Supplemental Material: supporting references
Supporting references for immune dysregulation, inflammation, oxidative stress,
mitochondrial dysfunction and environmental toxicant exposures in ASD
Immune dysregulation and inflammation
A total of 437 publications investigated a relationship between immune dysregulation
and/or inflammation and ASD, with 416 implicating a relationship between immune
dysregulation and/or inflammation and ASD. Twenty-one publications (all clinical studies) 1-21
failed to find an association between immune dysregulation or inflammation and ASD.
Publications implicating a relationship between immune dysregulation and/or inflammation and
ASD either reported about generalized immune dysregulation/inflammation, or reported these in
a specific organ system (e.g., brain or gastrointestinal tract). An association between ASD and
generalized immune dysregulation and/or inflammation was implicated in 320 publications,
including 155 clinical studies 22-176, 91 review articles or hypothesis-generating papers 177-267, 34
studies using animal models 268-301, 19 publications on Rett syndrome 302-320 and 21 clinicaltreatment studies 321-341. Neuroinflammation or brain immune dysregulation were implicated in
ASD in 52 clinical studies 342-393 and 13 review articles 394-406. Gastrointestinal (GI)
inflammation or immune dysregulation were implicated in ASD in 24 clinical studies 407-430 and
7 review articles 431-437. Ninety-five publications 438-532 (not included in the initial 437
publications) discussed a possible link between vaccines (mainly MMR vaccine) and immune
dysregulation and/or inflammation (especially of the GI tract) in ASD and were not included in
this analysis; the majority of these 95 publications reported no significant association.
1
Oxidative stress
A total of 115 publications investigated a relationship between oxidative stress and ASD,
with all 115 implicating an association. These publications included 51 clinical studies 22, 27, 32, 40,
88, 119, 120, 150, 173, 337, 345, 346, 354, 533-570
, 41 review articles or hypothesis-generating papers 184, 188, 190,
194, 200, 203, 204, 206-208, 215, 221, 239, 253-255, 402, 405, 571-593
, 7 clinical-treatment studies 322, 594-599, 6
publications reporting animal models 283, 600-604 and 10 publications on Rett syndrome 605-614.
Mitochondrial dysfunction
A total of 153 publications investigated a relationship between mitochondrial dysfunction
and ASD or Rett syndrome, with 145 implicating a relationship and 8 publications (all clinical
studies) failing to find an association between mitochondrial dysfunction and ASD 615-621 or Rett
syndrome 622. The 145 publications implicating an association between mitochondrial
dysfunction and ASD included 63 clinical studies 32, 108, 172, 536, 539, 541, 552, 558, 569, 570, 623-675, 22
review articles or hypothesis-generating papers 200, 203, 204, 207, 208, 215, 253, 254, 402, 573, 578, 591, 676-685, 11
publications reporting animal models 283, 296, 297, 602, 686-692 and 49 studies of Rett syndrome 306, 607610, 613, 693-735
.
Environmental toxicant exposures
2
A total of 190 publications investigated a relationship between environmental toxicant
exposures (such as pesticides, chemicals, phthalates, PCBs, solvents, heavy metals or other
pollutants) and ASD, with 170 implicating a relationship and 20 publications (19 clinical studies
and 1 letter to the editor)
3, 15, 151, 736-752
failing to find an association between environmental
toxicant exposures and ASD. The 170 publications implicating an association between
environmental toxicant exposures and ASD included 71 clinical studies 35, 66, 157, 159, 322, 379, 386, 387,
412, 516, 533, 537, 541, 545, 546, 552, 561, 567, 594, 623, 753-803
, 67 review articles or hypothesis-generating papers
180, 182, 186-188, 192, 194, 203-205, 207, 215, 222, 225, 233, 234, 250, 402, 437, 573, 575, 578, 579, 583, 585, 587, 804-844
, 26
publications of animal models 270, 277, 278, 283, 293, 296, 600, 602, 845-862 and 6 clinical studies on
treatments for toxicants 863-868. Forty-seven publications (not included in the initial 190
publications) examined a possible association between thimerosal (ethylmercury) in vaccines and
ASD, with 37 publications reporting no significant association 21, 447, 449, 459, 462, 481, 497, 498, 869-897
and 10 (all but one publication were from the same authors) reporting some type of an
association 457, 898-906. No publications reported an association or lack of an association between
environmental toxicant exposures and Rett syndrome.
3
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