Psychiatric sequelae of adolescent cannabis use in the Northern Finland 1986 Birth Cohort

Adolescence is a time of significant brain development, and this maturation process is thought to represent a time of heightened vulnerability to the adverse effects of environmental risk factors such as cannabis. While the association of adolescent cannabis use and subsequent psychosis and depression has received considerable attention in the existing literature, very few prospective studies have focused on the association of early cannabis exposure with severe self-harm or suicide, bipolar disorder, or anxiety disorders. Moreover, though there are reports focusing on the prognostic effect of cannabis use in patients at high risk for psychosis, populationbased studies examining the prognosis of non-treatment-seeking adolescents with both psychotic-like experiences (PLEs) and cannabis exposure are scarce. The aim of this thesis was to examine the association of early cannabis use with severe self-harm requiring medical attention, bipolar disorder, and depressive or anxiety disorders (studies I–III). Secondly, the prognosis of adolescents with PLEs with or without cannabis exposure was examined with respect to several psychiatric sequelae (study IV). A prospective general population-based Northern Finland 1986 Birth Cohort (N=9432) was utilized. Data on substance use including cannabis use and early psychopathology including PLEs were gathered in a field study in 2001– 02 when the participants were aged 15–16 years. The participants were followed for 18 years (until the year 2018, when they were 33 years). Data on diagnoses made in clinical practice from nationwide registers were utilized as outcome measures. Early cannabis use was found to be associated with severe self-harm (Study I). While an independent association of this exposure was seen with depressive/anxiety disorders (Study II), the association with a bipolar disorder attenuated to nonsignificance after adjusting for types of other substance use (Study III). In study IV, participants with both PLEs and early cannabis exposure were found to display a greater odds for adverse psychiatric sequelae than participants with only PLEs. In summary, the findings support the proposal that early cannabis use is an adverse prognostic marker for other psychiatric sequelae in addition to psychosis.Nuorten kannabiksen käytön mielenterveydellinen ennuste Pohjois-Suomen 1986 syntymäkohortissa Nuoren kehittyvien aivojen arvellaan olevan erityisen haavoittuvia kannabiksen kaltaisille ympäristöriskitekijöille. Kannabiksen käytön ja psykoosin välistä yhteyttä on tutkittu monimuotoisesti, mutta varhaisen kannabikselle altistumisen ja itsensä vahingoittamisen, kaksisuuntaisen mielialahäiriön sekä ahdistuneisuushäiriöiden välistä yhteyttä on tutkittu merkitsevästi tätä vähemmän. Lisäksi siinä missä kannabiksen ennustevaikutusta psykoosiriskissä olevilla potilailla on jonkin verran tietoa, lievempien psykoosin kaltaisten oireiden ja samanaikaisen kannabiksen käytön mielenterveydellistä ennustetta nuorilla ei ole juuri kartoitettu yleisväestöpohjaisissa pitkittäistutkimuksissa. Väitöskirjatyön tarkoitus oli tutkia varhaisen kannabiksen käytön ja vakavan itsensä vahingoittamiskäyttäytymisen, kaksisuuntaisen mielialahäiriön ja masennusja ahdistuneisuushäiriöiden välistä yhteyttä (tutkimukset I–III). Lisäksi varhaisen kannabiksen käytön vaikutusta mielenterveydelliseen ennusteeseen tutkittiin nuorilla, joilla oli psykoosin kaltaisia kokemuksia ja varhaista kannabiksen käyttöä. Aineistona käytettiin yleisväestöön pohjautuvaa Pohjois-Suomen 1986 syntymäkohorttia (N=9432). Kannabiksen ja muiden päihteidenkäyttöä ja psykoosin kaltaisia kokemuksia kartoitettiin kenttätutkimuksessa vuosina 2001–02 nuorten ollessa 15– 16-vuotiaita. Tutkittavia seurattiin 18 vuoden ajan (vuoteen 2018 ja 33 vuoden ikään asti). Vastemuuttujat muodostettiin kansallisista rekistereistä saatavista diagnoositiedoista. Nuoruusiän Varhainen kannabiksen käyttö oli yhteydessä vakavaan itsensä vahingoittamiskäyttäytymiseen (tutkimus I). Yhteys nuoruusiän kannabiskäytön ja masennus- ja ahdistuneisuushäiriöiden välillä havaittiin (tutkimus II), mutta yhteys kaksisuuntaiseen mielihäiriöön ei jäänyt tilastollisesti merkitseväksi monimuuttujamalleissa (tutkimus III), kun muu päihdekäyttö otettiin huomioon. Sekä psykoosin kaltaisia kokemuksia että kannabiksen käyttöä raportoineilla nuorilla oli suurempi riski erilaisiin mielenterveyshäiriöihin kuin niillä nuorilla, joilla oli psykoosin kaltaisia kokemuksia ilman varhaista kannabiksen käyttöä. Tutkimuslöydökset viittaavat siihen, että varhainen kannabiksen käyttö on riskitekijä myöhemmille mielenterveyden häiriöille

