Angela J. Dean

Are child and adolescent mental health problems increasing in the 21st century? A systematic review

Objective: Up to one in five children experience mental health problems. Social and cultural factors may influence emergence of mental health problems. The 21st century has led to changes in many of these factors, but it is unclear whether rates of internalizing and externalizing problems have also changed in recent cohorts of young people. Methods: A comprehensive literature search was undertaken to locate cohort or population studies that examined changes in mental health of children over time, where participants were aged 18 years and under, and the time frame for change was at least 10 years, with data for at least one time point in the 21st century being statistically compared to at least one time point in the 20th century. Studies were reviewed for quality and outcome. Results: Nineteen studies met criteria for review. These included studies of toddlers, children, and adolescents. Seventeen studies examined internalizing problems, and 11 studies examined externalizing problems. For both children and toddlers, recent cohorts did not exhibit worsening of mental health symptoms. In adolescents, the burden of externalizing problems appear to be stable. However, the majority of studies report an increase in internalizing problems in adolescent girls. The findings for internalizing problems in boys were mixed. Conclusions: These findings suggest that recent cohorts of adolescent girls are experiencing increases in internalizing symptoms compared to previous cohorts. Approaches for prevention and early intervention should be explored.

The molecular genetics of executive function: role of monoamine system genes.

Executive control processes, such as sustained attention, response inhibition, and error monitoring, allow humans to guide behavior in appropriate, flexible, and adaptive ways. The consequences of executive dysfunction for humans can be dramatic, as exemplified by the large range of both neurologic and neuropsychiatric disorders in which such deficits negatively affect outcome and quality of life. Much evidence suggests that many clinical disorders marked by executive deficits are highly heritable and that individual differences in quantitative measures of executive function are strongly driven by genetic differences. Accordingly, intense research effort has recently been directed toward mapping the genetic architecture of executive control processes in both clinical (e.g., attention-deficit/hyperactivity disorder) and nonclinical populations. Here we review the extant literature on the molecular genetic correlates of three exemplar but dissociable executive functions: sustained attention, response inhibition, and error processing. Our review focuses on monoaminergic gene variants given the strong body of evidence from cognitive neuroscience and pharmacology implicating dopamine, noradrenaline, and serotonin as neuromodulators of executive function. Associations between DNA variants of the dopamine beta hydroxylase gene and measures of sustained attention accord well with cognitive-neuroanatomical models of sustained attention. Equally, functional variants of the dopamine D2 receptor gene are reliably associated with performance monitoring, error processing, and reinforcement learning. Emerging evidence suggests that variants of the dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4) show promise for explaining significant variance in individual differences in both behavioral and neural measures of inhibitory control.

Methylphenidate But Not Atomoxetine or Citalopram Modulates Inhibitory Control and Response Time Variability

BACKGROUND Response inhibition is a prototypical executive function of considerable clinical relevance to psychiatry. Nevertheless, our understanding of its pharmacological modulation remains incomplete. METHODS We used a randomized, double-blind, placebo-controlled, crossover design to examine the effect of an acute dose of methylphenidate (MPH) (30 mg), atomoxetine (ATM) (60 mg), citalopram (CIT) (30 mg), and placebo (PLAC) (dextrose) on the stop signal inhibition task in 24 healthy, right-handed men 18-35 years of age. Participants performed the task under each of the four drug conditions across four consecutive sessions. RESULTS Methylphenidate led to a reduction in both response time variability and stop-signal reaction time (SSRT), indicating enhanced response inhibition compared with all other drug conditions. Crucially, the enhancement of response inhibition by MPH occurred without concomitant changes in overall response speed, arguing against a simple enhancement of processing speed. We found no significant differences between ATM and PLAC, CIT and PLAC, or ATM and CIT for either response time variability or SSRT. CONCLUSIONS An acute dose of MPH but not ATM or CIT was able to improve SSRT and reduce response time variability in nonclinical participants. Improvements in response inhibition and response variability might underlie the reported clinical benefits of MPH in disorders such as attention-deficit/hyperactivity disorder.

