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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
- Associated with enterovirus
71 infection Gau
et al, 2008
- Possible association with Coxsackievirus
B4 Chu
et al, 2009
- A high prevalence in HIV-1 infected children Zeegers
et al, 2010
- Pneumococcus
Polysaccaride 14 antibodies have been reported more frequently in affected
twins Bilenberg
et al, 2011
- Rash causing maternal viral diseases (measles, rubella, varicella)
have been associated with the devlopment of ADHD in children Arpino
et al, 2005
- Prior streptococcal infection has been associated with incident diagnoses
of ADHD Leslie
et al, 2008
- A consequence of pyogenic meningitis
caused by Haemophilus influenzae type b Rauter
and Mutz 1994.
- Associated withy maternal genitourinary infection and candidiasis
Mann
and McDermott, 2010
- Initially reported in a patient with ONJ onfection (osteonecrosis
of the jaw) Donev
and Thome 2010
- Toxoplasmosis
(case report) Brynska
et al, 2001
- Lyme
disease caused by Borrelia burgdorferi infection can mimic ADHD
symptoms
Fallon et al, 1998
- A high prevalence of ADHD in HIV-infected children Zeegers
et al, 2010
- Mould exposure has been associated with ADHD (mycotoxins from fungi)
Ezra
et al, 2011
- Poor oral health and dental caries have been associated with ADHD
Kohlboeck
et al, 2012
- Pet ownership has been associated with child hyperactivity/inattention
Casas
et al, 2013
Immunity/Allergy
- Association with allergic rhinitis Suwan
et al, 2011 and other atopic diseases (asthma, eczema ) Schmitt
et al, 2013
- A higher frequency of food allergies is observed in ADHD Almog
et al, 2010
- Early food allergy and respiratory allergy symptoms independently
and synergistically contribute to higher risk of ADHD Jiang
et al, 2018.
- Thimerosal-containing vaccines (organic mercury) have been linked
with a number of neurodevelopmental disorders including ADHD and autism
Young
et al, 2008
- Increasing organic-Hg exposure from Thimerosal-containing vaccines
heightens the risk of a "Hyperkinetic syndrome of childhood"
diagnosis Geier
et al, 2016.
- Association between atopic dermatitis and ADHD in children and adults
Strom
et al, 2016
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 see also
Bauer et al, 2018
- 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 has 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 wit\h 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
- Children exposed to maternal hypothyroxinemia in early pregnancy had
more ADHD symptoms Modesto
et al, 2015
- Maternal hyperthyroidism diagnosed and treated for the first time
after the birth of the child increased the risk of ADHD in the child
Andersen
et al, 2014
- ADHD risk in the offspring is associated with parental immune disorders
(multiple sclerosis, rheumatoid arthritis, type 1 diabetes, asthma and
hypothyroidism ) Instanes
et al, 2015
- 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
- Maternal stress during pregnancy, postpartum depression, and changes
in the primary caretaker during first 3 years associated with ADHD Park
et al, 2014
- Higher maternal circulating levels of vitamin D (25-hydroxyvitamin
D3) in pregnancy associated with lower risk of developing ADHD-like
symptoms in childhood Morales
et al, 2015.
- Prenatal antidepressant use during pregnancy associated with the subsequent
development of ADHD in the offspring Clements
et al, 2015
- Maternal chemical intolerance associated with ADHD and autism in the
offspring Heilbrun
et al, 2015
- Birth month asociated with the incidence of ADHD (upward trend towards
the later part of the year peaking in November: northern hemisphere)
Boland
et a, 2015
- Maternal medium/high use of cell phones during pregnancy may be associated
with an increased risk for behavioral problems, particularly hyperactivity/inattention
problems, in the offspring Birks
et al, 2017.
- Maternal obesity before pregnancy is a risk factor for ADHD in children.
Maternal obesity as well as underweight may also be associated with
an increased risk for Autism spectrum disorders Andersen
et al, 2017.
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
- Polybrominated diphenyl ether flame retardant exposure has been associated
with ADHD Sagiv
et al, 2015
- 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 Hong
et al, 2014
- 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
- Pyrethroid pesticide use linked to ADHD (stronger in boys -` `urinary
levels of pyrethroid metabolite 3-phenoxybenzoic acid) Wagner-Schuman
et al, 2015
- 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 and 2018
- Hexachlorobenzene has been associated with ADHD Ribas-Fitó
et al, 2007
- Exposure to organophosphate pesticides has been associated with ADHD
Marks
et al, 2010
- dimethylphosphate (organophosphate metabolite) urinary levels asociated
with ADHD Yu
et al, 2016
- Prenatal chlorpyrifos levels have been associated with ADHD Rauh
et al, 2006
- Exposure to Phthalates has been associated with ADHD Jurewicz
and Hanke, 2011
- Iatrogenic exposure to di(2-ethylhexyl)phthalate metabolites during
intensive care (circulating phthalates leaching from indwelling medical
devices) associated with the important attention deficit observed in
children 4 years after critical illness Verstraete
et al, 2016
- 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
- Prenatal or childhood exposure to Bisphenol A has been associated
with ADHD Mustieles
et al, 2015
- 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
- Higher reports of ADHD symptomatology in areas supplied with fluoridated
water Malin
and Till, 2015
- 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
- A traditional-healthy dietary pattern associated with lower odds having
ADHD and a snack pattern with higher odds Woo
et al, 2014.
