Creation of the Youth Integration Project Framework: A Narrative Synthesis of the Youth Mental Health Integrated Care Literature.

Introduction: Integrated care has been posited as a potential solution to the global burden of youth mental health (YMH), but there is limited evidence on how best to design, staff, and evaluate different integrated care models. Our review aimed to consolidate the evidence on integrated models of mental healthcare for young people, to identify the core components of integration, and create a framework that can be used to analyse levels of YMH integration. Methods: We conducted a systematic review of literature across PubMed, SCOPUS, and PsycINFO databases and the grey literature We performed a narrative synthesis extracting core components of integrated YMH care. Results: Inductive themes from the literature described core components of integrated care. These themes were mapped into a novel framework combining the World Health Organisation health system building blocks and six intensity levels of integrated care to consider how best to implement and sustain integrated care within the YMH system. Discussion: The Youth Integration Project framework can form a basis for the development, implementation and evaluation of well-articulated models of youth integrated mental health pathways, assisting services identify what operational changes are needed to best implement and sustain integrated care.

Moving from idea to reality: The barriers and enablers to implementing Child and Family Hubs policy into practice in NSW, Australia.

BACKGROUND: Adverse childhood experiences can impact physical and mental health throughout the lifespan. To support families experiencing adversity and improve child health and developmental equity, an integrated, multi-sector response is required. Child and Family Hubs (Hubs) are a feasible and acceptable approach to providing such a response. In the Australian context, a number of federal and New South Wales (NSW) state policies support an integrated, multi-sector response using Hubs to support families experiencing adversity. This study examined NSW policy stakeholder and health service manager perspectives on the barriers and enablers to translating policy into practice in the implementation of Child and Family Hubs. METHODS: Semi-structured interviews were conducted with 11 NSW government policy stakeholders and 13 community health service managers working in child and family policy and planning or child and family community-based services. Interviews were of 30-60 min duration and explored stakeholder knowledge, perspectives and experiences around childhood adversity, and barriers and enablers to operationalizing policies supporting Hubs. Analysis of barriers and facilitators to implementation of Hub models of care was undertaken using the Consolidated Framework for Implementation Research (CFIR). RESULTS: Key barriers that emerged included short-term and inconsistent funding, lack of resourcing for a Hub co-ordinator, limited support for evaluation and insufficient time to plan for Hub implementation. Key enablers included flexibility and adaptability of Hub models to meet local needs, formal change management processes, strong governance structures and engagement among Hub practitioners. Key insights included the importance of targeted strategies to support sustained individual practice change and the need for organization-wide commitment to enable the successful adoption and maintenance of the Hub model of care. CONCLUSIONS: This study provides valuable insights and contributes evidence around what is needed to strengthen and support the operationalization and scalability of the Hub model of care. Key recommendations for Hub practitioners include the importance of formal change management processes and establishment of strong governance structures, while key recommendations for policymakers include the need for sustainable Hub funding and a standardized, evidence-based framework to support Hub implementation and evaluation.

Sex Differences in the Broad Autism Phenotype: Insights from the Australian Biobank.

Examining sub-threshold autistic traits in non-autistic first-degree relatives of individuals on the autism spectrum, known as the Broad Autism Phenotype (BAP), could provide new insights into the associations and familial aggregation of autistic traits. This study was a retrospective cross-sectional study of parents (n = 1008), probands with autism (n = 613), and unaffected siblings (n = 221) of probands with autism. BAP traits were examined by the BAP Questionnaire and Communication Checklist-Adult in parents, Autism Developmental Observation Scale-Second edition in probands, and Social Responsiveness Scale in siblings. Multivariable linear regression analyses were used to investigate the associations of parental BAP traits on autistic traits in probands and unaffected sibling BAP traits. Fathers showed significantly increased aloofness, pragmatic language difficulties, and social engagement problems compared to mothers. Female siblings showed increased difficulties with social cognition compared to male siblings. Adjusted models of the regression analyses showed that all BAP traits in fathers were significantly associated with BAP trait expression in probands with autism. Additionally, all of mother's BAP traits were significantly associated with unaffected siblings' BAP trait expression while only fathers' aloofness and rigidity traits were inversely associated with siblings' BAP trait expression. Finally, there were significant inverse interactions noted between parent's BAP traits and their children's BAP trait expression. This study demonstrated differences in how males and females express BAP traits and also identified differences in parent-child associations by sex, with fathers having a greater effect on their proband children's expression of BAP traits than mothers.

