Centre for Youth Mental Health - Research Publications

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    Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders
    Eratne, D ; Kang, M ; Malpas, C ; Simpson-Yap, S ; Lewis, C ; Dang, C ; Grewal, J ; Coe, A ; Dobson, H ; Keem, M ; Chiu, W-H ; Kalincik, T ; Ooi, S ; Darby, D ; Brodtmann, A ; Hansson, O ; Janelidze, S ; Blennow, K ; Zetterberg, H ; Walker, A ; Dean, O ; Berk, M ; Wannan, C ; Pantelis, C ; Loi, SM ; Walterfang, M ; Berkovic, SF ; Santillo, AF ; Velakoulis, D (SAGE PUBLICATIONS LTD, 2024-01)
    OBJECTIVE: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. METHODS: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). RESULTS: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. CONCLUSIONS: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
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    Perfectionism as a moderator of the relationship between orthorexia nervosa and obsessive-compulsive symptoms
    Huynh, PA ; Miles, S ; Nedeljkovic, M (SPRINGER, 2024-01-10)
    PURPOSE: Orthorexia nervosa (ON), a proposed disorder describing an obsessive focus on "healthy" eating, is characterised as having overlapping symptoms with obsessive-compulsive disorder. However, ON/obsessive-compulsive (OC) symptom relationships are inconsistently reported. The current study aimed to investigate if the contribution of OC symptoms and beliefs explain variability in ON symptoms and determine if perfectionism, a transdiagnostic factor, moderates the ON/OC symptom relationship. METHODS: The study comprised 190 participants (Mage = 28.63, SDage = 9.88; 80% female) recruited via an undergraduate research programme, social media, advocacy organisations, and a participant registry. Participants completed an online questionnaire assessing ON, OC, and perfectionism symptoms. RESULTS: A linear regression analysis found OC symptoms and beliefs explained 22.9% variability in ON symptoms (p < 0.001, f2 = 0.38) and perfectionism moderated the ON/OC symptom relationship, where higher levels of perfectionism with higher levels of OC symptoms was associated with higher levels of ON symptoms, explaining 2.2% variability (p = .01, f2 = 0.03). CONCLUSION: OC symptoms appear more common in ON than previous studies indicate. However, the interaction between perfectionism and OC symptoms may drive obsessions in ON. Findings help refine our current understanding of ON phenomenology with implications for ON treatment development. Future research should further explore perfectionism in ON phenomenology. LEVEL OF EVIDENCE: Level V (Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees).
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    Johan Christoffer Cullberg (6th January 1934-14th June 2022)1.
    Johannessen, JO ; McGorry, PD (Wiley, 2023-01)
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    Psychological, Physical, and Sexual Violence Against Children in Australian Community Sport: Frequency, Perpetrator, and Victim Characteristics.
    Pankowiak, A ; Woessner, MN ; Parent, S ; Vertommen, T ; Eime, R ; Spaaij, R ; Harvey, J ; Parker, AG (SAGE Publications, 2023-02)
    Childhood sport participation is associated with physical, social, and mental health benefits, which are more likely to be realized if the sport environment is safe. However, our understanding of children's experience of psychological, physical, and sexual violence in community sport in Australia is limited. The aims of this study were to provide preliminary evidence on the extent of experiences of violence during childhood participation in Australian community sport and to identify common perpetrators of and risk factors for violence. The Violence Towards Athletes Questionnaire (VTAQ) was administered online to a convenience sample of Australian adults (>18 years), retrospectively reporting experiences of violence during childhood community sport. Frequencies of experience of violence were calculated and Chi-square tests were conducted to determine differences between genders. In total, there were 886 respondents included in the analysis. Most survey respondents were women (63%) and about a third were men (35%). About 82% of respondents experienced violence in sport as a child. Psychological violence was most prevalent (76%), followed by physical (66%) and sexual (38%) violence. Peers perpetrated the highest rates of psychological violence (69%), and the rates of physical and psychological violence by coaches (both >50%) were also high. Age, sexual orientation, disability, and hours of weekly sport participation as a child were all associated with childhood experience of violence in sport. The rates of interpersonal violence against children in sport were high. This novel data on perpetrators of the violence and the risk factors for experiencing violence provides further context to inform safeguarding strategies in sport. A national prevalence study is recommended to advance our understanding of the childhood experiences of violence in Australian sport.
