ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications

Homaei, Selina Cannon; Barone, Helene; Kleppe, Rune; Betari, Nibal; Reif, Andreas; Haavik, Jan

doi:10.1016/j.neubiorev.2021.11.012

Cited by 29 publications

(17 citation statements)

References 213 publications

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“…Several inborn errors of amino acid metabolism and transporters appear to converge on common mechanisms that may affect neurotransmitter functions and may be related to co-occurring neuropsychiatric symptoms. For example, inborn errors of aromatic amino acid metabolism in phenylketonuria and tyrosinemia type 1 are characterized by disturbances of dopamine synthesis and symptoms of ADHD ( 31 , 32 ). Fernandez-Castillo et al recently conducted a systematic search in the Online Mendelian Inheritance in Man (OMIM) database for Mendelian disorders for genes and diseases presenting with hyperactivity and/or inattention.…”

Section: Comorbid Conditionsmentioning

confidence: 99%

Genome Guided Personalized Drug Therapy in Attention Deficit Hyperactivity Disorder

Haavik

2022

Front. Psychiatry

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ADHD is a common behavioral syndrome with a heritability of 70–80%. Genome wide sequencing and association studies indicate that ADHD risk variants are distributed across a wide range of allele frequencies and relative risks. Several common single nucleotide variants (SNPs) have been identified that increase the risk of ADHD with a few percent. Many of the reported risk genes and copy number variants are shared with other neuropsychiatric disorders. Moreover, ADHD often coexists with common or rare somatic diseases, including rare Mendelian neurometabolic diseases that can affect normal brain development and function. Some genetic/metabolic syndromes masquerading as common ADHD may lead to irreversible brain damage if not properly identified and treated during early childhood. As ADHD is such a heterogeneous condition in terms of severity, clinical features and most probably also underlying biology, it is crucial to offer individualized treatments. Recent progress in ADHD genetics is reviewed, prospects of using this information for targeted pharmacotherapy are discussed and critical knowledge gaps are identified. It is suggested that genome guided therapies could be introduced gradually, starting with rare ADHD syndromes with highly penetrant risk genes. Routine diagnostic application of whole exome or whole genome sequencing combined with metabolomic screening, and brain imaging may be needed in cases with suspected neurometabolic disorders. Identification and treatment of ADHD patients with defined neurometabolic aberrations could be a first step toward genome guided personalized treatment of ADHD. Possibly, screening for relevant biomarkers may gradually be implemented to guide treatment choices in larger patient groups.

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Section: Comorbid Conditionsmentioning

confidence: 99%

Genome Guided Personalized Drug Therapy in Attention Deficit Hyperactivity Disorder

Haavik

2022

Front. Psychiatry

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“…The symptoms of ADHD are classified into three groups: attention deficit disorder, hyperactivity, and impulsivity [8]. The diagnostic criteria for these disorders are cataloged in detail in both the DSM-5 and ICD-10 [9].…”

Section: Introductionmentioning

confidence: 99%

Neurological Mechanisms of Diagnosis and Therapy in School Children with ADHD in Poland

Nermend

Flaga-Gieruszyńska²,

Kroplewski³

et al. 2022

IJERPH

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The paper aims to present a holistic view of attention deficit hyperactivity disorder (ADHD) in pedagogical, psychological, legal, and social dimensions in Polish schools. The authors present the benefits of neurofeedback therapy for elementary school pupils. In order to verify the validity, the paper compares the concordance of a medical diagnosis confirming ADHD syndrome with the occurrence of abnormal electrical brain function recording and abnormalities therein as well as the effectiveness of the neurofeedback therapy. The study confirms that the reported problems faced by pupils and affecting their emotional functioning are reflected in their EEG records. Conclusions from the study lead to the proposal that the neurofeedback assessment should be performed at schools, which should result in the implementation of effective therapy. Moreover, the neurofeedback method should be promoted in Polish schools as an alternative to pharmacological therapy, which, as the research proves, is not always effective. Neurofeedback therapy, similarly to behavioral therapy, is very much needed and useful because it provides optimal conditions for the child’s development and shapes their relations with the environment effectively and harmlessly.

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“…Tyrosine hydroxylase (TH) is an enzyme involved in the metabolism of amino acids and neurotransmitters. The L-tyrosine is converted by L-dihydroxyphenylalanine (L-DOPA) decarboxylase into p-tyramine, which is also a neuromodulator, or by tyrosine aminotransferase (TAT) and fumarylacetoacetate hydrolase (FAH) into fumarate 10 . Catecholamine neurotransmitters may also be synthesized by the hydroxylation of tyrosine to L-DOPA, which is then converted to dopamine as a result of catalysis by the enzyme DOPA decarboxylase 16 .…”

Section: Introductionmentioning

confidence: 99%

Metabolic profiles and fingerprints for the investigation of the influence of nitisinone on the metabolism of the yeast Saccharomyces cerevisiae

Kostina-Bednarz

Płonka

Nowak

et al. 2022

Preprint

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Nitisinone (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, NTBC) is considered a potentially effective drug for the treatment of various metabolic diseases associated with disorders of L-tyrosine metabolism however, side-effects impede its widespread use. This work aimed to broaden the knowledge of the influence of NTBC and its metabolites 2-amino-4-(trifluoromethyl)benzoic acid (ATFA), 2-nitro-4-(trifluoromethyl)benzoic acid (NTFA), and cyclohexane-1,3-dione (CHD) on the catabolism of L-tyrosine and other endogenous compounds in Saccharomyces cerevisiae. Based on a targeted analysis performed by LC-ESI-MS/MS, based on multiple reaction monitoring, it was found that the dissipation kinetics of the parent compound and its metabolites are compatible with a first-order reaction mechanism. The same mode of analysis was used to reveal that NTBC metabolites formed in the model organism cause a 15–59% decrease in L-tyrosine, L-tryptophan, and L-phenylalanine compared to the untreated model organism. The overall changes in the metabolism of yeast exposed to NTBC or its derivatives were evaluated by non-targeted analysis via LC-ESI-MS/MS in the ion trap scanning mode. Based on principal components analysis, a statistically significant similarity between metabolic responses of yeast treated with ATFA or NTFA was observed. These findings facilitate further studies investigating the influence of NTBC on the human body and the mechanism of its action.

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ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications

Cited by 29 publications

References 213 publications

Genome Guided Personalized Drug Therapy in Attention Deficit Hyperactivity Disorder

Genome Guided Personalized Drug Therapy in Attention Deficit Hyperactivity Disorder

Neurological Mechanisms of Diagnosis and Therapy in School Children with ADHD in Poland

Metabolic profiles and fingerprints for the investigation of the influence of nitisinone on the metabolism of the yeast Saccharomyces cerevisiae

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