EPIC-CP pilot trial study protocol: a multicentre, randomised controlled trial investigating the feasibility and acceptability of social prescribing for Australian children with cerebral palsy.

INTRODUCTION: The social determinants of health contribute to poorer health outcomes for children with cerebral palsy (CP) and are barriers to families accessing health services. At an individual level, social determinants of health are experienced as unmet social needs, for example, unsafe housing conditions. There is emerging evidence that clinical pathways for the systematic identification and referral to services for unmet social needs can support families to address these needs. These clinical pathways have not been implemented for children with CP. The objectives are to investigate the feasibility and acceptability of two co-designed social needs clinical pathways for parents/caregivers of children with CP-social prescribing (ie, Community Linker plus resource pack) compared with resource pack only. METHODS AND ANALYSIS: This pilot randomised controlled trial will run at the three tertiary paediatric rehabilitation services in New South Wales, Australia. A total of 120 participants will be recruited, with randomisation stratified by study site. A survey tool will be used to identify families experiencing unmet social needs. Parents/caregivers who report one or more unmet social need/s and consent will be eligible. The active control group will receive a resource pack containing information on community services to support unmet social needs. The social prescribing intervention group will receive one-on-one Community Linker support, in addition to the resource pack. The survey tool, intervention, logic model, and resource pack were co-designed with patient families and their healthcare workers. Feasibility of the research design and the clinical pathways will be evaluated using the number/proportion of parents/caregivers who complete the survey tool, consent, engage with the intervention, and complete research measures. Acceptability will be evaluated using questionnaires and qualitative interviews. ETHICS AND DISSEMINATION: Human research ethics approval was granted by the Sydney Children's Hospitals Network Human Research Ethics Committee (2022/ETH01688). Participants and stakeholders will receive updates and findings via regular communication channels including meetings, presentations, and publications. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry: 12622001459718.

Sociodemographic and clinical indicators of children and young people with cerebral palsy and reported unmet social needs.

AIM: To determine the frequency, type, clinical, and sociodemographic associations of unmet social needs in children with cerebral palsy (CP). METHOD: We conducted a cross-sectional study of parents and carers of children with CP attending a specialist hospital clinic between July and September 2022. Unmet social needs were self-identified using a survey, guided by the WE CARE survey instrument and adapted to the local context. Sociodemographic and clinical data were obtained from medical records. We performed descriptive analysis of participants' unmet social needs, sociodemographic factors, and clinical factors, and examined for associations using a χ2 test and logistic regression. RESULTS: A total of 105 parents and carers completed the survey. Of these, 68 (64.8%) reported one or more unmet social need, with 24 (22.9%) reporting three or more unmet needs. A higher number (three or more) of unmet needs was associated with Gross Motor Function Classification System levels IV and V (odds ratio [OR] = 3.77, 95% confidence interval [CI] = 1.44-9.86) and intellectual disability (OR = 4.63, 95% CI = 1.61-13.31), but were not significant when corrected for neighbourhood socioeconomic disadvantage. The greatest socioeconomic disadvantage was associated with housing concerns (p = 0.002), food (p = 0.026), and financial insecurity (p = 0.02). INTERPRETATION: Unmet social needs are experienced by most families of children with CP. This study highlights the importance of systematic pathways to identify and address unmet social needs.

Functional brain networks associated with the urge for action: Implications for pathological urge.

