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As with all risk factors, these do not cause ADHD: they add an element of risk and may act in synergy with other risk factors or susceptibility genes. Their risk promoting ability may be increased or decreased by these other factors.

Genes, environmental risk factors and medical conditions associated with Attention deficit hyperactivity disorder (ADHD)

Ongoing clinical trails, worldwide, can be interrogated at ClinicalTrials.Gov a service of the US National Institutes of Health

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OMIM Online Mendelian Inheritance in Man, a database of human genes and genetic disorders developed by staff at Johns Hopkins University

 

 

 

 

 

Risk Factor (Links to Wikipedia and Pubmed)

Genes associated with ADHD KEGG pathway analysis of ADHD genes See also ADHDGene from CAS for genes and pathway enrichment

Genome wide association: See:- Genome.gov and HuGE navigator

A2BP1 ABHD13 ADAMTS2 ADH1C AK094352 AMOTL1 ASTN2 ATPBD4 ATP2C2 ATP8B1 BCL11A BMPR1B C5orf15 C7orf60 C9orf98 C10orf79 C12orf28 C16orf46 C21orf34 CCDC46 CDH13 CHRNA7 CLYBL CREB5 CRYGC CSMD2 CWC15 DHODH DIRAS2 DMRT2 DNM1 ELOVL6 EMP2 EREG ETV3 ETV3L FAM190A FERMT3 FHIT FLJ31818 FLJ34870 FLJ39061 FOXP1 FZD7 GLT25D2 GPC6 GPR85 GRIK1 GSX1 HAS3 IL16 ITGAE ITGA11 JMJD2D KDM4D KIAA0174 KIF6 KIRREL3 LIG4 LOC643308 LOC389365 LOC729257 LOC390980 LOC729257 LPL LRRC7 MAN2A2 MAP1B MEIS2 MFHAS1 MGC33657 MMP24 MOBP MYT1L NAPRT1 NCKAP5 NT5DC3 NUDT22 OXER1 PAWR PDX1 PKD1L2 PKD1L3 PITRM1 PIWIL4 PPM1F PPM1K PTPRD REEP5 RGL1 RIT1 SEMA3A SLC6A1 SPATA8 SULF2 SUPT3H UGT1A9 SLC9A9 SLCO3A1 SULF2 TFEB TLL2 TRPT1 UNC5B YWHAZ XKR4 ZBTB16 ZNF423 ZNF544

Pre- and non-GWAS Copy number variations / deletions are highlighted in bold

Infectious agents PANDAS (Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) Refs

Immunity/Allergy

Prenatal factors and Birth related

  • ADHD risk has been reported to be increased in children born to women experiencing a viral rash during pregnancy (measles, varicella or rubella) Arpino et al, 2005.
  • Premature delivery symptoms, severe flu attacks and neonatal seizures have been asociated with the subsequent development of ADHD Pineda et al, 2003
  • The use of acetaminopen during pregnancy has been linked to the subsequent development of ADHD Liew et al, 2014
  • Low maternal folate has been associated with ADHD Schlotz et al, 2010
  • High intrauterine testosterone may be associated with ADHD James, 2008
  • Prenatal alcohol exposure hes been associated with ADHD Pineda et al, 2007 Toxicity of alcohol or acetaldehyde may be involved in relation to uterine exposure Abel, 1984
  • Prenatal methamphetamine exposure has been associated with ADHD LaGasse at al, 2012 and prenatal cocaine exposure has been associated with subsequent behavioural problems Levine et al, 2012
  • Association with pre-eclampsia Mann and McDermott, 2010
  • Gestational diabetes has been associated with the later development of ADHD in the offspring Nomura et al, 2011
  • Febrile seizures have been associated with ADHD Pineda et al, 2010
  • a relation between passive smoking and behavioural disorders including attention deficit/hyperactivity disorder (ADHD) has been reported Hofnuis et al, 2002
  • Prenatal tobacco use has been associated with ADHD Braun et al, 2006
  • Young maternal age and birthplace has been associated with ADHD, which predominantly affects males
  • Severe hyperbilirubinemia at birth has been associated wityh later development of autism and to a lesser extent, ADHD Jangaard et al, 2008
  • Children exposed to anaesthesia more than twice before the age of 3 are twice as likely to have ADHD than children who have not been exposed. Sprung et al, 2012
  • Maternal thyroid peroxidase autoantibodies have been associated with ADHD related problems in the children Ghassabian et al, 2012
  • Prenatal lead exposure (cord blood lead levels) has been associated with a 3.43 times higher risk for hyperactivity in both boys and girls: Prenatal p,p'-DDE (para,para dichlorodiphenyldichloroethylene )levels increased total prolems in girls and emotional problems were associated with prenatal cadmium levels in boys Sioen et al, 2013
  • Smoking in pregnancy, maternal urinary tract infection, induction of labour, and experiencing threatened preterm labor increased the risk of ADHD, with little gender difference. Early term deliveries marginally increased the risk of ADHD.oxytocin augmentation of labor appears protective for girls Silva et al, 2013

