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Evidence of a Causal Relationship Between Smoking Tobacco and Schizophrenia Spectrum Disorders.

ABSTRACT: There has been emerging evidence of an association between tobacco smoking and schizophrenia spectrum disorders (SSD). Two meta-analyses have reported that people who smoke tobacco have an ~2-fold increased risk of incident schizophrenia or psychosis, even after adjusting for confounding factors. This study aimed to critically appraise the research which has examined the association between tobacco smoking and SSD against the Bradford Hill criteria for causality, to determine the strength of the evidence for a causal relationship. Eight longitudinal studies (seven cohort studies and one case control study) were identified which examined tobacco smoking as an exposure and psychosis as an outcome. All seven cohort studies were assessed as being of high quality using the Newcastle-Ottawa Scale. Six of the eight studies found a statistically significant positive association between tobacco smoking and onset of SSD. These studies reported a consistent association with a moderate to large effect size and a dose response relationship. The studies adjusted for multiple potential confounders including age, sex, socioeconomic status, shared genetic risk, prodromal symptoms, and comorbid cannabis and other substance use. The studies did not adjust for exposure to childhood trauma or prenatal tobacco. There was substantial though inconclusive evidence supporting a causal relationship between tobacco smoking and increased risk of SSD. If a causal relationship does exist, nicotine is most likely responsible for this association. This raises serious public health concerns about the increasing use of e-cigarettes and other products, particularly by adolescents whose nicotine use may increase their risk of SSD. Research is urgently needed to examine the association between e-cigarette use and incident psychosis, particularly in adolescents and young adults.

SUBMITTER: Scott JG

PROVIDER: S-EPMC6255982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionAcademic achievement (AA) is associated with smoking rates. Can we determine the degree to which this relationship is likely a causal one?MethodsWe predict smoking in male conscripts (mean age 18.2) assessed from 1984 to 1991 (N = 233 248) and pregnant females (mean age 27.7) receiving prenatal care 1972-1990 (N = 494 995) from AA assessed in all students at 16. Instrumental variable (IV) analyses used the instrument month-of-birth as in each school year, older children have high AA. Co-relative analyses used AA-smoking associations in the population, cousins and siblings to predict the AA-smoking relationship in MZ twins, thereby controlling for familial confounding.ResultsIn males, higher AA was associated with a substantial decrease in risk for smoking (odds ratio [OR] [95% confidence intervals [CIs]] per standard deviation [SD] = 0.41 [0.40-0.41]) while the parallel figures obtain from our IV and co-relative analyses were 0.47 (0.39-0.57) and 0.51 (0.43-0.60), respectively. In females, these figures for pre-pregnancy smoking were, respectively, 0.39 (0.39-0.39), 0.50 (0.46-0.54) and 0.54 (0.51-0.58). Results for heavy versus light smoking suggested a causal effect but were inconsistent across methods. However, among females smoking prior to pregnancy, AA predicted a reduced risk for continued smoking with ORs for uncontrolled, IV, and co-relative analyses equaling, respectively, were 0.54 (0.53-0.55) 0.68 (0.56-0.82) and 0.78 (0.66-0.91), respectively.ConclusionsTwo different methods produced consistent evidence that higher AA has a causal effect on reducing smoking rates and increasing cessation rates in smoking pregnant females. Improving AA may result in meaningful gains in population health through reduced smoking.ImplicationsThis study provides consistent evidence across two different methods that high AA is causally related to reduced rates of smoking and increasing rates of smoking cessation among pregnant women. Our results suggest that interventions that improve educational achievement in adolescence would reduce tobacco consumption, thereby improving public health.

Project description:BackgroundThe role of thyroid health in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder, such as hypothyroidism or hyperthyroidism, is destructive in TMDs. This study aims to investigate the overall and specific causal effects of various thyroid conditions on TMDs.MethodsMendelian randomization (MR) studies were performed using genetic instruments for thyrotropin (TSH, N = 119,715), free thyroxine (fT4, N = 49,269), hypothyroidism (N = 410,141), hyperthyroidism (N = 460,499), and TMDs (N = 211,023). We assessed the overall effect of each thyroid factor via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Additionally, multivariable MR was conducted to evaluate the direct or indirect effects of hypothyroidism on TMDs whilst accounting for TSH, fT4 and hyperthyroidism, and vice versa.ResultsUnivariable MR analyses revealed a causal effect of hypothyroidism on an increased risk of TMDs (IVW OR: 1.12, 95% CI: 1.05-1.20, p = 0.001). No significant association between genetically predicted hyperthyroidism, TSH, or fT4 and TMDs. In the multivariable MR analyses, the effects of hypothyroidism on TMDs occurrence remained significant even after adjSusting for TSH, fT4 and hyperthyroidism (multivariable IVW OR: 1.10, 95% CI: 1.03-1.17, p = 0.006). No pleiotropy and heterogeneity were detected in the analyses (p > 0.05).ConclusionsHypothyroidism might causally increase the risk of TMDs through a direct pathway, highlighting the critical role of managing thyroid health in the prevention of TMDs. Clinicians should give heightened attention to patients with hypothyroidism when seeking medical advice for temporomandibular discomfort. However, caution is warranted due to the potential confounders, pleiotropy, and selection bias in the MR study.

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Evidence of a Causal Relationship Between Smoking Tobacco and Schizophrenia Spectrum Disorders.

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