Tics in Tourette syndrome (TS) are often preceded by sensory urges that drive the motor and vocal symptoms. Many everyday physiological behaviors are associated with sensory phenomena experienced as an urge for action, which may provide insight into the neural correlates of this pathological urge to tic that remains elusive. This study aimed to identify a brain network common to distinct physiological behaviors in healthy individuals, and in turn, examine whether this network converges with a network we previously localized in TS, using novel 'coordinate network mapping' methods. Systematic searches were conducted to identify functional neuroimaging studies reporting correlates of the urge to micturate, swallow, blink, or cough. Using activation likelihood estimation meta-analysis, we identified an 'urge network' common to these physiological behaviors, involving the bilateral insula/claustrum/inferior frontal gyrus/supplementary motor area, mid-/anterior- cingulate cortex (ACC), right postcentral gyrus, and left thalamus/precentral gyrus. Similarity between the urge and TS networks was identified in the bilateral insula, ACC, and left thalamus/claustrum. The potential role of the insula/ACC as nodes in the network for bodily representations of the urge to tic are discussed.

Integrated care models for youth mental health: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the effectiveness of integrated models of mental healthcare in enhancing clinical outcomes, quality of life, satisfaction with care and health service delivery outcomes in young people aged 12-25 years. A secondary objective was to identify common components of integrated mental health interventions. METHODS: A systematic review and meta-analysis of studies published 2001-2023 that assessed clinical or health service use outcomes of integrated care, relative to treatment as usual, for any mental health condition in 12-25 years old accessing community-based care. RESULTS: Of 11,444 titles identified, 15 studies met inclusion criteria and 6 studies were entered in the meta-analysis. Pooled effect size found integrated care was associated with a greater reduction in depressive symptoms relative to treatment as usual at 4-6 months (standardised mean difference = -0.260, 95% confidence interval = [-0.39, -0.13], p = 0.001). Of the seven studies reporting access or engagement, all reported higher rates of both in the intervention arm. The most frequent components of integration were use of a multidisciplinary team (13/15 studies), shared treatment planning (11/15) and workforce training in the model (14/15). CONCLUSIONS: Integrated models of mental healthcare are associated with a small, but significant, increase in effectiveness for depressive symptoms relative to treatment as usual. Given integrated care may increase access and engagement, future research should focus on assessing the impact of integrated care in a wider range of settings and outcomes, including clinical and functional recovery, satisfaction with care and system-level outcomes such as cost-effectiveness.

Utilising Behavioural and Sensory Profiles and Associated Perinatal Factors to Identify Meaningful Subgroups in Autism Spectrum Disorder.

The heterogeneity of autism spectrum disorder (ASD) clinically and aetiologically hinders intervention matching and prediction of outcomes. This study investigated if the behavioural, sensory, and perinatal factor profiles of autistic children could be used to identify distinct subgroups. Participants on the autism spectrum aged 2 to 17 years and their families were sourced via the Australian Autism Biobank (AAB). Latent class analysis was used to identify subgroups within this cohort, utilising twenty-six latent variables representing child's behavioural and sensory features and perinatal factors. Four distinct subgroups within the sample (n = 1168) distinguished by sensory and behavioural autism traits and exposure to perinatal determinants were identified. Class 2 and Class 4, which displayed the greatest behavioural and sensory impairment respectively, were associated with the highest perinatal factor exposure. Class 1, labelled "Most behavioural concerns and moderate sensory and behavioural skills concerns" had mixed exposure to perinatal determinants while Class 3, named "Least sensory and behavioural skills concerns" had the least perinatal determinant exposure, indicating a directly proportional correlation between severity of clinical features and perinatal factor exposure. Additionally, association between specific exposures such as maternal mental illness in Class 1 and significant behavioural concerns was recognised. Identifying distinct subgroups among autistic children can lead to development of targeted interventions and supports. Close monitoring of children exposed to specific perinatal determinants for developmental differences could assist early intervention and supports.

The relationship between hair cortisol concentration and autism diagnosis.

