Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-27T11:46:19.752Z Has data issue: false hasContentIssue false
  • English
  • Français

Association between phthalates and externalizing behaviors and cortical thickness in children with attention deficit hyperactivity disorder

Published online by Cambridge University Press:  12 November 2014

S. Park ,
J.-M. Lee ,
J.-W. Kim ,
J. H. Cheong ,
H. J. Yun ,
Y.-C. Hong ,
Y. Kim ,
D. H. Han ,
H.J. Yoo  and
M.-S. Shin
...Show all authors
S. Park
Affiliation:
Department of Child and Adolescent Psychiatry, Seoul National Hospital, Seoul, Republic of Korea
J.-M. Lee
Affiliation:
Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea
J.-W. Kim
Affiliation:
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea College of Medicine and Behavioral Medicine Institute, Seoul National University, Seoul, Republic of Korea
J. H. Cheong
Affiliation:
Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul, Republic of Korea
H. J. Yun
Affiliation:
Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea
Y.-C. Hong
Affiliation:
Department of Preventive Medicine, Seoul National University College of Medicine and Institute of Environmental Medicine, Seoul, Republic of Korea
Y. Kim
Affiliation:
Department of Child and Adolescent Psychiatry, Seoul National Hospital, Seoul, Republic of Korea
D. H. Han
Affiliation:
Department of Psychiatry, Chung Ang University, College of Medicine, Seoul, Republic of Korea
H.J. Yoo
Affiliation:
College of Medicine and Behavioral Medicine Institute, Seoul National University, Seoul, Republic of Korea Department of Psychiatry, Seoul National University Bung dang Hospital, Seongnam, Republic of Korea
M.-S. Shin
Affiliation:
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea College of Medicine and Behavioral Medicine Institute, Seoul National University, Seoul, Republic of Korea
S.-C. Cho
Affiliation:
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea College of Medicine and Behavioral Medicine Institute, Seoul National University, Seoul, Republic of Korea
B.-N. Kim*
Affiliation:
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea College of Medicine and Behavioral Medicine Institute, Seoul National University, Seoul, Republic of Korea
*
*Address for correspondence: Dr B.-N. Kim, Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University, College of Medicine, College of Medicine, 101 Daehakro, Chongro-Gu, Seoul, South Korea. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background.

Previous studies have implicated the relationship between environmental phthalate exposure and attention deficit hyperactivity disorder (ADHD) symptoms of childhood, but no studies have been conducted in children who have a confirmed diagnosis of ADHD obtained through meticulous diagnostic testing. We aimed to determine whether phthalate metabolites in urine would be higher in children with ADHD than in those without ADHD and would correlate with symptom severity and cortical thickness in ADHD children.

Method.

A cross-sectional examination of urine phthalate metabolite concentrations was performed; scores for ADHD symptoms, externalizing problems, and continuous performance tests were obtained from 180 children with ADHD, and brain-imaging data were obtained from 115 participants. For the control group, children without ADHD (N = 438) were recruited. Correlations between phthalate metabolite concentrations and clinical measures and brain cortical thickness were investigated.

Results.

Concentrations of phthalate metabolites, particularly the di(2-ethylhexyl) phthalate (DEHP) metabolite, were significantly higher in boys with ADHD than in boys without ADHD. Concentrations of the di-n-butyl phthalate (DBP) metabolite were significantly higher in the combined or hyperactive-impulsive subtypes compared to the inattentive subtype, and the metabolite was positively correlated with the severity of externalizing symptoms. Concentrations of the DEHP metabolite were negatively correlated with cortical thickness in the right middle and superior temporal gyri.

Conclusions.

The results of this study suggest an association between phthalate concentrations and both the diagnosis and symptom severity of ADHD. Imaging findings suggest a negative impact of phthalates on regional cortical maturation in children with ADHD.

