Association of adolescent symptoms of depression and anxiety with alcohol use disorders in young adulthood : findings from the Victorian Adolescent Health Cohort Study

Objective: To examine the association of adolescent depression and anxiety symptoms with alcohol abuse or dependence in young adulthood.

Design, setting and participants: Cohort study of the health and wellbeing of adolescents and young adults in Victoria, assessed at 8 waves (periods) of data collection, from age 14 to 24 years, between 1992 and 2003. Young people who participated in the cohort study at least once during the six adolescent assessment points (conducted 6 months apart, from age 14 to 17 years), at least once during young adulthood and who were alive at Wave 8 (n = 1758).

Main outcome measure: Alcohol abuse or dependence assessed using the alcohol and substance abuse modules of the Composite International Diagnostic Interview at age 24 years.

Results: Adolescents with moderate to high levels of depression and anxiety symptoms (measured by the revised Clinical Interview Schedule) had an increased risk of alcohol abuse or dependence in young adulthood, compared with young adults with low levels of adolescent depression and anxiety symptoms, after adjusting for potential confounding factors. Risk was higher for those with symptoms at more than two adolescent assessment points (odds ratio [OR] 1.9; 95% CI, 1.7–2.0) and for those with symptoms at one or two assessment points (OR 1.3; 95% CI, 1.2–1.4), compared with those with no above-threshold symptoms in adolescence.

Conclusions: Adolescents with depression and anxiety symptoms are at increased risk for alcohol use disorders into young adulthood. They warrant vigilance from primary care providers in relation to alcohol use well into adulthood.

Adolescent depressive symptoms and subsequent pregnancy, pregnancy completion and pregnancy termination in young adulthood : findings from the Victorian Adolescent Health Cohort Study

Study Objective: To examine relationships between depressive symptoms in adolescence (14-18 years of age) and becoming pregnant, completing a pregnancy (live birth) and terminating a pregnancy in young adulthood (21-24 years of age).

Participants and Design: Data from 1000 females were drawn from a larger sample of 1943 young Australians participating in a longitudinal study of adolescent health and development, followed across 8 waves from adolescence (waves 1-6) to young adulthood (waves 7 and 8).

Setting: Victoria, Australia.

Main Outcome Measures: Pregnancy, pregnancy completion and pregnancy termination between 21-24 years of age.

Results: We observed a twofold increase in the odds of becoming pregnant in those reporting persisting patterns of depressive symptoms during adolescence (2þ waves); however, after staged adjustment for adolescent antisocial behaviour, drug use and socioeconomic disadvantage, there was no evidence of association. Of particular note, and consistent with previous research, adolescent antisocial and drug use behavior were strongly associated with becoming pregnant and pregnancy termination in young adulthood.

Conclusions: Adolescent antisocial and drug use behavior, not depressive symptoms, independently predict pregnancy outcomes in young adulthood.

COMT Val158Met and 5HTTLPR functional loci interact to predict anxiety across adolescence : results from the Victorian Adolescent Health Cohort Study (1992-2006)

We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val158Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose–response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met158 [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76–0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79–0.99, P = 0.033). There was no evidence for a dose–response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29–0.70, P < 0.001) among carriers homozygous for both the COMT Met158 and the 5HTTLPR Short alleles (Met158Met + Short-Short) compared with the remaining cohort. The double-recessive effect remained after multivariate adjustment for a range of psychosocial predictors of anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.

Childhood sexual abuse and adolescent eating disorder : findings from the Victorian Adolescent Health Cohort study

Objective: To examine the relationship between childhood sexual abuse (CSA) before the age of 16 years and later onset of bulimia and anorexia nervosa symptoms in females.

Design: A longitudinal cohort study of adolescents observed from August 1992 to March 2003. The cohort was defined in a 2-stage cluster sample using 44 Australian schools in Victoria.

Setting: Population based.

Participants: A total of 1936 persons participated at least once and survived to the age of 24 years, including 999 females. The mean (SD) age of females at the start of follow- up was 14.91 (0.39) years; and at completion, 24.03 (0.55) years.

Main Exposure: Self-reported CSA before the age of 16 years was ascertained retrospectively at the age of 24 years.

Outcome Measures: Incident Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)–defined partial syndromes of anorexia and bulimia nervosa were identified between waves 4 (mean age, 16.3 years) and 6 (mean age, 17.4 years) using the Branched Eating Disorder Test.

