The Amygdala's Neurochemical Ratios after 12 Weeks Administration of 20 mg Long-acting Methylphenidate in Children with Attention Deficit and Hyperactivity Disorder: A Pilot Study Using1H Magnetic Resonance Spectroscopy
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OBJECTIVE: Recent pediatric studies have suggested a correlation between decreased amygdala volume and attention deficit and hyperactivity disorder (ADHD) symptoms, including the emotional dysregulation. To investigate the hypothesis that medication treatment of ADHD specifically improves amygdala function, we used (1)H magnetic resonance spectroscopy (MRS) to study the effect of 12 weeks of treatment with daily 20 mg long-acting methylphenidate on the Glu/Cr, NAA/Cr, Cho/Cr, and mI/Cr ratios in the amygdala of medication-naïve children with ADHD. METHODS: This was a prospective study, using a pre- and post-test design, on a single group of 21 children (average age 8.52 years, 17 males and 4 females) diagnosed with ADHD. Low Time Echo MRS scans sampled voxels of interest (1.5×1.5×2.0) from both the right and left amygdala. RESULTS: There was significant clinical improvement after 12 weeks of treatment with 20 mg long-acting methylphenidate. On 1H MRS, there were no statistical significant differences of NAA/Cr ratio, Cho/Cr ratio, mI/Cr ratio before and after 12 weeks administration of 20 mg long-acting methylphenidate both in the right and left amygdala. In addition, Glu/Cr ratio decreased 14.1% in the right amygdala (p=0.029) and 11.4% in the left amygdala (p=0.008). Standardized mean effect sizes ranged from 0.14-0.32. CONCLUSION: The findings are consistent with the possibility that hyperglutamatergic processes in the amygdale are related to the hyperactive-impulsive symptoms of ADHD.
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The normalization effects of stimulants could also modulate frontolimbic abnormalities.
“the normalization effects of stimulants could also modulate the frontolimbic abnormalities (Wiguna, Guerrero, Wibisono, & Sastroasmoro, 2014).”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Wiguna, Guerrero, Wibisono, & Sastroasmoro, 2014
The Results report reduced glutamate-to-creatine ratios in both amygdalae after 12 weeks of methylphenidate, and the Introduction discusses prefrontal–limbic abnormalities in children with ADHD. But the study measured the amygdala, not frontolimbic circuitry, and had no healthy control group to establish normalization (Discussion). It supports a possible limbic effect, not the broader normalization claim. (LLM, conf=0.82)
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- Authors
- Wiguna, T., Guerrero, A. P. S., Wibisono, S., & Sastroasmoro, S.
- Affiliations
- University of Indonesia (ID)
- University of Hawaiʻi at Mānoa (US)
- Corresponding author
- Wiguna, Tjhin
- Venue
- Clinical Psychopharmacology and Neuroscience
- Published
- 2014-08-28
- Volume
- 12
- Issue
- 2
- Pages
- 137-141
- ISSN
- 1738-1088 (ISSN-L)
- 2093-4327
- PMC
- PMC4153860
- OpenAlex
- W2033616733
- Cited by
- 17
- References
- 40
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Clinical Psychopharmacology and Neuroscience (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, methylphenidate, amygdala, glutamate, emotional dysregulation, children, ADHD medication, hyperactive-impulsive symptoms
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