From the Editor

I don’t quite know when the shift occurred, but somewhere between the zeal of residency and the busyness of life as an attending physician, I stopped documenting nicotine use disorder. Indeed, working with severely ill patients, it was a given that they did smoke, and thus hardly worth mentioning. (Studies suggest that smoking is thrice as prevalent among those with schizophrenia compared to the general population.)

For many of our patients, tobacco use is a deadly problem – a major reason why people with severe, persistent mental illness have a life expectancy much shorter than ours.

This week, we consider a new paper from The American Journal of Psychiatry. The University of Academisch Medisch Centrum Universiteit van Amsterdam’s Dr. Jentien M. Vermeulen and her co-authors consider smoking in those with psychosis, their families and a control group, studying the impact on smoking on cognition – and also the impact of smoking cessation on cognition. Though work has been done in this area, the Vermenulen et al. paper is strong: they consider two comparison groups and follow people for six years. Spoiler alert: smoking cessation improved cognition in people with psychosis.

1304701062nosmokingButt out, think better?

In this Reading, we consider the paper, as well as the editorial by the University of Miami’s Philip D. Harvey, who raises some good points about what is – and isn’t – in the data.

We close the Reading with a couple of housekeeping items, including my new podcast (which may be of interest to Ontario doctors).



Smoking and Cognition

“Association Between Smoking Behavior and Cognitive Functioning in Patients With Psychosis, Siblings, and Healthy Control Subjects: Results From a Prospective 6-Year Follow-Up Study”

Jentien M. Vermeulen, Frederike Schirmbeck, Matthijs Blankers, Mirjam van Tricht, Richard Bruggeman, Wim van den Brink, Lieuwe de Haan, Genetic Risk and Outcome of Psychosis (GROUP) investigators

The American Journal of Psychiatry, November 2018

Tobacco use is an undisputed risk factor for increased mortality in both the general population and psychiatric patients. A meta-analysis showed that smoking is three times more prevalent among schizophrenia patients than in the general population, and adults with schizophrenia are almost 10 times more likely to die from chronic obstructive pulmonary disease compared with the general population (standardized mortality ratio=9.9, 95% CI=9.6–10.2). Although tobacco use has declined in the general population in recent decades, smoking prevalence among patients with psychosis is still high.

Cognitive deficits also occur frequently in patients with psychosis. The severity and range of the affected cognitive domains in patients vary widely. Cognitive domains are influenced by various underlying pharmacological mechanisms, and nicotine is known to enhance attention in patients and in the general population. The short-term effects of nicotine have been studied intensively in patients with schizophrenia, given that the nicotinergic acetylcholine receptor (nAChR) system that is implicated in cognitive functioning appears to be dysregulated in these patients. Preclinical evidence has shown that nicotine affects several neurotransmitter systems, including acetylcholine, dopamine, glutamate, and γ-aminobutyric acid (GABA), and patients with psychotic disorders may experience short-term cognitive benefits from nicotine administration. However, the most recent reviews on this topic showed that nicotine or nAChR-based treatments do not enhance cognition in patients with schizophrenia.

The long-term effects of smoking on cognitive functioning have been studied more extensively in the general population than in patients. A meta-analysis that included prospective studies with at least 12 months of follow-up showed that elderly smokers in the general population are at a higher risk of cognitive decline than nonsmokers. In a large cohort study (N=10,308), similar results were found for middle-aged smokers compared with nonsmokers. In addition, the risk of poor cognition was lower among people who had stopped smoking compared with current smokers. Longitudinal research on the association between long-term smoking and cognition in patients with psychotic disorders, however, is scarce. Cross-sectional studies have found contradictory results…

Longitudinal evidence regarding the associations between smoking and specific cognitive functions in patients with psychosis is lacking… In this study, we examined 1) the cross-sectional association between current smoking behavior and performance in specific cognitive domains and 2) the longitudinal association between smoking behavior and cognitive functioning, as well as changes in these parameters, in a large prospective study that included patients with psychotic disorders, unaffected relatives (siblings), and healthy control subjects. We hypothesized that smoking is associated with reduced cognitive functioning compared with not smoking and that smoking cessation is associated with partial cognitive recovery in all groups.

profielfoto_jentien_vermeulen-1160x1160Jentien M. Vermeulen

So begins a paper by Vermeulen et al.

Here’s what they did:

  • The data was drawn from a larger naturalistic, multicentre cohort study. Participants were recruited from the Netherlands and Belgium.
  • People were included with a nonaffective psychotic spectrum diagnosis, their unaffected siblings, and healthy controls.
  • There were baselines assessments, as well as assessments done at 3 and 6 years. (!)
  • Smoking was defined as daily smoking for 1 month or more in the past year. Different scales were used, including the Composite International Diagnostic Interview (for smoking), as well as some or all of the WAIS-III, the Auditory Verbal Learning Test, and the Continuous Performance Test (for cognition).
  • They considered different co-variables including age, years of education, cannabis use (using a urinalysis).
  • Different statistical analyses were done, including student t tests, Pearson chi-square tests, and one-way analysis of variance.

