Brain iron concentration in childhood ADHD: A systematic review of neuroimaging studies.

Iron deficiency may play a role in the pathophysiology of Attention Deficit/Hyperactivity Disorder (ADHD). Due to its preponderant function in monoamine catecholamine and myelin synthesis, brain iron concentration may be of primary interest in the investigation of iron dysregulation in ADHD. This study reviewed current evidence of brain iron abnormalities in children and adolescents with ADHD using magnetic resonance imaging methods, such as relaxometry and quantitative susceptibility mapping, to assess brain iron estimates. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed for studies published between January 1, 2008 and July 7, 2023 in Medline, Scopus and Proquest. Regions of interest, brain iron index values and phenotypical information were extracted from the relevant studies. Risk of bias was assessed using a modified version of the National Heart, Lung, and Blood Institute quality assessment tool. Seven cross-sectional studies comparing brain iron estimates in children with ADHD with neurotypical children were included. Significantly reduced brain iron content in medication-naïve children with ADHD was a consistent finding. Two studies found psychostimulant use may increase and normalize brain iron concentration in children with ADHD. The findings were consistent across the studies despite differing methodologies and may lay the early foundation for the recognition of a potential biomarker in ADHD, although longitudinal prospective neuroimaging studies using larger sample sizes are required. Lastly, the effects of iron supplementation on brain iron concentration in children with ADHD need to be elucidated.

Effects of dietary omega-3 intake on vigilant attention and resting-state functional connectivity in neurotypical children and adolescents.

BACKGROUND: Vigilant Attention (VA) is a critical cognitive function allowing to maintain our attention, particularly in redundant or intellectually unchallenging situations. Evidence has shown that, as the brain develops, VA abilities rapidly improve throughout childhood and adolescence. Dietary omega-3 polyunsaturated fats (PUFA), playing a critical role for proper brain development and maturation of cortical regions, may contribute to variations in VA abilities. OBJECTIVE: The present study investigated the effect of dietary omega-3 PUFA intake (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) on resting-state functional connectivity (rsFC) of a meta-analytically defined VA network in 24 neurotypical children and adolescents (7.3-17.2 years) from the Healthy Brain Network databank. METHODS: Functional MRI and phenotypical information were collected from the Healthy Brain Network databank. Intake of omega-3 DHA and EPA was assessed using a food frequency questionnaire and was adjusted for total calorie intake. Out of scanner VA-related performance was assessed using the VA condition of the Adaptive Cognitive Evaluation tool. RESULTS: Overall, reported intake of omega-3 PUFA was not significantly associated with VA-related performance. Furthermore, energy-adjusted omega-3 intake was not significantly correlated with rsFC within the VA network. A complementary whole-brain analysis revealed that energy-adjusted omega-3 intake was correlated with decreased rsFC between parieto-occipital brain regions. CONCLUSION: The present study was not able to detect a relationship between dietary omega-3 and rsFC or VA performance.

Using acute tryptophan depletion to investigate predictors of treatment response in adolescents with major depressive disorder: study protocol for a randomised controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are amongst the most prescribed antidepressants for adolescents with depressive symptoms and major depressive disorder. However, SSRIs have significant shortcomings as a first-line treatment considering that not all patients respond to these antidepressants. Amongst paediatric populations, meta-analyses indicate that up to approximately 40% of patients do not respond, and for those who do show benefit, there is substantial heterogeneity in response onset. The neurotransmitter serotonin (5-HT) plays a role in the clinical effectiveness and mechanisms of action of SSRIs. However, the exact and complete mechanism of action and reasons for the low response rate to SSRIs in some adolescent populations remains unknown. METHODS: To examine SSRI response and the role of 5-HT, this study will employ a randomised double-blind within subject, repeated measures design, recruiting adolescent patients with major depressive disorder. Participants will be subjected to acute tryptophan depletion (ATD) and the balanced control condition on two separate study days within a first study phase (Phase A), and the order in which these conditions (ATD/balanced control condition) occur will be random. This phase will be followed by Phase B, where participants will receive open label pharmacological treatment as usual with the SSRI fluoxetine and followed-up over a 12-week period. DISCUSSION: ATD is a neurodietary method typically used to investigate the impact of lowered brain 5-HT synthesis on mood and behaviour. The major hypothesis of this study is that ATD will be negatively associated with mood and cognitive functioning, therefore reflecting individual serotonergic sensitivity and related depressive symptoms. Additionally, we expect the aforementioned effects of ATD administration on mood to predict clinical improvement with regard to overall depressive symptomatology 12 weeks into SSRI treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001561471 . Registered on 11 November 2016.