Smoking and mental health - NCSCT

Neurobiological and behavioural mechanisms linking smoking and mental disorders 3
correlation in the literature: one adolescent twin study reported high genetic, and
moderate-to-high environmental, correlations between a general externalising
liability factor and nicotine use, 138 although ADHD was not directly measured.
Few molecular genetic studies have explored the effects of specific genetic
variants on both smoking/tobacco dependence and ADHD. However, evidence
from a rat model of ADHD, which exhibits nicotinic receptor deficits relative to
wild-type animals, 139 suggests that some such variants exist. Genome-wide
association studies (GWAS) of ADHD have reported a modest association with
variation (including duplications) in the human homologue of the same receptor
subunit. 140,141 These findings are promising, and future work should utilise more
global approaches (eg GWAS, twin studies) to explore additional shared genetic
and environmental risk factors contributing to the phenotypic association.
Although the precise nature of the relationship has yet to be untangled, clinicians
should note that maternal smoking – particularly during pregnancy – and
adolescent smoking are reasonably robust indicators of a liability to ADHD.
3.5.2 Evidence from animal studies
ADHD is routinely treated using drugs (eg methylphenidate and
dexamphetamine) with stimulant properties, which resemble to some extent the
psychopharmacological properties of nicotine. Smoking is more prevalent in
patients with ADHD and it seems reasonable to suggest that patients with this
condition may use tobacco as a form of self-medication. Although a number of
authors have discussed their findings in the context of rationalising the putative
role of ADHD in tobacco dependence, few studies have sought to explore the
effects of nicotine in animal models of ADHD specifically. Studies with
experimental rats and mice suggest that nicotine can improve sustained attention
in some tasks such as the five-choice serial reaction time task (5CSRTT) 142–145 or
a signal detection task. 146,147 In the latter task, nicotine also attenuates the deficit
in attention evoked by the N-methyl-D-aspartate (NMDA) receptor antagonist
dizolcipine. 148,149
It has been suggested that the neurobiological mechanisms that underpin the
ability of nicotine to improve attention and, especially, attenuate the impairment
of attention may explain the vulnerability of patients with ADHD to
nicotine/tobacco dependence. 118 Other studies have shown that nicotine
improves attention and vigilance in performing the 5CSRTT in animals that
exhibit less than optimal (90% correct). 150 This group
also noted, however, that, in rats pre-treated with nicotine using a regimen
designed to elicit sensitisation to the drug, nicotine evoked a significant increase
in anticipatory responding which may be characteristic of disinhibition or
impulsivity. Previous studies, using a different experimental paradigm, also
suggest that repeated or chronic nicotine elicits disinhibition in experimental
© Royal College of Physicians 2013 49