Cannabis and Intentional Self-injury : a Narrative Review

Purpose of Review: Observational studies assessing the association of cannabis use with subsequent intentional self-injury have reported mixed findings. Longitudinal studies examining the association of cannabis use with subsequent suicide death are notably rare. Our objective was to review longitudinal studies examining cannabis use and subsequent self-harm, suicide attempt, or suicide death. Recent Findings: Few population-based studies have focused on self-harm with considerable variability across studies in how this outcome has been operationalized. Studies assessing the association between cannabis use and suicide attempt are equivocal in their conclusions and heterogenous in terms of samples utilized and assessment of confounding bias. The results of one meta-analysis were suggestive of dose dependency. For suicide death, the findings are inconsistent, and there is reason for concern of selection bias. Summary: The existing evidence base on these associations is not yet rigorous enough to allow drawing conclusions on causality. However, cannabis might be seen as an adverse prognostic marker for intentional self-injury.publishedVersionPeer reviewe

Exposure to alcohol and overall survival in head and neck cancer: A regional cohort study

Background There is a paucity of knowledge regarding the association of alcohol use with overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC).Methods All 1033 patients treated for new HNSCC in Southwest Finland regional referral center of Turku University Hospital in 2005-2015. Cox regression analysis was used. Tumor TNM classification, age at baseline and tobacco smoking status were assessed as potential confounders.Results A history of severe harmful alcohol use with major somatic complications (HR: 1.41; 95%CI: 1.06-1.87; p = 0.017) as well as current use of at least 10 units per week (HR: 1.44, 95%CI: 1.16-1.78; p = 0.001) were associated with OS.Conclusions Alcohol consumption of 10-20 units/week, often regarded as moderate use, was found to increase risk of mortality independent of other prognostic variables. Systematic screening of risk level alcohol use and prognostic evaluation of alcohol brief intervention strategies is highly recommended.</p

Is early exposure to cannabis associated with bipolar disorder? Results from a Finnish birth cohort study

Background and aims: 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.Design, setting and participants: Observational study linking a sample from the northern Finland birth cohort 1986 (n = 6325) to nation-wide register data to examine the association of life-time cannabis exposure at age 15/16 years and subsequent bipolar disorder until age 33 (until the end of 2018); 6325 individuals (48.8% males) were included in the analysis.Measurements: Cannabis exposure was measured via self-report. Bipolar disorder was measured via bipolar disorder-related diagnostic codes (ICD-10: F30.xx, F31.xx) collected from the Care Register for Health Care 2001-18, the Register of Primary Health Care Visits 2011-18, the medication reimbursement register of the Social Insurance Institution of Finland 2001-05 and the disability pensions of the Finnish Center for Pensions 2001-16. Potential confounders included demographic characteristics, parental psychiatric disorders, emotional and behavioral problems and other substance use.Findings: Three hundred and fifty-two adolescents (5.6%) reported any cannabis use until the age of 15-16 years. Of the whole sample, 66 (1.0%) were diagnosed with bipolar disorder. Adolescent cannabis use was associated with bipolar disorder [hazard ratio (HR) = 3.46; 95% confidence interval (CI) = 1.81-6.61]. This association remained statistically significant after adjusting for sex, family structure and parental psychiatric disorders (HR = 3.00; 95% CI = 1.47-6.13) and after further adjusting for adolescent emotional and behavioral problems (HR = 2.34; 95% CI = 1.11-4.94). Further adjustments for frequent alcohol intoxications, daily smoking and lifetime illicit drug use attenuated the associations to statistically non-significant.Conclusions: In Finland, the positive association between early cannabis exposure and subsequent development of bipolar disorder appears to be confounded by other substance use.</p

Adolescent cannabis use, depression and anxiety disorders in the Northern Finland Birth Cohort 1986

