Biomarkers and attention-deficit/hyperactivity disorder

A systematic review and meta-analyses

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Objective: To determine whether peripheral biochemical markers (biomarkers) might differentiate patients with attention-deficit/hyperactivity disorder (ADHD) from non-ADHD individuals. Method: We conducted a systematic search and a series of meta-analyses of case-control studies comprising studies from 1969 to 2011. Results: We identified 210 studies in the following categories: 71 studies of the main metabolites and metabolism enzymes of monoaminergic neurotransmission pathway; 87 studies of environmental risk factors divided into heavy metals (18 studies), substance/chemical exposures (16 studies), and nutritional factors (trace elements: 29 studies; essential fatty acids: 24 studies); 22 studies of the hypothalamic-pituitary-adrenal axis (HPA) pathway; 31 studies indicated with "other." After screening for the availability for meta-analyses of drug naïve/free case-control studies and Bonferroni correction, five comparisons were statistically significant (Norepinephrine [NE], 3-Methoxy-4-hydroxyphenylethylene glycol [MHPG], monoamine oxidase [MAO], Zinc [Zn], cortisol), five of the significant findings found support in studies of response to ADHD medications (NE, MHPG, MAO, b-phenylethylamine [PEA], cortisol), six in studies of symptoms severity (NE, MHPG, MAO, ferritin, Zn, cortisol) and three in studies of neurophysiological or cognitive functioning (lead-ferritin-Zn). No evidence of publication bias was found, whereas significant heterogeneity of effect sizes across studies was found for three of the five biomarkers that differentiated ADHD from control subjects. Suggestive associations were evidenced for neuropeptide Y (NPY), manganese, and dehydroepiandrosterone (DHEA). Conclusions: This study provides evidence for several peripheral biomarkers as being associated with ADHD both in diagnosis and in treatment efficacy. Further studies are warranted to replicate these findings, to assess their specificity for ADHD, and to quantify the degree to which they are sufficiently precise to be useful in clinical settings.

Original languageEnglish
Pages (from-to)1003-1019
Number of pages17
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume51
Issue number10
DOIs
Publication statusPublished - Oct 2012

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Attention Deficit Disorder with Hyperactivity
Meta-Analysis
Biomarkers
Monoamine Oxidase
Hydrocortisone
Zinc
Norepinephrine
Glycols
Ferritins
Case-Control Studies
Phenethylamines
Publication Bias
Essential Fatty Acids
Dehydroepiandrosterone
Neuropeptide Y
Trace Elements
Manganese
Heavy Metals
Synaptic Transmission
Enzymes

Keywords

  • attention-deficit/hyperactivity disorder
  • biochemical markers
  • diagnosis
  • drug treatment efficacy
  • meta-analyses

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental and Educational Psychology

Cite this

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title = "Biomarkers and attention-deficit/hyperactivity disorder: A systematic review and meta-analyses",
abstract = "Objective: To determine whether peripheral biochemical markers (biomarkers) might differentiate patients with attention-deficit/hyperactivity disorder (ADHD) from non-ADHD individuals. Method: We conducted a systematic search and a series of meta-analyses of case-control studies comprising studies from 1969 to 2011. Results: We identified 210 studies in the following categories: 71 studies of the main metabolites and metabolism enzymes of monoaminergic neurotransmission pathway; 87 studies of environmental risk factors divided into heavy metals (18 studies), substance/chemical exposures (16 studies), and nutritional factors (trace elements: 29 studies; essential fatty acids: 24 studies); 22 studies of the hypothalamic-pituitary-adrenal axis (HPA) pathway; 31 studies indicated with {"}other.{"} After screening for the availability for meta-analyses of drug na{\"i}ve/free case-control studies and Bonferroni correction, five comparisons were statistically significant (Norepinephrine [NE], 3-Methoxy-4-hydroxyphenylethylene glycol [MHPG], monoamine oxidase [MAO], Zinc [Zn], cortisol), five of the significant findings found support in studies of response to ADHD medications (NE, MHPG, MAO, b-phenylethylamine [PEA], cortisol), six in studies of symptoms severity (NE, MHPG, MAO, ferritin, Zn, cortisol) and three in studies of neurophysiological or cognitive functioning (lead-ferritin-Zn). No evidence of publication bias was found, whereas significant heterogeneity of effect sizes across studies was found for three of the five biomarkers that differentiated ADHD from control subjects. Suggestive associations were evidenced for neuropeptide Y (NPY), manganese, and dehydroepiandrosterone (DHEA). Conclusions: This study provides evidence for several peripheral biomarkers as being associated with ADHD both in diagnosis and in treatment efficacy. Further studies are warranted to replicate these findings, to assess their specificity for ADHD, and to quantify the degree to which they are sufficiently precise to be useful in clinical settings.",
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author = "Catia Scassellati and Cristian Bonvicini and Faraone, {Stephen V.} and Massimo Gennarelli",
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AU - Faraone, Stephen V.

