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UncoverADHD

Etiology

The exact cause of ADHD is unknown. The exact nature and functional significance of this information is still under debate.

SEVERAL FACTORS SUGGEST ADHD HAS A DISTINCT PATHOPHYSIOLOGY

NEUROBIOLOGY

ADHD is thought to be associated with dysregulation of various regions in the prefrontal cortex (PFC)1

Neurobiology
Dorsolateral PFC

Impairment may lead to symptoms of inattention and distraction1,2

Ventromedial PFC

Impairment may lead to symptoms of inappropriate emotional responses or social behavior1,3

Right inferior PFC

Impairment may lead to symptoms of impulsivity and hyperactivity1,4

Other brain regions may be involved in the pathophysiology of ADHD.

Norepinephrine (NE) and dopamine (DA) play a critical role in PFC function*3,5

Neurobiology Neurobiology

Insufficient NE and DA levels, which impair PFC function,
have been associated with symptoms of ADHD.3,6

*Other neurotransmitters may be involved in the pathophysiology of ADHD.

DA=dopamine; NE=norepinephrine; PFC=prefrontal cortex.

GENETIC FACTORS

ADHD demonstrates a high degree of heritability, but it is likely that this is mediated by a relatively mild influence of multiple candidate genes7,8

Heritability

Hypothetical portrayal.

Genes with a small effect on heritability include*7:

DRD4
DRD5
SLC6A3

Mediate dopaminergic function

DBH

Mediates dopaminergic/ noradrenergic function

SLC6A3
HTR1B

Mediate serotonergic function

SNAP25

Mediates synaptic function

*The genes listed here are not a comprehensive list of candidate genes in the pathophysiology of ADHD.

ENVIRONMENTAL FACTORS*

Preterm birth

PRETERM BIRTH

(<32 weeks OR 3.34 [95% CI: 1.56, 7.17])†8,9

Maternal smoking

MATERNAL SMOKING

(OR 1.43 [95% CI: 1.22, 1.69])†8,9

Alcohol exposure

ALCOHOL EXPOSURE
DURING PREGNANCY

(OR 2.5 [95% CI: 1.1, 5.5])‡8,10

*Other environmental factors may play a role in the pathophysiology of ADHD.

Based on an analysis of the register of diagnosis at the Department of Child and Adolescent Psychiatry in Malmö, Sweden, including 419 children
born between 1978 to 2001 and subsequently clinically diagnosed with ADHD according to DSM-III-R® or DSM-IV® criteria.9

Based on an analysis of data from 2 hospital-based case-control family studies of ADHD in male and female children aged 6 to 17 years at the time of ascertainment.10

DSM-III-R® and DSM-IV® are registered trademarks of the American Psychiatric Association.

The exact cause of ADHD is unknown.

References: 1. Arnsten AF, Scahill L, Findling RL. Alpha-2 adrenergic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: emerging concepts from new data. J Child Adolesc Psychopharmacol. 2007;17(4):393-406. 2. Chao LL, Knight RT. Human prefrontal lesions increase distractibility to irrelevant sensory inputs. Neuroreport. 1995;6(12):1605-1610. 3. Arnsten AF. Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology: an important role for prefrontal cortex dysfunction. CSN Drugs. 2009;23(suppl 1):33-41. 4. Aron AR, Robbins TW, Poldrack RA. Inhibition and the right inferior frontal cortex. Trends Cogn Sci. 2004;8(4):170-177. 5. Levy F. Dopamine vs noradrenaline: inverted-U effects and ADHD theories. Aust N Z J Psychiatry. 2009;43(2):101-108.6. Volkow ND, Wang G-J, Kollins SH, et al. Evaluating dopamine reward pathway in ADHD. JAMA. 2009;302(10):1084-1091. 7. Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet. 2005;366(9097):237-248. 8. American Psychiatric Association. Attention-deficit/hyperactivity disorder. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013:59-65. 9. Gustafsson P, Källén K. Perinatal, maternal, and fetal characteristics of children diagnosed with attention-deficit-hyperactivity disorder: results from a population-based study utilizing the Swedish Medical Birth Register. Dev Med Child Neurol. 2011;53(3):263-268. 10. Mick E, Biederman J, Faraone SV, Sayer J, Kleinman S. Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy. J Am Acad Child Adolesc Psychiatry. 2002;41(4):378-385.