Centre for Youth Mental Health - Research Publications

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    Arterial stiffness in underweight and weight-restored anorexia nervosa
    Jenkins, ZM ; Phillipou, A ; Castle, DJ ; Eikelis, N ; Lambert, EA (WILEY, 2021-11)
    Cardiovascular complications have been demonstrated in patients with anorexia nervosa (AN) in both the state of starvation and during weight restoration, however, the underlying mechanisms remain unclear. The current study aimed to assess arterial stiffness via carotid-femoral pulse wave velocity (cfPWV) in the acute and weight-restored states of AN. The study also aimed to determine the association between psychological distress and cfPWV. The sample included 37 participants; 10 participants with AN, 17 who were weight-restored (AN-WR; minimum body mass index >18.5 for at least 12 months) and 10 healthy controls (HCs). cfPWV via applanation tonometry was conducted to assess arterial stiffness. Psychological distress was assessed using the depression anxiety stress scale (DASS-21) and the state-trait anxiety inventory (STAI). Between-group comparisons were performed to determine differences between groups, a two-stage hierarchical regression model was performed to determine the contribution of physiological and psychological variables on cfPWV and correlation analyses were also performed. Vascular stiffness was significantly increased in the AN and AN-WR groups, relative to HCs. The total DASS score was the only significant predictor of cfPWV across the sample. There were positive associations between cfPWV and depression, anxiety and stress, as assessed by the DASS. Furthermore, cfPWV was positively associated with STAI trait anxiety. Arterial stiffness was increased in individuals in the acute and weight-restored states of AN, demonstrating early signs of the development of arteriosclerotic cardiovascular disease. Increased arterial stiffness was associated with increased psychological distress, which may be a contributing mechanism to the increased cardiovascular risk in AN.
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    Cross disorder comparisons of brain structure in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 deletion syndrome: A review of ENIGMA findings
    Cheon, E-J ; Bearden, CE ; Sun, D ; Ching, CRK ; Andreassen, OA ; Schmaal, L ; Veltman, DJ ; Thomopoulos, S ; Kochunov, P ; Jahanshad, N ; Thompson, PM ; Turner, JA ; van Erp, TGM (WILEY, 2022-05)
    This review compares the main brain abnormalities in schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and 22q11.2 Deletion Syndrome (22q11DS) determined by ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium investigations. We obtained ranked effect sizes for subcortical volumes, regional cortical thickness, cortical surface area, and diffusion tensor imaging abnormalities, comparing each of these disorders relative to healthy controls. In addition, the studies report on significant associations between brain imaging metrics and disorder-related factors such as symptom severity and treatments. Visual comparison of effect size profiles shows that effect sizes are generally in the same direction and scale in severity with the disorders (in the order SZ > BD > MDD). The effect sizes for 22q11DS, a rare genetic syndrome that increases the risk for psychiatric disorders, appear to be much larger than for either of the complex psychiatric disorders. This is consistent with the idea of generally larger effects on the brain of rare compared to common genetic variants. Cortical thickness and surface area effect sizes for 22q11DS with psychosis compared to 22q11DS without psychosis are more similar to those of SZ and BD than those of MDD; a pattern not observed for subcortical brain structures and fractional anisotropy effect sizes. The observed similarities in effect size profiles for cortical measures across the psychiatric disorders mimic those observed for shared genetic variance between these disorders reported based on family and genetic studies and are consistent with shared genetic risk for SZ and BD and structural brain phenotypes.
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    Baseline data of a sequential multiple assignment randomized trial (STEP study)
    Hartmann, JA ; Nelson, B ; Amminger, GP ; Spark, J ; Yuen, HP ; Kerr, MJ ; Polari, A ; Wallis, N ; Blasioli, J ; Dixon, L ; Carter, C ; Loewy, R ; Niendam, TA ; Shumway, M ; McGorry, PD (WILEY, 2022-10)
    AIM: Research has shown that preventative intervention in individuals at ultra-high risk of psychosis (UHR) improves symptomatic and functional outcomes. The staged treatment in early psychosis (STEP) trial aims to determine the most effective type, timing and sequence of interventions in the UHR population by sequentially studying the effectiveness of (1) support and problem solving, (2) cognitive-behavioural case management and (3) antidepressant medication with an embedded fast-fail option of (4) omega-3 fatty acids or low-dose antipsychotic medication. This paper presents the recruitment flow and baseline clinical characteristics of the sample. METHODS: STEP is a sequential multiple assignment randomized trial. We present the baseline demographics, clinical characteristics and acceptability and feasibility of this treatment approach as indicated by the flow of participants from first contact up until enrolment into the trial. Recruitment took place between April 2016 and January 2019. RESULTS: Of 1343, help-seeking young people who were considered for participation, 402 participants were not eligible and 599 declined/disengaged, resulting in a total of 342 participants enrolled in the study. The most common reason for exclusion was an active prescription of antidepressant medication. Eighty-five percent of the enrolled sample had a non-psychotic DSM-5 diagnosis and symptomatic/functional measures showed a moderate level of clinical severity and functional impairment. DISCUSSION: The present study demonstrates the acceptability and participant's general positive appraisal of sequential treatment. It also shows, in line with other trials in UHR individuals, a significant level of psychiatric morbidity and impairment, demonstrating the clear need for care in this group and that treatment is appropriate.
