George J. Youssef

Brain development during adolescence: A mixed-longitudinal investigation of cortical thickness, surface area, and volume

What we know about cortical development during adolescence largely stems from analyses of cross‐sectional or cohort‐sequential samples, with few studies investigating brain development using a longitudinal design. Further, cortical volume is a product of two evolutionarily and genetically distinct features of the cortex ‐ thickness and surface area, and few studies have investigated development of these three characteristics within the same sample. The current study examined maturation of cortical thickness, surface area and volume during adolescence, as well as sex differences in development, using a mixed longitudinal design. 192 MRI scans were obtained from 90 healthy (i.e., free from lifetime psychopathology) adolescents (11‐20 years) at three time points (with different MRI scanners used at time 1 compared to 2 and 3). Developmental trajectories were estimated using linear mixed models. Non‐linear increases were present across most of the cortex for surface area. In comparison, thickness and volume were both characterised by a combination of non‐linear decreasing and increasing trajectories. While sex differences in volume and surface area were observed across time, no differences in thickness were identified. Furthermore, few regions exhibited sex differences in the cortical development. Our findings clearly illustrate that volume is a product of surface area and thickness, with each exhibiting differential patterns of development during adolescence, particularly in regions known to contribute to the development of social‐cognition and behavioral regulation. These findings suggest that thickness and surface area may be driven by different underlying mechanisms, with each measure potentially providing independent information about brain development. Hum Brain Mapp 37:2027–2038, 2016.

Early risk and protective factors for problem gambling: A systematic review and meta-analysis of longitudinal studies

This systematic review aimed to identify early risk and protective factors (in childhood, adolescence or young adulthood) longitudinally associated with the subsequent development of gambling problems. A systematic search of peer-reviewed and grey literature from 1990 to 2015 identified 15 studies published in 23 articles. Meta-analyses quantified the effect size of 13 individual risk factors (alcohol use frequency, antisocial behaviours, depression, male gender, cannabis use, illicit drug use, impulsivity, number of gambling activities, problem gambling severity, sensation seeking, tobacco use, violence, undercontrolled temperament), one relationship risk factor (peer antisocial behaviours), one community risk factor (poor academic performance), one individual protective factor (socio-economic status) and two relationship protective factors (parent supervision, social problems). Effect sizes were on average small to medium and sensitivity analyses revealed that the results were generally robust to the quality of methodological approaches of the included articles. These findings highlight the need for global prevention efforts that reduce risk factors and screen young people with high-risk profiles. There is insufficient investigation of protective factors to adequately guide prevention initiatives. Future longitudinal research is required to identify additional risk and protective factors associated with problem gambling, particularly within the relationship, community, and societal levels of the socio-ecological model.

Inhibitory Control in Young Adolescents: The Role of Sex, Intelligence, and Temperament

OBJECTIVE Inhibitory control is associated with temperament and intelligence, which together form an essential component of the ability to adaptively regulate behavior. Impairments in inhibitory control have been linked with a host of common and debilitating conditions, often in a sex-dependent manner. However, sex differences in inhibitory control are often not expressed experimentally during task performance. Here, we sought to examine how sex, temperament, and intelligence are related to different aspects of inhibitory control. METHOD We recruited a large sample of early adolescents (n = 153; mean age 12.6 years) to comprehensively investigate the relationship between sex, self-reported and parent-reported temperamental effortful control, and intelligence with different aspects of inhibitory control--namely, strategic (or proactive) control and evaluative (or reactive) control, assessed using a modified Stroop task. RESULTS Compared with males, females were more efficient in their use of strategic control to reduce the magnitude of response conflict. There was no sex difference in evaluative control. Further, whereas high intelligence was associated with fewer errors for both males and females, effortful control was associated with performance accuracy only in females. CONCLUSIONS These findings highlight sex differences in the relationship of inhibitory control to individual differences in temperamental effortful control in early adolescents and reinforce the generalized positive effects of intelligence.

Different clinical courses of children exposed to a single incident of psychological trauma: a 30‐month prospective follow‐up study

BACKGROUND We investigated the distinct longitudinal trajectories of posttraumatic stress symptoms in a sample of 167 children, who witnessed death of two mothers of their schoolmates. METHODS The cohort was followed-up at 2 days (T1), 2 months (T2), 6 months (T3), and 30 months (T4) after the traumatic event. The childrens posttraumatic stress symptoms (T1-T4), depression (T1, T3 and T4), state anxiety (T1, T3 and T4), and quality of life (T4) were assessed, along with parental stress related to child rearing (T4). Different trajectory patterns of the childrens posttraumatic stress symptoms were identified using growth mixture modeling (GMM). RESULTS Four different patterns of symptom change were identified, which were consistent with the prototypical model, and were named Recovery (19.9%), Resilience (72.7%), Chronic Dysfunction (1.8%), and Delayed Reactions (5.6%). Significant differences were found in depression and anxiety scores, childrens quality of life, and parental rearing stress according to the distinct longitudinal trajectories of posttraumatic stress symptoms. CONCLUSIONS The present study suggests that individual differences should be taken into account in the clinical course and outcome of children exposed to psychological trauma. The two most common trajectories were the Resilience and the Recovery types, together suggesting that over 90% of children were evidenced with a favorable 30-month outcome. The latent classes were associated with significant mean differences in depression and anxiety scores, supporting the clinical validity of the distinct trajectories.

