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Official websites use. Share sensitive information only on official, secure websites. Turku, Finland. Email: aldeni utu. There are few longitudinal studies assessing the association of cannabis use and subsequent onset of bipolar disorder. We aimed to measure the association between early cannabis exposure and subsequent bipolar disorder. Potential confounders included demographic characteristics, parental psychiatric disorders, emotional and behavioral problems and other substance use. Of the whole sample, 66 1. In Finland, the positive association between early cannabis exposure and subsequent development of bipolar disorder appears to be confounded by other substance use. Keywords: Adolescent, bipolar disorders, birth cohort, cannabis, mood disorders, substance use. Bipolar disorder is a severe mental disorder which frequently first presents in early adulthood \[ 1 \], and is associated with significant morbidity \[ 2 \] and reduced life expectancy \[ 3 \]. The endocannabinoid system has been implicated in mood control functions \[ 4 \], and acute tetrahydrocannabinol THC ingestion has been demonstrated to alter mood in several clinical trials \[ 5 , 6 \]. Thus, it is plausible that perturbations of the endocannabinoid system caused by cannabis use might contribute to the onset of bipolar disorder. However, the few existing prospective longitudinal studies examining the association between cannabis use and the onset of bipolar disorder have had mixed findings. Five such studies have utilized an adult sample \[ 7 , 8 , 9 , 10 , 11 \] and four examined the association with adolescent cannabis use \[ 12 , 13 , 14 , 15 \]. In addition to this, although polysubstance use is common in adolescence and thus presents as a potential source of confounding \[ 19 \], only one of these studies adjusted for other substance use \[ 13 \]. This enables the examination of association between adolescent cannabis use and bipolar disorder in a robust analytical framework accounting for potential confounding factors. This methodological approach ensures minimal attrition, thus enhancing the generalizability of the results. Participants who provided informed consent and answered questions on cannabis were included in the present study. To account for the effect of prior mental health disorders to study variables, we excluded those who had been diagnosed with any prior psychiatric disorder before the age of The final sample totaled individuals The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of , as revised in and having complied with the Strengthening the Reporting of Observational Studies in Epidemiology STROBE guidelines for cohort studies \[ 21 \] The STROBE checklist is included in the Supporting information. Data on these diagnostic codes were obtained from the Care Register for Health Care —18, the Register of Primary Health Care Visits —18, the medication reimbursement register of the Social Insurance Institution of Finland —05 and the disability pensions of the Finnish Center for Pensions — The Care Register contains information on patients discharged from inpatient care, and since also on specialized outpatient care. Detailed information concerning these registers is provided in previous studies \[ 22 , 23 , 24 \]. Information on deaths and times of emigration, which were used as censoring points in our analyses, were obtained from the Population Register data and the Registry for causes of death. The sum of scores can be operationalized as YSR total score, YSR internalizing or externalizing scores or eight subscales \[ 25 \]. If there were three or fewer missing values in a subscale, they were replaced by the mean value of items. If more than three items were missing from any subscale, the total score of the YSR was classified as missing \[ 26 \]. Family structure was defined dichotomously as a both parents living with the participant continuously and b other families. Linear regression and multicollinearity diagnostics with variance inflation factor VIF scores were used to detect correlation between multiple covariates. Dose—response was studied with a trend test using a categorical cannabis use variable never, one to four times, at least five times as continuous in a logistic regression model with odds ratios OR and confidence intervals. The Cox proportional hazard assumption was examined by using hazard logarithms and scaled Schoenfeld residuals. To assess the effects of missing data, multiple imputations were conducted using fully conditional specifications with 10 data sets. Thus, inverse probability weighting \[ 27 \] was used to weight the sample data by sex, parental psychiatric disorder and urbanicity. Both the weighted and unweighted data were analyzed with logistic regression analysis and ORs. Statistical significance was retained in the weighted analyses of cannabis exposure and onset of bipolar disorder for all those associations that were statistically significant in the unweighted analyses, and the strength of the associations were of similar magnitude data available from the authors. Of participants, adolescents 5. In all, Based on register information 1. Association of