BACKGROUND: Autistic children are prone to experience heightened levels of distress and physiological reactivity to a range of sensory, social, and emotional stimuli. In line with this, multiple studies have demonstrated that autistic children have higher acute cortisol stress responses to adverse or threatening stimuli and altered cortisol awakening responses. However, few studies have examined whether this sensitivity may relate to heightened levels of chronic stress and persistently elevated hypothalamic-pituitary-adrenal (HPA) axis activity. The measurement of cortisol accumulation in hair is considered a non-invasive biomarker of chronic stress and has been associated with several childhood diseases. Here, we investigated whether hair cortisol concentration in a large sample of autistic children differed from non-autistic children, and after accounting for a range of child, parental and family-level characteristics. METHODS: Hair cortisol concentration was measured in 307 autistic children and 282 non-autistic controls aged between 2 and 17 years recruited from four Australian states who participated in providing hair samples and demographic data to the Australian Autism Biobank. Independent samples t-test or one-way analysis of variance (ANOVA) were conducted to determine significant differences in the mean hair cortisol concentration (pg/mg) between potential covariates. Primary analysis included multivariable regression modelling of the collapsed sample to identify variables that were significantly associated with hair cortisol concentration after controlling for covariates. We also accounted for the potential interaction of multiple biological (e.g., age, sex, BMI) and psychosocial characteristics at the level of the child, the mother and the father, and the family unit. RESULTS: Our findings suggest that the diagnosis of autism was not a significant predictor of chronic stress, as measured by hair cortisol concentration. However, findings of the multivariable regression analysis showed that key factors such as area of residence (Queensland vs Victorian state of residence) and decrease in child's age were significantly associated with higher hair cortisol concentration whereas lower family income was significantly associated with higher hair cortisol concentration. CONCLUSION: To our knowledge, this is the first study to show that socioeconomic factors such as family annual income affect hair cortisol status in autistic children, indicating that the psychosocial environment may be a potential mediator for chronic stress in autistic children just as it has been demonstrated in non-autistic children.

Difficult Toddler Temperament - Prevalence and Associated Factors at 18-Month Follow-Up of a Birth Cohort.

Purpose: Difficult temperament coupled with other risk factors may lead to mental health problems in childhood and have long-lasting effects in adolescence and adulthood. This study aimed to investigate the prevalence of parental perception of difficult temperament in toddlers and identify significant factors associated with individual and family-level sociodemographic risk factors. Patients and Methods: The prevalence of parental perception of difficult temperament was derived from items in the 18-month follow-up questionnaire within the Watch Me Grow (WMG) longitudinal birth cohort study in a multicultural and socioeconomically disadvantaged community in Sydney, Australia. Data was available for 500 children and their parents. Descriptive analysis was used to calculate the participant characteristics and the prevalence of parental perception of difficult temperament, whereas multivariable logistic regression analysis was used to assess significant risk factors associated with a difficult temperament. Results: Parental perception of difficult temperament in the cohort was 7.3% (n = 492). Findings of the multivariable logistic regression showed that screen time >2 hours a day (AOR 2.43, 95% CI: 1.2, 4.9), child not being read to (AOR 3.92, 95% CI: 1.8, 8.5), and family history of mental health problems (AOR 2.69, 95% CI: 1.1, 6.5) significantly increased the odds of having a difficult temperament. Conclusion: Toddlers with difficult temperament were less likely to have received stimulatory experiences, and their families were more likely to be under greater stress. The findings emphasize the importance of parental support and anticipatory guidance in promoting nurturing care to facilitate child health and development, particularly in disadvantaged communities.

Editorial: Equity, diversity and inclusion in child and adolescent mental health - equality of opportunities should be every child's right and every society's obligation.

Socio-ecological factors are major determinants of poor mental health across the life span. These factors can lead to health inequalities, which refer to differences in the health of individuals or groups (Kirkbride et al., 2024). Health inequity "is a specific type of health inequality that denotes an unjust, avoidable, systematic and unnecessary difference in health" (Arcaya, Arcaya, & Subramanian, 2015). Among several intersecting social adversities, inequity is one of the most pervasive contributors to poor mental health across all regions (Venkatapuram & Marmot, 2023). Structural inequity creates institutional power structures that marginalise large sections of the population and concentrate resources in the hands of a small minority (Shim, Kho, & Murray-García, 2018). The world is now more prosperous than it has ever been, yet the world is witnessing more within country inequality with the vast majority of the world's resources in the hands of a small minority of individuals or regions (United Nations, 2020).

