Strengthening mental health research outcomes through genuine partnerships with young people with lived or living experience: A pilot evaluation study.

BACKGROUND: Despite increasing support for stakeholder inclusion in research, there is limited evaluative research to guide safe (i.e., youth-friendly) and meaningful (i.e., non-tokenistic) partnerships with young people with lived experience of mental ill-health in research. This paper describes a pilot evaluation and iterative design of a Youth Lived Experience Working Group (LEWG) protocol that was established by the Youth Mental Health and Technology team at The University of Sydney's Brain and Mind Centre, based on the results of two studies. METHODS: Study one consisted of a pilot evaluation of the extent to which youth partners felt empowered to contribute, to qualitatively explore how LEWG processes could be improved. Youth partners completed online surveys, and results were shared over two LEWG meetings in 2021 to empower youth partners to collectively identify actions of positive change regarding LEWG processes. These meetings were audio-recorded and transcripts were subsequently coded using thematic analysis. Study two assessed whether LEWG processes and proposed improvements were acceptable and feasible from the perspective of academic researchers via an online survey in 2022. RESULTS: Quantitative and qualitative data collected from nine youth partners and 42 academic researchers uncovered initial learnings regarding facilitators, motivators, and barriers to partnering with young people with lived experience in research. Implementing clear processes for youth partners and academic researchers on effective partnership strategies, providing training opportunities for youth partners to develop research skills, and providing regular updates on how youth partner contributions led to research outcomes were identified as key facilitators. CONCLUSIONS: This pilot study provides insight into a growing international field on how to optimise participatory processes so that researchers and young people with lived experience can be better supported and engaged to make meaningful contributions to mental health research. We argue that more transparency is needed around participatory research processes so that partnerships with young people with lived experience are not merely tokenistic. CONSUMER CONTRIBUTIONS: Our study has also been approved by and reflects the concepts and priorities of our youth lived experience partners and lived experience researchers, all of whom are authors of this paper.

Measuring, Modeling, and Forecasting the Mental Wealth of Nations.

The COVID-19 pandemic has exposed the deep links and fragility of economic, health and social systems. Discussions of reconstruction include renewed interest in moving beyond GDP and recognizing "human capital", "brain capital", "mental capital", and "wellbeing" as assets fundamental to economic reimagining, productivity, and prosperity. This paper describes how the conceptualization of Mental Wealth provides an important framing for measuring and shaping social and economic renewal to underpin healthy, productive, resilient, and thriving communities. We propose a transdisciplinary application of systems modeling to forecast a nation's Mental Wealth and understand the extent to which policy-mediated changes in economic, social, and health sectors could enhance collective mental health and wellbeing, social cohesion, and national prosperity. Specifically, simulation will allow comparison of the projected impacts of a range of cross-sector strategies (education sector, mental health system, labor market, and macroeconomic reforms) on GDP and national Mental Wealth, and provide decision support capability for future investments and actions to foster Mental Wealth. Finally, this paper introduces the Mental Wealth Initiative that is harnessing complex systems science to examine the interrelationships between social, commercial, and structural determinants of mental health and wellbeing, and working to empirically challenge the notion that fostering universal social prosperity is at odds with economic and commercial interests.

Optimizing Strategies for Improving Mental Health in Victoria, Australia during the COVID-19 Era: A System Dynamics Modelling Study.

The ongoing COVID-19 pandemic has impacted the mental health of populations and highlighted the limitations of mental health care systems. As the trajectory of the pandemic and the economic recovery are still uncertain, decision tools are needed to help evaluate the best interventions to improve mental health outcomes. We developed a system dynamics model that captures causal relationships among population, demographics, post-secondary education, health services, COVID-19 impact, and mental health outcomes. The study was conducted in the Australian state of Victoria. The model was calibrated using historical data and was stratified by age group and by geographic remoteness. Findings demonstrate that the most effective intervention combination includes economic, social, and health sector initiatives. Assertive post-suicide attempt care is the most impactful health sector intervention, but delaying implementation reduces the potency of its impact. Some evidence-based interventions, such as population-wide community awareness campaigns, are projected to worsen mental health outcomes when implemented on their own. Systems modelling offers a powerful decision-support tool to test alternative strategies for improving mental health outcomes in the Victorian context.

Missing in action: the right to the highest attainable standard of mental health care.