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    Acceptability and feasibility of a multidomain harmonized data collection protocol in youth mental health
    Youn, S ; Mamsa, S ; Allott, K ; Berger, M ; Polari, A ; Rice, S ; Schmaal, L ; Wood, S ; Lavoie, S (WILEY, 2023-05)
    OBJECTIVE: To develop targeted treatment for young people experiencing mental illness, a better understanding of the biological, psychological, and social changes is required, particularly during the early stages of illness. To do this, large datasets need to be collected using standardized methods. A harmonized data collection protocol was tested in a youth mental health research setting to determine its acceptability and feasibility. METHOD: Eighteen participants completed the harmonization protocol, including a clinical interview, self-report measures, neurocognitive measures, and mock assessments of magnetic resonance imaging (MRI) and blood. The feasibility of the protocol was assessed by recording recruitment rates, study withdrawals, missing data, and protocol deviations. Subjective responses from participant surveys and focus groups were used to examine the acceptability of the protocol. RESULTS: Twenty-eight young people were approached, 18 consented, and four did not complete the study. Most participants reported positive subjective impressions of the protocol as a whole and showed interest in participating in the study again, if given the opportunity. Participants generally perceived the MRI and neurocognitive tasks as interesting and suggested that the assessment of clinical presentation could be shortened. CONCLUSION: Overall, the harmonized data collection protocol appeared to be feasible and generally well-accepted by participants. With a majority of participants finding the assessment of clinical presentation too long and repetitive, the authors have made suggestions to shorten the self-reports. The broader implementation of this protocol could allow researchers to create large datasets and better understand how psychopathological and neurobiological changes occur in young people with mental ill-health.
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    "Our Job is to be so Temporary": Designing Digital Tools that Meet the Needs of Care Managers and their Patients with Mental Health Concerns.
    Kornfield, R ; Lattie, EG ; Nicholas, J ; Knapp, AA ; Mohr, DC ; Reddy, M (Association for Computing Machinery (ACM), 2023-10)
    Digital tools have potential to support collaborative management of mental health conditions, but we need to better understand how to integrate them in routine healthcare, particularly for patients with both physical and mental health needs. We therefore conducted interviews and design workshops with 1) a group of care managers who support patients with complex health needs, and 2) their patients whose health needs include mental health concerns. We investigate both groups' views of potential applications of digital tools within care management. Findings suggest that care managers felt underprepared to play an ongoing role in addressing mental health issues and had concerns about the burden and ambiguity of providing support through new digital channels. In contrast, patients envisioned benefiting from ongoing mental health support from care managers, including support in using digital tools. Patients' and care managers' needs may diverge such that meeting both through the same tools presents a significant challenge. We discuss how successful design and integration of digital tools into care management would require reconceptualizing these professionals' roles in mental health support.
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    Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.
    Groenewold, NA ; Bas-Hoogendam, JM ; Amod, AR ; Laansma, MA ; Van Velzen, LS ; Aghajani, M ; Hilbert, K ; Oh, H ; Salas, R ; Jackowski, AP ; Pan, PM ; Salum, GA ; Blair, JR ; Blair, KS ; Hirsch, J ; Pantazatos, SP ; Schneier, FR ; Talati, A ; Roelofs, K ; Volman, I ; Blanco-Hinojo, L ; Cardoner, N ; Pujol, J ; Beesdo-Baum, K ; Ching, CRK ; Thomopoulos, SI ; Jansen, A ; Kircher, T ; Krug, A ; Nenadić, I ; Stein, F ; Dannlowski, U ; Grotegerd, D ; Lemke, H ; Meinert, S ; Winter, A ; Erb, M ; Kreifelts, B ; Gong, Q ; Lui, S ; Zhu, F ; Mwangi, B ; Soares, JC ; Wu, M-J ; Bayram, A ; Canli, M ; Tükel, R ; Westenberg, PM ; Heeren, A ; Cremers, HR ; Hofmann, D ; Straube, T ; Doruyter, AGG ; Lochner, C ; Peterburs, J ; Van Tol, M-J ; Gur, RE ; Kaczkurkin, AN ; Larsen, B ; Satterthwaite, TD ; Filippi, CA ; Gold, AL ; Harrewijn, A ; Zugman, A ; Bülow, R ; Grabe, HJ ; Völzke, H ; Wittfeld, K ; Böhnlein, J ; Dohm, K ; Kugel, H ; Schrammen, E ; Zwanzger, P ; Leehr, EJ ; Sindermann, L ; Ball, TM ; Fonzo, GA ; Paulus, MP ; Simmons, A ; Stein, MB ; Klumpp, H ; Phan, KL ; Furmark, T ; Månsson, KNT ; Manzouri, A ; Avery, SN ; Blackford, JU ; Clauss, JA ; Feola, B ; Harper, JC ; Sylvester, CM ; Lueken, U ; Veltman, DJ ; Winkler, AM ; Jahanshad, N ; Pine, DS ; Thompson, PM ; Stein, DJ ; Van der Wee, NJA (Springer Science and Business Media LLC, 2023-03)
    There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