Keywords

Attention-deficit hyperactivity disordercortical thicknessneuropsychologyphthalate
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 8 , June 2015 , pp. 1601 - 1612
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Almeida Montes, LG, Prado Alcantara, H, Martinez Garcia, RB, De La Torre, LB, Avila Acosta, D, Duarte, MG (2013). Brain cortical thickness in ADHD: age, sex, and clinical correlations. Journal of Attention Disorders 17, 641–654.Google Scholar
Aron, AR, Poldrack, RA (2005). The cognitive neuroscience of response inhibition: relevance for genetic research in attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 1285–1292.Google Scholar
CDC, U.S. Department of Health and Human Services (2005). Third National Report on Human Exposure to Environmental Chemicals. National Center for Environmental Health, Division of Laboratory Sciences: Atlanta, GA.Google Scholar
Cho, SC, Bhang, SY, Hong, YC, Shin, MS, Kim, BN, Kim, JW, Yoo, HJ, Cho, IH, Kim, HW (2010). Relationship between environmental phthalate exposure and the intelligence of school-age children. Environmental Health Perspectives 118, 1027–1032.CrossRefGoogle ScholarPubMed
Engel, SM, Miodovnik, A, Canfield, RL, Zhu, C, Silva, MJ, Calafat, AM, Wolff, MS (2010). Prenatal phthalate exposure is associated with childhood behavior and executive functioning. Environmental Health Perspectives 118, 565–571.Google Scholar
Fahim, C, He, Y, Yoon, U, Chen, J, Evans, A, Perusse, D (2011). Neuroanatomy of childhood disruptive behavior disorders. Aggressive Behavior 37, 326–337.Google Scholar
Faraone, SV, Biederman, J, Weber, W, Russell, RL (1998). Psychiatric, neuropsychological, and psychosocial features of DSM-IV subtypes of attention-deficit/hyperactivity disorder: results from a clinically referred sample. Journal of the American Academy of Child and Adolescent Psychiatry 37, 185–193.Google Scholar
Fennell, TR, Krol, WL, Sumner, SC, Snyder, RW (2004). Pharmacokinetics of dibutylphthalate in pregnant rats. Toxicol Sci 82, 407–418.Google Scholar
Fromme, H, Bolte, G, Koch, HM, Angerer, J, Boehmer, S, Drexler, H, Mayer, R, Liebl, B (2007). Occurrence and daily variation of phthalate metabolites in the urine of an adult population. International Journal of Hygiene and Environmental health 210, 21–33.Google Scholar
Gadow, KD, Sprafkin, J, Schneider, J, Nolan, EE, Schwartz, J, Weiss, MD (2007). ODD, ADHD, versus ODD + ADHD in clinic and community adults. Journal of Attention Disorders 11, 374–384.CrossRefGoogle ScholarPubMed
Genovese, CR, Lazar, NA, Nichols, T (2002). Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 15, 870–878.CrossRefGoogle ScholarPubMed
Greenberg, LM, Waldman, ID (1993). Developmental normative data on the test of variables of attention (T.O.V.A.). Journal of Child Psychology and Psychiatry, and Allied Disciplines 34, 1019–1030.Google Scholar
Grizenko, N, Paci, M, Joober, R (2010). Is the inattentive subtype of ADHD different from the combined/hyperactive subtype? Journal of Attention Disorders 13, 649–657.Google Scholar
Hoppin, JA, Brock, JW, Davis, BJ, Baird, DD (2002). Reproducibility of urinary phthalate metabolites in first morning urine samples. Environmental Health Perspectives 110, 515–518.Google Scholar
Kim, BN, Cho, SC, Kim, Y, Shin, MS, Yoo, HJ, Kim, JW, Yang, YH, Kim, HW, Bhang, SY, Hong, YC (2009). Phthalates exposure and attention-deficit/hyperactivity disorder in school-age children. Biological Psychiatry 66, 958–963.CrossRefGoogle ScholarPubMed
Kim, YS, Cheon, KA, Kim, BN, Chang, SA, Yoo, HJ, Kim, JW, Cho, SC, Seo, DH, Bae, MO, So, YK, Noh, JS, Koh, YJ, McBurnett, K, Leventhal, B (2004). The reliability and validity of kiddie-schedule for affective disorders and schizophrenia-present and lifetime version- Korean version (K-SADS-PL-K). Yonsei Medical Journal 45, 81–89.Google Scholar
Koch, H, Christensen, KL, Harth, V, Lorber, M, Bruning, T (2012). Di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) metabolism in a human volunteer after single oral doses. Archives of Toxicology 86, 1829–1839.Google Scholar