BACKGROUND: The right to the highest attainable standard of mental health remains a distant goal worldwide. The Report of the UN Special Rapporteur on the right of all people to enjoyment of the highest attainable standard of physical and mental health pleaded the urgent need for governments to act through appropriate laws and policies. We argue that Australia is in breach of international obligations, with inadequate access to mental health services, inconsistent mental health legislation across jurisdictions and ongoing structural (systematic) and individual discrimination. DISCUSSION: Inadequate access to mental health services is a worldwide phenomenon. Australia has committed to international law obligations under the Convention on the Rights of Persons with Disabilities (CRPD) to 'promote, protect and ensure the full and equal enjoyment of all human rights and fundamental freedoms by all persons with disability, with respect to their inherent dignity'. This includes people with mental health impairment and this convention includes the right to 'the highest attainable standard of mental health'. Under the Australian Constitution, ratification of this convention enables the national government to pass laws to implement the convention obligations, and such national laws would prevail over any inconsistent state (or territory) laws governing mental health service provision. The authors argue that enabling positive rights through legislation and legally binding mental health service standards may facilitate enhanced accountability and enforcement of such rights. These steps may support critical key stakeholders to improve the standards of mental health service provision supported by the implementation of international obligations, thereby accelerating mental health system reform. Improved legislation would encourage better governance and the evolution of better services, making mental health care more accessible, without structural or individual discrimination, enabling all people to enjoy the highest attainable standard of health.

A Dynamic Approach to Economic Priority Setting to Invest in Youth Mental Health and Guide Local Implementation: Economic Protocol for Eight System Dynamics Policy Models.

Background: Mental illness costs the world economy over US2.5 Bn each year, including premature mortality, morbidity, and productivity losses. Multisector approaches are required to address the systemic drivers of mental health and ensure adequate service provision. There is an important role for economics to support priority setting, identify best value investments and inform optimal implementation. Mental health can be defined as a complex dynamic system where decision makers are challenged to prospectively manage the system over time. This protocol describes the approach to equip eight system dynamics (SD) models across Australia to support priority setting and guide portfolio investment decisions, tailored to local implementation context. Methods: As part of a multidisciplinary team, three interlinked protocols are developed; (i) the participatory process to codesign the models with local stakeholders and identify interventions for implementation, (ii) the technical protocol to develop the SD models to simulate the dynamics of the local population, drivers of mental health, the service system and clinical outcomes, and (iii) the economic protocol to detail how the SD models will be equipped to undertake a suite of economic analysis, incorporating health and societal perspectives. Models will estimate the cost of mental illness, inclusive of service costs (health and other sectors, where necessary), quality-adjusted life years (QALYs) lost, productivity costs and carer costs. To assess the value of investing (disinvesting) in interventions, economic analysis will include return-on-investment, cost-utility, cost benefit, and budget impact to inform affordability. Economic metrics are expected to be dynamic, conditional upon changing population demographics, service system capacities and the mix of interventions when synergetic or antagonistic interactions. To support priority setting, a portfolio approach will identify best value combinations of interventions, relative to a defined budget(s). User friendly dashboards will guide decision makers to use the SD models to inform resource allocation and generate business cases for funding. Discussion: Equipping SD models to undertake economic analysis is intended to support local priority setting and help optimise implementation regarding the best value mix of investments, timing and scale. The objectives are to improve allocative efficiency, increase mental health and economic productivity.

Participatory Methods for Systems Modeling of Youth Mental Health: Implementation Protocol.

BACKGROUND: Despite significant investment, mental health issues remain a leading cause of death among young people globally. Sophisticated decision analysis methods are needed to better understand the dynamic and multisector drivers of youth mental health. System modeling can help explore complex issues such as youth mental health and inform strategies to effectively respond to local needs and achieve lasting improvements. The advantages of engaging stakeholders in model development processes have long been recognized; however, the methods for doing so are often not well-described. OBJECTIVE: This paper aims to describe the participatory procedures that will be used to support systems modeling for national multisite implementation. The Right Care, First Time, Where You Live research program will focus on regional youth mental health applications of systems modeling in 8 different sites across Australia. METHODS: The participatory model development approach involves an iterative process of engaging with a range of participants, including people with lived experience of mental health issues. Their knowledge of the local systems, pathways, and drivers is combined with the academic literature and data to populate the models and validate their structure. The process centers around 3 workshops where participants interact and actively engage in group model-building activities to define, refine, and validate the systems models. This paper provides a detailed blueprint for the implementation of this process for mental health applications. RESULTS: The participatory modeling methods described in this paper will be implemented at 2 sites per year from 2022 to 2025. The 8 selected sites have been chosen to capture variations in important factors, including determinants of mental health issues and access to services. Site engagement commenced in August 2021, and the first modeling workshops are scheduled to commence in February 2022. CONCLUSIONS: Mental health system decision makers require tools to help navigate complex environments and leverage interdisciplinary problem-solving. Systems modeling can mobilize data from diverse sources to explore a range of scenarios, including the impact of interventions in different combinations and contexts. Involving stakeholders in the model development process ensures that the model findings are context-relevant and fit-for-purpose to inform decision-making. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/32988.

