The Frontal Cortex

Schizophrenia and Smoking

Why are schizophrenics three to four times more likely to smoke cigarettes than the general population? Over at Brainblogger, Dirk Hanson has a fascinating summary of a few recent papers that tried to understand this saga of self-medication. Nicotine, it turns out, can significantly reduce the sensory symptoms associated with the mental illness. And given that we’re unlikely to untangle the genetic causes of schizophrenia anytime soon – the most recent genetic analyses demonstrated just how stunningly complex the illness is – the palliative effects of cigarettes are an important window into the anatomy of the disease:

The review of studies through 1999, undertaken by Lyon and published in Psychiatric Services, shows unequivocally that schizophrenic smokers are self-medicating to improve processing of auditory stimuli and to reduce many of the cognitive symptoms of the disease. “Neurobiological factors provide the strongest explanation for the link between smoking and schizophrenia,” Lyons writes, “because a direct neurochemical interaction can be demonstrated.”

Of particular interest is the interaction between nicotine and dopamine in the nucleus accumbens and prefrontal cortex. Several of the symptoms of schizophrenia appear to be associated with dopamine release in these brain areas. A 2005 German study concluded that nicotine improved cognitive functions related to attention and memory. “There is substantial evidence that nicotine could be used by patients with schizophrenia as a ‘self-medication’ to improve deficits in attention, cognition, and information processing and to reduce side effects of antipsychotic medication,” the German researchers concluded.

In addition, the process known as “sensory gating,” which lowers response levels to repeated auditory stimuli, so that a schizophrenic’s response to a second stimulus is greater than a normal person’s, is also impacted by cigarettes. Sensory gating may be involved in the auditory hallucinations common to schizophrenics. Receptors for nicotine are involved in sensory gating, and several studies have shown that sensory gating among schizophrenics is markedly improved after smoking.

I’d be curious to see what effect, if any, cigarettes have on working memory deficits in schizophrenics. There’s some initial evidence that nicotine improves visual working memory in people with the illness, which is particularly interesting since it doesn’t seem to improve working memory in control groups. (So don’t start smoking just to make yourself smarter. It won’t work.)

On a completely unrelated note, I’m still fascinated by this 2007 paper, which found that smokers with damaged insulas – the brain area was usually damaged by a stroke – were 136 times more likely to quit cigarettes than smokers with damage in other parts of their brains. Why? According to the scientists, the insula is largely responsible for detecting the pleasant bodily rituals and signals associated with smoking – the escalated pulse, the slow inhalation, the slight nicotine rush – which then get integrated into our mental state. When we crave a cigarette what we are actually craving are these somatic changes: they are the emotional core of addiction. It’s also likely that having an offline insula makes it easier to deal with the negative feelings of nicotine withdrawal. The insula, after all, has long been seen as a crucial component of the pain pathway.


  1. #1 Jim Fortune
    July 8, 2009

    In the mid 70’s I enjoyed a very memorable presentation by Sabin on people & epidemiology etc. One bit I remember & have not been able to track down was some Italian work that indicated the high incidence of smoking in mental institutions – & apparent lack of correlation with cancer. Another one of those interesting facts about human populations. While it doesn’t address cancer the following paper suggests some positive influences – we still have a few things to learn.

    Am J Psychiatry 160:2216-2221, December 2003
    © 2003 American Psychiatric Association



    Investigating the Association Between Cigarette Smoking and Schizophrenia in a Cohort Study
    Stanley Zammit, M.R.C.Psych., Peter Allebeck, M.D., Christina Dalman, M.D., Ingvar Lundberg, M.D., Tomas Hemmingsson, Ph.D., and Glyn Lewis, Ph.D.
    OBJECTIVE: Many case-control and cross-sectional studies have observed an association with cigarette smoking after the onset of schizophrenia, and there is evidence to suggest that smoking may improve symptoms in people with this disorder. Here, the authors investigated whether cigarette smoking alters the risk of subsequently developing schizophrenia. No longitudinal studies have previously examined this relationship. METHOD: A cohort of 50,087 Swedish conscripts (98% were ages 18–20) was followed up by record linkage to the National Register of Inpatient Care from 1970 to 1996 to determine hospital admission for schizophrenia. Cox regression was used to obtain hazard ratios and 95% confidence intervals (CIs) for schizophrenia, according to smoking status. RESULTS: Smoking cigarettes at ages 18–20 was associated with a lower rate of developing schizophrenia after adjustment for confounders. There was a linear relationship between the number of cigarettes smoked and a lower risk of schizophrenia (adjusted hazard ratio for linear trend across smoking categories, 0.8 [95% CI=0.7–0.9]), with an adjusted hazard ratio for heavy smokers of 0.5 (95% CI=0.3–0.9) compared to that of nonsmokers. This association persisted when analysis was restricted to subjects diagnosed after the first 5 years following conscription to reduce possible prodromal effects of schizophrenia on smoking. CONCLUSIONS: Cigarette smoking may be an independent protective factor for developing schizophrenia. These results are consistent with animal models showing both neuroprotective effects of nicotine and differential release of prefrontal dopamine in response to nicotine. The harmful effects of cigarette smoking vastly outweigh any possible benefits, but nevertheless, further investigation may lead to important insights regarding the etiology of schizophrenia at a molecular level.