Koch, H, Preuss, R, Angerer, J (2006). Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure– an update and latest results. International Journal of Andrology 29, 155–165.CrossRefGoogle Scholar
Koch, HM, Bolt, HM, Angerer, J (2004). Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium-labelled DEHP. Archives of Toxicology 78, 123–130.Google ScholarPubMed
Konrad, K, Eickhoff, SB (2010). Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder. Human Brain Mapping 31, 904–916.Google Scholar
Latini, G (2005). Monitoring phthalate exposure in humans. Clinica Chimica Acta 361, 20–29.Google Scholar
Lerch, JP, Evans, AC (2005). Cortical thickness analysis examined through power analysis and a population simulation. Neuroimage 24, 163–173.Google Scholar
MacDonald, D, Kabani, N, Avis, D, Evans, AC (2000). Automated 3-D extraction of inner and outer surfaces of cerebral cortex from MRI. Neuroimage 12, 340–356.Google Scholar
Makris, N, Biederman, J, Valera, EM, Bush, G, Kaiser, J, Kennedy, DN, Caviness, VS, Faraone, SV, Seidman, LJ (2007). Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder. Cerebral Cortex 17, 1364–1375.Google Scholar
Masuo, Y, Morita, M, Oka, S, Ishido, M (2004). Motor hyperactivity caused by a deficit in dopaminergic neurons and the effects of endocrine disruptors: a study inspired by the physiological roles of PACAP in the brain. Regulatory Peptides 123, 225–234.Google Scholar
National Institute of Mental Health (1970). Clinical Global Impressions. National Institute of Mental Health: Chevy Chase, Maryland.Google Scholar
Oh, KJ, Lee, H, Hong, KE, Ha, EH (1997). K-CBCL. Chung Ang Aptitude Publishing Co: Seoul, Korea.Google Scholar
Seidman, LJ, Valera, EM, Makris, N (2005). Structural brain imaging of attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 1263–1272.CrossRefGoogle ScholarPubMed
Shaw, P, Eckstrand, K, Sharp, W, Blumenthal, J, Lerch, JP, Greenstein, D, Clasen, L, Evans, A, Giedd, J, Rapoport, JL (2007). Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proceedings of the National Academy of Sciences USA 104, 19649–19654.Google Scholar
Shin, MS, Cho, S, Chun, SY, Hong, KE (2000). A study of the development and standardization of ADHD Diagnostic System. Korean Journal of Child & Adolescent Psychiatry 11, 91–99.Google Scholar
Silva, RR, Alpert, M, Pouget, E, Silva, V, Trosper, S, Reyes, K, Dummit, S (2005). A rating scale for disruptive behavior disorders, based on the DSM-IV item pool. Psychiatric Quarterly 76, 327–339.Google Scholar
Smith, CA, Macdonald, A, Holahan, MR (2011). Acute postnatal exposure to di(2-ethylhexyl) phthalate adversely impacts hippocampal development in the male rat. Neuroscience 193, 100–108.Google Scholar
So, YK, Noh, JS, Kim, YS, Ko, SG, Koh, YJ (2002). The reliability and validity of Korean parent and teacher ADHD rating scale. Journal of the Korean Neuropsychiatric Association 41, 283–289.Google Scholar
Tanida, T, Warita, K, Ishihara, K, Fukui, S, Mitsuhashi, T, Sugawara, T, Tabuchi, Y, Nanmori, T, Qi, WM, Inamoto, T, Yokoyama, T, Kitagawa, H, Hoshi, N (2009). Fetal and neonatal exposure to three typical environmental chemicals with different mechanisms of action: mixed exposure to phenol, phthalate, and dioxin cancels the effects of sole exposure on mouse midbrain dopaminergic nuclei. Toxicology Letters 189, 40–47.Google Scholar
U.S. EPA (2007). Phthalates: Toxicity and Exposure Assessment for Children's Health (TEACH): Chemical Summary. U.S. Environmental Protection Agency: Chicago, IL.Google Scholar
Wahlund, K, Kristiansson, M (2009). Aggression, psychopathy and brain imaging – Review and future recommendations. International Journal of law and Psychiatry 32, 266–271.Google Scholar
Wormuth, M, Scheringer, M, Vollenweider, M, Hungerbuhler, K (2006). What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Analysis 26, 803–824.Google Scholar
Yang, YH, Kim, JW, Kim, YN, Cho, SC & Kim, BN (2008). Screening of attention deficit hyperactivity disorder in Seoul. Jouirnal of the Korean Neuropsychiatric Association 47, 292–298.Google Scholar
Supplementary material: File

Park Supplementary Material

Figure S1 and Table S1

Download Park Supplementary Material(File)
File 2.4 MB