Centre for Youth Mental Health - Research Publications

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    What do Australian consumers with lived experience of bipolar disorder want from early intervention services?
    Gates, J ; Bendall, S ; Tremain, H ; Shelton, C ; Hammond, D ; Macneil, C ; McGorry, P ; Berk, M ; Cotton, S ; Murray, G ; Ratheesh, A (SAGE PUBLICATIONS LTD, 2024-03)
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    Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?
    Russell, SE ; Wrobel, AL ; Ashton, MM ; Turner, A ; Mohebbi, M ; Berk, M ; Cotton, S ; Dodd, S ; Ng, CH ; Malhi, GS ; Dean, OM (KOREAN COLL NEUROPSYCHOPHARMACOLOGY, 2023-08)
    OBJECTIVE: Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. METHODS: Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (+4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. RESULTS: There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. CONCLUSION: There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.
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    The Study of Ketamine for Youth Depression (SKY-D): study protocol for a randomised controlled trial of low-dose ketamine for young people with major depressive disorder
    Schwartz, OS ; Amminger, P ; Baune, BT ; Bedi, G ; Berk, M ; Cotton, SM ; Daglas-Georgiou, R ; Glozier, N ; Harrison, B ; Hermens, DF ; Jennings, E ; Lagopoulos, J ; Loo, C ; Mallawaarachchi, S ; Martin, D ; Phelan, B ; Read, N ; Rodgers, A ; Schmaal, L ; Somogyi, AA ; Thurston, L ; Weller, A ; Davey, CG (BMC, 2023-10-24)
    BACKGROUND: Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD). METHODS: SKY-D is a double-masked, randomised controlled trial funded by the Australian Government's National Health and Medical Research Council (NHMRC). Participants aged between 16 and 25 years (inclusive) with moderate-to-severe MDD will be randomised to receive either low-dose ketamine (intervention) or midazolam (active control) via subcutaneous injection once per week for 4 weeks. The primary outcome is change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment. Further follow-up assessment will occur at 8 and 26 weeks from treatment commencement to determine whether treatment effects are sustained and to investigate safety outcomes. DISCUSSION: Results from this trial will be important in determining whether low-dose subcutaneous ketamine is an effective treatment for young people with moderate-to-severe MDD. This will be the largest randomised trial to investigate the effects of ketamine to treat depression in young people. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ID: ACTRN12619000683134. Registered on May 7, 2019. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377513 .
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    Predictors of suicidal ideation severity among treatment-seeking young people with major depressive disorder: The role of state and trait anxiety
    Moller, C ; Badcock, PB ; Hetrick, SE ; Rice, S ; Berk, M ; Witt, K ; Chanen, AM ; Dean, OM ; Gao, C ; Cotton, SM ; Davey, CG (SAGE PUBLICATIONS LTD, 2023-08)
    OBJECTIVE: Depression and suicidal ideation are closely intertwined. Yet, among young people with depression, the specific factors that contribute to changes in suicidal ideation over time are uncertain. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. Our aim was to identify contributors to fluctuations in suicidal ideation severity over a 12-week period in young people with major depressive disorder receiving cognitive behavioural therapy. METHODS: Data were drawn from two 12-week randomised, placebo-controlled treatment trials. Participants (N = 283) were 15-25 years old, with moderate to severe major depressive disorder. The primary outcome measure was the Suicidal Ideation Questionnaire, administered at baseline and weeks 4, 8 and 12. A series of linear mixed models was conducted to examine the relationship between Suicidal Ideation Questionnaire score and demographic characteristics, comorbid psychopathology, personality traits and alcohol use. RESULTS: Depression and anxiety symptom severity, and trait anxiety, independently predicted higher suicidal ideation, after adjusting for the effects of time, demographics, affective instability, non-suicidal self-injury and alcohol use. CONCLUSIONS: Both state and trait anxiety are important longitudinal correlates of suicidal ideation in depressed young people receiving cognitive behavioural therapy, independent of depression severity. Reducing acute psychological distress, through reducing depression and anxiety symptom severity, is important, but interventions aimed at treating trait anxiety could also potentially be an effective intervention approach for suicidal ideation in young people with depression.
