Assessment of associations between mitochondrial DNA haplogroups and attention deficit and hyperactivity disorder in Korean children

Hwang, In Wook; Kwon, Bit Na; Kim, Hyung Jun; Han, Soon Woo; Lee, Noo Ri; Lim, Myung Ho; Kwon, Ho Jang; Jin, Han Jun

doi:10.1016/j.mito.2018.11.003

Cited by 14 publications

(9 citation statements)

References 42 publications

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“…Several recent studies have detected sex-dependent differences in mitochondrial proteins related to ADHD symptoms. Lee et al (2019) observed different expression patterns of mitochondrial HtrA2 serine protease in boys and girls with ADHD [ 74 ], and similarly, Hwang et al (2019) found that different mitochondrial DNA haplogroups had gender-dependent different functions in ADHD patients [ 75 ]. Interestingly, these studies suggested a greater sensitivity to mitochondrial protein changes in girls, in accordance with a previous study that demonstrated a higher susceptibility of female neuron mitochondria during hypoxia-ischemic injury [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA–INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study

Santa‐Marina

Lertxundi

Andiarena

et al. 2020

IJERPH

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Ferritin status during prenatal brain development may influence the risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. We investigated the association of maternal ferritin in pregnancy and ADHD-like symptoms in offspring. A total of 1095 mother-child pairs from three birth cohorts of the INMA Project (Spain) were studied. Maternal plasma ferritin in pregnancy was measured at 11.57 weeks of gestation. Children′s ADHD-like symptoms at ages 4–5 years were assessed using the ADHD Rating Scale-IV. The count model of the zero-inflated Poisson regression model showed a significant inverse association between ferritin (continuous variable) and inattention, β = −0.19 (−0.32, −0.07), for boys. Comparing ferritin level by tertiles, significant differences were observed between the first tertile ([1.98, 20.92]) and the second ([20.92, 38.79]) and third tertiles ([38.79, 216.5]) (mg/L).The number of symptoms was lower for those in the third tertile, β = −0.3 (−0.55, −0.5), and for those in the second one, β = −0.37 (−0.6, −0.14). The model stratification by sex also showed this inverse association for boys only, β = −0.21 (−0.34, −0.08). No associations were found between ferritin level and hyperactivity or total ADHD symptoms. High ferritin levels during pregnancy show a protective association with child inattentive-type ADHD symptoms.

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Section: Discussionmentioning

confidence: 99%

Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA–INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study

Santa‐Marina

Lertxundi

Andiarena

et al. 2020

IJERPH

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“…The NAc also seems to be altered in animal models showing anxiety disorders [ 61 ]. Rats showing lower levels of adenosine triphosphate (ATP) in the NAc are more likely to show anxiety; lower levels of ATP availability may indicate mitochondrial dysfunction [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…While factors such as genetics and iodine levels in the body may impact the potency of exposure impacts [ 11 , 13 ], more research is needed to determine exactly what leads to susceptibility. Several published articles have postulated that fluoride could be producing alterations in mitochondrial DNA; mitochondrial DNA has many implications in various mental disorders [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Impacts of Fluoride Neurotoxicity and Mitochondrial Dysfunction on Cognition and Mental Health: A Literature Review

Adkins

Brunst

2021

IJERPH

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This review focuses on the synthesis of current experimental and observational data regarding the effect of fluoride exposure on childhood mental health and the role of mitochondrial function as a mechanism of action. We aggregated data on the relationships between fluoride neurotoxicity, mitochondrial function, and cognitive and mental health using PubMed. Current animal and human research suggest that prenatal and perinatal fluoride exposure might have neurotoxic effects. These studies observed physical changes (fur loss and delayed reflex development in animals), intelligence loss, increased hyperactivity, and irregular moods associated with fluoride exposure. Two gaps in the literature were identified: (1) there is limited research on the mental and emotional impacts of fluoride exposure compared to research on cognitive outcomes, and (2) human studies primarily focus on prenatal and perinatal exposure, with little research conducted at other time points (e.g., adolescence). Furthermore, there is no agreed-upon mechanism for the neurotoxic effects of fluoride; however, fluoride can induce mitochondrial damage, including decreasing circulating mitochondrial DNA content, dysregulating biogenesis, and circular structure loss. Additionally, many neurodevelopmental conditions have mitochondrial underpinnings. More work is needed to elucidate the impact and timing of fluoride exposure on mental health and the role of mitochondrial function as a biological mechanism

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“…In addition, the ubiquitin signal could interact with autophagy and then cause the mitochondria damage and degradation 47 . Hwang et al found that mitochondrial DNA haplogroups polymorphism was associated with ADHD children in Korean population 48 . As such, how rs3908461 could affect ADHD expression through the specific molecular pathways deserve further exploration.…”

Section: Discussionmentioning

confidence: 99%

A potential association of RNF219‐AS1 with ADHD: Evidence from categorical analysis of clinical phenotypes and from quantitative exploration of executive function and white matter microstructure endophenotypes

Chen

et al. 2021

CNS Neurosci Ther

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Aims Attention‐deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder of substantial heritability, yet emerging evidence suggests that key risk variants might reside in the noncoding regions of the genome. Our study explored the association of lncRNAs (long noncoding RNAs) with ADHD as represented at three different phenotypic levels guided by the Research Domain Criteria (RDoC) framework: (i) ADHD caseness and symptom dimension, (ii) executive functions as functional endophenotype, and (iii) potential genetic influence on white matter architecture as brain structural endophenotype. Methods Genotype data of 107 tag single nucleotide polymorphisms (SNP) from 10 candidate lncRNAs were analyzed in 1040 children with ADHD and 630 controls of Chinese Han descent. Executive functions including inhibition and set‐shifting were assessed by STROOP and trail making tests, respectively. Imaging genetic analyses were performed in a subgroup of 33 children with ADHD and 55 controls using fractional anisotropy (FA). Results One SNP rs3908461 polymorphism in RNF219‐AS1 was found to be significantly associated with ADHD caseness: with C‐allele detected as the risk genotype in the allelic model (P = 8.607E‐05) and dominant genotypic model (P = 9.628E‐05). Nominal genotypic effects on inhibition (p = 0.020) and set‐shifting (p = 0.046) were detected. While no direct effect on ADHD core symptoms was detected, mediation analysis suggested that SNP rs3908461 potentially exerted an indirect effect through inhibition function [B = 0.21 (SE = 0.12), 95% CI = 0.02‐0.49]. Imaging genetic analyses detected significant associations between rs3908461 genotypes and FA values in corpus callosum, left superior longitudinal fasciculus, left posterior limb of internal capsule, left posterior thalamic radiate (include optic radiation), and the left anterior corona radiate (P FWE corrected < 0.05). Conclusion Our present study examined the potential roles of lncRNA in genetic etiological of ADHD and provided preliminary evidence in support of the potential RNF219‐AS1 involvement in the pathophysiology of ADHD in line with the RDoC framework.

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Assessment of associations between mitochondrial DNA haplogroups and attention deficit and hyperactivity disorder in Korean children

Cited by 14 publications

References 42 publications

Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA–INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study

Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA–INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study

Impacts of Fluoride Neurotoxicity and Mitochondrial Dysfunction on Cognition and Mental Health: A Literature Review

A potential association of RNF219‐AS1 with ADHD: Evidence from categorical analysis of clinical phenotypes and from quantitative exploration of executive function and white matter microstructure endophenotypes

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