AU - Gennarelli, Massimo

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N2 - Objective: To determine whether peripheral biochemical markers (biomarkers) might differentiate patients with attention-deficit/hyperactivity disorder (ADHD) from non-ADHD individuals. Method: We conducted a systematic search and a series of meta-analyses of case-control studies comprising studies from 1969 to 2011. Results: We identified 210 studies in the following categories: 71 studies of the main metabolites and metabolism enzymes of monoaminergic neurotransmission pathway; 87 studies of environmental risk factors divided into heavy metals (18 studies), substance/chemical exposures (16 studies), and nutritional factors (trace elements: 29 studies; essential fatty acids: 24 studies); 22 studies of the hypothalamic-pituitary-adrenal axis (HPA) pathway; 31 studies indicated with "other." After screening for the availability for meta-analyses of drug naïve/free case-control studies and Bonferroni correction, five comparisons were statistically significant (Norepinephrine [NE], 3-Methoxy-4-hydroxyphenylethylene glycol [MHPG], monoamine oxidase [MAO], Zinc [Zn], cortisol), five of the significant findings found support in studies of response to ADHD medications (NE, MHPG, MAO, b-phenylethylamine [PEA], cortisol), six in studies of symptoms severity (NE, MHPG, MAO, ferritin, Zn, cortisol) and three in studies of neurophysiological or cognitive functioning (lead-ferritin-Zn). No evidence of publication bias was found, whereas significant heterogeneity of effect sizes across studies was found for three of the five biomarkers that differentiated ADHD from control subjects. Suggestive associations were evidenced for neuropeptide Y (NPY), manganese, and dehydroepiandrosterone (DHEA). Conclusions: This study provides evidence for several peripheral biomarkers as being associated with ADHD both in diagnosis and in treatment efficacy. Further studies are warranted to replicate these findings, to assess their specificity for ADHD, and to quantify the degree to which they are sufficiently precise to be useful in clinical settings.

AB - Objective: To determine whether peripheral biochemical markers (biomarkers) might differentiate patients with attention-deficit/hyperactivity disorder (ADHD) from non-ADHD individuals. Method: We conducted a systematic search and a series of meta-analyses of case-control studies comprising studies from 1969 to 2011. Results: We identified 210 studies in the following categories: 71 studies of the main metabolites and metabolism enzymes of monoaminergic neurotransmission pathway; 87 studies of environmental risk factors divided into heavy metals (18 studies), substance/chemical exposures (16 studies), and nutritional factors (trace elements: 29 studies; essential fatty acids: 24 studies); 22 studies of the hypothalamic-pituitary-adrenal axis (HPA) pathway; 31 studies indicated with "other." After screening for the availability for meta-analyses of drug naïve/free case-control studies and Bonferroni correction, five comparisons were statistically significant (Norepinephrine [NE], 3-Methoxy-4-hydroxyphenylethylene glycol [MHPG], monoamine oxidase [MAO], Zinc [Zn], cortisol), five of the significant findings found support in studies of response to ADHD medications (NE, MHPG, MAO, b-phenylethylamine [PEA], cortisol), six in studies of symptoms severity (NE, MHPG, MAO, ferritin, Zn, cortisol) and three in studies of neurophysiological or cognitive functioning (lead-ferritin-Zn). No evidence of publication bias was found, whereas significant heterogeneity of effect sizes across studies was found for three of the five biomarkers that differentiated ADHD from control subjects. Suggestive associations were evidenced for neuropeptide Y (NPY), manganese, and dehydroepiandrosterone (DHEA). Conclusions: This study provides evidence for several peripheral biomarkers as being associated with ADHD both in diagnosis and in treatment efficacy. Further studies are warranted to replicate these findings, to assess their specificity for ADHD, and to quantify the degree to which they are sufficiently precise to be useful in clinical settings.

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