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Abstract

Introduction: In schizophrenia, the number of patients who smoke is very high,

nearly three times the rate in the general population and higher than the elevated rates

of smoking in patients with other psychiatric illnesses. Usually they start smoke at

mid teens and start before their illness began. Patients with schizophrenia who smoke

are also heavier smokers than those in the general population and those with other

psychiatric disorders.

Discussion: They are three possibility why patient with schizophrenia smoke

at excessive rates. The three possibility are something about the illness leads patients

to smoke; smoking is another risk factor for schizophrenia; or a third factor leads to

both schizophrenia and smoking.

Conclusion: As we know, smoke will affect patient’s life. Smoke influence the

health, financial and social life of patient with schizophrenia. So, cessation smoking in

schizophrenia, will be a challenge to improve quality life of the patient.


Introduction

Schizophrenia is a clinical syndrome of variable, but profoundly disruptive,

psychopathology that involves cognition, emotion, perception, and other aspects

behavior. The expression of these manifestations varies across patients and over time,

but the effect of the illness is always severe and is usually long lasting. The disorder

usually begins before age 25, persists throughout life, and affects person of all social

class. (6)

Cigarette smoking is a major preventable cause of disease worldwide.

According to The World Health Organization (WHO), there are one billion smokers

worldwide, and they smoke six trillion cigarettes a year. The WHO also estimates that

tobacco kills more than 3 million persons each year. (6)

In schizophrenia, the number of patients who smoke is very high. One study

reported the prevalence to be 88%, nearly three times the rate in the general

population and higher than the elevated rates of smoking in patients with other

psychiatric illnesses. The increased prevalence persists even after adjustment for

marital status, alcohol use and socio-economic status. A number of more recent cross-

sectional studies from different countries have reported high rates of smoking in

patients with schizophrenia. Smoking occurs at much higher rates than other types of

substance misuse or dependence, which have been shown also to be elevated among

patients with schizophrenia. (4)

The average age when patients with schizophrenia started smoking was the

same as in the general population, namely mid-teens; 90% of patients who smoked

had started smoking before their illness began. Patients with schizophrenia who

smoke are also heavier smokers than those in the general population and those with

other psychiatric disorders. (4)


In one study, 68% of patients with schizophrenia who smoked were classed

as heavy smokers (25 or more cigarettes daily) compared with only 11% of the

general population who smoke. Patients with schizophrenia who smoked had much

higher levels of the nicotine metabolite cotinine in comparison with other smokers.

Excessive smoking tends to be a lifelong habit among patients with schizophrenia.

The proportion of those who quit is lower than in the general population. (4)

Unburned cured tobacco contains nicotine, carcinogens, and other toxins

capable of causing gum disease and oral cancer. When tobacco is burned, the resultant

smoke contains, in addition to nicotine, carbon monoxide and 4000 other compounds

that result from volatilization, pyrolysis, and pyrosynthesis of tobacco and various

chemical additives used in making different tobacco products. (1)

The psychoactive component of tobacco is nicotine, which affects the central

nervous system (CNS) by acting as an agonist at the nicotinic subtype of acetylcholine

receptors. About 25 percent of the nicotine inhaled during smoking reaches the brain

within 15 seconds. The half life of nicotine is about 2 hours. Nicotine is believed to

produce its positive reinforcing and addictive properties by activating the

dopaminergic pathway projecting from the ventral tegmental area to the cerebral

cortex and the limbic system. In addition to activating this dopamine reward system,

nicotine causes an increase in the concentrations of circulating norepinephrine and

epinephrine and an increase in the release of vasopressin, β -endorphin,

adrenocorticotropic hormone (ACTH), and cortisol. These hormones are thought to

contribute to the basic stimulatory effects of nicotine on the CNS. (4)


Discussion

Why do patients with schizophrenia smoke at these excessive rates? There

are three possible explanations for the association: something about the illness leads

patients to smoke; smoking is another risk factor for schizophrenia; or a third factor

leads to both schizophrenia and smoking. (4)

The first possibility has received most attention. It has been suggested that

smoking may be a marker of a more severe illness process. Smokers are more often

young and male; they have an earlier onset of illness, increased numbers of hospital

admissions and receive higher doses of neuroleptic medication. Cigarette smoking

may decrease antipsychotic side effects through a pharmacokinetic interaction.

