Early Life Stress and Child Temperament Style as Predictors of Childhood Anxiety and Depressive Symptoms: Findings from the Longitudinal Study of Australian Children

Objective. The purpose of this study was to determine whether the relationship between stressful infant environments and later childhood anxiety and depressive symptoms varies as a function of individual differences in temperament style. Methods. Data was drawn from the Longitudinal Study of Australian Children (LSAC). This study examined 3425 infants assessed at three time points, at 1-year, at 2/3 years and at 4/5 years. Temperament was measured using a 12-item version of Toddler Temperament Scale (TTS) and was scored for reactive, avoidant, and impulsive dimensions. Logistic regression was used to model direct relationships and additive interactions between early life stress, temperament, and emotional symptoms at 4 years of age. Analyses were adjusted for socioeconomic status, parental education, and marital status. Results. Stressful family environments experienced in the infant's first year of life (high versus low) and high reactive, avoidant, and impulsive temperament styles directly and independently predicted anxiety and depressive problems in children at 4 years of age. There was no evidence of interaction between temperament and family stress exposure. Conclusions. Both infant temperament and stress exposures are independent and notable predictors of later anxiety and depressive problems in childhood. The risk relationship between stress exposure in infancy and childhood emotion problems did not vary as a function of infant temperament. Implications for preventive intervention and future research directions are discussed

30 Years on : some key insights from the Australian Temperament Project

In 2013, the Australian Temperament Project (ATP) longitudinal study celebrated its 30th anniversary. This article provides a brief overview of the ATP, and highlights some key findings that have emerged over the past three decades. From amongst the many research areas explored in the ATP, topics covered here include temperament, learning problems, mental health, risk-taking, bullying, positive development, and relationships with parents in adulthood. Future plans for the study are also presented, including the new ATP Generation 3 Study which commenced in 2011 - a unique longitudinal study of the children of the ATP participants

Investigating Direct Links between Depression, Emotional Control, and Physical Punishment with Adolescent Drive for Thinness and Bulimic Behaviors, Including Possible Moderation by the Serotonin Transporter 5-HTTLPR Polymorphism

Objectives: To examine the relationship between psychological and social factors (depression, emotional control, sexual abuse, and parental physical punishment) and adolescent drive for Thinness and Bulimic behaviors in a large community sample, and to investigate possible genetic moderation.Method: Data were drawn from the Australian Temperament Project (ATP), a population-based cohort study that has followed a representative sample of 2443 participants from infancy to adulthood across 16 waves since 1983. A subsample of 650 participants (50.2% female) of Caucasian descent who provided DNA were genotyped for a serotonin transporter promoter polymorphism (5-HTTLPR). Adolescent disordered eating attitudes and behaviors were assessed using the Bulimia and Drive for Thinness scales of the Eating Disorder Inventory-2 (15–16 years). Depression and emotional control were examined at the same age using the Short Mood and Feelings Questionnaire, and an ATP-devised measure of emotional control. History of sexual abuse and physical punishment were assessed retrospectively (23–24 years) in a subsample of 467 of those providing DNA.Results: EDI-2 scores were associated with depression, emotional control, and retrospectively reported parental physical punishment. Although there was statistically significant moderation of the relationship between parental physical punishment and bulimic behaviors by 5-HTTLPR (p = 0.0048), genotypes in this subsample were not in Hardy–Weinberg Equilibrium. No other G×E interactions were significant. Conclusion: Findings from this study affirm the central importance of psychosocial processes in disordered eating patterns in adolescence. Evidence of moderation by 5-HTTLPR was not conclusive; however, genetic moderation observed in a subsample not in Hardy–Weinberg Equilibrium warrants further investigation

Stress-sensitive neurosignalling in depression : an integrated network biology approach to candidate gene selection for genetic association analysis

Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response. Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stress-related behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders

Variation in the gene coding for the M5 Muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction: evidence from a prospective population based cohort study of young adults

Background: The mesolimbic structures of the brain are important in the anticipation and perception of reward. Moreover, many drugs of addiction elicit their response in these structures. The M5 muscarinic receptor (M5R) is expressed in dopamine-containing neurones of the substantia nigra pars compacta and ventral tegmental area, and regulates the release of mesolimbic dopamine. Mice lacking M5R show a substantial reduction in both reward and withdrawal responses to morphine and cocaine. The CHRM5, the gene that codes for the M5R, is a strong biological candidate for a role in human addiction. We screened the coding and core promoter sequences of CHRM5 using denaturing high performance liquid chromatography to identify common polymorphisms. Additional polymorphisms within the coding and core promoter regions that were identified through dbSNP were validated in the test population. We investigated whether these polymorphisms influence substance dependence and dose in a cohort of 1947 young Australians.Results: Analysis was performed on 815 participants of European ancestry who were interviewed at wave 8 of the cohort study and provided DNA. We observed a 26.8% increase in cigarette consumption in carriers of the rs7162140 T-allele, equating to 20.1 cigarettes per week (p=0.01). Carriers of the rs7162140 T-allele were also found to have nearly a 3-fold increased risk of developing cannabis dependence (OR=2.9 (95%CI 1.1-7.4); p=0.03).Conclusion: Our data suggest that variation within the CHRM5 locus may play an important role in tobacco and cannabis but not alcohol addiction in European ancestry populations. This is the first study to show an association between CHRM5 and substance use in humans. These data support the further investigation of this gene as a risk factor in substance use and dependence.<br /