National estimates of Australian gambling prevalence: findings from a dual-frame omnibus survey

Abstract Background, aims and design The increase in mobile telephone‐only households may be a source of bias for traditional landline gambling prevalence surveys. Aims were to: (1) identify Australian gambling participation and problem gambling prevalence using a dual‐frame (50% landline and 50% mobile telephone) computer‐assisted telephone interviewing methodology; (2) explore the predictors of sample frame and telephone status; and (3) explore the degree to which sample frame and telephone status moderate the relationships between respondent characteristics and problem gambling. Setting and participants A total of 2000 adult respondents residing in Australia were interviewed from March to April 2013. Measurements Participation in multiple gambling activities and Problem Gambling Severity Index (PGSI). Findings Estimates were: gambling participation [63.9%, 95% confidence interval (CI) = 61.4–66.3], problem gambling (0.4%, 95% CI = 0.2–0.8), moderate‐risk gambling (1.9%, 95% CI = 1.3–2.6) and low‐risk gambling (3.0%, 95% CI = 2.2–4.0). Relative to the landline frame, the mobile frame was more likely to gamble on horse/greyhound races [odds ratio (OR) = 1.4], casino table games (OR = 5.0), sporting events (OR = 2.2), private games (OR = 1.9) and the internet (OR = 6.5); less likely to gamble on lotteries (OR = 0.6); and more likely to gamble on five or more activities (OR = 2.4), display problem gambling (OR = 6.4) and endorse PGSI items (OR = 2.4‐6.1). Only casino table gambling (OR = 2.9) and internet gambling (OR = 3.5) independently predicted mobile frame membership. Telephone status (landline frame versus mobile dual users and mobile‐only users) displayed similar findings. Finally, sample frame and/or telephone status moderated the relationship between gender, relationship status, health and problem gambling (OR = 2.9–7.6). Conclusion Given expected future increases in the mobile telephone‐only population, best practice in population gambling research should use dual frame sampling methodologies (at least 50% landline and 50% mobile telephone) for telephone interviewing.

Dual‐axis hormonal covariation in adolescence and the moderating influence of prior trauma and aversive maternal parenting

Adversity early in life can disrupt the functioning of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes and increase risk for negative health outcomes. The interplay between these axes and the environment is complex, and understanding needs to be advanced by the investigation of the multiple hormonal relationships underlying these processes. The current study examined basal hormonal associations between morning levels of cortisol, testosterone, and dehydroepiandrosterone in a cohort of adolescents (mean age 15.56 years). The moderating influence of childhood adversity was also examined, as indexed by self-reported trauma (at mean age 14.91), and observed maternal aggressive parenting (at mean age 12.41). Between-person regressions revealed significant associations between hormones that were moderated by both measures of adversity. In females, all hormones positively covaried, but also interacted with adversity, such that positive covariation was typically only present when levels of trauma and/or aggressive parenting were low. In males, hormonal associations and interactions were less evident; however, interactions were detected for cortisol-testosterone - positively covarying at high levels of aggressive parenting but negatively covarying at low levels - and DHEA-cortisol - similarly positively covarying at high levels of parental aggression. These results demonstrate associations between adrenal and gonadal hormones and the moderating role of adversity, which is likely driven by feedback mechanisms, or cross-talk, between the axes. These findings suggest that hormonal changes may be the pathway through which early life adversity alters physiology and increases health risks, but does so differentially in the sexes; however further study is necessary to establish causation.

Adolescent Cannabis Use: What is the Evidence for Functional Brain Alteration?

BACKGROUND Cannabis use typically commences during adolescence, a period during which the brain undergoes profound remodeling in areas that are high in cannabinoid receptors and that mediate cognitive control and emotion regulation. It is therefore important to determine the impact of adolescent cannabis use on brain function. OBJECTIVE We investigate the impact of adolescent cannabis use on brain function by reviewing the functional magnetic resonance imaging studies in adolescent samples. METHOD We systematically reviewed the literature and identified 13 functional neuroimaging studies in adolescent cannabis users (aged 13 to 18 years) performing working memory, inhibition and reward processing tasks. RESULTS The majority of the studies found altered brain function, but intact behavioural task performance in adolescent cannabis users versus controls. The most consistently reported differences were in the frontal-parietal network, which mediates cognitive control. Heavier use was associated with abnormal brain function in most samples. A minority of studies controlled for the influence of confounders that can also undermine brain function, such as tobacco and alcohol use, psychopathology symptoms, family history of psychiatric disorders and substance use. CONCLUSION Emerging evidence shows abnormal frontal-parietal network activity in adolescent cannabis users, particularly in heavier users. Brain functional alterations may reflect a compensatory neural mechanism that enables normal behavioural performance. It remains unclear if cannabis exposure drives these alterations, as substance use and mental health confounders have not been systematically examined.