Smoking results in increased metabolism of neuroleptics. This pharmacokinetic effect

has been shown to result in 1) an increased average dose of antipsychotic medication

to achieve similar blood levels in smokers compared with nonsmokers or 2) similar

average doses of antipsychotics with lower blood levels in smokers compared with

nonsmokers. (2, 4)

Three groups have demonstrated increased clearance of neuroleptics

associated with cigarette smoking, ranging from 44% to 67% for orally administered

haloperidol and fluphenazine and 133% for fluphenazine decanoate. Most surveys

have found a correspondingly higher mean neuroleptic daily dose administered to

smokers than to non smokers. One study demonstrated lower levels of

chlorpromazine- induced sedation in smokers, which they attributed to lower

chlorpromazine plasma concentrations. Another study demonstrated changes in

chlorpromazine plasma concentrations and side effects in a schizophrenic patient who

stopped and subsequently resumed smoking. (3)


Another suggestion is that patients smoke as a form of self-medication with

nicotine, which may help regulate a dysfunctional mesolimbic dopamine system. It

has also been shown that nicotine administration enhances cognitive performance on a

number of tasks. However, in general, patients with schizophrenia who smoke report

similar reasons to other smokers ("addicted", "relaxation" and "to calm down"). (4)

Cigarette smoking might affect schizophrenic symptoms and antipsychotic

actions through the modulation of dopamine activity. Nicotinic acetylcholine

receptors have been identified on mesolimbic and nigrostriatal dopaminergic neurons.

Smoking may increase dopamine release in the pre-frontal cortex and alleviate

positive and negative symptoms. In rats, acute administration of nicotine stimulates

release of dopamine in the striatum and nucleus accumbens by acting on presynaptic

nicotine receptors. Nicotine also acutely elevates levels of the enzyme tyrosine

hydroxylase in the nucleus accumbens, indicating enhanced dopamine turnover. Some

evidence suggests that the stimulatory effect of anticholinergic agents on

dopaminergic activity may result in part from an increase in acetylcholine acting on

nicotinic receptors. So, patients with schizophrenia may smoke heavily as a result of

antipsychotic medication, which produces marked dopamine receptor blockade.

Possibly, a very high level of smoking is necessary to overcome this blockade and

produce the reward effects. (3)

Most patients who smoke began to do so before psychotic aspects of the

illness appeared, premorbid characteristics are perhaps important. It is noteworthy that

patients who smoked were as children more poorly adjusted socially than those who

were not smokers. (4)

A second explanation for the association between schizophrenia and

smoking is that smoking acts as an etiological risk factor for schizophrenia. It may be
that repeated activation by nicotine of the mesolimbic system over a long time

precipitates the onset of schizophrenia in vulnerable individuals. One study explain

that the earlier the age of starting smoking, the earlier was the onset of psychotic

illness in women. Among the adolescents in one study, who had been screened and

found not to be suffering from major psychopathology, cigarette smoking was

associated with greater risk for later hospitalization for schizophrenia. This higher

prevalence remained significant after we controlled for possible confounders

associated with smoking behavior. There was a significant association between the

number of cigarettes smoked and the risk for schizophrenia, with heavier smoking

being associated with greater risk for schizophrenia. (4, 7)

Interestingly, nicotine acts like other drugs of addiction such as cocaine and

amphetamine, activating the mesolimbic dopamine system; this effect appears to be of

critical importance for the reinforcing and reward properties of the drug. The nicotine

in cigarettes causes chronic activation of mesolimbic dopamine neurotransmission,

which in predisposed individuals might increase the risk of the appearance of

psychosis, thus giving cigarettes a causative role in the pathway toward the later

appearance of schizophrenia. Also, nicotine has been shown to increase burst activity

in the dopamine neurons of the ventral tegmental area, a form of firing pattern of these

cells that is physiologically associated with basic motivational processes underlying

learning and cognition. (4,7)

Third, genetic and/or environmental factors might predispose individuals to

develop both schizophrenia and nicotine addiction. The modes of genetic transmission

in schizophrenia are unknown, but several genes appear to make a contribution to

schizophrenia. One of specific candidate genes that influential in schizophrenia is

alpha-7 nicotinic receptor (CHRNA7). The CHRNA7 receptor is decreased in


expression in the hippocampus, cortex, and reticular nucleus of the thalamus in

schizophrenic subjects.. The CHRNA7 receptor is one of the genes differentially

regulated by smoking in schizophrenia, at both the mRNA and protein levels.

Generally, the expression of differentially regulated genes was abnormal in

schizophrenic nonsmokers and was brought to control levels by smoking, suggesting

that smoking is normalizing gene expression in the patients. The regulatory region

haplotypes seem to be related to both smoking and schizophrenia. A single haplotype

was strongly associated with abnormal auditory gating (P50). Two haplotypes were

associated with both smoking and schizophrenia, but the association was strongest

with smoking. The data suggest that the CHRNA7 genotype may regulate smoking

behavior. Much work in the genetics of both schizophrenia and nicotine addiction has

focused on the dopamine receptor system. (4, 5, 6)

