ADHD - Thyroid - PFAS - Inverse U - Reference Set III

All adverse health effects of fluoride are related to thyroid hormone metabolism.
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ADHD - Thyroid - PFAS - Inverse U - Reference Set III

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Abel MH, Ystrom E, Caspersen IH, Meltzer HM, Aase H, Torheim LE, Askeland RB, Reichborn-Kjennerud T, Brantsæter AL - "Maternal Iodine Intake and Offspring Attention-Deficit/Hyperactivity Disorder: Results from a Large Prospective Cohort Study" Nutrients 9(11):1239 (2017) doi: 10.3390/nu9111239 MoBa
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707711/
"The maternal use of supplemental iodine was associated with an increased risk of child ADHD diagnosis and a higher mean ADHD symptom score...Initiating iodine supplement use in the first trimester was associated with an increased risk of ADHD diagnosis, whereas use before pregnancy was associated with increased child ADHD symptom scores."

Aimuzi R, Luo K, Huang R, Huo X, Nian M, Ouyang F, Du Y, Feng L, Wang W, Zhang J; Shanghai Birth Cohort Study - "Perfluoroalkyl and polyfluroalkyl substances and maternal thyroid hormones in early pregnancy" Environ Pollut 264:114557 (2020) doi: 10.1016/j.envpol.2020.114557
https://www.sciencedirect.com/science/a ... 9120301810
"The exposure-response curves show that there was a significant inverse U shape relationship for PFHxS and PFHpA with FT4."

Coperchini F, Croce L, Ricci G, Magri F, Rotondi M, Imbriani M, Chiovato L - "Thyroid Disrupting Effects of Old and New Generation PFAS" Front Endocrinol (Lausanne) 11:612320 (2021) doi: 10.3389/fendo.2020.612320
https://www.frontiersin.org/articles/10 ... 12320/full
"Among AbTPO negative women only a weak positive correlation between PFHxS and FT3 levels and an inverse U shaped relationship between PFHxS and FT4 was observed. In contrast, when only the TPO Ab positive women were taken into account, a significant direct correlation between PFNA and FT4 and significant, U-shaped, correlations between PFUNDA, PFOS, PFNA, and PFHxS with TSH levels was observed."

Derakhshan A, Kortenkamp A, Shu H, Broeren MAC, Lindh CH, Peeters RP, Bornehag CG, Demeneix B, Korevaar TIM - "Association of per- and polyfluoroalkyl substances with thyroid homeostasis during pregnancy in the SELMA study" Environ Int 167:107420 (2022). doi: 10.1016/j.envint.2022.107420 SELMA
https://www.sciencedirect.com/science/a ... 2022003476
"Higher PFUnDA levels were associated with lower TT4 and there was an inverted U-shaped association of PFOS with TT4".

Engel SM, Villanger GD, Herring A, Nethery RC, Drover SSM, Zoeller RT, Meltzer HM, Zeiner P, Knudsen GP, Reichborn-Kjennerud T, Longnecker MP, Aase H - "Gestational thyroid hormone concentrations and risk of attention-deficit hyperactivity disorder in the Norwegian Mother, Father and Child Cohort Study" Paediatr Perinat Epidemiol 37(3):218-228 (2023) doi: 10.1111/ppe.12941
https://onlinelibrary.wiley.com/doi/10.1111/ppe.12941. MoBa
"Both high and low concentrations of maternal thyroid hormones, although within population reference ranges, increase the risk of ADHD in offspring."

Gao X, Ni W, Zhu S, Wu Y, Cui Y, Ma J, Liu Y, Qiao J, Ye Y, Yang P, Liu C, Zeng F - "Per- and polyfluoroalkyl substances exposure during pregnancy and adverse pregnancy and birth outcomes: A systematic review and meta-analysis" Environ Res 201:111632 (2021) doi: 10.1016/j.envres.2021.111632
https://www.sciencedirect.com/science/a ... 5121009269
"...perfluorononanoate (PFNA) and perfluorooctanoate (PFOA) exposure showed inverted U-shaped associations with preterm birth risk..."

Itoh S, Yamazaki K, Suyama S, Ikeda-Araki A, Miyashita C, Ait Bamai Y, Kobayashi S, Masuda H, Yamaguchi T, Goudarzi H, Okada E, Kashino I, Saito T, Kishi R - "The association between prenatal perfluoroalkyl substance exposure and symptoms of attention-deficit/hyperactivity disorder in 8-year-old children and the mediating role of thyroid hormones in the Hokkaido study" Environ Int 159:107026 (2022) doi: 10.1016/j.envint.2021.107026
https://www.sciencedirect.com/science/a ... 2021006516
"Assuming causality, we found only one significant association: maternal FT4 mediated 17.6% of the estimated effect of perfluoroundecanoic acid exposure on hyperactivity–impulsivity among first-born children."

Kim IJ, Kim BN, Lee YA, Shin HS, Hong YC, Døssing LD, Hildebrandt G, Lim YH - "Association between early-childhood exposure to perfluoroalkyl substances and ADHD symptoms: A prospective cohort study" Science of The Total Environment 163081 (2023)
https://doi.org/10.1016/j.scitotenv.2023.163081
"All six PFAS exhibited inverted U-shaped curves..."