- Energy drinks associated with attention/hyperactivity problems in
youth Schwartz
et al, 2015
- Sugar sweetened beverages associated with ADHD Yu
et al, 2016
- Maternal Licorice Consumption During Pregnancy associated with an
increased risk of ADHD in children: Girls and boys exposed to high
maternal glycyrrhizin consumption scored lower on tests of intelligence
quotient, had poorer memory , and had 3.3-fold higher odds of ADHD problems
compared with children whose mothers consumed little to no glycyrrhizinRäikkönen
et al, 2017
- Increased mean platelet volume has been observed in ADHD children.Yorbik
et al, 2014
Drugs and treatments
- Ritalin
(methylphenidate) is most commonly used Refs
- lisdexamfetamine
dimesylate has been reported to be of benefit Brams
et al, 2011
- natural polyphenols ( Pycnogenol
) may be beneficial in therapy of this disease Viktorinova
et al, 2009
- Niaprazine
has been reported to be of benefit Niederhofer,
2010
- Vitamin B6/ Magnesium supplements have been reported to be effective
Mousain-Bosc
et al, 2006
- Treatment with carnitine has been reported to decrease the attention
problems and aggressive behavior in boys with ADHD Van
Oudheusden and Scholte, 2002
- Omega-3 fatty acid supplementation, particularly with higher doses
of eicosapentaenoic acid has been shown to be moderately effective Bloch
and Qawasmi, 2011
- A review noted that Zinc, iron, Pinus marinus (French maritime pine
bark), and a Chinese herbal formula (Ningdong) may be beneficial Sarris
et al, 2011
- A combination of omega-3 and omega-6 fatty acids as well as magnesium
and zinc has been reported to be effective Huss
et al, 2010
Association with other diseases and conditions
- Associations with autism spectrum disorders Banaschewski
et al, 2011
- Association with childhood asthma Mogensen
et al, 2011
- It has been suggested that this may be due to the use of inhaled
corticosteroids and leukotriene antagonists Sancoban
et al, 2011
- Association with eczema Camfferman
et al, 2010
- Association with childhood obesity Koshy
et al, 2011 and with maternal obesity pre-pregnancy Daraki
et al, 2017
- Nocturnal enuresis (bedwetting) Zavadenko
et al, 2011
- Associated with thyroid hormone resistance Hauser
et al, 1993
- Children with ADHD have significantly longer sleep onset latency and
a more irregular sleep patterns Hvbolby
et al, 2008
- Obstructive sleep apnea syndrome has been associated with and may
cause ADHD Lal
et al, 2012
- Adolescents and adults with Maple
syrup Urine disease are at increased risk for ADHD, depression,
and anxiety disorders Strauss
et al, 2006
- An association of adult ADHD with the subsequent development of Lewy
body dementia Golimstok
et al, 2011
- ADHD symptoms can be observed in Trichotillomania
(the urge to pull one's own hair) Golubchik
et al, 2011
- ADHD and obsessive compulsive disorder symptoms are observed in Sydenham's
chorea ( a disease caused by childhood infection with Group A beta-hemolytic
Streptococci leading to an autoimmune response that destroys cells in
the basal ganglia) Ridel
et al, 2010
- Associated with Argininosuccinate Lyase Deficiency Nagamani
et al, 2011
- Increased incidence has been reported with in
vitro fertilisation Finnstrom
et al, 2011
- ADHD disagosis has been linked to the subsequent risk of substance
abuse and smoking Wilens
et al, 2011
- Food addiction has been associated with ADHD as well as with Binge
Eating Disorder and depression Davis
et al, 2011
- ADHD is a significant risk factor for the development of substance
abuse and cigarette smoking in both sexes Wilens
et al, 2011
- ADHD has been linked to the subsequent development of borderline personality
disorder Storebø
and Simonsen, 2013
- Dextro-Transposition of the great arteries (See
CDC) has been associated with ADHD DeMaso
et al, 2014
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.
- circulating levels of miRNA 18a-5p, 22-3p, 24-3p, 106b-5p and 107
levels significantly decreased in ADHD patients Kandemir
et al, 2014
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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