Nicotine use patterns and symptomatology in schizophrenia: Assessing the reliability of self-reported tobacco use using urinary cotinine levels

INTRODUCTION

Schizophrenia, a complex and debilitating mental disorder, remains a subject of intense research and clinical scrutiny. It is characterized by a diverse range of symptoms, including hallucinations, delusions, thought disorders, and cognitive impairments, that significantly impact a patient’s ability to function in daily life. Among the various factors influencing schizophrenia and its symptomatology, the role of nicotine consumption has garnered substantial attention over the years.

Nicotine, the primary psychoactive component in tobacco, has long been associated with an increased risk of schizophrenia and a propensity for individuals with schizophrenia to engage in tobacco use. The interplay between nicotine and schizophrenia is multifaceted, with both genetic and neurobiological factors contributing to this complex relationship. In recent years, an emerging body of evidence has suggested that nicotine consumption may exert a modulating effect on specific symptom domains of schizophrenia and potentially ameliorate cognitive deficits associated with the disorder.^[1]

Epidemiological studies have consistently reported a higher prevalence of smoking among individuals with schizophrenia compared to the general population. The current prevalence of tobacco use was found to be 61.54% among the patients with schizophrenia, and the majority (65.6%) of them were tobacco chewers with initiation of tobacco use during the second to third decades of life.^[2] The prevalence of tobacco use in patients with schizophrenia is 45–88% compared with <16% of the general population.^[3] Most notable are schizophrenic patients, who have smoking rates of 70–90% compared to about 25% for the general population.^[4] This association raises crucial questions about whether nicotine consumption serves as a form of self-medication to alleviate specific symptom clusters or cognitive deficits in this population.^[5] Schizophrenia is characterized by substantial cognitive impairments across various domains, including attention, working memory, and executive functioning.^[6] Emerging research suggests that nicotine may transiently improve illness-related cognitive deficits as well as antipsychotic-related cognitive deficits in schizophrenia patients, sparking interest in its potential as a cognitive enhancer. The primary evidence linking nicotine to schizophrenia is the improvement in sensory gating observed in schizophrenia patients who smoke or use nicotine.^[7]

Cotinine, the major metabolite of nicotine, has gained prominence as an objective biomarker for assessing nicotine exposure.^[8] Its concentration in bodily fluids, such as urine, is directly proportional to the amount of nicotine consumed, providing a quantitative measure of nicotine intake.^[9] One of cotinine’s key advantages as a biomarker is its stability and relatively long half-life compared to nicotine. Cotinine remains in the body for an extended period, making it a reliable indicator of chronic nicotine exposure.^[10]

Understanding the patterns of nicotine consumption in schizophrenia patients is paramount. Urinary cotinine analysis allows for the quantification of nicotine intake, shedding light on variations in consumption levels and potentially identifying subgroups of patients with different patterns of tobacco use.^[11] Investigating the relationship between urinary cotinine levels and specific symptom domains in schizophrenia is of great interest. Recent studies suggest that nicotine may impact symptom severity, with varying effects on positive and negative symptom clusters.^[12-14] This paper explores the potential link between symptomatology of schizophrenia and nicotine consumption, and urinary cotinine levels are used to validate the self-report of nicotine use.

While substantial research has examined the connection between nicotine consumption and schizophrenia, there is a scarcity of Indian studies in this domain. India exhibits unique patterns of nicotine use, including forms such as gutka, khaini, bidi, and cigarettes. Investigating nicotine use patterns in symptomatic and remitted schizophrenia patients in this context is essential for a comprehensive understanding of the relationship between the symptomatic state and nicotine use.

MATERIAL AND METHODS

RESULTS

Initially, 170 patients were evaluated, out of which 157 met the inclusion criteria. Seven patients did not meet the age criteria, and six patients refused to provide consent for the study. Among the 157 patients who met the inclusion criteria, 74 patients were excluded. This exclusion included 49 patients with co-morbid substance use (alcohol, cannabis, opioids, inhalants, etc.), 21 patients with histories suggestive of post-schizophrenic depression, two patients with onset of dementia, one patient with a history of stroke and hemiparesis, and one patient who was taking tablet ibuprofen 400 mg for headaches. Ultimately, 83 patients met both the inclusion and exclusion criteria. Of these, eight patients, despite giving consent, did not provide urine samples for cotinine level measurement. The missing urinary cotinine data from 8 patients were excluded from the analysis, which may have affected the robustness of the findings. Therefore, the final study included 75 patients [Figure 1].

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Figure 1:

Patient selection.