covariates and cannabis use and bipolar disorder in northern Finland birth cohort The results of the multivariable analyses are summarized in Table 2. Violations of the Cox proportional hazard assumption were not detected. The results in the complete case sample were similar to those in the imputed sample model 3, data available from the authors. Hazard ratios HR for the risk of bipolar disorder in northern Finland birth cohort in different groups of cannabis use. Model 1: sex, family structure, parental psychiatric disorder; model 2: sex, family structure, parental psychiatric disorder, YSR total; model 3: sex, family structure, parental psychiatric disorder, YSR total, frequent alcohol intoxications past year, daily smoking, other illicit substance use. Statistically significant results in bold type. Furthermore, the mean of age of onset of bipolar disorder was similar in participants with or without cannabis exposure at baseline \[ In this birth cohort study, we report a crude association between adolescent cannabis use and subsequent onset of bipolar disorder. This association remained significant after adjusting for sex, family structure, parental psychiatric disorders and baseline adolescent emotional and behavioral problems. Early cannabis use was thus not found to be associated with onset of bipolar disorder after extensive confounder control including adolescent substance use other than cannabis. However, while an independent association between cannabis use and bipolar disorder was not seen due to confounding by other substance use, the data still suggest early cannabis exposure to be an adverse clinical marker for onset of bipolar disorder. Therefore, reducing cannabis use in adolescents is an important public health priority. However, neither controlled for other substance use. This underscores the limitations of the evidence base concerning a possible independent association between cannabis use and onset of bipolar disorder. The cumulative incidence of bipolar disorder 1. Although higher prevalence rates have been reported in Type 2 bipolar disorder for females \[ 32 \], bipolar disorder is thought to be equally prevalent in both sexes \[ 33 \]. We find the mean age of bipolar affective disorder register diagnosis to be, on average, 10 years after cannabis exposure, which reduces the likelihood of reverse causality. Parental psychiatric disorders were also controlled for, which is to be regarded as a strength, as genetic diathesis contributes significantly to the risk of bipolar disorder \[ 42 \]. The NFBC birth cohort provides data on a large community sample with high ethnic and genetic homogeneity. However, there are also limitations. This is the most significant limitation of the study, as cannabis exposure may vary from one episode of cannabis experimentation to heavy use and it is not biologically plausible that a single exposure would lead to bipolar disorder years later, and the use and compression of cannabis exposure information in the form of a categorical dichotomous variable may introduce an unwanted bias \[ 45 \]. Also, information on the potency of the cannabis products consumed and mode of consumption was unavailable for analysis. Also, in this sample only 5. However, this source of bias would more probably weaken the observed associations, rather than inflate them. Lastly, complementary sources of information on substance use such as biometrical assay data were unavailable for analysis. Future studies need to consider other substance use when evaluating the association of cannabis use with bipolar disorder. E, NorFA Grant no. Alexander Denissoff: Conceptualization; formal analysis. Antti Mustonen: Conceptualization; formal analysis. James Scott: Formal analysis. Musa Sami: Formal analysis. Jouko Miettunen: Formal analysis. Table S1. Frequencies and percentages of covariates of within different cannabis use categories. Table S2 a : Prospective longitudinal studies assessing the association between adolescent cannabis use and bipolar disorder. Table S2 b : Prospective longitudinal studies assessing association between adult cannabis use and onset of bipolar disorder or mania. We thank all cohort members and researchers who have participated in the study. We also wish to acknowledge the work of the NFBC project center. The funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication. Is early exposure to cannabis associated with bipolar disorder? Results from a Finnish birth cohort study. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Find articles by Alexander Denissoff. Find articles by Antti Mustonen. Find articles by James G Scott. Find articles by Musa B Sami. Find articles by Jouko Miettunen. Open in a new tab. Frequencies and percentages of covariates of within different cannabis use categories Table S2 a : Prospective longitudinal studies assessing the association between adolescent cannabis use and bipolar disorder Table S2 b : Prospective longitudinal studies assessing association between adult cannabis use and onset of bipolar disorder or mania. Click here for additional data file. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

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