  2. #2 Mark
    July 8, 2009

    No mention of the fact that anti-dopaminergics taken for psychotic disorders are cholinergic agents? Patients on neuroleptics have to take anti-cholinergics which themselves have an array of annoying side effects. Nicotine modestly mitigates the effects of anti-cholinergics.

  3. #3 Joe
    July 9, 2009

    “The patch” is a useful non-cancer-causing way of getting nicotine for schizophrenics and others. Let’s not encourage smoking unnecessarily.

  4. #4 Anibal
    July 11, 2009

    Smoking is a self-medication strategy used by schizophrenic patients because it increase their attention span via cholinergic pathways stimulation.

  5. #5 N. Evans
    July 11, 2009

    …so, you’d have to be crazy to be a smoker??
    Nah. But, anyone can use the patch…
    so, why not the next ‘teen high/craze??

  6. #6 David Kronholm
    July 14, 2009

    As a former smoker, I think the last paragrahp of Jonah’s post on the results with stroke patients feels very right. I think I realized at some point that the cravings were cravings for the transition state – and funnily enough, deep breaths and a healthy walk would totally satisfy that urge to modify breathing and heart rate that a cigarette used to give.

    It still occasionally arises – about 18 months later, and I still solve it the same way, if sitting, get up, walk around, few deep breaths, go for a walk, etc. The craving doesn’t seem to come if I am active.

  7. #7 Will
    July 16, 2009

    I started working at 212 bed facility for people with schizophrenia and other mental illnesses recently and I knew going into it how many people with MIs smoked, but it was still amazing to see. I knew there had to be reason so I did some of my own research and came up with much the same. Kind of odd because there is always a constant battle at work to get people to quit smoking for financial and health reasons, but if it is a coping mechanism, do you really want to take that away from them? There are also nicotine inhalers, patches, and lozenges, but they tend to be more expensive than the Coffin (coughin’) Nails.

    I’m interested in what Brainblogger quoted about smoking reducing the levels of antipsychotics in the blood. I know quite a few residents who are at maximum dosages for Clozaril, smoke, and are still highly disorganized or delusional. I wonder if quitting smoking would be a good or bad thing for them: taking away a coping mechanism but raising the level of the drug. I also wonder if this is common knowledge to psychiatrists so they know to watch their patients for quitting smoking and antipsychotic levels.

  8. #8 Will
    July 20, 2009

    Hey, I know this isn’t classy, but I wrote a bit about it too on my blog for anyone who’s interested.

  9. #9 e-cigarette
    August 31, 2009

    We’ve been working with a Harvard medical team on a study for electronic cigarettes because of the issue with schizophrenics and smoking. The reason schizophrenics smoke is to counter the effects of their medication, which makes their brains ‘lethargic’ and calm. The nicotine gives them a boost. However, the smoke from traditional cigarettes also decreases the effectiveness of their medication, thus most smoking schizophrenics are on double the dose of medication. It is a vicious cycle.
    Our study is focused on using electronic cigarettes, which still give the schizophrenics the nicotine boost but do not contain the harmful chemicals of cigarettes.
    We are only in the beginning of forming this study, but according to the researchers the e-cigarette could be a great ‘harm reduction alternative’ for committed smokers, as well as schizophrenics.

  10. #10 Sarah
    March 31, 2010

    i have schizophrenia and recently tried to give up smoking. By the third day i became sligfhtly phycotic and needed to smoke. I have been smoking for two days and feel slightly worried at the emergence of pychotic symptoms but they have subsided.

  11. #11 Electronic Cigarettes
    March 30, 2011

    I’m interested in what Brainblogger quoted about smoking reducing the levels of antipsychotics in the blood. I know quite a few residents who are at maximum dosages for Clozaril, smoke, and are still highly disorganized or delusional. I wonder if quitting smoking would be a good or bad thing for them: taking away a coping mechanism but raising the level of the drug. I also wonder if this is common knowledge to psychiatrists so they know to watch their patients for quitting smoking and antipsychotic levels.

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