Results: The incidence of bulimic syndrome during adolescence was 2.5 (95% confidence interval, 0.80-8.0) times higher among those who reported 1 episode of CSA and 4.9 (95% confidence interval, 1.9-12.7) times higher among those who reported 2 or more episodes of CSA, compared with females reporting no episodes, adjusted for age and background factors. The association persisted after adjusting for possible confounders or mediators measured 6 months earlier, including psychiatric morbidity and dieting behavior. There was little evidence of an association between CSA and partial syndromes of incident anorexia nervosa.

Conclusion: Childhood sexual abuse seems to be a risk factor for the development of bulimic syndromes, not necessarily mediated by psychiatric morbidity or severe dieting.

Drinking patterns of adolescents who develop alcohol use disorders: results from the Victorian adolescent health cohort study

Objective: We identify drinking styles that place teensat greatest risk of later alcohol use disorders (AUD).Design: Population-based cohort study.Setting: Victoria, Australia.

Participants: A representative sample of 1943adolescents living in Victoria in 1992.Outcome measures: Teen drinking was assessed at6 monthly intervals (5 waves) between mean ages 14.9and 17.4 years and summarised across waves as none,one, or two or more waves of: (1) frequent drinking(3+ days in the past week), (2) loss of control overdrinking (difficulty stopping, amnesia), (3) bingedrinking (5+ standard drinks in a day) and (4) heavybinge drinking (20+ and 11+ standard drinks in a dayfor males and females, respectively). Young AdultAlcohol Use Disorder (AUD) was assessed at 3 yearlyintervals (3 waves) across the 20s (mean ages 20.7through 29.1 years).

Results: We show that patterns of teen drinkingcharacterised by loss of control increase risk for AUDacross young adulthood: loss of control over drinking(one wave OR 1.4, 95% CI 1.1 to 1.8; two or morewaves OR 1.9, CI 1.4 to 2.7); binge drinking (one waveOR 1.7, CI 1.3 to 2.3; two or more waves OR 2.0, CI1.5 to 2.6), and heavy binge drinking (one wave OR2.0, CI 1.4 to 2.8; two or more waves OR 2.3, CI 1.6 to3.4). This is not so for frequent drinking, which wasunrelated to later AUD. Although drinking was morecommon in males, there was no evidence of sexdifferences in risk relationships.

Conclusions: Our results extend previous work byshowing that patterns of drinking that represent loss ofcontrol over alcohol consumption (however expressed)are important targets for intervention. In addition tocurrent policies that may reduce overall consumption,emphasising prevention of more extreme teenagebouts of alcohol consumption appears warranted.

Association between the COMT Val158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health

Objectives: Catechol-O-methyltransferase plays a central role in the metabolism of biogenic amines such as norepinephrine, dopamine and serotonin. Functional studies have demonstrated a dose relationship between Val158Met genotypes and catechol-O-methyltransferase activity. Compared with the Val158Val genotype, the Val158Met and Met158Met genotypes result in two- and four-fold reductions in catechol-O-methyltransferase activity, respectively. Two recent reports have observed the association between the Met158Met genotype and risk of anxiety in adult populations. We examined the association between the Val158Met genotypes and propensity to anxiety across adolescence.

Methods: Participants were drawn from an eight-wave study of the mental and behavioural health of over 2000 young Australians followed from 14 to 24 years of age (Victorian Adolescent Health Cohort Study, 1992 to present). DNA was received from 962 participants using a cheek swab collection method.

Results: The odds of reporting persistent episodic anxiety (phobic avoidance, panic attacks) were doubled among carriers of the Met158Met genotype (odds ratio 2.0, 95% confidence interval 1.1-3.4, P=0.014). A dose relationship between additional copies of the Met158 allele and persistent episodic anxiety was also observed (1.5, 1.1-1.94, P=0.007). Stratification by sex showed that the risk effect of the Met158 allele was among females only. No association was observed for measures of neuroticism, persistent generalized anxiety, or a composite measure of psychiatric distress.

Conclusion: These data replicate previous findings suggesting association between the Val158Met polymorphism and specific expressions of anxiety among females.

Cannabis use from adolescence to adulthood: a population-based cohort study

Twelve peer-reviewed published papers arising from the Victorian Adolescent Health Cohort Study are presented. These have contributed to the international understanding of the causes and consequences of adolescent cannabis use. The overall conclusion must be that adolescent cannabis is not harmless and, for some, has quite grave consequences in adulthood.