Correlations between smoking and movement disorders have also received

special attention. Several crosssectional reports have suggested that cigarette smoking

is associated with a decrease in the likelihood of idiopathic Parkinson’s disease. It has

been speculated that this may be due to the effect of nicotine on striatal dopamine

systems affected in this condition. Similarly, there is evidence to suggest that smoking

is associated with a reduced incidence of neuroleptic-induced parkinsonism. Several

studies found that measures of neuroleptic-induced parkinsonism were lower among

smokers than among nonsmokers with schizophrenia who were treated with

neuroleptics. (2)

Several studies suggest that tardive dyskinesia and smoking

may also be associated. One study reported that tardive dyskinesia

was more prevalent among smokers than among nonsmokers with

schizophrenia who were treated with neuroleptics, Another study


reported results from a large, older male population sample and

found that dyskinesias were strongly and independently associated

with exposure to neuroleptics and daily cigarette smoking. Indeed,

the risk of dyskinesias increased with the number of cigarettes

smoked per day. (2)

Schizophrenia is associated with a 20% reduced life expectancy and

increased rates of smoking-related respiratory and cardiovascular diseases compared

to members of the general population. Besides health, tobacco use results in other

consequences, with smokers suffering financially and socially. Smokers with

schizophrenia spend almost one-third of their monthly disability income on cigarettes.

Smoking influences community integration because smokers have less income to

spend on clothing and housing. (8)

Despite the magnitude of tobacco use problems, quit rates for seriously

mentally ill smokers are significantly lower than in the general population. Individuals

with schizophrenia are able to quit smoking, although the success is about half that of

other groups. Contributing factors likely include lower motivation to quit tobacco use,

fewer lifetime quit attempts, and increased severity of nicotine dependence. (8)
Conclusion

In schizophrenia, the number of patients who smoke is very high, nearly

three times the rate in the general population and higher than the elevated rates of

smoking in patients with other psychiatric illnesses. Patients with schizophrenia

usually start smoking about mid-teens and start smoking before their illness began.

They were classified as heavy smokers. Excessive smoking tends to be a lifelong

habit among patients with schizophrenia. So, it is not easy for patient with

schizophrenia to quit smoking.

But, why do patients with schizophrenia smoke at these excessive rates?

There are three possible explanations for the association: something about the illness

leads patients to smoke; smoking is another risk factor for schizophrenia; or a third

factor leads to both schizophrenia and smoking.

The first possibility is related with the medication. Cigarette smoking may

decrease antipsychotic side effects. Beside that, smoke as a form of self-medication

for patient and nicotine enhances cognitive performance of the patient. Another

possibility is that smoking acts as an etiological risk factor for schizophrenia. And the

third, genetic and/or environmental factors might predispose individuals to develop

both schizophrenia and nicotine addiction. Much work in the genetics of both

schizophrenia and nicotine addiction has focused on the dopamine receptor system.

Smoke influence the health of patient with schizophrenia. Besides that,

tobacco use results in other consequences, with smokers suffering financially and

socially. But there is one problem, quit rates for seriously mentally ill smokers are

significantly lower than in the general population. But, still patient is able to quit

smoke.
References

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Harrison’s Principles of Internal Medicine volume 2 16th edition. McGraw

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2. Dalack GW, Healy DJ, Meador-Woodruff JH. Nicotine Dependence in

Schizophrenia: Clinical Phenomena and Laboratory Findings. Am J Psychiatry

1998; 1490-1501.

3. Goff DC, Henderson DC, Amico A. Cigarette Smoking in Schizophrenia:

Relationship to Psychopathology and Medication Side Effects. AmJ

Psychiatry 1992; 149:1189-1194

4. Kelly C, McCreadie R. Cigarette Smoking and Schizophrenia. Advances in

Psychiatric Treatment (2000) 6: 327-331.

5. Leonard S. Human Genetic Determinants of Schizophrenia and Nicotine

Addiction. Available at: http://www.nida.nih.gov/whatsnew/meetings/

frontiers2005/neurobiological.html Accessed November 23, 2008.

6. Sadock BJ, Sadock VA. Kaplan and Sadock’s Synopsis of Psychiatry

Behavioral Sciences/Clinical Psychiatry 10th edition. Philadelphia: Lippincott

Williams and Wilkins. 2007. p 438-40; 467-71

7. Weiser M, Reichenberg A, Grotto I, et al. Higher Rates of Cigarette Smoking

in Male Adolescents Before the Onset of Schizophrenia: A Historical-

Prospective Cohort Study. Am J Psychiatry 2004; 161:1219-1223.

8. Williams JM, Foulds J. Successful Tobacco Dependence Treatment in

Schizophrenia. Am J Psychiatry 164:222-227, February 2007


The Correlations Between Smoking and Schizophrenia

by

Osman Wijaya

03005165

Faculty of Medicine

Trisakti University

Jakarta

2008