Parenting

Dietary factors, environment, pollution and toxins
  • Increased blood concentrations of lead , manganese and zinc have been associated with ADHD Yousef et al, 2011 See also Bellinger 2011
  • Lead and polychlorinated biphenyls have been associated with ADHD Eubig et al, 2010
  • High cadmium exposure has been associated with ADHD, in those with higher lead levels Ciesielski et al, 2012
  • Manganese exposure has been asociated with ADHD Farias et al, 2010
  • High mercury levels have been associated with ADHD Cheuk and Wong 2006
  • Traffic pollution (elemental carbon attributed to traffic) during the child's first year of life was significantly associated with Hyperactivity T-scores at 7 years of age Newman et al, 2013
  • Lower zinc levels have been asociated with ADHD Oner et al, 2010
  • Iron deficiency has been associated with ADHD Calarge et al, 2010
    • Lower ferritin levels have also been associated Refs
  • Zinc deficiency has been associated with ADHD Dodig-Curkovic et al, 2010
  • Particulate pollution from motor vehicles has been associated with ADHD Siddique et al, 2010
  • Early-life exposure to air pollution from indoor gas appliances has been associated with ADHD Morales et al, 2009
  • Children with ADHD consumed half the amount of fish/seafood, meat and eggs when compared to the norm Nq et a, 2009
  • Fatty acid deficiency symptoms of dry hair and skin, frequent thirst and urination have been observed to be higher in children with attention deficit hyperactivity disorder Sinn, 2007
  • Food colorings, including tartrazine or carmoisine, Rowe 1988 and food additives (sodium benzoate) have been implicated in hyperactivity Connolly et al, 2010
  • The contentious colourings are: sunset yellow FCF (E110), quinoline yellow (E104), carmoisine (E122), allura red (E129), tartrazine (E102) and ponceau 4R (E124)) A Guide to E numbers
    • The effects of food additives are modified by HNMT polymorphisms, suggesting an effect related to histamine Stevenson et al, 2010
    • Those affected by food additives may also be sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and oranges Stevens et al, 2011.
  • Trichlorophenols (organochlorine compounds in pesticides) have been linked to ADHD Xu et al, 2011 Organochlorines Sagiv et al, 2012
  • Prenatal exposure to polycyclic aromatic hydrocarbons (air pollutants from fossil fuel burning and other combustion sources) has been associated with attention deficits Perera et al, 2012
  • Hexachlorobenzene has been associated with ADHD Ribas-Fitó et al, 2007
  • Exposure to organophosphate pesticides has been associated with ADHD Marks et al, 2010
  • Prenatal chlorpyrifos levels have been associated with ADHD Rauh et al, 2006
  • Exposure to Phthalates has been associated with ADHD Jurewicz and Hanke, 2011
  • Polyfluoroalkyl chemical exposure has been linked to ADHD Hoffmann et al, 2010
  • Exposure to polybromodiphenyl ethers used as flame retardants has been linked to ADHD Gascon et al, 2011
  • High serum serum concentrations of persistent organic pollutants belonging to the categories of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans have been associated with ADHD Lee et al, 2007
  • omega-3 and omega-6 fatty acids as well as magnesium and zinc have been reported to improve symptoms Huss et al, 2010
  • Some ADHD children are sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and orange Stevens et al, 2011.
  • The ScanBrit study has reported significant improvement with gluten and casein free diets in autism spectrum disorders, including ADHD Whiteley et al, 2010
  • There is a lower prevalence of ADHD in areas with high solar intensity ( not found for the prevalence of autism spectrum disorders or major depressive disorder) Arns et al, 2013
Drugs and treatments Association with other diseases and conditions Others
  • Gene expression studies in ADHD brains converge on immune related pathways , oxidative stress and mitochondrial pathways Lintas et al, 2010
  • Low levels of 3-hydroxykynurenine have been reported Oades et al, 2010
  • Inattention may be greater in the evening and hyperactivity greater in the evening in males Bae et al, 2010
  • A lower ADHD prevalence has been found in regions of high solar intensity Arns et al, 2013

