug use were assessed. Baseline ACC CBF was lower in the EST than the STN group (p = 0.03), although CBF response to MPH was similar between the three groups (p = 0.23). ADHD symptom severity was higher in the STN group compared to the other groups (p < 0.01). In addition, the EST group reported more depressive symptoms (p = 0.04), but not anxiety (p = 0.26), and less recreational drug use (p = 0.04). In line with extensive pre-clinical data, our data suggest that early, but not late, stimulant treatment long-lastingly affects the human brain and behavior, possibly indicating fundamental changes in the dopamine system.

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Schrantee A, Bouziane C, Bron EE, Klein S, Bottelier MA, Kooij JJS et al. Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder. Brain Imaging and Behavior. 2018;12(2):402-410. https://doi.org/10.1007/s11682-017-9707-x

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