Causal inference in multi-cohort studies using the target trial approach

Longitudinal cohort studies provide the opportunity to examine causal effects of complex exposures on long-term health outcomes. Utilizing data from multiple cohorts has the potential to add further benefit by improving precision of estimates through data pooling and allowing examination of effect heterogeneity across contexts. However, the interpretation of findings can be complicated by biases that may be compounded when pooling data or may contribute to discrepant findings when analyses are replicated across cohorts. Here we extend the target trial framework, already well established as a powerful tool for causal inference in single-cohort studies, to address the specific challenges that can arise in the multi-cohort setting. The approach considers the target trial as a central point of reference, as opposed to comparing one study to another. This enables clear definition of the target estimand and systematic consideration of sources of bias within each cohort and additional sources of bias arising from data pooling. Consequently, analyses can be designed to reduce these biases and the resulting findings appropriately interpreted. We use a case study to demonstrate the approach and its potential to strengthen causal inference in multi-cohort studies through improved analysis design and clarity in the interpretation of findings.Comment: 34 pages, 3 figure

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

Inequalities in the distribution of COVID-19-related financial difficulties for Australian families with young children

BACKGROUND: We examine (1) the frequency of financial difficulties in Australian families with young children (0-8 years) in the early and later phases of the pandemic; (2) the extent to which parents' pre-pandemic socio-economic disadvantage (SED) predicted financial difficulties; and (3) whether grandparent intergenerational SED further amplified this risk. METHOD: Data: Australian Temperament Project (ATP; established 1983, N = 2443) and ATP Generation 3 study (ATPG3; established 2012; N = 702), of which 74% (N = 553) completed a COVID-specific module in the early (May-September 2020) and/or later (October-December 2021) phases of the pandemic. OUTCOMES: Parent-reported loss of employment/reduced income, difficulty paying for essentials, and financial strain. EXPOSURES: Pre-pandemic parent and grandparent education and occupation. ANALYSIS: Logistic regressions, estimated via generalized estimating equations, were used to examine associations between the pre-pandemic SED of parents and grandparents and their interaction with financial difficulties, adjusting for potential confounders. RESULTS: At both pandemic time points, a third of parents reported adverse financial impacts (early: 34%, 95% confidence interval [CI] = 30-38; later: 32%, 95% CI = 28-36). Each standard deviation increase in the parents' pre-pandemic SED was associated with a 36% increase in the odds of reporting multiple financial difficulties (odds ratio [OR] = 1.36, 95% CI = 1.04-1.78). There was little evidence of an interaction between the SED of parents and grandparents. CONCLUSIONS: Financial impacts related to the COVID-19 pandemic were common and, irrespective of grandparent SED, disproportionately borne by parents with higher pre-pandemic SED. Given the well-established relationship between disadvantage and child health and development, sustained and well-targeted government supports will be critical to minimizing adverse impacts in years to come

Pre-conception self-harm, maternal mental health and mother-infant bonding problems:a 20-year prospective cohort study

Background: Self-harm in young people is associated with later problems in social and emotional development. However, it is unknown whether self-harm in young women continues to be a marker of vulnerability on becoming a parent. This study prospectively describes the associations between pre-conception self-harm, maternal depressive symptoms and mother&ndash;infant bonding problems.MethodsThe Victorian Intergenerational Health Cohort Study (VIHCS) is a follow-up to the Victorian Adolescent Health Cohort Study (VAHCS) in Australia. Socio-demographic and health variables were assessed at 10 time-points (waves) from ages 14 to 35, including self-reported self-harm at waves 3&ndash;9. VIHCS enrolment began in 2006 (when participants were aged 28&ndash;29 years), by contacting VAHCS women every 6 months to identify pregnancies over a 7-year period. Perinatal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale during the third trimester, and 2 and 12 months postpartum. Mother&ndash;infant bonding problems were assessed with the Postpartum Bonding Questionnaire at 2 and 12 months postpartum.ResultsFive hundred sixty-four pregnancies from 384 women were included. One in 10 women (9.7%) reported pre-conception self-harm. Women who reported self-harming in young adulthood (ages 20&ndash;29) reported higher levels of perinatal depressive symptoms and mother&ndash;infant bonding problems at all perinatal time points [perinatal depressive symptoms adjusted &beta; = 5.40, 95% confidence interval (CI) 3.42&ndash;7.39; mother&ndash;infant bonding problems adjusted &beta; = 7.51, 95% CI 3.09&ndash;11.92]. There was no evidence that self-harm in adolescence (ages 15&ndash;17) was associated with either perinatal outcome.ConclusionsSelf-harm during young adulthood may be an indicator of future vulnerability to perinatal mental health and mother&ndash;infant bonding problems.</jats:sec