Sound Decision Making in Uncertain Times: Can Systems Modelling Be Useful for Informing Policy and Planning for Suicide Prevention?

The COVID-19 pandemic demonstrated the significant value of systems modelling in supporting proactive and effective public health decision making despite the complexities and uncertainties that characterise an evolving crisis. The same approach is possible in the field of mental health. However, a commonly levelled (but misguided) criticism prevents systems modelling from being more routinely adopted, namely, that the presence of uncertainty around key model input parameters renders a model useless. This study explored whether radically different simulated trajectories of suicide would result in different advice to decision makers regarding the optimal strategy to mitigate the impacts of the pandemic on mental health. Using an existing system dynamics model developed in August 2020 for a regional catchment of Western Australia, four scenarios were simulated to model the possible effect of the COVID-19 pandemic on levels of psychological distress. The scenarios produced a range of projected impacts on suicide deaths, ranging from a relatively small to a dramatic increase. Discordance in the sets of best-performing intervention scenarios across the divergent COVID-mental health trajectories was assessed by comparing differences in projected numbers of suicides between the baseline scenario and each of 286 possible intervention scenarios calculated for two time horizons; 2026 and 2041. The best performing intervention combinations over the period 2021-2041 (i.e., post-suicide attempt assertive aftercare, community support programs to increase community connectedness, and technology enabled care coordination) were highly consistent across all four COVID-19 mental health trajectories, reducing suicide deaths by between 23.9-24.6% against the baseline. However, the ranking of best performing intervention combinations does alter depending on the time horizon under consideration due to non-linear intervention impacts. These findings suggest that systems models can retain value in informing robust decision making despite uncertainty in the trajectories of population mental health outcomes. It is recommended that the time horizon under consideration be sufficiently long to capture the full effects of interventions, and efforts should be made to achieve more timely tracking and access to key population mental health indicators to inform model refinements over time and reduce uncertainty in mental health policy and planning decisions.

Partnering with Aboriginal and Torres Strait Islander Peoples: An Evaluation Study Protocol to Strengthen a Comprehensive Multi-Scale Evaluation Framework for Participatory Systems Modelling through Indigenous Paradigms and Methodologies.

The social and emotional wellbeing of young Aboriginal and Torres Strait Islander peoples should be supported through an Indigenous-led and community empowering approach. Applying systems thinking via participatory approaches is aligned with Aboriginal and Torres Strait Islander research paradigms and can be an effective method to deliver a decision support tool for mental health systems planning for Indigenous communities. Evaluations are necessary to understand the effectiveness and value of such methods, uncover protective and healing factors of social and emotional wellbeing, as well as to promote Aboriginal and Torres Strait Islander self-determination over allocation of funding and resources. This paper presents modifications to a published evaluation protocol for participatory systems modelling to align with critical Aboriginal and Torres Strait Islander guidelines and recommendations to support the social and emotional wellbeing of young people. This paper also presents a culturally relevant participatory systems modelling evaluation framework. Recognizing the reciprocity, strengths, and expertise Aboriginal and Torres Strait Islander methodologies can offer to broader research and evaluation practices, the amended framework presented in this paper facilitates empowering evaluation practices that should be adopted when working with Aboriginal and Torres Strait Islander peoples as well as when working with other diverse, non-Indigenous communities.

Circadian rhythm sleep-wake disturbances and depression in young people: implications for prevention and early intervention.