The relationship between mental health reforms and general population suicide rates in Australia over the past three and a half decades: 1987-2021.

Nearly 3,000 Australians tragically end their lives by suicide each year, underscoring a major national public health challenge with substantial socio-economic ramifications. Australia's National Mental Health Plans (NMHPs) aim to improve mental health and reduce suicide rates. This study investigates their effectiveness by analyzing how age-standardized suicide rates across Australian jurisdictions have fluctuated alongside the implementation of five NMHPs from 1987 to 2021. Findings reveal mixed impacts, with some plans linked to decreases and others associated with increases in suicide rates across different periods and regions. Notably, the recent decline in 2020 requires careful consideration amidst COVID-19 pandemic influences. These insights not only provide valuable evidence for shaping future mental health policies and initiatives but also for future health services research.

Evidence-based brief interventions targeting acute mental health presentations for children and adolescents: systematic review.

BACKGROUND: Brief intervention services provide rapid, mobile and flexible short-term delivery of interventions to resolve mental health crises. These interventions may provide an alternative pathway to the emergency department or in-patient psychiatric services for children and young people (CYP), presenting with an acute mental health condition. AIMS: To synthesise evidence on the effectiveness of brief interventions in improving mental health outcomes for CYP (0-17 years) presenting with an acute mental health condition. METHOD: A systematic literature search was conducted, and the studies' methodological quality was assessed. Five databases were searched for peer-reviewed articles between January 2000 and September 2022. RESULTS: We synthesised 30 articles on the effectiveness of brief interventions in the form of (a) crisis intervention, (b) integrated services, (c) group therapies, (d) individualised therapy, (e) parent-child dyadic therapy, (f) general services, (g) pharmacotherapy, (h) assessment services, (i) safety and risk planning and (j) in-hospital treatment, to improve outcomes for CYP with an acute mental health condition. Among included studies, one study was rated as providing a high level of evidence based on the National Health and Medical Research Council levels of evidence hierarchy scale, which was a crisis intervention showing a reduction in length of stay and return emergency department visits. Other studies, of moderate-quality evidence, described multimodal brief interventions that suggested beneficial effects. CONCLUSIONS: This review provides evidence to substantiate the benefits of brief interventions, in different settings, to reduce the burden of in-patient hospital and readmission rates to the emergency department.

Evidence-based long term interventions targeting acute mental health presentations for children and adolescents: systematic review.

Background: Long term intervention services have proven to be effective in improving mental health (MH) outcomes and the quality of life for children and young people (CYP). Aim: To synthesize evidence on the effectiveness of long-term interventions in improving MH outcomes for CYP, 0-17 years, presenting with MH conditions. Methods: A systematic search was carried out and the methodological quality of included long term MH intervention studies were assessed. Six databases were searched for peer-reviewed articles between January 2000 and September 2022. Results: We found 30 studies that reported on the effectiveness of a range of long-term MH interventions in the form of (i) group therapy, (ii) multisystemic behavior therapy, (iii) general services, (iv) integrated services, (v) psychotherapy, (vi) intensive intervention services, (vii) comprehensive collaborative care, (viii) parent training, and (ix) home outreach service. Among the included studies, seven were rated as high level of evidence based on the National Health and Medical Research Council (NHMRC) levels of evidence hierarchy scale and seven were of moderate quality evidence. Others were rated as lower-quality evidence. Among the studies providing high quality evidence, most were reported for group therapy, general services, and psychotherapy studies demonstrating beneficial effects. Conclusion: This systematic review provides evidence to demonstrate the benefits of a range of long-term interventions, in a range of settings, can be effective in improving MH outcomes for CYP and their families. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022323324.

Combined Effect of Maternal Separation and Early-Life Immune Activation on Brain and Behaviour of Rat Offspring.