Prediction of perinatal depression from adolescence and before conception (VIHCS): 20-year prospective cohort study

BACKGROUND: Perinatal depression is a neglected global health priority, affecting 10-15% of women in high-income countries and a greater proportion in low-income countries. Outcomes for children include cognitive, behavioural, and emotional difficulties and, in low-income settings, perinatal depression is associated with stunting and physical illness. In the Victorian Intergenerational Health Cohort Study (VIHCS), we aimed to assess the extent to which women with perinatal depressive symptoms had a history of mental health problems before conception. METHODS: VIHCS is a follow-up study of participants in the Victorian Adolescent Health Cohort Study (VAHCS), which was initiated in August, 1992, in the state of Victoria, Australia. In VAHCS, participants were assessed for health outcomes at nine timepoints (waves) from age 14 years to age 29 years. Depressive symptoms were measured with the Revised Clinical Interview Schedule and the General Health Questionnaire. Enrolment to VIHCS began in September, 2006, during the ninth wave of VAHCS; depressive symptoms at this timepoint were measured with the Composite International Diagnostic Interview. We contacted women every 6 months (from age 29 years to age 35 years) to identify any pregnancies. We assessed perinatal depressive symptoms with the Edinburgh Postnatal Depression Scale (EPDS) by computer-assisted telephone interview at 32 weeks of gestation, 8 weeks after birth, and 12 months after birth. We defined perinatal depression as an EPDS score of 10 or more. FINDINGS: From a stratified random sample of 1000 female participants in VAHCS, we enrolled 384 women with 564 pregnancies. 253 (66%) of these women had a previous history of mental health problems at some point in adolescence or young adulthood. 117 women with a history of mental health problems in both adolescence and young adulthood had 168 pregnancies, and perinatal depressive symptoms were reported for 57 (34%) of these pregnancies, compared with 16 (8%) of 201 pregnancies in 131 women with no preconception history of mental health problems (adjusted odds ratio 8·36, 95% CI 3·34-20·87). Perinatal depressive symptoms were reported at one or more assessment points in 109 pregnancies; a preconception history of mental health problems was reported in 93 (85%) of these pregnancies. INTERPRETATION: Perinatal depressive symptoms are mostly preceded by mental health problems that begin before pregnancy, in adolescence or young adulthood. Women with a history of persisting common mental disorders before pregnancy are an identifiable high-risk group, deserving of clinical support throughout the childbearing years. Furthermore, the window for considering preventive intervention for perinatal depression should extend to the time before conception. FUNDING: National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Colonial Foundation, Australian Rotary Health Research and Perpetual Trustees.

Association between 5-HTTLPR genotypes and persisting patterns of anxiety and alcohol use : results from a 10-year longitudinal study of adolescent mental health

The serotonin transporter gene (5-HTT) encodes a transmembrane protein that plays an important role in regulating serotonergic neurotransmission and related aspects of mood and behaviour. The short allele of a 44 bp insertion/deletion polymorphism (S-allele) within the promoter region of the 5-HTT gene (5-HTTLPR) confers lower transcriptional activity relative to the long allele (L-allele) and may act to modify the risk of serotonin-mediated outcomes such as anxiety and substance use behaviours. The purpose of this study was to determine whether (or not) 5-HTTLPR genotypes moderate known associations between attachment style and adolescent anxiety and alcohol use outcomes. Participants were drawn from an eight-wave study of the mental and behavioural health of a cohort of young Australians followed from 14 to 24 years of age (Victorian Adolescent Health Cohort Study, 1992 - present). No association was observed within low-risk attachment settings. However, within risk settings for heightened anxiety (ie, insecurely attached young people), the odds of persisting ruminative anxiety (worry) decreased with each additional copy of the S-allele (B30% per allele: OR 0.77, 95% CI 0.62–0.97, P¼0.029). Within risk settings for binge drinking (ie, securely attached young people), the odds of reporting persisting high-dose alcohol consumption (bingeing) decreased with each additional copy of the S-allele (B35% per allele: OR 0.74, 95% CI 0.64–0.86, Po0.001). Our data suggest that the S-allele is likely to be important in psychosocial development, particularly in those settings that increase risk of anxiety and alcohol use problems.

