Smoking and mental health - NCSCT

Smoking and mental health
3.2.1 Genetic evidence
Twin studies have long been used to explore the genetic and environmental
influences underlying human phenotypes such as smoking, because they provide
an opportunity to separate the contributions of several latent sources of variance:
genetic factors, environmental factors shared by both twins and environmental
factors that are unique to one twin. This is accomplished by comparing the
phenotypic correlation of monozygotic twins, who share all their genes, to that of
dizygotic twins, who share on average half of their segregating genes identical by
descent. If monozygotic twins are more similar to one another than dizygotic
twins, genetic influences are likely to be an important contributor to variation in
that phenotype. A straightforward bivariate extension of the standard twin
model enables researchers to investigate whether smoking is genetically and/or
environmentally correlated with other disorders. This method can be used to
quantify shared latent genetic factors, and can be followed up by molecular
genetic studies aimed at identifying specific genes or variants that underlie the
latent factor. Genetic evidence specific to associations between nicotine use and
selected mental disorders is summarised in later sections.
3.2.2 Animal models
Much of the evidence from studies in animals derives from studies testing the
hypothesis that nicotine exerts effects in the brain which ameliorate the
symptoms of underlying mental disorders, and thus provide a form of selfmedication.
30,31 Nicotine deprivation produces withdrawal effects that often
include impairments in mood and cognition, 32,33 but nicotine may also have
beneficial effects on mood and cognition that are independent of its ability to
reverse nicotine withdrawal symptoms, 34 eg nicotinic acetylcholine receptors
(nAChRs) have been implicated in the pathophysiology of depression 35 and
nicotine and nAChR agonists have demonstrated antidepressant effects in animal
models of the disease. 36,37 In addition, nicotine stimulates dopamine release in
the mesolimbic system, and chronic nicotine administration may sensitise this
effect (ie lower the threshold of stimulation needed for release), particularly in
stressful situations. 38 Reduced bioavailability of dopamine in this region of the
brain has been implicated in causing the anhedonia associated with depressive
disorders. 39 In addition, the effects of nicotine on the hypothalamic–pituitary–
adrenal (HPA) axis appear to play an important role in the anxiolytic effects of
nicotine in response to acute and chronic stress. 32
Cholinergic innervation of areas of the brain involved in the stress response,
most notably the HPA axis, is probably critical in modulating anxiety and
there are a large variety of nAChR subtypes expressed in these pathways.
Animal studies have also demonstrated that nicotine stimulates the release of
allopregnanolone and neuropeptide Y, both of which act to reduce anxiety. 40,41
40 © Royal College of Physicians 2013