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Association between peripheral manganese levels and attention-deficit/hyperactivity disorder: a preliminary meta-analysis

Authors Shih JH, Zeng BY, Lin PY, Chen TY, Chen YW, Wu CK, Tseng PT, Wu MK

Received 13 February 2018

Accepted for publication 18 April 2018

Published 18 July 2018 Volume 2018:14 Pages 1831—1842


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Wai Kwong Tang

Jun-Hao Shih,1,2,* Bing-Yan Zeng,3,* Pao-Yen Lin,4,5 Tien-Yu Chen,6,7 Yen-Wen Chen,8 Ching-Kuan Wu,9 Ping-Tao Tseng,10 Ming-Kung Wu4

1Department of Occupational and Environmental Health Consultation, EMHA Consulting International Incorporation, Hsinchu, Taiwan; 2Certified Occupational Medicine Physician & Deputy Secretary General, Taiwan Environmental and Occupational Medicine Association, Tainan, Taiwan; 3Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan; 4Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 6Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 7Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; 8Prospect Clinic for Otorhinolaryngology and Neurology, Kaohsiung, Taiwan; 9Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai’s Home, Kaohsiung, Taiwan; 10WinShine Clinics in Specialty of Psychiatry, Kaohsiung, Taiwan

*These authors contributed equally to this work

Abstract: Evidence has suggested that dysregulation of the dopaminergic system may play a significant role in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD) in children. Manganese, a neurotoxicant, has been reported to exert its neurotoxicity by affecting the dopaminergic system. However, the association between peripheral manganese levels and ADHD has not been comprehensively reviewed. This study aimed to investigate the association between peripheral manganese levels and ADHD in children. An electronic search was performed on databases including PubMed, ProQuest, ClinicalKey, Cochrane Library,, Embase, Web of Science, and ScienceDirect with last search on March 25th, 2018. As per the inclusion criteria, human observational studies investigating peripheral manganese levels in children with ADHD and controls were included. The meta-analysis was performed using a random-effects model, and possible confounders were examined by subgroup analysis. In total, four articles with 175 ADHD children and 999 controls were recruited. The manganese levels were significantly higher in ADHD children than in controls (p=0.033), when studies investigating blood levels and those investigating hair levels were included. However, when only studies investigating blood levels were included, there was no significant difference between ADHD children and controls (p=0.076). Our results support higher peripheral manganese levels in children diagnosed with ADHD than those in controls. Further primary studies are needed to clarify this association.

Keywords: meta-analysis, manganese, ADHD, pediatric psychiatry, review

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