Relationships between problematic alcohol consumption and delinquent behaviour from adolescence to young adulthood

BACKGROUND Heavy episodic drinking (HED) has been associated with increased risk for short- and long-term injury and harms, such as violence and delinquent behaviour; however, the temporal relationship between the two remains unclear, particularly on transition to young adulthood. This study investigates transactional pathways between HED and delinquent behaviour from adolescence to emerging adulthood. METHODS Data were drawn from the Australian Temperament Project; a population-based longitudinal study that has followed the health and development of participants (and parents) across 30 years from birth in 1982. The analytic sample was 1650 participants and included five measurement waves spanning adolescence (3 waves: 13-18 years) and young adulthood (2 waves; 19-24 years). RESULTS There was strong continuity across waves of both HED and delinquency, as well as across-time associations between them. Delinquent behaviour in adolescence was associated with up to twofold increases in the odds of HED at each subsequent adolescent wave. HED in the late teens was associated with over fourfold increases in the odds of persistent (two waves) HED in young adulthood. HED in the late teens was associated with increases in the odds of delinquent behaviour in young adulthood (over twofold for male and one and a half-fold for female participants). CONCLUSIONS While delinquent behaviour predicts both future HED and future delinquent behaviour in adolescence, once young people reach the legal drinking age of 18 years, HED becomes a predictor of current and future delinquent behaviour and future HED, suggesting that increased access to alcohol increases the likelihood of young people engaging in delinquent behaviour. [Miller PG, Butler E, Richardson B, Staiger PK, Youssef GJ, Macdonald JA, Sanson A, Edwards B, Olsson CA. Relationships between problematic alcohol consumption and delinquent behaviour from adolescence to young adulthood. Drug Alcohol Rev 2016;35:317-325].

Association between serotonin transporter genotype, brain structure and adolescent-onset major depressive disorder: a longitudinal prospective study

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.

Parkinson's disease alters multisensory perception: Insights from the Rubber Hand Illusion

Background: Manipulation of multisensory integration induces illusory perceptions of body ownership. Patients with Parkinsons disease (PD), a neurodegenerative disorder characterised by striatal dopamine deficiency, are prone to illusions and hallucinations and have sensory deficits. Dopaminergic treatment also aggravates hallucinations in PD. Whether multisensory integration in body ownership is altered by PD is unexplored. Objective: To study the effect of dopamine neurotransmission on illusory perceptions of body ownership. Methods: We studied the Rubber Hand Illusion (RHI) in 21 PD patients (on‐ and off‐medication) and 21 controls. In this experimental paradigm, synchronous stroking of a rubber hand and the subjects hidden real hand results in the illusory experience of ‘feeling’ the rubber hand, and proprioceptive mislocalisation of the real hand towards the rubber hand (‘proprioceptive drift’). Asynchronous stroking typically attenuates the RHI. Results: The effect of PD on illusory experience depended on the stroking condition (b = −2.15, 95% CI [−3.06, −1.25], p < .0001): patients scored questionnaire items eliciting the RHI experience higher than controls in the illusion‐attenuating (asynchronous) condition, but not in the illusion‐promoting (synchronous) condition. PD, independent of stroking condition, predicted greater proprioceptive drift (b = 15.05, 95% CI [6.05, 24.05], p = .0022); the longer the disease duration, the greater the proprioceptive drift. However, the RHI did not affect subsequent reaching actions. On‐medication patients scored both illusion (critical) and mock (control) questionnaire items higher than when off‐medication, an effect that increased with disease severity (log (OR) =.014, 95% CI [.01, .02], p < .0001). Conclusion: PD affects illusory perceptions of body ownership in situations that do not typically induce them, implicating dopamine deficit and consequent alterations in cortico‐basal ganglia‐thalamic circuitry in multisensory integration. Dopaminergic treatment appears to increase suggestibility generally rather than having a specific effect on own‐body illusions, a novel finding with clinical and research implications. HighlightsParkinsons disease affects own‐body perception in the Rubber Hand Illusion (RHI).Patients do not reject RHI as strongly as controls after asynchronous stroking.RHI strength is similar between patients and controls after synchronous stroking.Parkinsons disease increases proprioceptive drift independent of stroking.Dopaminergic drugs increased agreement with questionnaire items non‐discriminately.