BackgroundCannabis use has been associated with increased risk of psychiatric disorders. However, associations between adolescent cannabis use, depression and anxiety disorders are inconsistently reported in longitudinal samples.AimsTo study associations of adolescent cannabis use with depression and anxiety disorders.MethodWe used data from the Northern Finland Birth Cohort 1986, linked to nationwide registers, to study the association between adolescent cannabis use and depression and anxiety disorders until 33 years of age (until 2018).ResultsWe included 6325 participants (48.8% male) in the analyses; 352 (5.6%) participants reported cannabis use until 15–16 years of age. By the end of the follow-up, 583 (9.2%) participants were diagnosed with unipolar depression and 688 (10.9%) were diagnosed with anxiety disorder. Cannabis use in adolescence was associated with an increased risk of depression and anxiety disorders in crude models. After adjusting for parental psychiatric disorder, baseline emotional and behavioural problems, demographic factors and other substance use, using cannabis five or more times was associated with increased risk of anxiety disorders (hazard ratio 2.01, 95% CI 1.15–3.82), and using cannabis once (hazard ratio 1.93, 95% CI 1.30–2.87) or two to four times (hazard ratio 2.02, 95% CI 1.24–3.31) was associated with increased risk of depression.ConclusionsCannabis use in adolescence was associated with an increased risk of future depression and anxiety disorders. Further research is needed to clarify if this is a causal association, which could then inform public health messages about the use of cannabis in adolescence.</p

Is early exposure to cannabis associated with bipolar disorder? : Results from a Finnish birth cohort study

Background and aims: 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. Design, Setting and Participants: Observational study linking a sample from the northern Finland birth cohort 1986 (n = 6325) to nation-wide register data to examine the association of life-time cannabis exposure at age 15/16 years and subsequent bipolar disorder until age 33 (until the end of 2018); 6325 individuals (48.8% males) were included in the analysis. Measurements: Cannabis exposure was measured via self-report. Bipolar disorder was measured via bipolar disorder-related diagnostic codes (ICD-10: F30.xx, F31.xx) collected from the Care Register for Health Care 2001–18, the Register of Primary Health Care Visits 2011–18, the medication reimbursement register of the Social Insurance Institution of Finland 2001–05 and the disability pensions of the Finnish Center for Pensions 2001–16. Potential confounders included demographic characteristics, parental psychiatric disorders, emotional and behavioral problems and other substance use. Findings: Three hundred and fifty-two adolescents (5.6%) reported any cannabis use until the age of 15–16 years. Of the whole sample, 66 (1.0%) were diagnosed with bipolar disorder. Adolescent cannabis use was associated with bipolar disorder [hazard ratio (HR) = 3.46; 95% confidence interval (CI) = 1.81–6.61]. This association remained statistically significant after adjusting for sex, family structure and parental psychiatric disorders (HR = 3.00; 95% CI = 1.47–6.13) and after further adjusting for adolescent emotional and behavioral problems (HR = 2.34; 95% CI = 1.11–4.94). Further adjustments for frequent alcohol intoxications, daily smoking and lifetime illicit drug use attenuated the associations to statistically non-significant. Conclusions: In Finland, the positive association between early cannabis exposure and subsequent development of bipolar disorder appears to be confounded by other substance use.publishedVersionPeer reviewe

Trajectories of adolescent psychotic-like experiences and early cannabis exposure: Results from a Finnish Birth Cohort Study

Background: Longitudinal studies examining the effect of cannabis exposure (CE) on the prognosis of adolescents with psychotic-like experiences (PLEs) are scarce. We examined trajectories of mental health in adolescents with PLEs and cannabis exposure.Methods: The Northern Finland Birth Cohort 1986 (n = 6552) with linkage to nationwide register data was used. Information on lifetime cannabis exposure was collected when participants were aged 15/16. Register-based outcome data on diagnoses made in clinical practice were obtained until age 33. Logistic regression was used to study the association of PLE/CE patterns and subsequent psychiatric disorders. The group with neither PLEs nor CE was utilized as the reference group. Parental psychiatric disorders, family structure, sex, frequent alcohol intoxications, daily smoking and illicit substance use other than cannabis were adjusted for.Results: In all, 6552 subjects (49.2 % males) were included in analysis. PLEs with cannabis exposure were associated with any psychiatric disorder (OR = 2.59; 95 % CI 1.82-3.68), psychotic disorders (OR = 3.86; 95 % CI 1.83-8.11), mood disorders (OR 4.07; 95 % CI 2.74-6.04), depressive disorders (OR = 4.35; 95 % CI 2.93-6.48), anxiety disorders (OR = 2.06; 95 % CI 1.34-3.17) and substance use disorders (OR = 2.26; 95 % CI 1.13-4.50) compared to reference group. Effect sizes were greater for group with both PLEs and cannabis use than for group with PLEs only.Conclusions: Early-onset cannabis use is an adverse prognostic marker for adolescents with PLEs after extensive confounder control including other substance use.</p

Does cannabis use in adolescence predict self-harm or suicide? Results from a Finnish Birth Cohort Study