Plasma/serum levels

  • Lower plasma cortisol in ADHD Ma et al, 2011
  • Low plasma levels of phenylalanine, tyrosine, tryptophan, histidine, and isoleucine Bornstein et al, 1990
  • higher omega-3 levels polyunsaturated fatty acid levels were associated with decreased inattention, hyperactivity, emotional and conduct difficulties and increased levels of prosocial behaviour Kirby et al, 2010.
  • Increased plasma levels of BDNF Shim et al, 2008
  • Low levels of intact parathyroid hormone Humble et al, 2010
  • Increased levels of malondialdehde ( a marker of oxidative stress and lipid peroxidation) Bulut et al, 2007
  • ADHD is associated with increased antennary fucosylation of biantennary glycans and decreased levels of some complex glycans with three or four antennas.Pivac et al, 2011
  • Glutathione peroxidase activities of ADHD patients were significantly lower and catalase levels higher Ceylan et al, 2010
  • Lower levels of glutathione Dvoráková et al, 2006
  • Low levels of pregnelonone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate are associated with hyperactivity Strous et al, 2001
  • total and HDL cholesterol levels were significantly increased in patients with low monoamine oxidase activity Kiive at al, 2005
  • Overall symptom ratings have been associated with increases of the interleukins IL16 and IL13, inveresly correlated with S100B levels: Increased response time variability has been related to lower TNF-alpha, and higher Interferon gamma levels Oades et al, 2010
  • Low serum levels of docasahexaenoic, dihomogammalinolenic, and arachidonic acids have been reported Mitchell et al, 1987 along with low plasma levels of alpha-linoleic acid and oleic acid Spahis et al, 2008
  • plasma gamma-linolenic acid in ADHD children was higher than that in controls . For phospholipids isolated from red blood cell membranes, oleic acid was significantly higher, whereas nervonic acid , linoleic acid , arachidonic acid , and docosahexaenoic acid were lower in subjects with ADHD Chen et al, 2004.

An article on the developmental toxicity of industrial chemicals Labie 2007

European Food safety authority

Pesticides and disease database including childhood developmental disorders

DEVNERTOX Toxic threats to the developing nervous system: in vivo and in vitro studies on the effects of mixture of neurotoxic substances potentially contaminating food

HAZMAP A Relational Database of Hazardous Chemicals and Occupational Diseases

IVTIP In vitro testing industrial platform

Toxics Release Inventory (TRI) Program : USA environmental protection agency

Dangerous household chemicals

TOXNET - Databases on toxicology, hazardous chemicals, environmental health, and toxic releases.

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