Modesto T, Tiemeier H, Peeters RP, Jaddoe VW, Hofman A, Verhulst FC, Ghassabian A - "Maternal Mild Thyroid Hormone Insufficiency in Early Pregnancy and Attention-Deficit/Hyperactivity Disorder Symptoms in Children" JAMA Pediatr 169(9):838-45 (2015) doi: 10.1001/jamapediatrics.2015.0498
https://jamanetwork.com/journals/jamape ... le/2344550
"Children exposed to maternal hypothyroxinemia in early pregnancy had more ADHD symptoms, independent of confounders."

Reardon AJF, Khodayari Moez E, Dinu I, Goruk S, Field CJ, Kinniburgh DW, MacDonald AM, Martin JW; APrON Study - "Longitudinal analysis reveals early-pregnancy associations between perfluoroalkyl sulfonates and thyroid hormone status in a Canadian prospective birth cohort" Environ Int 129:389-399 (2019) doi: 10.1016/j.envint.2019.04.023 APrON
https://www.sciencedirect.com/science/a ... 2018332094

Skogheim TS, Weyde KVF, Aase H, Engel SM, Surén P, Øie MG, Biele G, Reichborn-Kjennerud T, Brantsæter AL, Haug LS, Sabaredzovic A, Auyeung B, Villanger GD - "Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with attention-deficit/hyperactivity disorder and autism spectrum disorder in children" Environ Res 202:111692 (2021) doi: 10.1016/j.envres.2021.111692 MoBa
https://www.sciencedirect.com/science/a ... 5121009865
Note: Inverse-U-shape
"In addition, there appeared to be an inverse U-shaped pattern between PFOA and ASD diagnosis in children, with highest risk in the mid-range levels of PFOA."
Image

Villanger GD, Ystrom E, Engel SM, Longnecker MP, Pettersen R, Rowe AD, Reichborn-Kjennerud T, Aase H - "Neonatal thyroid-stimulating hormone and association with attention-deficit/hyperactivity disorder" Paediatr Perinat Epidemiol 34(5):590-596 (2020) doi: 10.1111/ppe.12643
https://onlinelibrary.wiley.com/doi/10.1111/ppe.12643. MoBa
"In multivariable, quintile models the relationship appeared to follow a U-shaped pattern with elevated odds ratios (OR) at lower and higher TSH levels."
  • see: Alvarez-Pedrerol M, Ribas-Fitó N, Torrent M, Julvez J, Ferrer C, Sunyer J - "TSH concentration within the normal range is associated with cognitive function and ADHD symptoms in healthy preschoolers" Clin Endocrinol (Oxf) 66(6):890-8 (2007)
    https://onlinelibrary.wiley.com/doi/10. ... 07.02871.x

    Pérez-Lobato R, Ramos R, Arrebola JP, Calvente I, Ocón-Hernández O, Dávila-Arias C, Pérez-García M, Olea N, Fernández MF - "Thyroid status and its association with cognitive functioning in healthy boys at 10 years of age" Eur J Endocrinol 172(2):129-39 (2015)
    https://eje.bioscientifica.com/view/jou ... /2/129.xml
    "Thus, poor child cognitive function is significantly associated with higher TSH levels but not with intermediate levels, following an inverse U-shaped curve."
Yao Q, Vinturache A, Lei X, Wang Z, Pan C, Shi R, Yuan T, Gao Y, Tian Y - "Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid hormones, and infant neurodevelopment" Environ Res 206:112561 (2022) doi: 10.1016/j.envres.2021.112561
https://www.sciencedirect.com/science/a ... 5121018624
"Using a contemporaneous birth cohort, we found an inverse association between prenatal exposure to PFAS including PFBS or PFHxS and neurodevelopmental scores at 1 year of age, especially in gross motor domain. After stratification by infant sex, the significant negative associations were only found among male infants...PFBS and PFHxS were negatively associated with early neurodevelopment, especially consistent in gross motor domain. The associations were partly explained by TSH and FT4."

Deiodinase Studies:

Cheng Y, Cui Y, Chen HM, Xie WP - "Thyroid disruption effects of environmental level perfluorooctane sulfonates (PFOS) in Xenopus laevis" Ecotoxicology 20(8):2069-78 (2011)doi: 10.1007/s10646-011-0749-3
https://link.springer.com/article/10.10 ... 011-0749-3
"PFOS exposure resulted in up-regulation of thyroid hormone-regulated genes-thyroid receptor beta A (TRβA), basic transcription element-binding protein (BTEB) and type II deiodinase (DI2) mRNA expression, presented as an inverted U-shaped dose response pattern."

SEE more: PFAS and D2 & D3 Deiodinase
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Ghassabian A, Bongers-Schokking JJ, de Rijke YB, van Mil N, Jaddoe VW, de Muinck Keizer-Schrama SM, Hooijkaas H, Hofman A, Visser W, Roman GC, Visser TJ, Verhulst FC, Tiemeier H - "Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: the Generation R Study" Thyroid 22(2):178-86 (2012). doi: 10.1089/thy.2011.0318
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271370/
"However, elevated titers of TPOAbs in mothers were associated with externalizing problems in children (odds ratio [OR]=1.64, 95% confidence interval [CI]: 1.17–2.29, p=0.004). In particular, children of TPOAb-positive mothers were at a higher risk of attention deficit/hyperactivity problems (OR=1.77, 95% CI: 1.15–2.72, p=0.01)."
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