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    Emergency Department Use, Hospitalization, and Their Sociodemographic Determinants among Patients with Substance-Related Disorders: A Worldwide Systematic Review and Meta-Analysis
    Armoon, B ; Fleury, M-J ; Griffiths, MDD ; Bayani, A ; Mohammadi, R ; Ahounbar, E (TAYLOR & FRANCIS INC, 2023-02-23)
    Background: Identifying the determinants of emergency department (ED) use and hospitalization among patients with substance-related disorders (SRD) can help inform healthcare services and case management regarding their unmet health needs and strategies to reduce their acute care. Objectives: The present study aimed to identify sociodemographic characteristics, type of used drug, and risky behaviors associated with ED use and hospitalization among patients with SRD. Methods: Studies in English published from January 1st, 1995 to April 30th, 2022 were searched from PubMed, Scopus, Cochrane Library, and Web of Science to identify primary studies on ED use and hospitalization among patients with SRD. Results: Of the 17,348 outputs found, a total of 39 studies met the eligibility criteria. Higher ED use and hospitalization among patients with SRD were associated with a history of homelessness (ED use: OR = 1.93, 95%CI = 1.32-2.83; hospitalization: OR = 1.53, 95%CI = 1.36-1.73) or of injection drug use (ED use: OR = 1.34, 95%CI = 1.13-1.59; hospitalization: OR = 1.42, 95%CI = 1.20-1.69). Being female (OR = 1.24, 95%CI = 1.14-1.35), using methamphetamine (OR = 1.99, 95%CI = 1.24-3.21) and tobacco (OR = 1.25, 95%CI = 1.11-1.42), having HIV (OR = 1.70, 95%CI = 1.47-1.96), a history of incarceration (OR = 1.90, 95%CI = 1.27-2.85) and injury (OR = 2.62, 95%CI = 1.08-6.35) increased ED use only, while having age over 30  years (OR = 1.40, 95%CI = 1.08-1.81) and using cocaine (OR = 1.60, 95%CI = 1.32-1.95) increased hospitalization only among patients with SRD. Conclusions: The finding outline the necessity of developing outreach program and primary care referral for patients with SRD. Establishing a harm reduction program, incorporating needle/syringe exchange programs, and safe injection training with the aim of declining ED use and hospitalization, is likely be another beneficial strategy for patients with SRD.
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    Feedforward connectivity patterns from visual areas to the front of the brain contain information about sensory stimuli regardless of awareness or report.
    Rowe, EG ; Garrido, MI ; Tsuchiya, N (Elsevier BV, 2024-03)
    Current theories of consciousness can be categorized to some extent by their predictions about the putative role of the prefrontal cortex (PFC) in conscious perception. One family of the theories proposes that the PFC is necessary for conscious perception. The other postulates that the PFC is not necessary and that other areas (e.g., posterior cortical areas) are more important for conscious perception. No-report paradigms could potentially arbitrate the debate as they disentangle task reporting from conscious perception. While previous no-report paradigms tend to point to a reduction in PFC activity, they have not examined the critical role of the PFC in "monitoring" or "reading out" the patterns of activity in the sensory cortex to generate conscious perception. To address this, we reanalysed electroencephalography (EEG) data from a no-report inattentional blindness paradigm (Shafto & Pitts, 2015). We examined the role of feedforward input patterns to the PFC from sensory cortices. We employed nonparametric spectral Granger causality and quantified the amount of information that reflected the contents of consciousness using multivariate classifiers. Unexpectedly, regardless of whether the stimulus was consciously seen or not, we found that information relating to the current sensory stimulus was present in the pattern of inputs from visual areas to the PFC. In light of these findings, we suggest various theories of consciousness need to be revised to accommodate the fact that the contents of consciousness are decodable from the input patterns from posterior sensory regions to the PFC, regardless of awareness (or report).
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    Combining Clinical With Cognitive or Magnetic Resonance Imaging Data for Predicting Transition to Psychosis in Ultra High-Risk Patients: Data From the PACE 400 Cohort.
    Hartmann, S ; Cearns, M ; Pantelis, C ; Dwyer, D ; Cavve, B ; Byrne, E ; Scott, I ; Yuen, HP ; Gao, C ; Allott, K ; Lin, A ; Wood, SJ ; Wigman, JTW ; Amminger, GP ; McGorry, PD ; Yung, AR ; Nelson, B ; Clark, SR (Elsevier BV, 2023-12-03)
    BACKGROUND: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging. METHODS: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality-cognition, cortical structure information, and the neuroanatomical measure of brain age gap-to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231). RESULTS: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%-12%, brain age gap 7%, cognition 0%-16%). CONCLUSIONS: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis.