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

Figures & data

Figure 1 The flowchart of meta-analysis.

Abbreviation: ADHD, attention-deficit hyperactivity disorder.

Table 1 Characteristics of the recruited studies

Study	Criteria of ADHD	Sample source	Comparison	Subject	Mean age	Female (%)	Cognitive function		ADHD subtype			Parental history of ADHD	Country
							ADHD (IQ)	Control (IQ)	Inattentive	Hyperactive	Combined
Shin et al^Citation20	DSM-IV	Hair	ADHD	40	9.4±3.0	15.0	101.8±14.9	112.4±10.4	N/A	N/A	N/A	Not mentioned	Republic of Korea
			Control	43	10.3±3.1	16.3
Hong et al^Citation19	DISC-IV	Blood	ADHD	43	9.1±0.8	16.3	106.1±13.8	111.0±14.2	N/A	N/A	N/A	Not mentioned	Republic of Korea
			Control	847	9.1±0.7	48.5
Yousef et al^Citation16	DSM-IV	Blood	ADHD	18	8.3±1.8	N/A	N/A	N/A	38.9%	33.3%	27.8%	Not mentioned	United Arab Emirates
			Control	74
Farias et al^Citation18	DSM-IV	Blood	ADHD-combined	50	8.0±1.2	14.0	102.0±14.0	101.0±17.0	33.0%	0.0%	67.0%	Not mentioned	Brazil
			ADHD-inattentive	24	9.0±1.4	21.0	93.0±10.0
			ADHD-combined and Mx	21	9.0±1.8	19.0	98.0±14.0
			ADHD-inattentive and Mx	11	10.0±1.7	0.0	97.0±10.0
			Control	35	9.0±1.2	20.0

Abbreviations: ADHD, attention-deficit/hyperactivity disorder; DISC-IV, Diagnostic Interview Schedule for Children Version IV; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; IQ, intelligence quotient; Mx, medication; N/A, not available.

Table 2 Comparison of previous and current meta-analyses

Study	Study designs included	Manganese exposure measure	Observed effect
Scassellati et al^Citation21	Case–control	N/A	N/A
Rodríguez-Barranco et al^Citation17	Case–control, cohort, cross-sectional	Blood, cord blood, hair, placenta, tooth, water	Full-scale IQ, performance IQ, verbal IQ
Current study	Case–control, cross-sectional	Blood, hair	ADHD

Abbreviations: ADHD, attention-deficit/hyperactivity disorder; IQ, intelligence quotient; N/A, not available.

Figure 2 Meta-analysis of (A) overall manganese levels in ADHD children and controls, (B) blood manganese levels in ADHD children and controls, and (C) pooled adjusted OR for the association between manganese levels and ADHD.

Notes: (A) There were significantly higher overall manganese levels in ADHD children than those in controls (Hedges’ g=0.305, 95% CI=0.025–0.585, p=0.033). (B) There were no significantly different blood manganese levels in ADHD children and controls (Hedges’ g=0.329, 95% CI=−0.035 to 0.693, p=0.076). (C) There was a significant association between manganese levels and diagnosis of ADHD as shown by pooled adjusted OR (OR=1.849, 95% CI=1.149–2.976, p=0.011).
Abbreviations: ADHD, attention-deficit/hyperactivity disorder; C-type, combined type; DISC-IV, Diagnostic Interview Schedule for Children Version IV; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; I-type, inattention type.

Figure S1 Whole flowchart of the meta-analysis.

Abbreviations: ADHD, attention-deficit/hyperactivity disorder; N/A, not available.

Table S1 Results of Newcastle–Ottawa Scale scores of recruited studies

Study	Criteria	Source	Sample method	Newcastle–Ottawa Scale					Country
				Selection	Performance	Detection	Information	Total
Shin et al^Citation1	DSM-IV	Hair	Inductively coupled plasma mass spectrometry	1	5	4	5	15	Republic of Korea
Hong et al^Citation2	DISC-IV	Blood	Graphite furnace atomic absorption spectrometry	3	5	5	4	17	Republic of Korea
Yousef et al^Citation3	DSM-IV	Blood	N/A	2	5	4	4	15	United Arab Emirates
Farias et al^Citation4	DSM-IV	Blood	Graphite furnace atomic absorption spectrometry	2	5	4	4	15	Brazil

Abbreviations: DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; DISC-IV, Diagnostic Interview Schedule for Children Version IV; N/A, not available.

Table S2 Excluded studies and reasons

Not related to manganese and ADHD (n=4)

Konstantopoulos et al^Citation5

Hu et al^Citation6

Konrad et al^Citation7

Han et al^Citation8

Meta-analysis (n=2)

Rodríguez-Barranco et al^Citation9

Scassellati et al^Citation10

Review articles (n=3)

Zeng et al^Citation11

Grandjean and Landrigan^Citation12

Lucchini et al^Citation13

Not definite diagnosis of ADHD (n=5)

Hong et al^Citation14

Bouchard et al^Citation15

Lucchini et al^Citation16

Chan et al^Citation17

Ericson et al^Citation18

Compare treatment effect of micronutrient but not related to manganese and ADHD (n=1)

Rucklidge et al^Citation19

Use the same data sample sources of Hong et al^Citation2 (n=1)

Bhang et al^Citation20

Lack of control (n=1)

Liu et al^Citation21

Collecting manganese when ADHD children were just given birth (n=1)

Ode A et al^Citation22

Abbreviation: ADHD, attention-deficit/hyperactivity disorder.

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