Genetic imaging study with [Tc-99m] TRODAT-1 SPECT in adolescents with ADHD using OROS-methylphenidate

Akay, Aynur Pekcanlar; Kaya, Gamze Çapa; Köse, Samet; Yazıcıoğlu, Çiğdem Eresen; Erkuran, Handan Özek; Güney, Sevay Alşen; Oğuz, Kaya; Keskin, Duygu; Baykara, Burak; Emiroğlu, Neslihan İnal; Eren, Mine Şencan; Kızıldağ, Sefa; Ertay, Türkan; Özsoylu, Dua; Miral, Süha; Durak, Hatice; Gönül, Ali Saffet; Rohde, Luís Augusto

doi:10.1016/j.pnpbp.2018.04.008

Cited by 9 publications

(9 citation statements)

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“…Therapy with MPH lead to reduced striatal DAT availability (and ADHD core symptomatology). In the latter study, a subgroup comparison showed that the patients with significantly reduced ADHD core symptomatology by MPH, also showed a greater decrease in DAT availability (16). However, all patients included in our studies received long-term MPH treatment, which has been discussed to lead to an upregulation of DAT in adaption to long-term MPH treatment (10).…”

Section: Discussionmentioning

confidence: 71%

“…Responsivity of the striatal dopamine system to methylphenidatea within-subject I-123-ß-CIT-SPECT study in adolescent males with ADHD adolescent ADHD. Results from both studies indicate that MPH treatment leads to a decrease in DAT availability in response to MPH treatment (16). However, only one of the two studies found a relation to clinical symptoms based on a subgroup analysis.…”

Section: Introductionmentioning

confidence: 90%

“…Although the dopaminergic system undergoes substantial development changes (14,15), to our knowledge only two studies investigating the effect of MPH therapy on DAT have been published in Responsivity of the striatal dopamine system to methylphenidatea within-subject I-123-ß-CIT-SPECT study in adolescent males with ADHD adolescent ADHD. Results from both studies indicate that MPH treatment leads to a decrease in DAT availability in response to MPH treatment (16). However, only one of the two studies found a relation to clinical symptoms based on a subgroup analysis.…”

Section: Introductionmentioning

confidence: 90%

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Responsivity of the striatal dopamine system to methylphenidate – a within-subject I-123-ß-CIT-SPECT study in children and adolescents with Attention-Deficit/Hyperactivity Disorder

Aster

Romanos

Walitza

et al. 2021

Preprint

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BackgroundMethylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight in how effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning.MethodsThirteen adolescent male patients (9-16 years) with diagnosis of ADHD according to DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-ß-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in on and off-MPH status balanced for order across participants. A virtual-reality continuous-performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH.ResultsOn-MPH status was associated with a highly significant decrease (−27,6%) of striatal DAT BP as compared to off-MPH (t=4.93, p<0.001). More pronounced decrease in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r=0.68, p=0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings off-MPH (Pearson r=0.56, p=0.04). In further exploratory analysis in left vs. right striatal sub-regions, stronger decrease in DAT BP in the right caudate nucleus was weakly associated with improved performance in the continuous-performance test (Pearson r= - 0.54, p=0.07).ConclusionOur findings corroborate previous reports from mainly adult samples that MPH reduces striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity. More speculatively, regional specific responsivity of DAT BP to MPH may reflect treatment response with respect to cognitive functioning. However, implications from this small patient sample should be treated with caution and warrant replication.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 90%

See 1 more Smart Citation

Responsivity of the striatal dopamine system to methylphenidate – a within-subject I-123-ß-CIT-SPECT study in children and adolescents with Attention-Deficit/Hyperactivity Disorder

Aster

Romanos

Walitza

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Therapy with MPH leads to reduced striatal DAT availability (and ADHD core symptomatology). In the latter study, a subgroup comparison showed that the patients with significantly reduced ADHD core symptomatology by MPH also showed a greater decrease in DAT availability ( 16 ). However, all patients included in our studies received long-term MPH treatment, which has been discussed to lead to an upregulation of DAT in adaption to long-term MPH treatment ( 10 ).…”

Section: Discussionmentioning

confidence: 96%

“…Although the dopaminergic system undergoes substantial development changes ( 14 , 15 ), to our knowledge, only two studies investigating the effect of MPH therapy on DAT have been published in adolescent ADHD. Results from both studies indicate that MPH treatment leads to a decrease in DAT availability in response to MPH treatment ( 16 ). However, only one of the two studies found a relation to clinical symptoms based on a subgroup analysis.…”

Section: Introductionmentioning

confidence: 99%

Responsivity of the Striatal Dopamine System to Methylphenidate—A Within-Subject I-123-β-CIT-SPECT Study in Male Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

et al. 2022

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Background:Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight on how the effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning.MethodsThirteen adolescent male patients (9–16 years) with a diagnosis of ADHD according to the DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-β-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in an on- and off-MPH status balanced for order across participants. A virtual reality continuous performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH.ResultsOn-MPH status was associated with a highly significant change (−29.9%) of striatal DAT BP as compared to off-MPH (t = −4.12, p = 0.002). A more pronounced change in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r = 0.68, p = 0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings (Pearson r = 0.56, p = 0.04).ConclusionOur findings corroborate previous reports from mainly adult samples that MPH changes striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity.

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Molecular Imaging Studies in Stimulant Addiction: A Cross-Species Perspective

Jones¹,

Russell²,

Dalley³

2020

PET and SPECT in Psychiatry

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Genetic imaging study with [Tc-99m] TRODAT-1 SPECT in adolescents with ADHD using OROS-methylphenidate

Cited by 9 publications

References 38 publications

Responsivity of the striatal dopamine system to methylphenidate – a within-subject I-123-ß-CIT-SPECT study in children and adolescents with Attention-Deficit/Hyperactivity Disorder

Responsivity of the striatal dopamine system to methylphenidate – a within-subject I-123-ß-CIT-SPECT study in children and adolescents with Attention-Deficit/Hyperactivity Disorder

Responsivity of the Striatal Dopamine System to Methylphenidate—A Within-Subject I-123-β-CIT-SPECT Study in Male Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Molecular Imaging Studies in Stimulant Addiction: A Cross-Species Perspective

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