Young adult sequelae of adolescent cannabis use: an integrative analysis

 Background: Debate continues about the consequences of adolescent cannabis use. Existing data are limited in statistical power to examine rarer outcomes and less common, heavier patterns of cannabis use than those already investigated; furthermore, evidence has a piecemeal approach to reporting of young adult sequelae. We aimed to provide a broad picture of the psychosocial sequelae of adolescent cannabis use. Methods: We integrated participant-level data from three large, long-running longitudinal studies from Australia and New Zealand: the Australian Temperament Project, the Christchurch Health and Development Study, and the Victorian Adolescent Health Cohort Study. We investigated the association between the maximum frequency of cannabis use before age 17 years (never, less than monthly, monthly or more, weekly or more, or daily) and seven developmental outcomes assessed up to age 30 years (high-school completion, attainment of university degree, cannabis dependence, use of other illicit drugs, suicide attempt, depression, and welfare dependence). The number of participants varied by outcome (N=2537 to N=3765). Findings: We recorded clear and consistent associations and dose-response relations between the frequency of adolescent cannabis use and all adverse young adult outcomes. After covariate adjustment, compared with individuals who had never used cannabis, those who were daily users before age 17 years had clear reductions in the odds of high-school completion (adjusted odds ratio 0·37, 95% CI 0·20-0·66) and degree attainment (0·38, 0·22-0·66), and substantially increased odds of later cannabis dependence (17·95, 9·44-34·12), use of other illicit drugs (7·80, 4·46-13·63), and suicide attempt (6·83, 2·04-22·90). Interpretation: Adverse sequelae of adolescent cannabis use are wide ranging and extend into young adulthood. Prevention or delay of cannabis use in adolescence is likely to have broad health and social benefits. Efforts to reform cannabis legislation should be carefully assessed to ensure they reduce adolescent cannabis use and prevent potentially adverse developmental effects. Funding: Australian Government National Health and Medical Research Council. © 2014 Elsevier Ltd.

Adolescent substance use and educational attainment: an integrative data analysis comparing cannabis and alcohol from three Australasian cohorts

BACKGROUND: The relative contributions of cannabis and alcohol use to educational outcomes are unclear. We examined the extent to which adolescent cannabis or alcohol use predicts educational attainment in emerging adulthood. METHODS: Participant-level data were integrated from three longitudinal studies from Australia and New Zealand (Australian Temperament Project, Christchurch Health and Development Study, and Victorian Adolescent Health Cohort Study). The number of participants varied by analysis (N=2179-3678) and were assessed on multiple occasions between ages 13 and 25. We described the association between frequency of cannabis or alcohol use prior to age 17 and high school non-completion, university non-enrolment, and degree non-attainment by age 25. Two other measures of alcohol use in adolescence were also examined. RESULTS: After covariate adjustment using a propensity score approach, adolescent cannabis use (weekly+) was associated with 1½ to two-fold increases in the odds of high school non-completion (OR=1.60, 95% CI=1.09-2.35), university non-enrolment (OR=1.51, 95% CI=1.06-2.13), and degree non-attainment (OR=1.96, 95% CI=1.36-2.81). In contrast, adjusted associations for all measures of adolescent alcohol use were inconsistent and weaker. Attributable risk estimates indicated adolescent cannabis use accounted for a greater proportion of the overall rate of non-progression with formal education than adolescent alcohol use. CONCLUSIONS: Findings are important to the debate about the relative harms of cannabis and alcohol use. Adolescent cannabis use is a better marker of lower educational attainment than adolescent alcohol use and identifies an important target population for preventive intervention.

Modeling gene-environment interaction in longitudinal data : risk for neuroticism due to interaction between maternal care and the Dopamine 4 Receptor gene (DRD4)

The purpose of this study was to investigate risk for neuroticism due to the joint action of low maternal care and compromised mesocorticolimbic ‘reward’ system function linked to a variable number tandem repeat (VNTR) in the dopamine 4 receptor gene (DRD4). Data were drawn from the Victorian Adolescent Health Cohort Study, a longitudinal study of the health and well-being of 2,000 young Australians followed from adolescence to young adulthood across 8 waves from 14- to 28-years. Genetic risk was defined by carriage of at least one copy of the 7-repeat allele or derivative alleles 5, 6, and 8 (labeled 7R+). Neuroticism was assessed in adolescence and young adulthood. We observed an approximately fourfold increase in the odds of reporting neurotic symptoms in carriers of the 7R+ disposition who reported low maternal care compared with non-carriers who reported high maternal care. The percentage of risk attributable to mechanisms in which both factors played a role was 35%. Findings are discussed in terms of implications for prevention.