Adversity during early life, a critical period for brain development, increases vulnerability and can have a lasting impact on the brain and behaviour of a child. However, the long-term effects of cumulative early-life stressors on brain and behaviour are not well known. We studied a 2-hit rat model of early-life adversity using maternal separation (MS) and immune activation (lipopolysaccharide (LPS)). Rat pups underwent MS for 15 (control) or 180 (MS) minutes per day from postnatal day (P)2-14 and were administered saline or LPS (intraperitoneal) on P3. Open-field (OFT) and object-place recognition tests were performed on rat offspring at P33-35 and P42-50, respectively. The pre-frontal cortex (PFC) and hippocampus were removed at the experimental endpoint (P52-55) for mRNA expression. MS induced anxiety-like behaviour in OFT in male and reduced locomotor activity in both male and female offspring. LPS induced a subtle decline in memory in the object-place recognition test in male offspring. MS increased glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor expression in PFC and ionised calcium-binding adapter molecule-1 expression in male hippocampus. MS and LPS resulted in distinct behavioural phenotypes in a sex-specific manner. The combination of MS and LPS had a synergistic effect on the anxiety-like behaviour, locomotor activity, and GFAP mRNA expression outcomes.

Using visual attention estimation on videos for automated prediction of autism spectrum disorder and symptom severity in preschool children.

Atypical visual attention in individuals with autism spectrum disorders (ASD) has been utilised as a unique diagnosis criterion in previous research. This paper presents a novel approach to the automatic and quantitative screening of ASD as well as symptom severity prediction in preschool children. We develop a novel computational pipeline that extracts learned features from a dynamic visual stimulus to classify ASD children and predict the level of ASD-related symptoms. Experimental results demonstrate promising performance that is superior to using handcrafted features and machine learning algorithms, in terms of evaluation metrics used in diagnostic tests. Using a leave-one-out cross-validation approach, we obtained an accuracy of 94.59%, a sensitivity of 100%, a specificity of 76.47% and an area under the receiver operating characteristic curve (AUC) of 96% for ASD classification. In addition, we obtained an accuracy of 94.74%, a sensitivity of 87.50%, a specificity of 100% and an AUC of 99% for ASD symptom severity prediction.

Quality of Life in Hungarian Parents of Autistic Individuals.

PURPOSE: Parents of autistic individuals have been known to have a lower overall quality of life (QQL) than those of typically developing children. We present the first Hungarian large-sample study whose objective was to explore the differences in QOL between parents of autistic individuals (AS) and those of neurotypical (NT) persons. METHODS: Based on the ABCX model we developed a questionnaire comprising standardized scales to characterize the life of parents involved. Our data came from parents of 842 individuals (ASD = 521, NT = 321) between 0 and 49 years. Battery deployed standardized instruments to examine quality of life (WHO-QQL BREF and Quality of Life in Autism questionnaire, QOLA). We assessed the families' socio-economic/demographic characteristics, parents' psychological well-being, the autistic/neurotypical individuals' characteristics, and the interventions. RESULTS: Our data showed significantly lower QOL in parents of autistic individuals in all domains of questionnaires. We analyzed 20 relevant factors to uncover the predictors of parental QOL. We confirmed the existence of most but not all predictors present in earlier literature and identified intervention-related predictors. CONCLUSION: Our study confirms the importance of supporting parents in their role, and of providing health and social supports that focus on quality of life, in addition to child care.

Immp2l Enhances the Structure and Function of Mitochondrial Gpd2 Dehydrogenase.

