A Comparative Review of Non-Essential Metal Exposures in

Overview

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Key numbers

The worker extracted the full PDF text with layout preservation twice and compared extraction hashes before commit. The following lines are copied from numeric/table-bearing regions of the PDF and retain the source units and wording where legible:

phased out in the U.S. by the late 1980s, historical emissions specifically to bind to proteins meant to bind Ca and Zn has
severe psychiatric disorder affecting ~ 1% of the global to negatively influence the NMDAr via metal dysregulation
Analysis“(Publication Type) OR “Editorial“(Publication essential metals (n = 24); studies in which genetic polymor-
“Letter“(Publication Type) OR “Case Reports“(Publication on clinical assay validation (n = 7); studies in which metal
Type) OR “Med Hypotheses“(Journal)). Search filters exposure was not a primary focus (n = 7); studies primarily
were applied to include only human data, and only epide- evaluating antipsychotic treatment effects (n = 3); and stud-
miological data was included in the final dataset, excluding ies examining non-SCZ disease outcomes (n = 3).
selected based on prior evidence demonstrating their classi- tables. Sallmén et al., (46) was excluded due to its nature
terms was used to generate results strictly examining SCZ as ducted in Finland with a large sample size (N = 11,863),
cally n = 1) and often exceptional results not widely general- tant area of inquiry beyond the scope of this review (48).
ing results to only include human subjects, there were 193 outside of the scope of this review. Additional papers (n =
(39), and Iraq (41), respectively (Table 1). the same case-control cohort (N = 440). These two studies
Table 1 Summary of studies included in final analysis. Studies by Ghaderi et al., (37), Liu et al., (31), and Karim et al., (42) did not identify associations between non-essential metal exposures
China Li et 440 Cross-sectional 221:219 Age, sex Adult blood ICP-MS Ba, W, U ↑ W, U W Q4: OR 1.87 (95% CI 1.08–3.21)
China Shen et 440 Cross-sectional 221:219 Age, sex Adult blood ICP-MS Pb, As, Cd, ↑ Pb OR 3.62 (95% CI: 1.80–7.28) for Q4 com- (2026) 13:30
al., (34) case control serum As Cr in later (95% CI 0.10–0.73)
Table 1 (continued)
As: OR 2.624 (95% CI 1.340–5.138), p = Page 6 of 14
China Liu et 228 Cross-sectional 114:114 Age, sex Adult blood ICP-MS Ni, Mo, As, ↑ Mn, ↓ Se, Cu Mn: OR 19.269 (95%CI: 1.436–258.626)
al., (31) case control (matched); serum Al, Cr, Mn, Se: OR 16.837, 95%CI: 2.130–133.113)
United States Opler 200 Nested case- 71:129 Maternal Second-tri- LC-40 FD Pb (indi- ↑ prenatal OR 1.92 (95% CI 1.05–3.52)
and SCZ were additionally noted (Table 1). Three studies
Table 1 (continued)
and nutrition (56, 57). Additionally, the length of time stratification provided meaningful differences in the find-
(56). Infants and young children retain approximately 50% tration of Pb in bone over time following exposure, which
66). Specifically, within ~ 1 month of exposure, 90% of Pb accumulation in bone and brain tissue (74–76).
is sequestered in bone tissue, 2–8% in various soft tissues, Another potential confounding factor in metal quantifi-
and 2–5% remains in circulating blood (60). Remobiliza- cation from bio sampling is smoking. Smoking status, and
A minor fraction of Pb (~ 8%) is eliminated through kera- Methodological limitations—including less sensitive
ture review, and wrote the manuscript, including generation of Table 1. those on anti-psychotic medication. J Res Med Sci Off J Isfahan

Methods (brief)

Ca influx in the post-synaptic neuron after dislodging Zn aspartate receptors (NMDArs) to Pb interference.
OR aluminum OR nickel(Title/abstract) OR uranium(Title/ as the primary disease outcome, primary data collected and
terms was used to generate results strictly examining SCZ as ducted in Finland with a large sample size (N = 11,863),
this portion of the search due to their low sample size (typi- epigenetic inheritance via the paternal germline—an impor-
pled plasma mass spectrometry (ICP-MS), graphite fur- et al., (38) examined Pb, Cd, As, and Cr, focusing on mecha-
nace atomic absorption spectrometry (GFAAS), and flame nistic analyses, Li et al., (36) focused on barium (Ba), tung-
atomic absorption spectrometry (FAAS). ICP-MS is gener- sten (W), and uranium (U), emphasizing mixture effects and
blood or serum, followed by GFAAS (49, 50). In contrast, study from Opler (29). These studies used a nested case-
FAAS is less sensitive to human blood serum samples and control design within prospective birth cohorts to investi-
particularly in environmental samples (51). Of note, ICP- development of SCZ Both leveraged archived maternal
MS has been shown to be more sensitive to Pb in blood serum samples collected during the 2nd or 3rd trimester
15 newly diagnosed, unmedicated SCZ patients, and 20 controls. Instrument and analytical method abbreviations include graphite atomic absorption spectrophotometry (GFAAS), inductively
coupled plasma mass spectrometry (ICP-MS), laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), atomic absorption spectrophotometer (AAS), flame atomic absorption
spectroscopy (FAAS), LC-40 fluorescence detection (LC-40 FD)
India Ray et 80 Cross-sectional 40:40 Stroop test Adult whole GFAAS Pb, As, Al, ↑ Pb, Cd, ↓ As Pb: p = 0.015
China Li et 440 Cross-sectional 221:219 Age, sex Adult blood ICP-MS Ba, W, U ↑ W, U W Q4: OR 1.87 (95% CI 1.08–3.21)
China Shen et 440 Cross-sectional 221:219 Age, sex Adult blood ICP-MS Pb, As, Cd, ↑ Pb OR 3.62 (95% CI: 1.80–7.28) for Q4 com- (2026) 13:30
Iran Ghaderi 171 Cross-sectional 56:58:57 None Adult blood GFAAS Tl, As, Cd, None (no direct None reported (no ORs)

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Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.

Commit	Date	Change	Description
b01ec52c	2026-08-04	major	2 sections added
d49e450f	2026-08-03	major	5 sections added; narrative text revised