A rate-limiting step in the prevention and early intervention of depressive disorders in young people is our insufficient understanding of causal mechanisms. One plausible pathophysiological pathway is disturbance in the 24 h sleep-wake cycle and the underlying circadian system. Abnormalities in circadian rhythms are well documented in adults with various depressive disorders and have been linked to core clinical features, including unstable mood, daytime fatigue, non-restorative sleep, reduced motor activity, somatic symptoms, and appetite and weight change. In this Review, we summarise four areas of research: basic circadian biology and animal models of circadian disturbances; developmental changes in circadian rhythms during adolescence and implications for the emergence of adolescent-onset depressive syndromes; community and clinical studies linking 24 h sleep-wake cycle disturbances and depressive disorders; and clinical trials of circadian-based treatments. We present recommendations based on a highly personalised, early intervention model for circadian-linked depression in young people.

Autism spectrum disorder: An examination of sex differences in neuropsychological and self-report measures of executive and non-executive cognitive function.

LAY ABSTRACT: Research comparing females and males with a diagnosis of autism suggests that there are sex differences in some characteristics such as behaviour regulation. One area not studied in detail is whether females and males with autism perform differently in tests of cognitive ability. The results of previous research are quite mixed. One explanation may be that some research comparing females and males with autism did not include a neurotypical control group for comparison. As a result, it is not clear whether the sex differences in cognitive ability observed in people with autism are similar to differences between neurotypical males and females. To better understand whether there are unique differences between males and females with autism, it is important to also compare them with neurotypical males and females. In our research, we included a neurotypical group and compared males and females with and without a diagnosis of autism. We found that the sex differences in autism are similar to what we observe in males and females without autism. Our study showed that compared with males, females (with and without autism) do better in assessments of processing speed, cognitive flexibility, verbal learning and memory and semantic fluency. Our results suggest that although females show different cognitive performance to males, these sex differences were not specific to the group with a diagnosis of autism.

Supporting Clinicians to Use Technology to Deliver Highly Personalized and Measurement-Based Mental Health Care to Young People: Protocol for an Evaluation Study.

BACKGROUND: Australia's mental health care system has long been fragmented and under-resourced, with services falling well short of demand. In response, the World Economic Forum has recently called for the rapid deployment of smarter, digitally enhanced health services to facilitate effective care coordination and address issues of demand. The University of Sydney's Brain and Mind Centre (BMC) has developed an innovative digital health solution that incorporates 2 components: a highly personalized and measurement-based (data-driven) model of youth mental health care and a health information technology (HIT) registered on the Australian Register of Therapeutic Goods. Importantly, research into implementation of such solutions considers education and training of clinicians to be essential to adoption and optimization of use in standard clinical practice. The BMC's Youth Mental Health and Technology Program has subsequently developed a comprehensive education and training program to accompany implementation of the digital health solution. OBJECTIVE: This paper describes the protocol for an evaluation study to assess the effectiveness of the education and training program on the adoption and optimization of use of the digital health solution in service delivery. It also describes the proposed tools to assess the impact of training on knowledge and skills of mental health clinicians. METHODS: The evaluation study will use the Kirkpatrick Evaluation Model as a framework with 4 levels of analysis: Reaction (to education and training), Learning (knowledge acquired), Behavior (practice change), and Results (client outcomes). Quantitative and qualitative data will be collected using a variety of tools, including evaluation forms, pre- and postknowledge questionnaires, skill development and behavior change scales, as well as a real-time clinical practice audit. RESULTS: This project is funded by philanthropic funding from Future Generation Global. Ethics approval has been granted via Sydney Local Health District's Human Research Ethics Committee. At the time of this publication, clinicians and their services were being recruited to this study. The first results are expected to be submitted for publication in 2021. CONCLUSIONS: The education and training program teaches clinicians the necessary knowledge and skills to assess, monitor, and manage complex needs; mood and psychotic syndromes; and trajectories of youth mental ill-health using a HIT that facilitates a highly personalized and measurement-based model of care. The digital health solution may therefore guide clinicians to help young people recover low functioning associated with subthreshold diagnostic presentations and prevent progression to more serious mental ill-health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/24697.

Age-related parietal GABA alterations in children with autism spectrum disorder.