Effects of Vitamin D Supplementation on Cognitive and Emotional Functioning in Young Adults – A Randomised Controlled Trial

Background Epidemiological research links vitamin D status to various brain-related outcomes. However, few trials examine whether supplementation can improve such outcomes and none have examined effects on cognition. This study examined whether Vitamin D supplementation led to improvements in diverse measures of cognitive and emotional functioning, and hypothesised that supplementation would lead to improvements in these outcomes compared to placebo. Methods/Principal Findings Healthy young adults were recruited to a parallel-arm, double-blind trial conducted at The University of Queensland. Participants were randomly allocated to receive Vitamin D (one capsule daily, containing 5000 IU cholecalciferol) or identical placebo capsule for six weeks. All participants and outcome assessors were blinded to group assignment. Primary outcome measures assessed at baseline and 6 weeks were working memory, response inhibition and cognitive flexibility. Secondary outcomes were: hallucination-proneness, psychotic-like experiences, and ratings of depression, anxiety and anger. 128 participants were recruited, randomised and included in primary analyses (vitamin D n = 63; placebo n = 65). Despite significant increases in vitamin D status in the active group, no significant changes were observed in working memory (F = 1.09; p = 0.30), response inhibition (F = 0.82; p = 0.37), cognitive flexibility (F = 1.37; p = 0.24) or secondary outcomes. No serious adverse effects were reported. Conclusions Our findings indicate that vitamin D supplementation does not influence cognitive or emotional functioning in healthy young adults. Future controlled trials in targeted populations of interest are required to determine whether supplementation can improve functioning in these domains. Australian and New Zealand Clinical Trials Registry; ACTRN12610000318088.

CoralWatch: education, monitoring, and sustainability through citizen science

CoralWatch, launched in 2002, is a citizen-science program that seeks to integrate education and global reef monitoring by examining coral bleaching and uses a monitoring network to educate the public about reef biology, climate change, and environmental stewardship. The organizations development from research and monitoring to education and ecotourism has presented a number of challenges.

Dopamine d2 receptor modulation of human response inhibition and error awareness

Response inhibition, comprising action cancellation and action restraint, and error awareness are executive functions of considerable clinical relevance to neuropsychiatric disorders. Nevertheless, our understanding of their underlying catecholamine mechanisms, particularly regarding dopamine, is limited. Here, we used the dopamine D2 agonist cabergoline to study its ability to improve inhibitory control and modulate awareness of performance errors. A randomized, double-blind, placebo-controlled, crossover design with a single dose of cabergoline (1.25 mg) and placebo (dextrose) was employed in 25 healthy participants. They each performed the stop-signal task, a well-validated measure of action cancellation, and the Error Awareness Task, a go/no-go measure of action restraint and error awareness, under each drug condition. Cabergoline was able to selectively reduce stop-signal RT, compared with placebo, indicative of enhanced action cancellation (p < .05). This enhancement occurred without concomitant changes in overall response speed or RT variability and was not seen for errors of commission on the Error Awareness Task. Awareness of performance errors on the go/no-go task was, however, significantly improved by cabergoline compared with placebo (p < .05). Our results contribute to growing evidence for the dopaminergic control of distinct aspects of human executive ability, namely, action cancellation and error awareness. The findings may aid the development of new, or the repurposing of existing, pharmacotherapy that targets the cognitive dysfunction of psychiatric and neurological disorders. They also provide further evidence that specific cognitive paradigms have correspondingly specific neurochemical bases.

Do Antisocial Females Exhibit Poor Outcomes in Adulthood? An Australian Cohort Study

Objective: Antisocial behaviour in young people is common and associated with adverse effects in adulthood. The question whether these effects are observed in both genders remains controversial. A typology of antisocial behaviour that captures childhood limited (CL), adolescent onset (AO) and life course persistent behaviour (LCP) through both developmental stages is utilized to examine young adult outcomes in both sexes. Methods: The Mater–University of Queensland Study of Pregnancy (MUSP) data set is a longitudinal study following up a cohort of 7223 infants and mothers from antenatal care to the childs 21st year. Data on child antisocial behaviour was collected at ages 5 and 14 years. At the 21-year follow up, self-reported outcomes were collected on antisocial behaviour, use of alcohol, tobacco and cannabis, physical and mental health functioning. The relationship between the three antisocial sub-types and negative young adult outcomes was examined for both males and females using a series of logistic regressions. Results: Complete data across 21 years was available for 3173 participants. Males experienced higher levels of antisocial behaviour. In both males and females, AO and LCP groups exhibited elevated risk of negative outcomes including continuing antisocial behaviour, cannabis use, general health problems and depression/anxiety symptoms. The CL group exhibited poorer outcomes in physical and mental health but not in other domains. Conclusion: Both males and females exhibiting AO and LCP antisocial behaviour are at increased risk of serious adverse outcomes in young adulthood. The significant loss to follow up of high-risk groups suggests the important relationship between early antisocial behaviour and problems in adulthood have been underestimated. Further research is required to understand antisocial behaviour in adolescence, identify factors that reinforce its continuity into adulthood, and identify interventions which are able to modify adult outcomes.