Here’s what they found:

  • “In total, we analyzed data from 1,094 patients with a nonaffective psychosis, 1,047 siblings, and 579 control subjects at baseline.”
  • Most patients had schizophrenia (65.5%).
  • In terms of smoking. “Baseline smoking rates were significantly higher in patients compared with siblings and compared with healthy control subjects (66.6%, 38.3%, and 25.2%, respectively)…” There was, not surprisingly, difference in the baseline cognitive scores, with the lowest scores in the patient group.
  • In terms of smoking behaviour. “We found that smoking behavior remained unchanged in most individuals from one assessment to the next (patients, 89.6%; siblings, 86.1%; control subjects, 90.7%). Over time, however, more individuals quit smoking (patients, 6.7%; siblings, 7.8%; control subjects, 5.4%) than started smoking (patients, 3.7%; siblings, 6.1%; control subjects, 3.9%).”
  • In terms of smoking and cognition. For patients (with mixed-effects analyses): “a significant negative association between smoking and score on the digit-symbol coding task…” And (with a post hoc analysis): “a similar negative association between number of cigarettes per day and score on the digit-symbol coding task.” For siblings: “significant negative associations were found between smoking and score on the arithmetic task and the block design task…” And (post hoc analyses): “negative associations between number of cigarettes per day and score on the block design task…” For control subjects: “a significant negative association between smoking and score on the digit-symbol coding task…”
  • In terms of cognition and smoking behaviour. “We found a significant positive association between smoking cessation and change scores on the digit-symbol coding task (estimate=4.90, SE=1.73, p=0.005), indicating that processing speed improved in patients who quit smoking compared with patients who did not change their smoking behavior… This association was not found in siblings and control subjects.”


A few thoughts:

  1. This is a good study.
  1. There is much to like with this study: a large sample size, follow up over years, and two comparison groups.
  1. Of course, there are limitations, including the reliance on self-reporting for tobacco use.
  1. There are various theories as to why people with mental illness turn to tobacco; by considering family members of people with psychosis, this paper sheds some light on the issue. An interesting finding here was that their siblings smoke more than the general population. The authors write: “our finding that smoking is more prevalent in both patients and unaffected siblings of patients (i.e., siblings without illness-related confounders) compared with healthy control subjects points to the presence of shared genetic or environmental factors that increase the risk of both smoking and psychosis.”
  1. In terms of the results, smoking cessation did improve cognition – and rapidly. It’s a big result. There are other findings worth noting: the number of cigarettes used was inversely correlated with the cognitive performance; also, the smoking-related effects on processing speed were seen in both patients and healthy control subjects. These last two findings aren’t exactly surprising.

philipharveythumbPhilip D. Harvey

  1. The paper appears with a thoughtful editorial, “Cigarette Smoking, Cognitive Performance, and Severe Mental Illness: Quitting Smoking Really Does Seem to Matter.”  He summarizes the paper, and put it into a larger perspective:

The Vermeulen et al. study had a very large sample and was longitudinal, with relatives and healthy control subjects also examined, and the researchers were able to examine the effects of quitting smoking on cognition. Their findings fit into the bigger picture of smoking and cognition, in that in the general population, the longer you smoke and the more you smoke, the greater your risk for late-life cognitive decline. The findings also fit into the picture of severe mental illness, in that current smoking in both schizophrenia and bipolar disorder is associated not only with poorer cognition but also with greater real-world disability and challenges in the ability to perform everyday living tasks, as reported in a previous study by a different research group…

But he notes the good news, too:

Time since quitting was not correlated with cognitive performance, suggesting that effects on cognition could be rapid, as suggested in the Vermeulen et al. study.

He goes on to discuss the questions raised:

  • Why smokers who continue smoking experience more adverse cognitive effects over time instead of fewer?
  • Why some people with schizophrenia are able to quit smoking while others continue?
  • Why some people with schizophrenia never start smoking?

These are all good questions. The third is especially interesting. He writes:

If there is shared vulnerability to psychosis and smoking (or at least abnormalities in the nicotinic system), then we might expect that the minority of patients with severe mental illness who never smoked would look fundamentally different in some ways from those who do or did smoke. Comparisons of never smokers and quitters have found minimal differences in symptoms or cognition between them, even in the context of substantial lifetime smoking on the part of quitters.

The editorial can be found here:

  1. We often talk to patients about the importance of tobacco cessation. How many of us mention improvement to cognition?



A couple of quick housekeeping items:

First, next week is our last Reading of the Week of the year. We will be looking at the best of 2018. Suggestions are welcome.

Second, I released new podcasting, in partnership with CAMH Education, which considers the new Ontario Ministry of Transportation rules for reporting. I interview Drs. Poynter and Barron (both of CAMH) and discuss real-world examples. I also speak with Kendra Naidoo (CAMH legal counsel).


Speaking with Kendra Naidoo

The podcasts will be most relevant to those practicing in Ontario.

You can find them here:


Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.