GABA is the primary inhibitory neurotransmitter in the brain, and is essential to the balance of cortical excitation and inhibition. Reductions in GABA are proposed to result in an overly excitatory cortex that may cause, or contribute to, symptoms of autism spectrum disorder (ASD). This study employed a cross-sectional design to explore GABA+ differences in ASD and the impact of age, comparing 4-12 year olds with ASD (N = 24) to typically developing children (N = 35). GABA+ concentration was measured using edited magnetic resonance spectroscopy in the left parietal lobe. This study used a mixed model to investigate group differences between children with ASD and typically developing children. There was a significant difference in GABA+ levels between the groups, a significant effect of age and interaction between age and diagnostic group. The ASD group showed an association between GABA+ and age, with GABA+ levels gradually increasing with age (r = 0.59, p = 0.003). Typically developing children did not show age-related change in GABA+ concentration (r = 0.09, p = 0.60). By the age of 9, children with ASD showed GABA+ levels that were comparable to their typically developing peers. This study suggests that children with ASD have initially lower levels of GABA+ in the left parietal lobe compared to typically developing children, and that these initially lower levels of GABA+ increase with age in ASD within this region. It is suggested that this developmental shift of GABA+ levels within the left parietal lobe provides a possible explanation for the previously found reductions in childhood that does not persist in adults. LAY SUMMARY: This study measured levels of GABA in the left parietal lobe using magnetic resonance spectroscopy in children with ASD and typically developing children. GABA levels were initially lower in the ASD group, and increased with age, while GABA did not change with age in the typically developing group. This suggests that alterations in GABA signaling may be associated with ASD in childhood. Autism Res 2021, 14: 859-872. © 2021 International Society for Autism Research, Wiley Periodicals LLC.

Distress, quality of life and disability in treatment-seeking young adults with social anxiety disorder.

AIM: This study aimed to: (a) examine whether treatment-seeking young adults with social anxiety disorder (SAD) demonstrate similar degrees of distress, quality of life (QoL) and disability to those with other mental disorders; and (b) investigate the impact of comorbidity, specific comorbid conditions and antidepressants use on distress, QoL and disability in treatment-seeking young adults with SAD. METHODS: A cohort of treatment-seeking young adults (aged 16-45) diagnosed with SAD (N = 298) or other mental health disorders (N = 842; including depression, N = 349; bipolar, N = 141; psychosis, N = 173) completed self-report assessments of distress, QoL and disability. RESULTS: Young adults with SAD showed distress and disability of similar degree to those with most other mental disorders. Specifically, young adults with SAD reported significantly lower QoL than those with major depressive disorder or obsessive-compulsive disorder. Furthermore, young adults with SAD had the most difficulties in getting along with others and the second highest level of distress in comparison to other psychiatric groups. In comparison to antidepressants use, the presence of comorbidity showed a substantial negative influence on these health outcomes, particularly when presenting with comorbid depression or obsessive-compulsive disorder. CONCLUSIONS: Findings highlight significant impairments in young adults seeking treatment for SAD and the important moderating influence of comorbidity. This emphasizes the urgent need for effective management and treatment for its presentation and comorbidities in mental health services targeting young adults.

Validation of the 21-item Depression, Anxiety, and Stress Scales (DASS-21) in individuals with autism spectrum disorder.

The purpose of the study was to examine the internal consistency and validity of the 21-item Depression Anxiety Stress Scale (DASS-21) in individuals with Autism Spectrum Disorder (ASD) and without intellectual disability (IQ >= 70). Participants (NN = 123) were consecutively recruited from the Brain and Mind Centre in New South Wales, Australia. Internal consistency was determined using Cronbach's alpha. Item-total correlations were evaluated by Pearson's product-moment correlation coefficient. The convergent validity of the DASS-21 was examined by measuring its associations with quality of life and other measures of depression and anxiety. Factorial validity was assessed using confirmatory factor analysis. The DASS-21 demonstrated good internal consistency, adequate convergent validity, and all items exhibited satisfactory item-total correlations. Considering fit indices and factor loadings, the confirmatory factor analysis results provided support for the original 3-factor oblique model consisting of depression, anxiety, and stress factors. The model fit could be further improved with some modifications. Overall, the results indicate that the DASS-21 is a viable self-report screening measure for depression, anxiety, and stress in individuals with ASD and without intellectual disability.

Circuits for social learning: A unified model and application to Autism Spectrum Disorder.

