Pubmed (TDAH) du 03/01/26
1. Bruton AM, Ast HK, Norby-Adams L, Srikanth P, Robinette LM, Hatsu IE, Leung BMY, Arnold LE, Zava D, Johnstone JM. Kynurenine metabolites unchanged after multinutrient supplementation in children with ADHD: a secondary data analysis from the MADDY study. J Neural Transm (Vienna). 2026.
Attention-deficit/hyperactivity disorder (ADHD) affects up to 10% of children, often presenting with emotional dysregulation (irritability, anger). The kynurenine pathway, by which the amino acid tryptophan is converted into both neuroprotective and neurotoxic metabolites, was investigated for its role in ADHD pathophysiology. The MADDY study was an 8-week, multi-site, randomized controlled trial of a multinutrient supplement versus placebo in children 6-12 years old with symptoms of ADHD and emotional dysregulation. Participants from two U.S. sites (n = 84) provided baseline and week 8 urinary samples, analyzed via liquid chromatography-mass spectrometry for neurotransmitter levels. Linear mixed-effects models assessed change over time for seven analytes. Missing values were imputed, and results adjusted for multiple comparisons. Baseline neurotransmitter concentrations were not different between treatment groups. Changes over time in the seven analytes were not different between treatment groups. Nine participants had neurotransmitter levels below the lower limit of detection and were imputed; demographic characteristics were not different between these and other participants. Eight weeks of multinutrient supplementation did not change concentrations of urinary tryptophan, serotonin, or kynurenines in this sample of children 6-12 years old with ADHD and emotional dysregulation.
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2. Hu J, Ma JY, Tang FD, Wang JY, Xu JY, Wang BH, Pan YL, Wang Y, Xuan XB, Chen J. Dietary inflammatory index (DII) and attention deficit hyperactivity disorder: a cross-sectional study in US children and adolescents and Mendelian randomization study. Eur J Med Res. 2026.
BACKGROUND: Diet may impact the risk of attention deficit hyperactivity disorder (ADHD) via altering inflammation. However, no investigations have been conducted to evaluate the relationship between ADHD and the diet’s inflammatory potential. The study sought to investigate the relationship between ADHD and the dietary inflammatory index (DII). METHODS: We used data from the cross-sectional National Health and Nutrition Examination Survey 2001-2004 to investigate the relationship between DII and ADHD in 6481 children and adolescents aged 6-19 years. The relationship between ADHD and DII was investigated using weighted logistic regression and restricted cubic spline (RCS). We also explored the potential causal associations between ADHD and 187 types of food preferences using Mendelian randomization (MR). RESULTS: Despite thorough multivariate correction, a significant association between lower DII scores and an elevated probability of ADHD persisted (OR = 0.91, 95% CI 0.82-0.99). Nevertheless, when stratifying the DII into quartiles (T1-T4) for analysis, no statistically significant correlation was seen between DII and ADHD (P > 0.05). RCS analysis indicated a U-shaped correlation between DII and ADHD, with an inflection point at approximately 2.9. Mediation analysis indicated that the Frailty Index partly mediated the association between DII and ADHD, representing about 5.49% of the overall impact. The findings from the univariate MR analysis revealed that fruit liking is significantly linked to a reduced risk of ADHD. Conversely, a liking for red meat, such as lamb, as well as a fondness for flavorings like onions, is significantly associated with an increased risk of ADHD. Reverse two-sample MR analyses revealed that genetic predisposition to ADHD significantly altered 37 food preferences (FDR < 0.05). CONCLUSIONS: We observed a U-shaped association between the DII and ADHD risk. The Frailty Index may partially mediate (5.49%) the association between DII and ADHD. However, the cross-sectional design precludes causal inference. Fruit liking lowered ADHD risk, while red meat/onion liking increased risk. ADHD was associated with a generalized reduction in liking for a wide range of foods. Future studies should investigate the role of a moderate-inflammatory diet in ADHD prevention.