'Inner mitochondrial membrane peptidase 2 like' (IMMP2L) is a nuclear-encoded mitochondrial peptidase that has been conserved through evolutionary history, as has its target enzyme, 'mitochondrial glycerol phosphate dehydrogenase 2' (GPD2). IMMP2L is known to cleave the mitochondrial transit peptide from GPD2 and another nuclear-encoded mitochondrial respiratory-related protein, cytochrome C1 (CYC1). However, it is not known whether IMMP2L peptidase activates or alters the activity or respiratory-related functions of GPD2 or CYC1. Previous investigations found compelling evidence of behavioural change in the Immp2lKD-/- KO mouse, and in this study, EchoMRI analysis found that the organs of the Immp2lKD-/- KO mouse were smaller and that the KO mouse had significantly less lean mass and overall body weight compared with wildtype littermates (p < 0.05). Moreover, all organs analysed from the Immp2lKD-/- KO had lower relative levels of mitochondrial reactive oxygen species (mitoROS). The kidneys of the Immp2lKD-/- KO mouse displayed the greatest decrease in mitoROS levels that were over 50% less compared with wildtype litter mates. Mitochondrial respiration was also lowest in the kidney of the Immp2lKD-/- KO mouse compared with other tissues when using succinate as the respiratory substrate, whereas respiration was similar to the wildtype when glutamate was used as the substrate. When glycerol-3-phosphate (G3P) was used as the substrate for Gpd2, we observed ~20% and ~7% respective decreases in respiration in female and male Immp2lKD-/- KO mice over time. Together, these findings indicate that the respiratory-related functions of mGpd2 and Cyc1 have been compromised to different degrees in different tissues and genders of the Immp2lKD-/- KO mouse. Structural analyses using AlphaFold2-Multimer further predicted that the interaction between Cyc1 and mitochondrial-encoded cytochrome b (Cyb) in Complex III had been altered, as had the homodimeric structure of the mGpd2 enzyme within the inner mitochondrial membrane of the Immp2lKD-/- KO mouse. mGpd2 functions as an integral component of the glycerol phosphate shuttle (GPS), which positively regulates both mitochondrial respiration and glycolysis. Interestingly, we found that nonmitochondrial respiration (NMR) was also dramatically lowered in the Immp2lKD-/- KO mouse. Primary mouse embryonic fibroblast (MEF) cell lines derived from the Immp2lKD-/- KO mouse displayed a ~27% decrease in total respiration, comprising a ~50% decrease in NMR and a ~12% decrease in total mitochondrial respiration, where the latter was consistent with the cumulative decreases in substrate-specific mediated mitochondrial respiration reported here. This study is the first to report the role of Immp2l in enhancing Gpd2 structure and function, mitochondrial respiration, nonmitochondrial respiration, organ size and homeostasis.

Predicting Communication Skills Outcomes for Preschool Children with Autism Spectrum Disorder Following Early Intervention.

Purpose: This study aims to assess changes in the receptive and expressive language skills and to determine if the baseline characteristics such as communication, cognitive and motor skills, predict outcomes in preschool children with Autism Spectrum Disorder (ASD) following early intervention. Methods: We recruited 64 children participating in the Early Start Denver Model (ESDM) early intervention program at an Autism Specific Early Learning and Care Center (ASELCC) in Australia. Baseline characteristics across various developmental domains was measured using the Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behaviour Scales, 2nd Edition (VABS-II), and the ESDM Curriculum Checklist. Linear mixed-effects models were used to examine the effects of the intervention on outcomes. Fixed-effects such as time, groups (verbal and minimally verbal), and time-by-group interactions were assessed whilst adjusting for covariates. Further, multiple linear regression models were used to determine if the baseline characteristics were significant predictors of the outcomes following the early intervention. Results: Among the 64 children who participated in this study, 38 children were verbal, whereas 26 were deemed to have minimal verbal skills. The mean age of the sample was 4.1 years with a significant male predilection (83%) and from a culturally and linguistically diverse (CALD) background (64%). Findings of the linear mixed effects model showed significant within and between group differences in the ESDM subscales, indicating higher magnitude of changes in the verbal group compared to the minimally verbal group. Finally, the multiple linear regression models suggested that baseline MSEL visual reception and expressive language scores were predictive of changes in the ESDM receptive and expressive communication scores. Conclusion: Understanding a child's baseline skill levels may provide valuable clues regarding what interventions would work best, or which interventions may be less suitable for individual preschool-aged children with ASD.