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    Impact of cyclooxygenase-2 inhibition on cannabis withdrawal and circulating endocannabinoids in daily cannabis smokers
    Haney, M ; Bedi, G ; Cooper, ZD ; Herrmann, ES ; Reed, SC ; Foltin, RW ; Kingsley, PJ ; Marnett, LJ ; Patel, S (WILEY, 2022-07)
    Attenuating enzymatic degradation of endocannabinoids (eCBs) by fatty acid amide hydrolase (FAAH) reduces cannabis withdrawal symptoms in preclinical and clinical studies. In mice, blocking cyclooxygenase-2 (COX-2) activity increases central eCB levels by inhibiting fatty acid degradation. This placebo-controlled study examined the effects of the FDA-approved COX-2 selective inhibitor, celecoxib, on cannabis withdrawal, 'relapse', and circulating eCBs in a human laboratory model of cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (12M, 3F) completed a crossover study comprising two 11-day study phases (separated by >14 days for medication clearance). In each phase, the effects of daily BID placebo (0 mg) or celecoxib (200 mg) on cannabis (5.3% THC) intoxication, withdrawal symptoms (4 days of inactive cannabis self-administration) and 'relapse' (3 days of active cannabis self-administration following abstinence) were assessed. Outcome measures included mood, cannabis self-administration, sleep, food intake, cognitive performance, tobacco cigarette use and circulating eCBs and related lipids. Under placebo maintenance, cannabis abstinence produced characteristic withdrawal symptoms (negative mood, anorexia and dreaming) relative to cannabis administration and was associated with increased OEA (a substrate of FAAH) and oleic acid (metabolite of OEA), with no change in eCB levels. Compared to placebo, celecoxib improved subjective (but not objective) measures of sleep and did not affect mood or plasma levels of eCBs or associated lipids and increased cannabis craving. The overall absence of effects on cannabis withdrawal symptoms, self-administration or circulating eCBs relative to placebo, combined with an increase in cannabis craving, suggests celecoxib does not show promise as a potential pharmacotherapy for CUD.
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    Cognitive flexibility and the risk of anorexia nervosa: An investigation using self-report and neurocognitive assessments
    Miles, S ; Phillipou, A ; Sumner, P ; Nedeljkovic, M (PERGAMON-ELSEVIER SCIENCE LTD, 2022-07)
    Impaired cognitive flexibility has been suggested as a risk factor for the development of anorexia nervosa (AN). The current study aimed to 1) investigate cognitive flexibility in people at various levels of risk of AN; and 2) compare people with a history of AN to people at different levels of risk of AN in cognitive flexibility. The sample comprised of 262 community participants (79% female) and 36 participants with a lifetime diagnosis of AN (97.2% female) aged between 18 and 64 years old. Participants completed self-report (the Depression Anxiety Stress Scale short-form version, the Eating Disorders Examination-Questionnaire, the Neuroticism Scale, and the Cognitive Flexibility Inventory) and neurocognitive (the Trail Making Test and the Wisconsin Card Sorting Test) assessments online to evaluate eating disorder symptoms, depression, neuroticism, and cognitive flexibility. Using a cluster analysis, participants were allocated into low-, medium-, and high-risk of AN groups (n = 88, 128, 46, and 36 respectively). Although high-risk participants self-reported significantly poorer cognitive flexibility than the other risk groups, performance on the neurocognitive tasks was similar across groups. Further, participants with lifetime AN reported significantly poorer cognitive flexibility than the low-risk group. People at high-risk of AN may perceive themselves to have poorer cognitive flexibility compared to those at a lower risk of AN. These results have implications for early identification of people at high-risk of AN.
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    Understanding self-report and neurocognitive assessments of cognitive flexibility in people with and without lifetime anorexia nervosa
    Miles, S ; Nedeljkovic, M ; Sumner, P ; Phillipou, A (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2022-09-03)
    Objective: Anorexia nervosa (AN) is a serious eating disorder associated with several cognitive difficulties including poor cognitive flexibility (i.e. difficulties in effectively adapting to changes in the environment and/or changing task demands). AN research has primarily assessed cognitive flexibility using neurocognitive tests, and little is known about the differences or similarities between self-report and neurocognitive assessments of cognitive flexibility. This study investigated the relationship between self-report and neurocognitive assessments of cognitive flexibility in people with no history of an eating disorder (n = 207) and people with a self-reported lifetime diagnosis of AN (n = 19).Methods: Participants completed self-report and neurocognitive assessments of cognitive flexibility through an online study.Results: No significant correlations were found between self-report and neurocognitive assessments of cognitive flexibility for either group of the sample, suggesting that these assessments may evaluate different aspects of cognitive flexibility. Further, negative mood and self-reported eating disorder symptoms were found to significantly relate to self-reported cognitive flexibility, but were not associated with performance on neurocognitive tests of cognitive flexibility.Conclusions: To provide a comprehensive understanding of perceived and objective cognitive flexibility in AN, future research and clinical assessments should include both self-report and neurocognitive assessments.