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3. Lv GG, Shan YD, Shao JJ, Ma CY, Yu ZF, Liu JZ, Zhang LM, Zhang W. 3-Methyladenine administration alleviates cognitive and memory dysfunction in attention-deficit/hyperactivity disorder by modulating autophagy. Psychopharmacology (Berl). 2026.
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD), a highly prevalent neurodevelopmental disorder among children, is directly associated with impairments in cognition and memory. In the nervous system, autophagy is essential for the development of neurons, the formation and remodeling of synapses, and the transmission of neurotransmitters. The 3-methyladenine (3-MA), an autophagy inhibitor, mitigates cognitive and memory impairment in neurological disorders. This study aimed to investigate the potential role of 3-MA in ADHD. METHODS: An ADHD model was established in offspring mice by intraperitoneal injection of S-ketamine during mid-to-late gestation. Postnatal day 14 offspring received intraperitoneal 3-MA (15 mg/kg/day) or vehicle for 7 consecutive days. To assess behavioral, electrophysiological, and pathological changes in mice, several tests were employed, including the open field test (OFT), novel object recognition (NOR) test, fear conditioning (FC), local field potential recording, western blot, transmission electron microscopy and immunofluorescence assays. RESULTS: Compared to controls, ADHD model mice exhibited: Increased total distance in OFT, Decreased recognition index in NOR, Reduced context- and cue-related freezing time in FC and Attenuated theta oscillation power in the prefrontal cortex. RNA sequencing revealed significant enrichment of the PI3KC3 pathway and autophagy-related genes. ADHD model mice showed upregulated autophagy-related protein expression, elevated LC3II/I ratio, increased autophagosomes, and accumulated abnormal organelles in the mPFC. TH-positive neurities and PSD95-positive puncta were significantly reduced in the mPFC. 3-MA treatment partially reversed these alterations. CONCLUSION: Cognitive and memory impairments in the mPFC due to ADHD are correlated with autophagy, and these impairments might be alleviated by 3-MA.
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4. Öztürk HH, Sezen S, Çağlar E, Elgün Ülkar S, Açıkel SB. Increased Serum Netrin-1 Levels Among Children Diagnosed With ADHD. J Atten Disord. 2026: 10870547251408127.
OBJECTIVE: ADHD is a common neurodevelopmental disorder of childhood characterized by altered projections of dopaminergic neurons and connectivity issues in various brain regions. In our study, we aim to investigate the potential effects of axon guidance molecules, Netrin-1 and Semaphorins 3A, 4D, and 7A, on these connectivity problems by examining the levels of these molecules in the peripheral blood of children with ADHD compared to healthy controls. METHODS: A total of 43 children with ADHD and 40 healthy controls 6 to 12 years of age were included in the study. The K-SADS-PL was administered to exclude any additional psychopathologies (excluding ODD in the ADHD group). The Revised Child Anxiety and Depression Scale was provided to the children, while parents completed the revised Conners’ Parent Rating Scale (CPRS-R), the Social Responsiveness Scale (SRS), and the Behavior Rating Inventory for Executive Functioning (BRIEF). Additionally, teachers of the ADHD group were given the Conners’ Teacher Rating Scale. Furthermore, the WISC-4 was administered to assess the IQ profile of 35 children in the ADHD group. RESULTS: Netrin-1 was found to be statistically higher in the ADHD group. When the R-CADS scores were recalculated taking the covariate into account, the significant increase in the ADHD group remained. There was no statistically significant difference between the two groups for semaphorin 3A, 4D, and 7A. The positive correlation of Netrin-1 with the hyperactivity subscores on the CPRS-R and the Global Executive Score on the BRIEF scale is noteworthy. CONCLUSION: Netrin-1 may play a role in the etiopathogenesis of ADHD. Further studies are needed to clarify the relationship between Netrin-1 and ADHD.