Early life social experiences shape neural pathways in infants to develop lifelong social skills. This review presents the first unified circuit-based model of social learning that can be applied to early life social development, drawing together unique human developmental milestones, sensitive learning periods, and behavioral and neural scaffolds. Circuit domains for social learning are identified governing Activation, Integration, Discrimination, Response and Reward (AIDRR) to sculpt and drive human social learning. This unified model can be used to identify social delays earlier in development. We propose social impairments observed in Autism Spectrum Disorder are underpinned by early mistimed sensitive periods in brain development and alterations in amygdala development to disrupt the AIDRR circuits. This model directs how interventions can target neural circuits for social development and be applied early in life. To illustrate, the role of oxytocin and its use as an intervention is explored. The AIDRR model shifts focus away from delivering broad treatments based only on diagnostic classifications, to specifying and targeting the relevant circuits, at the right time of development, to optimize social learning.

Validation of the 36-item and 12-item self-report World Health Organization Disability Assessment Schedule II (WHODAS-II) in individuals with autism spectrum disorder.

The World Health Organization Disability Assessment Schedule II (WHODAS-II) is one of the most widely used generic assessments for measuring disability levels in both clinical and nonclinical populations, with sound psychometrics that is also aligned with the International Classification of Functioning framework. However, its psychometric properties have not been explored extensively in individuals with autism spectrum disorder (ASD). This study examined the psychometric properties of the 36-item and 12-item Self-Report WHODAS-II from 109 individuals diagnosed with ASD and without intellectual disability (IQ ≥ 70). Participants were consecutively recruited from the Brain and Mind Centre in New South Wales, Australia. The WHODAS-II showed adequate internal consistency for all domain scores (α = 0.78-0.97 for 36-item) and for the summary scale (α = 0.95 for 36-item; 0.86 for 12-item). All items also exhibited satisfactory correlations with their respective domain (r = 0.39-0.94 for 36-item) and summary scores (r = 0.42-0.71 for 36-item; 0.42-0.67 for 12-item), except item 4.5 "sexual activity" from the 36-item WHODAS-II (r = 0.19). Concurrent validity was shown by moderate correlations between similar constructs across the WHODAS-II and the World Health Organization Quality of Life BREF (Ps < 0.05). The second-order 7-factor model showed the best fit for the 36-item WHODAS-II, while the second-order 6-factor model demonstrated an acceptable fit for the 12-item WHODAS-II. The model fit could be improved with some modifications. The Schmid-Leiman transformation further confirmed the appropriateness of the second-order factor structure. Overall, the results indicated that the WHODAS-II is a viable generic self-report measure for disability in autistic individuals without ID. Autism Res 2019, 12: 1101-1111. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The majority of autistic people have a disability with a profound or severe limitation in their core activities. However, there is currently limited research identifying reliable and valid self-report measures for disability in the autistic population. This study examined the psychometric properties of the World Health Organization Disability Assessment Schedule II (WHODAS-II) from 109 autistic individuals without intellectual disability. Our results suggest that the WHODAS-II is a viable generic self-report measure for disability in autistic individuals.

Disability, functioning, and quality of life among treatment-seeking young autistic adults and its relation to depression, anxiety, and stress.

In this study, we consecutively recruited treatment-seeking young autistic adults without intellectual impairment aged 16-30 years who presented to a mental health service and evaluated general health (distress, quality of life, and disability), functioning (work loss days and social functioning), and mood symptoms (depression, anxiety, and stress) in those diagnosed with autism spectrum disorder (n = 96). This group was compared to young adults presenting to the same service with primary mental health disorders (depression, n = 343; bipolar, n = 132; psychosis, n = 166; and anxiety, n = 303). This study also investigated the influence of mood symptoms on general health and functioning in the autism spectrum disorder group. Young autistic adults reported significant general health and functioning impairments that were of similar degree to those presenting with primary mental health disorders. Interestingly, the autistic group also reported similarly high levels of mood symptoms to those with primary depressive and anxiety disorders. In the autistic group, depressive symptoms were strongly associated with distress, quality of life, and work loss days, while stress symptoms were strongly associated with disability. This study highlights further research, and mental health services are required specifically targeting young autistic adults to address their significant unmet needs.

A Review of the Safety, Efficacy and Mechanisms of Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and Recommendations for Future Research.

