The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research, and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 datasets containing 38 802 European-ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analyzed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis1) with qualifying unpublished data were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction, and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalizable, but must be of modest effect size and only observable in limited situations.

Parental drinking was the strongest predictor of different drinking trajectories in adolescence. This finding underscores the importance of comprehensive public heath approaches that target both parental and adolescent drinking attitudes and behaviour.

Background Caregivers play a pivotal role in maintaining an economically viable health care system, yet they are characterized by low levels of psychological well-being and consistently report unmet needs for psychological support. Mobile app–based (mobile health [mHealth]) interventions present a novel approach to both reducing stress and improving well-being. Objective This study aims to evaluate the effectiveness of a self-guided mobile app–based psychological intervention for people providing care to family or friends with a physical or mental disability. Methods In a randomized, single-blind, controlled trial, 183 caregivers recruited through the web were randomly allocated to either an intervention (n=73) or active control (n=110) condition. The intervention app contained treatment modules combining daily self-monitoring with third-wave (mindfulness-based) cognitive-behavioral therapies, whereas the active control app contained only self-monitoring features. Both programs were completed over a 5-week period. It was hypothesized that intervention app exposure would be associated with decreases in depression, anxiety, and stress, and increases in well-being, self-esteem, optimism, primary and secondary control, and social support. Outcomes were assessed at baseline, postintervention, and 3-4 months postintervention. App quality was also assessed. Results In total, 25% (18/73) of the intervention participants were lost to follow-up at 3 months, and 30.9% (34/110) of the participants from the wait-list control group dropped out before the postintervention survey. The intervention group experienced reductions in stress (b=−2.07; P=.04) and depressive symptoms (b=−1.36; P=.05) from baseline to postintervention. These changes were further enhanced from postintervention to follow-up, with the intervention group continuing to report lower levels of depression (b=−1.82; P=.03) and higher levels of emotional well-being (b=6.13; P<.001), optimism (b=0.78; P=.007), self-esteem (b=−0.84; P=.005), support from family (b=2.15; P=.001), support from significant others (b=2.66; P<.001), and subjective well-being (b=4.82; P<.001). On average, participants completed 2.5 (SD 1.05) out of 5 treatment modules. The overall quality of the app was also rated highly, with a mean score of 3.94 out of a maximum score of 5 (SD 0.58). Conclusions This study demonstrates that mHealth psychological interventions are an effective treatment option for caregivers experiencing high levels of stress. Recommendations for improving mHealth interventions for caregivers include offering flexibility and customization in the treatment design. Trial Registration Australian New Zealand Clinical Trial Registry ACTRN12616000996460; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371170

Findings address an important gap in our understanding of the etiology of Abnormal Eating Attitudes and Behaviors in adolescence and suggest multiple targets for preventive intervention.

(BA(Hons), DEdPsych, MAPS) is an educational and developmental psychologist specialising in the interface between education and healthy development over the life course, with an emphasis on practice-and policy-relevant research. Her doctoral research used ATP data to explore pathways to positive development and the relationship between healthy functioning and mental health problems during the transition to adulthood.

The extent to which brain structural abnormalities might serve as neurobiological endophenotypes that mediate the link between the variation in the promoter of the serotonin transporter gene (5-HTTLPR) and depression is currently unknown. We therefore investigated whether variation in hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex volumes at age 12 years mediated a putative association between 5-HTTLPR genotype and first onset of major depressive disorder (MDD) between age 13–19 years, in a longitudinal study of 174 adolescents (48% males). Increasing copies of S-alleles were found to predict smaller left hippocampal volume, which in turn was associated with increased risk of experiencing a first onset of MDD. Increasing copies of S-alleles also predicted both smaller left and right medial OFC volumes, although neither left nor right medial OFC volumes were prospectively associated with a first episode of MDD during adolescence. The findings therefore suggest that structural abnormalities in the left hippocampus may be present prior to the onset of depression during adolescence and may be partly responsible for an indirect association between 5-HTTLPR genotype and depressive illness. 5-HTTLPR genotype may also impact upon other regions of the brain, such as the OFC, but structural differences in these regions in early adolescence may not necessarily alter the risk for onset of depression during later adolescence.

A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume.

While a range of factors have been found to increase the likelihood of alcohol-related harms among young people, little is known about their relative importance. This article aimed to identify the risks for alcohol-related harms at an age when alcohol use and problems tend to peak in Australia (19-20 years). A wide range of concurrent and antecedent factors from multiple domains were examined using path analysis, including individual characteristics, family environment, and externalising and internalising problems. The sample comprised of 941 individuals from the Australian Temperament Project, a large longitudinal community-based study. The path model controlled for current risky drinking and revealed a number of variables that were significant longitudinal predictors of alcohol-related harms within each of the domains, including adolescent antisocial behaviour and drinking behaviour, low agreeableness, impulsivity, and paternal drinking levels. The potential for developmental prevention approaches to reduce alcohol-related harms by targeting externalising behaviour problems, interpersonal influences, and individual characteristics is discussed. What is already known on this topic1 Many young Australians drink alcohol at levels that place them at risk of experiencing short or long-term problems. 2 Alcohol use and alcohol-related harms tend to peak as young Australians make the transition to adulthood. 3 The harms that young people experience as a consequence of drinking alcohol can't be explained simply by how much they drink; other factors also appear to be at play. What this paper adds1 Adolescent drinking, behaviour problems, low agreeableness, impulsivity, and fathers' drinking were all risk factors in experiencing alcohol-related harms. 2 These risk relationships could not be explained just by how much young people drank. 3 These risk factors can be taken into account to maximise the effectiveness of prevention and intervention programmes.