Resting-state networks and neurometabolites in children with ADHD after 10 weeks of treatment with micronutrients: results of a randomised placebo-controlled trial

ABSTRACT

Children with attention-deficit/hyperactivity disorder (ADHD) show significant abnormalities on MR imaging in network communication and connectivity. The prefrontal-striatal-cerebella circuitry, involved in attention is particularly disrupted. Neurometabolites, the biochemical structures that support neurological structural integrity, particularly in the prefrontal cortex and striatum are associated with symptoms. This study aimed to explore changes in neurometabolite levels through treatment with vitamins and minerals (micronutrients), hypothesising that treatment would impact neural circuitry and correspond to a reduction in symptoms. Twenty-seven non-medicated children (M = 10.75 years) with DSM5 diagnosed ADHD were randomised to receive daily micronutrients or placebo for 10 weeks. Main outcome measures included the Clinical Global Impression-Improvement Scale and ADHD-RS-IV Clinician Ratings of ADHD symptoms. Magnetic resonance spectroscopy of the bilateral pre-frontal cortex and bilateral striatum, resting state fMRI and structural images were acquired 1 week pre-treatment, and in the last week of intervention. Results did not show any significant differences in the measured brain metrics and the levels of neurometabolites between treatment and placebo groups after ten weeks of treatment with micronutrients. In the treatment group there was a trend for: decreased choline in the striatum; decreased glutamate in the prefrontal cortex; increased grey matter in the anterior thalamus; increased white matter in the fornix and improved network integrity of the default mode network, dorsal attention network and frontal executive network. The small sample size of the current study limits results, future studies with higher power are warranted to explore any association between micronutrient treatment and neurological changes.

KEYWORDS:

• ADHD
• magnetic resonance spectroscopy
• fMRI
• micronutrient
• vitamin
• treatment

Acknowledgements

Thanks to the University of Calgary, the GAMA Foundation, Vic Davis Memorial Trust (E5672), UC Foundation, the Department of Psychology, University of Canterbury for ongoing research support, Canterbury Medical Research Foundation, and a PhD Scholarship awarded through Gravida to support Kathryn Darling. Thanks also to David Pugh-Williams for assistance with randomisation; Leona Manna for providing cultural consultation; Lucy Kioa, Kate Harris, Anna Lee, Joanna Lothian, Hahna Retallick-Brown, Dr Brigette Gorman, Dr Heather Gordon and Molly Harvie for assistance with data collection and entry; MRI technologists at Pacific Radiology for neuroimaging; the Canterbury District Health Board, Whakatata House and other private referrers and all the families who participated. We thank Hardy Nutritionals for providing the micronutrient formula and matching placebo for free.

Ethical approval was obtained from the Human Ethics Committee of the University of Canterbury and the Southern Health and Disability Ethics Committee.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Processed MR data is available at 10.6084/m9.figshare.7144664

Notes on contributors

Nadia Borlase is a Research Associate at the New Zealand Brain Research Institute and is responsible for processing and analysing neuroimages. Nadia is primarily involved with neurodevelopmental research and uses multiple imaging modalities to identify associations between the brain and neurodevelopmental outcomes.

Tracy R. Melzer is the MRI Research Manager at the New Zealand Brain Research Institute and oversees all imaging research. Tracy is involved in a wide range of neurological research, including child development, mild traumatic brain injury, post-traumatic stress disorder, neurodegenerative diseases, and more. Tracy is also a Senior Research Fellow in the Department of Medicine, where his primary focus is on the development and application of Magnetic Resonance Imaging (MRI) techniques to advance our understanding of cognitive decline in Parkinson’s disease.

Matthew J.F. Eggleston is a Child and Adolescent Psychiatrist at the Child and Family North Community and Outreach Team, Canterbury District Health Board, New Zealand.

Kathryn A. Darling is a PhD student in the Mental Health and Nutrition Research Group and the University of Canterbury, Christchurch. She completed a Bachelor of Science with Honours from the University of Canterbury and is currently training to be a clinical psychologist.

Julia J. Rucklidge is a Professor of Clinical Psychology at the University of Canterbury in Christchurch, NZ. Her interests in nutrition and mental illness grew out of her own research showing poor outcomes for children with significant psychiatric illness despite receiving conventional treatments for their conditions. In the last decade, she and her lab has been running clinical trials investigating the role of broad-spectrum micronutrients in the expression of mental illness, specifically ADHD, mood disorders, anxiety and stress associated with the Canterbury earthquakes.

Additional information

Funding

This work was supported by the University of Calgary, the GAMA Foundation, Vic Davis Memorial Trust [grant number E5672], UC Foundation, Canterbury Medical Research Foundation, and a PhD Scholarship awarded through Gravida to support Kathryn Darling.