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Table 1 outlines the sociodemographic characteristics and a comprehensive overview of tobacco use patterns among individuals diagnosed with schizophrenia, shedding light on the prevalence, patterns, severity, and primary forms of tobacco use within the study population, along with the mFTND combined score and urine cotinine levels of 75 schizophrenia patients. The majority of the individuals fall within the age range of 18–30 years (48%). 48% of the patients were single, and 40% were married. Urban residents represent 60% of the sample. Education levels vary, with most having completed up to the 12^th grade (30.7%); 17.3% lack formal education. Unemployment in our sample was around 72%. Family composition includes 56% from joint families and 44% from nuclear ones. It shows that 80% of individuals diagnosed with schizophrenia are tobacco users, among whom around 40% are smokers, 35% are oral tobacco (smokeless) users, and 25% use both forms of tobacco. For the prominent form of tobacco use, it shows an equal distribution, with 50% of tobacco users being predominantly smokers and the other 50% being predominantly oral tobacco (smokeless) users. The mean FTND combined score is 76.50 ± 35.55, indicating dependence levels, with 71.7% showing severe dependence. Urine cotinine levels, averaging 1653.05 ± 743.49 ng/mL, further confirm the severity of tobacco dependence [Figure 2].

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Figure 2:

Urine cotinine level distribution.

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Table 2 shows the relationship between tobacco use patterns and symptomatology of schizophrenia patients, along with the association with urinary cotinine levels. The mean FTND combined score is significantly higher in symptomatic cases (n = 39, 86.67 ± 35.49) than in remitted cases (n = 21, 57.62 ± 27.55) (Wilcoxon test, p = 0.001), suggesting greater nicotine dependence in symptomatic individuals. However, the sample size is modest, and it is still divided into subgroups based on the severity of symptoms to understand the relation of nicotine use with symptom severity. Among schizophrenia subtypes (Positive, Negative, Mixed), no significant differences in nicotine dependence were observed: Positive (n = 8, 80.00 ± 23.09), Negative (n = 5, 80.00 ± 18.26), and Mixed (n = 62, 75.71 ± 38.24) (Kruskal–Wallis test, p = 0.73). The majority of participants fall under the category of “Mixed” Schizophrenia (82.7%), while a smaller percentage are categorized as “Positive” (10.7%) or “Negative” (6.7%). More than 50% (58.7%) of the participants are currently in a symptomatic state. The mean PANSS total score is 49.25 ± 12.62 (range: 30–7), highlighting the variability in overall symptom severity among the study participants. The mFTND score shows a significant positive correlation with the PANSS total score (Spearman’s Rho = 0.4, p = 0.001), indicating that higher nicotine dependence is linked to greater symptom severity. A similar significant correlation exists between mFTND scores and PANSS positive scores (Spearman’s Rho = 0.35, p = 0.007) as well as PANSS negative scores (Spearman’s Rho = 0.3, p = 0.021). Urinary cotinine levels moderately correlate with PANSS general psychopathology (Spearman’s Rho = 0.257, p = 0.048) but not with PANSS positive, negative, or total scores. In addition, a highly significant correlation exists between mFTND scores and urinary cotinine levels (Spearman’s Rho = 0.53, p < 0.001), validating cotinine as a reliable nicotine intake measure. The comparative study between primary smokers and primary SLT users on the basis of clinical variables showed no significant difference between the groups.

DISCUSSION

This study aimed to comprehensively assess the patterns and frequency of nicotine use among individuals diagnosed with schizophrenia in India, while also delving into the relationship between the severity of nicotine use, symptomatology, and cotinine levels within this unique population. As observed in earlier studies, a substantial proportion of our schizophrenia patients were unemployed, underscoring the impact of the disorder on occupational functioning.^[22,23]

In examining patterns of tobacco use, our study emphasizes the importance of considering region-specific factors when studying schizophrenia and nicotine use. Notably, a significant proportion of schizophrenia patients from urban backgrounds in our study were smokers, consistent with several local Indian studies.^[24-26] This finding, however, contrasts with national surveys in India, which generally show a higher percentage of oral tobacco or SLT users compared to smokers.^[27] These regional variations emphasize the need for tailored approaches when studying tobacco use among schizophrenia patients in India. In a study from India on the prevalence of tobacco use among Indian Schizophrenia patients and their nonpsychotic siblings, it was found that schizophrenia patients were more likely to be unemployed and single or separated.^[28-31] In contrast, most of our patients were married.

Nicotine dependence in individuals with schizophrenia has consistently been associated with symptom severity and clinical outcomes. The positive correlation between the severity of nicotine use and symptom severity in our study reaffirms the findings of previous research conducted in Western populations.^[9,10,28,30] This association has prompted several theories to explain the prevalence of tobacco use among schizophrenia patients, including self-medication for symptom relief and the influence of dopaminergic pathways.^[32,33] In our study, the severity of nicotine dependence and amount of tobacco use were not found to be associated with duration of illness and duration of tobacco use. This shows that the intervention for tobacco cessation should be done along with the treatment of schizophrenia, irrespective of the chronicity of the disease and duration of tobacco use.^[34,35]