In this article, we conduct a comprehensive review of existing evidence for the safety and therapeutic potential of intranasal oxytocin in pediatric populations. Unique considerations for dosing and delivery of oxytocin to the nasal passageway in pediatric populations and methods to promote adherence are reviewed. Intranasal oxytocin has been administered to 261 children in three open-label studies and eight randomized controlled trials. To date, the only published results in pediatric populations have focused on autism spectrum disorder (ASD) and Prader-Willi syndrome (PWS). Results regarding efficacy for improving social impairment in ASD are equivocal, partially due to mixed methodological designs, dosing regimens, and outcome measures. At present, there is no randomized controlled evidence that oxytocin provides benefit to individuals with PWS. There is no clear evidence of a link between oxytocin administration and any specific adverse event. Adverse events have been assessed using medical interviews, open reports, checklists, and physiological assessments. Adverse events reports have been largely classified as mild (n = 93), with few moderate (n = 9) or severe (n = 3) events reported. There were 35 additional adverse events reported, without severity ratings. Severe events, hyperactivity and irritability, occurred at first administration in both placebo and oxytocin groups, and subsided subsequent to discontinuation. We note that adverse event monitoring is inconsistent and often lacking, and reporting of its relationship to the study drug is poor. Only one study reported adherence data to suggest high adherence. Recommendations are then provided for the delivery of nasal sprays to the nasal passageway, monitoring, and reporting of efficacy, safety, and adherence for oxytocin nasal spray trials in pediatric populations.

Neuroticism and the Overlap Between Autistic and ADHD Traits: Findings From a Population Sample of Young Adult Australian Twins.

Neuroticism, a 'Big Five' personality trait, has been associated with sub-clinical traits of both autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The objective of the current study was to examine whether causal overlap between ASD and ADHD traits can be accounted for by genetic and environmental risk factors that are shared with neuroticism. We performed twin-based structural equation modeling using self-report data from 12 items of the Neo Five-Factor Inventory Neuroticism domain, 11 Social Responsiveness Scale items, and 12 Adult ADHD Self-Report Scale items obtained from 3,170 young adult Australian individual twins (1,081 complete pairs). Univariate analysis for neuroticism, ASD, and ADHD traits suggested that the most parsimonious models were those with additive genetic and unique environmental components, without sex limitation effects. Heritability of neuroticism, ASD, and ADHD traits, as measured by these methods, was moderate (between 40% and 45% for each respective trait). In a trivariate model, we observed moderate phenotypic (between 0.45 and 0.62), genetic (between 0.56 and 0.71), and unique environmental correlations (between 0.37and 0.55) among neuroticism, ASD, and ADHD traits, with the highest value for the shared genetic influence between neuroticism and self-reported ASD traits (r g = 0.71). Together, our results suggest that in young adults, genetic, and unique environmental risk factors indexed by neuroticism overlap with those that are shared by ASD and ADHD.

A cognitive-emotional biomarker for predicting remission with antidepressant medications: a report from the iSPOT-D trial.

Depression involves impairments in a range of cognitive and emotional capacities. It is unknown whether these functions can inform medication choice when considered as a composite predictive biomarker. We tested whether behavioral tests, grounded in the neurobiology of cognitive and emotional functions, predict outcome with common antidepressants. Medication-free outpatients with nonpsychotic major depressive disorder (N=1008; 665 completers) were assessed before treatment using 13 computerized tests of psychomotor, executive, memory-attention, processing speed, inhibitory, and emotional functions. Matched healthy controls (N=336) provided a normative reference sample for test performance. Depressed participants were then randomized to escitalopram, sertraline, or venlafaxine-extended release, and were assessed using the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) and the 17-item Hamilton Rating Scale for Depression. Given the heterogeneity of depression, analyses were furthermore stratified by pretreatment performance. We then used pattern classification with cross-validation to determine individual patient-level composite predictive biomarkers of antidepressant outcome based on test performance. A subgroup of depressed participants (approximately one-quarter of patients) were found to be impaired across most cognitive tests relative to the healthy norm, from which they could be discriminated with 91% accuracy. These patients with generally impaired cognitive task performance had poorer treatment outcomes. For this impaired subgroup, task performance furthermore predicted remission on the QIDS-SR16 at 72% accuracy specifically following treatment with escitalopram but not the other medications. Therefore, tests of cognitive and emotional functions can form a clinically meaningful composite biomarker that may help drive general treatment outcome prediction for optimal treatment selection in depression, particularly for escitalopram.