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    Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders
    Segal, A ; Parkes, L ; Aquino, K ; Kia, SM ; Wolfers, T ; Franke, B ; Hoogman, M ; Beckmann, CF ; Westlye, LT ; Andreassen, OA ; Zalesky, A ; Harrison, BJ ; Davey, CG ; Soriano-Mas, C ; Cardoner, N ; Tiego, J ; Yucel, M ; Braganza, L ; Suo, C ; Berk, M ; Cotton, S ; Bellgrove, MA ; Marquand, AF ; Fornito, A (NATURE PORTFOLIO, 2023-09)
    The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.
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    Distress, burden, and wellbeing in siblings of people with mental illness: a mixed studies systematic review and meta-analysis
    Jayasinghe, A ; Wrobel, A ; Filia, K ; Byrne, LK ; Melvin, G ; Murrihy, S ; Moller, C ; Berk, L ; Berk, M ; Cotton, S (CAMBRIDGE UNIV PRESS, 2023-11)
    BACKGROUND: Family members of people with mental illness (MI) may experience a host of psychological adversities such as increased stress, burden, and reduced wellbeing. However, relatively little is known about siblings. This study aimed to characterise the experience of distress (viz. depressive and anxiety symptoms), burden, and wellbeing in siblings of people with MI. METHODS: Studies reporting on quantitative measures of depression, anxiety, burden, or wellbeing in siblings; and/or qualitative findings on siblings' experience were eligible. The literature search was conducted up until 20th October 2022. RESULTS: Sixty-two studies comprising data from 3744 siblings were included. The pooled mean percentage of depressive symptoms fell in the mild range at 15.71 (k = 28, N = 2187, 95% CI 12.99-18.43) and anxiety symptoms fell in the minimal range at 22.45 (k = 16, N = 1122, 95% CI 17.09-27.80). Moderator analyses indicate that siblings of people with a schizophrenia spectrum disorder experience greater depressive symptoms than siblings of people with other types of MI (β = -16.38, p < 0.001). Qualitative findings suggest that individuals may be particularly vulnerable during their siblings' illness onset and times of relapse. Limited communication, confusion about MI, and the need to compensate may contribute to siblings' distress and/or burden. Siblings' experience of wellbeing and caregiving were closely related. CONCLUSION: This review highlights the complex psychological experience of siblings and the need for greater research and clinical support for this important yet often overlooked cohort.
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    Assessing Suicidal Ideation in Young People With Depression: Factor Structure of the Suicidal Ideation Questionnaire
    Moller, C ; Badcock, PB ; Hetrick, SE ; Rice, S ; Berk, M ; Dean, OM ; Chanen, AM ; Gao, C ; Davey, CG ; Cotton, SM (SAGE PUBLICATIONS INC, 2022-09-06)
    Evaluating suicidal ideation in young people seeking mental health treatment is an important component of clinical assessment and treatment planning. To reduce the burden of youth suicide, we need to improve our understanding of suicidal ideation, its underlying constructs, and how ideation translates into suicidal behaviour. Using exploratory factor analysis, we investigated the dimensionality of the Suicidal Ideation Questionnaire (SIQ) among 273 participants aged 15-25 with Major Depressive Disorder. Area under the receiver operating characteristic curve (AUROC) analysis was used to explore associations between latent factors and actual suicidal behaviour. Findings suggested that the SIQ assesses multiple factors underlying suicidal ideation. AUROC analyses demonstrated that latent factors relating to both active and passive suicidal ideation predicted past-month suicidal behaviour and suicide attempt. These findings contribute to an improved understanding of the complexities of suicidal ideation and relationships with suicidal behaviour in young people with depression.