Physical aggression during admission to a child and adolescent inpatient unit: predictors and impact on clinical outcomes

Objective: Aggressive behaviour is common in young people admitted to child and adolescent inpatient services. Little is known about how physical aggression during admission influences patient outcomes. The aim of the present study was to identify predictors of aggression in a child and adolescent inpatient unit and examine differences in clinical outcomes between aggressive and non-aggressive patients. Method: Episodes of aggression occurring within a child and adolescent inpatient unit were prospectively documented between October 2004 and December 2005. Patient factors (demographics, diagnoses, clinical history) were examined as predictors of aggression. Outcomes for admissions in which more than one episode of physical aggression occurred were compared to those in which no aggression occurred. Outcomes assessed were changes in symptom severity (as rated by the Health of the Nation Outcome Scales for Children and Adolescents) length of stay, and initiation of medications. Results: A total of 134 patients were admitted during the study period (61.9% female, mean age=13.8years, SD=2.9); 31 patients (23.1%) exhibited physical aggression during admission and 20 of these exhibited more than one episode of physical aggression. Factors that predicted persistent physical aggression included history of aggression, use of medications at presentation and absence of self-harm. Persistent aggression was also associated with increased length of stay, but did not compromise improvements in clinical symptom ratings between admission and discharge or lead to increased medication prescribing Conclusion: Contrary to hypotheses and existing research, aggression during admission does not appear to be a barrier to clinical improvement. Further research is necessary to clarify how aggressive children can receive the most benefit from inpatient admission while minimizing the risks to the patient and those around them.

A randomised, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms

BACKGROUND Depression and antidepressant use are prevalent in methadone maintenance patients (MMPs). However, antidepressant efficacy is not well established in this population. This study examined the efficacy of fluoxetine in improving depressive symptoms and reducing substance use in MMPs. METHODS Stabilised MMPs scoring over 21 on the Beck Depression Inventory were randomised to receive fluoxetine or placebo over 12 weeks. RESULTS Forty-nine subjects were randomised. In both groups, significant improvements were observed in depression, life functioning, and social impairment over 12 weeks. Poly-drug use improved in completers only. No fluoxetine effects were observed. CONCLUSIONS Little evidence supports use of fluoxetine as a treatment for depressive symptoms in MMPs.

Monoaminergic modulation of behavioural and electrophysiological indices of error processing

RationaleError processing is a critical executive function that is impaired in a large number of clinical populations. Although the neural underpinnings of this function have been investigated for decades and critical error-related components in the human electroencephalogram (EEG), such as the error-related negativity (ERN) and the error positivity (Pe), have been characterised, our understanding of the relative contributions of key neurotransmitters to the generation of these components remains limited.ObjectivesThe current study sought to determine the effects of pharmacological manipulation of the dopamine, noradrenaline and serotonin neurotransmitter systems on key behavioural and event-related potential correlates of error processing.MethodsA randomised, double-blinded, placebo-controlled, crossover design was employed. Monoamine levels were manipulated using the clinically relevant drugs methylphenidate, atomoxetine and citalopram, in comparison to placebo. Under each of the four drug conditions, participants underwent EEG recording while performing a flanker task.ResultsOnly methylphenidate produced significant improvement in performance accuracy, which was without concomitant slowing of reaction time. Methylphenidate also increased the amplitude of an early electrophysiological index of error processing, the ERN. Citalopram increased the amplitude of the correct-response negativity, another component associated with response processing.ConclusionsThe effects of methylphenidate in this study are consistent with theoretical accounts positing catecholamine modulation of error monitoring. Our data suggest that enhancing catecholamine function has the potential to remediate the error-monitoring deficits that are seen in a wide range of psychiatric conditions.