ObjectiveLongitudinal studies examining the association between adolescent cannabis use and self-harm are rare, heterogeneous and mixed in their conclusions. We study this association utilizing a large general population-based sample with prospective data.MethodsThe Northern Finland Birth Cohort 1986 (n = 6582) with linkage to nationwide register data was used to study the association of self-reported cannabis use at age 15–16 years and self-harm and suicide death until age 33 (until year 2018), based on register information. Cox regression analysis with Hazard Ratios (HR) and 95% confidence intervals (CI) was used. Psychiatric disorders, parental psychiatric disorders and other substance use were considered as confounders.ResultsIn all, 6582 (49.2% male) were included in the analysis, and 377 adolescents (5.7%) reported any cannabis use until the age of 15–16 years. Based on register information, 79 (55.7% male) had visited in health care services due to self-harm, and 22 (90.1% male) had died by suicide. In crude analyses, adolescent cannabis use was associated with self-harm (HR = 3.93; 95% CI 2.24–6.90). The association between cannabis use and self-harm remained statistically significant after adjusting for sex, psychiatric disorders at baseline, frequent alcohol intoxications, other illicit drug use, and parental psychiatric disorders (HR 2.06; 95% CI 1.07–3.95). In contrast, the association of cannabis use with suicide did not reach statistical significance even in crude analysis (HR 2.60; 95% CI 0.77–8.78).ConclusionCannabis use in adolescence may increase risk of self-harm independent of adolescent psychopathology and other substance use.</div

Traces of trauma – a multivariate pattern analysis of childhood trauma, brain structure and clinical phenotypes

Background: Childhood trauma (CT) is a major yet elusive psychiatric risk factor, whose multidimensional conceptualization and heterogeneous effects on brain morphology might demand advanced mathematical modeling. Therefore, we present an unsupervised machine learning approach to characterize the clinical and neuroanatomical complexity of CT in a larger, transdiagnostic context. Methods: We used a multicenter European cohort of 1076 female and male individuals (discovery: n = 649; replication: n = 427) comprising young, minimally medicated patients with clinical high-risk states for psychosis; patients with recent-onset depression or psychosis; and healthy volunteers. We employed multivariate sparse partial least squares analysis to detect parsimonious associations between combinations of items from the Childhood Trauma Questionnaire and gray matter volume and tested their generalizability via nested cross-validation as well as via external validation. We investigated the associations of these CT signatures with state (functioning, depressivity, quality of life), trait (personality), and sociodemographic levels. Results: We discovered signatures of age-dependent sexual abuse and sex-dependent physical and sexual abuse, as well as emotional trauma, which projected onto gray matter volume patterns in prefronto-cerebellar, limbic, and sensory networks. These signatures were associated with predominantly impaired clinical state- and trait-level phenotypes, while pointing toward an interaction between sexual abuse, age, urbanicity, and education. We validated the clinical profiles for all three CT signatures in the replication sample. Conclusions: Our results suggest distinct multilayered associations between partially age- and sex-dependent patterns of CT, distributed neuroanatomical networks, and clinical profiles. Hence, our study highlights how machine learning approaches can shape future, more fine-grained CT research

Adolescent alcohol and cannabis use and early adulthood educational attainment in the 1986 Northern Finland birth cohort study

Abstract Background Heavy alcohol and cannabis use during adolescence have been previously described as risk factors not only for morbidity in adulthood, but also social problems including adversities in educational attainment. Attempts to consider overlapping risk factors and confounders for these associations are needed. Methods Using weighted multivariable models, we examined prospective associations between age at first drink (AFD), age at first intoxication (AFI), frequency of alcohol intoxication, as well as self-reported alcohol tolerance (i.e., number of drinks needed for the subjective experience of intoxication), and lifetime cannabis use at age 15/16 years with subsequent educational attainment obtained from comprehensive registers until age 33 in the Northern Finland Birth Cohort 1986 (6,564 individuals, 49.1% male). Confounding variables including sex, family structure (intact vs. non-intact), maternal and paternal education level, behavioural/emotional problems in school at age 7/8 years, having a history of illicit substance use in adolescence, having any psychiatric diagnosis before age 16, and parental psychiatric diagnoses, were adjusted for. Results In this large birth cohort study with a 17-year follow-up, younger age at first intoxication, higher frequency of alcohol intoxication, and high self-reported alcohol tolerance at age 15/16 years were associated with poorer educational outcomes by the age of 33 years. These associations were evident regardless of potential confounders, including parental education and childhood behavioural/emotional problems. The association between adolescent cannabis use and educational attainment in adulthood was no longer statistically significant after adjusting for confounders including frequency of alcohol intoxication at age 15/16. Conclusions Assessments of age of first alcohol intoxication, high self-reported alcohol tolerance and frequency of intoxication during adolescence should be included when implementing screening strategies aimed at identifying adolescents at risk for subsequent social problems