A role for the DRD4 exon III VNTR in modifying the association between nicotine dependence and neuroticism

Introduction: Neurotic psychopathology has been extensively examined as a risk factor for nicotine dependence (ND). Genetic stratification may partially explain variability in risk estimates. Genetic variants that compromise dopaminergic neurotransmission may motivate exposure to dopamine-stimulating agents, including nicotine. The 7-repeat allele of a Variable Number Tandem Repeat (VNTR) polymorphism in DRD4 (and evolutionary derivatives 5, 6, and 8 repeats; 7R+) is associated with reduced dopamine receptor function. The purpose of this study was to examine association between both smoking initiation (SI) and progression to ND by young adulthood and (a) history of neuroticism during adolescence, (b) DRD4 7R+, and (c) interaction between neuroticism and DRD4 7R+.

Methods: Participants were drawn from the Victorian Adolescent Health Cohort Study, a longitudinal study of the health and well-being of young Australians across 8 waves (14–24 years). Neuroticism was measured at Waves 3 and 6 (mean 15.9 and 17.4 years). SI was defined as any smoking at any wave. ND was measured at Wave 8 (mean 24.1 years). Genotype data for the DRD4 VNTR were available for 839 participants.

Results: While adolescent neuroticism was associated with SI, evidence for association with progression to ND was weak. However, there was evidence of interaction between neuroticism and DRD4 7R+: The odds of progression to ND among those with a history of neuroticism were more than 3.5-fold higher among 7R+ carriers.

Conclusions: Without considering stratification by 7R+, the association between progression to ND and neuroticism would have been assumed barely significant. However, among those carrying DRD4 7R+, risk of progression was considerably intensified.

Gene-environment interaction in problematic substance use : interaction between DRD4 and insecure attachments

To investigate the combined effect of an exon III variable number tandem repeat in the dopamine receptor gene (DRD4) and insecure attachment style on risk for tobacco, cannabis and alcohol use problems in young adulthood. It was hypothesized that (1) individuals with 5, 6, 7 or 8 repeats (labelled 7R+) would be at increased risk for problematic drug use, and (2) risk for drug use would be further increased in individuals with 7R+ repeats who also have a history of insecure parent–child attachment relations. Data were drawn from the Victorian Adolescent Health Cohort Study, an eight-wave longitudinal study of adolescent and young adult development. DRD4 genotypes were available for 839 participants. Risk attributable to the combined effects of 7R+ genotype and insecure attachments was evaluated within a sufficient causes framework under the assumptions of additive interaction using a two-by-four table format with a common reference group. 7R+ alleles were associated with higher tobacco, cannabis and alcohol use (binging). Insecure attachments were associated with higher tobacco and cannabis use but lower alcohol use. For tobacco, there was evidence of interaction for anxious but not avoidant attachments. For cannabis, there was evidence of interaction for both anxious and avoidant attachments, although the interaction for anxious attachments was more substantial. There is no evidence of interaction for binge drinking. Results are consistent with a generic reward deficit hypothesis of drug addiction for which the 7R+ disposition may play a role. Interaction between 7R+ alleles and attachment insecurity may intensify risk for problematic tobacco and cannabis use.

Cohort Study on the Association Between Helmet Use and Traumatic Brain Injury in Snowboarders From a Swiss Tertiary Trauma Center.

BACKGROUND Since the introduction of helmets in winter sports there is on-going debate on whether they decrease traumatic brain injuries (TBI). METHODS This cohort study included 117 adult (≥ 16 years) snowboarders with TBI admitted to a level I alpine trauma center in Switzerland between 2000/2001 and 2010/2011. The primary objective was to examine the association between helmet use and moderate-to-severe TBI. Secondary objectives were to describe the epidemiology of TBI during the past decade in relation to increased helmet use. RESULTS Of 691 injured snowboarders evaluated, 117 (17%) suffered TBI. Sixty-six percent were men (median age, 23 years). Two percent of accidents were fatal. Ninety-two percent of patients sustained minor, 1% moderate, and 7% severe TBI according to the Glasgow coma scale. Pathologic computed tomography findings were present in 16% of patients, 26% of which required surgery. Eighty-three percent of TBIs occurred while riding on-slope. There was no trend in the TBI rate during the studied period, although helmet use increased from 10% to 69%. Comparing patients with and without a helmet showed no significant difference in odds ratios for the severity of TBI. However, of the 5 patients requiring surgery only 1 was wearing a helmet. Off-piste compared with on-slope snowboarders showed an odds ratio of 26.5 (P = 0.003) for sustaining a moderate-to-severe TBI. CONCLUSIONS Despite increased helmet use we found no decrease in TBI among snowboarders. The possibility of TBI despite helmet use and the dangers of riding off-piste should be a focus of future prevention programs.