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    Feasibility of wearable technology for 'real-world' gait analysis in children with Prader-Willi and Angelman syndromes
    Kraan, CM ; Date, P ; Rattray, A ; Sangeux, M ; Bui, QM ; Baker, EK ; Morison, J ; Amor, DJ ; Godler, DE (WILEY, 2022-08)
    BACKGROUND: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurodevelopmental disorders in need of innovative 'real-world' outcome measures to evaluate treatment effects. Instrumented gait analysis (IGA) using wearable technology offers a potentially feasible solution to measure "real-world' neurological and motor dysfunction in these groups. METHODS: Children (50% female; 6-16 years) diagnosed with PWS (n = 9) and AS (n = 5) completed 'real-world' IGA assessments using the Physilog®5 wearable. PWS participants completed a laboratory assessment and a 'real-world' long walk. The AS group completed 'real-world' caregiver-assisted assessments. Mean and variability results for stride time, cadence, stance percentage (%) and stride length were extracted and compared across three different data reduction protocols. RESULTS: The wearables approach was found to be feasible, with all participants able to complete at least one assessment. This study also demonstrated significant agreement, using Lin's concordance correlation coefficient (CCC), between laboratory and 'real-world' assessments in the PWS group for mean stride length, mean stance % and stance % CV (n = 7, CCC: 0.782-0.847, P = 0.011-0.009). CONCLUSION: 'Real-world' gait analysis using the Physilog®5 wearable was feasible to efficiently assess neurological and motor dysfunction in children affected with PWS and AS.
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    Perceptions of rural high school teachers - on the frontline of youth suicide
    Bowman, S ; McKinstry, C ; Howie, L ; Hepworth, G ; McGorry, P (WILEY, 2022-10)
    OBJECTIVE: This study aimed to investigate the perceptions and beliefs of rural high school teachers about student suicide completion in their school and their perceived self-efficacy in identification of suicidality in students (suicidal ideation, plans and behaviours). DESIGN: A cross-sectional survey methodology. SETTING: Gippsland and the Loddon Mallee regions of Victoria, Australia. PARTICIPANTS: Rural high school teachers. OUTCOME MEASURE: A survey that aimed to obtain participants' perceptions and self-reports about students who had died by suicide in their school within the last 5 years, their perceived self-efficacy in identifying suicidal students and barriers to helping students at risk. RESULTS: Two hundred and seventy-seven rural high school teachers participated and 86% reported that a student from their school had died by suicide within the last 5 years. Sixty-five per cent believed that more than one student had died by suicide and 70% perceived they were currently aware of students experiencing suicidality in their class. Receiving professional development about suicide and obtaining help from mental health clinicians predicted perceived self-efficacy in identification of suicidality in students. Participants perceived the barriers to help students at risk included insufficient numbers of school-based mental health professionals and community mental health services. CONCLUSIONS: Many rural high school teachers perceive they are at the front line of the youth suicide crisis due to unmet service need in youth mental ill health. Increased access to effective services immediately after teachers become aware of suicidality may assist in reducing youth suicide in rural areas.
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    Temporal changes in the epidemiology of sepsis-related intensive care admissions from the emergency department in Australia and New Zealand
    Jones, D ; Moran, J ; Udy, A ; Pilcher, D ; Delaney, A ; Peake, SL (WILEY, 2022-12)
    OBJECTIVES: The Australasian Resuscitation in Sepsis Evaluation (ARISE) study researched septic shock treatment within EDs. This study aims to evaluate whether: (i) conduct of the ARISE study was associated with changes in epidemiology and care for adults (≥18 years) admitted from EDs to ICUs with sepsis in Australia and New Zealand; and (ii) such changes differed among 45 ARISE trial hospitals compared with 120 non-trial hospitals. METHODS: Retrospective study using interrupted time series analysis in three time periods; 'Pre-ARISE' (January 1997 to December 2007), 'During ARISE' (January 2008 to May 2014) and 'Post-ARISE' (June 2014 to December 2017) using data from the Australian and New Zealand Intensive Care Society Adult Patient Database. RESULTS: Over 21 years there were 54 121 ICU admissions from the ED with sepsis; which increased from 8.1% to 16.4%; 54.6% male, median (interquartile range) age 66 (53-76) years. In the pre-ARISE period, pre-ICU ED length of stay (LOS) decreased in trial hospitals but increased in non-trial hospitals (P = 0.174). During the ARISE study, pre-ICU ED LOS declined more in trial hospitals (P = 0.039) as did the frequency of mechanical ventilation in the first 24 h (P = 0.003). However, ICU and hospital LOS, in-hospital mortality and risk of death declined similarly in both trial and non-trial hospitals. CONCLUSIONS: Sepsis-related admissions increased from 8.1% to 16.4%. During the ARISE study, there was more rapid ICU admission and decreased early ventilation. However, these changes were not sustained nor associated with decreased risk of death or duration of hospitalisation.