Our study further unravelled the multifaceted nature of the relationship between nicotine dependence and symptomatology. The positive correlation between combined mFTND scores and PANSS positive, negative, and general psychopathology scores suggests that the severity of nicotine dependence correlates with both positive and negative symptomatology as well as general psychopathology in schizophrenia. However, the urinary cotinine levels correlated only with general psychopathology and not with other symptoms. This finding aligns with previous research but also acknowledges the complexity of this association, as some studies have contradicted it.^[11,27,28] The differences in the time gap between tobacco consumption and urine cotinine collection may have led to variability in cotinine level, leading to its correlation only with general psychopathology. The involvement of the dopamine system in this relationship, potentially influenced by dopamine receptor blockade, highlights the intricate interplay between nicotine use and symptomatology in schizophrenia patients. Moreover, the effects of nicotine on neurotransmitter systems such as dopamine, glutamate, and GABA add further layers of complexity to this relationship.^[26]

Efforts to classify schizophrenia patients into distinct subgroups based on symptomatology did not yield significant differences in the severity of nicotine dependence in our study. This result may be attributed to the evolving understanding of schizophrenia as a broad clinical syndrome with diverse presentations, challenging the conventional categorization of patients based solely on symptomatology. Thus, a more nuanced approach is warranted when addressing nicotine dependence in schizophrenia patients. In our study, almost 80% of the patients had a mixed type of schizophrenia, which may be due to the vast difference in the number of patients in the subgroups, and no significant difference could be found in the severity of nicotine dependence.

To validate self-reported tobacco use, we employed urinary cotinine levels, a stable and reliable biomarker of nicotine exposure. Our study established a positive and significant correlation between the severity of nicotine use and urine cotinine levels. This finding reinforces the credibility of self-reported tobacco use assessments in symptomatic schizophrenia patients. It also contrasts with some previous research that reported low accuracy in self-reporting tobacco use compared to urinary cotinine levels.^[29] In addition, our results align with a study by Olincy et al. ^[30], which demonstrated significantly higher cotinine levels in schizophrenia patients who smoked compared to other smokers. This reaffirms the importance of urinary cotinine analysis in assessing nicotine use among schizophrenia patients.

In our study, we established the severity of nicotine dependence in patients with schizophrenia and even validated it with urinary cotinine levels. However, on comparing the clinical outcomes, including the severity of nicotine dependence between primary smokers and primary SLT users, we found no significant difference. This shows the importance of nicotine in patients with schizophrenia, which is irrespective of the form of tobacco used, and NRT will help in maintaining abstinence in both smokers and SLT users.^[31,36]

However, this study has some limitations that need to be considered when interpreting the findings. Its hospital-based nature may limit the external validity, as patients who never sought treatment at psychiatric hospitals may exhibit different clinical characteristics, levels of nicotine dependence, and readiness to quit. The inclusion of only male patients may also restrict the generalizability of the results to the entire population, including females and individuals seeking care in general hospitals with psychiatric units. Variability in the time period between the last tobacco use and cotinine sample collection could introduce variability in cotinine levels. Standardizing this timing in future studies may yield more specific results. Moreover, the absence of a control group, such as other psychiatric patients, individuals from the general population, or community-based schizophrenia patients, limits the ability to make comparisons regarding illness severity. Lastly, the cross-sectional nature of the study restricted the establishment of causal associations between the severity of nicotine dependence and schizophrenia. Future research should involve longitudinal, prospective studies to explore such relationships.

This study illuminates the significant issue of tobacco use among individuals diagnosed with schizophrenia in India. Recognizing the prevalence of tobacco use, particularly in the form of smoking, and the high levels of nicotine dependence within this population is imperative. Moreover, this research underscores the positive correlation between symptom severity and the severity of nicotine dependence, emphasizing the necessity for integrated interventions in the treatment of schizophrenia. The division of patients based on symptomatology is a limitation, as the number of patients in the group of patients with positive and negative symptoms was very small. Furthermore, our study contributes to the credibility of self-reported tobacco use assessments in clinical practice by validating them through urinary cotinine levels. Looking ahead, it is imperative to continue exploring the intricate relationship between tobacco use and schizophrenia, particularly within the Indian context. Future research should delve into the nuances of this association, considering regional variations in tobacco consumption patterns and the multifaceted nature of schizophrenia symptomatology. Ultimately, the findings of this study can inform targeted interventions and support strategies to address nicotine dependence among individuals living with schizophrenia in India.

CONCLUSION

This study found a high prevalence of tobacco use among patients with schizophrenia, predominantly in smoked forms, with a substantial proportion exhibiting severe nicotine dependence. Tobacco use was more common among symptomatic patients, and nicotine dependence showed a positive correlation with both illness severity and positive and negative symptom dimensions. Self-reported nicotine use severity was validated by urinary cotinine levels. Collectively, these findings highlight the need for routine assessment and integrated management of tobacco use and nicotine dependence in patients with schizophrenia, particularly among those with active and severe psychopathology.