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    Psychological distress in siblings of people with mental illness: A systematic review and meta-analysis
    Jayasinghe, A ; Wrobel, A ; Filia, K ; Byrne, LK ; Melvin, G ; Berk, L ; Berk, M ; Cotton, S (SAGE PUBLICATIONS LTD, 2023-05)
    OBJECTIVE: The objective of this study was to characterise the prevalence and/or severity of psychological distress (namely, depression and anxiety symptoms) in siblings of people with mental illness (MI) and to examine correlates of distress in siblings of people with MI. METHOD: Studies comparing distress in individuals with and without a sibling with MI were eligible. Studies reporting on correlates of distress in siblings were also eligible. A search of MEDLINE Complete, PsycINFO and Embase was conducted up until 17 March 2022. RESULTS: Fifteen studies comprising 2304 siblings and 2263 comparison individuals were included. Meta-analyses indicated individuals with a sibling with MI experience significantly greater depressive symptoms (Hedges's g = 0.53, 95% CI = [0.32, 0.73], siblings n = 1962, comparison individuals n = 2248) and anxiety symptoms (Hedges's g = 0.40, 95% CI = [0.19, 0.61], siblings n = 653, comparison individuals n = 533) than those without. The sibling relationship, siblings' locus of control, interpersonal functioning and their appraisal of the impacts of MI were identified as important and potentially modifiable correlates. CONCLUSION: Individuals with a sibling with MI experience greater depressive and anxiety symptoms than those without and would likely benefit from support. Future studies are required to elucidate the mechanisms underlying distress in siblings.
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    The specific phenotype of depression in recent onset schizophrenia spectrum disorders: A symptom profile and network comparison to recent onset major depressive disorder without psychotic features
    Herniman, SE ; Wood, SJ ; Cotton, SM ; Allott, KA ; Davey, C ; Berk, M ; Phillips, LJ (ELSEVIER, 2022-02)
    The specific phenotype of depression in recent-onset schizophrenia spectrum disorders (SSD) and its relation to non-psychotic depression is unknown. Symptom profile and network analysis are complementary statistical techniques that may provide important insights into the presentation and relative importance of individual symptoms that give rise to depression. The aim of the current study was to characterise the profile and network of depressive symptoms in SSD and compare it to individuals with major depressive disorder (MDD) without psychotic features. This study involved analysis of baseline data pertaining to 109 individuals with comorbid SSD and depression and 283 with MDD without psychotic features. Study cohorts were the Psychosis Recent Onset GRoningen Survey (PROGR-S) and Youth Depression Alleviation (YoDA) trials, respectively. Profile and network analyses revealed that SSD and MDD differed in the profile and relative importance of individual depressive symptoms. While reported sadness was the primary hallmark of depression in both SSD and MDD, individuals with depression in SSD were more likely to sleep more, and have lower lassitude and pessimism. While sadness had great importance in MDD and SSD, in SSD but not MDD lassitude, sleep, appetite, concentration difficulties, and inability to feel were important in the network of depressive symptoms. The specific phenotype of depression might be different in SSD compared to MDD. Symptom inequivalence or underlying functional mechanisms in SSD might result in depression in SSD that is similar to MDD with atypical features.
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    Childhood trauma relates to worse memory functioning in bipolar disorder
    Ehrlich, TJ ; Kim, H ; Ryan, KA ; Langenecker, SA ; Duval, ER ; Yocum, AK ; Diaz-Byrd, C ; Wrobel, AL ; Dean, OM ; Cotton, SM ; Berk, M ; McInnis, MG ; Marshall, DF (ELSEVIER, 2023-07-15)
    BACKGROUND: Childhood trauma is commonly experienced by individuals diagnosed with bipolar disorder (BP). In BP, childhood trauma is related to a more severe clinical course, but its association with cognition remains unclear. METHODS: This study evaluated 405 adult participants diagnosed with BP and 136 controls. Participants completed the Childhood Trauma Questionnaire and a comprehensive neuropsychological battery. High versus low childhood trauma was defined with one standard deviation above the control participant's mean Childhood Trauma Questionnaire score. Neuropsychological data was transformed into eight cognitive factors, including four executive functioning, auditory and visual memory, fine motor, and emotion processing. Multivariate analysis of covariance evaluated group differences in cognition, while adjusting for covariates. RESULTS: There were significant differences among the three groups, F(16, 968) = 4.05, p < .001, Wilks' Λ = 0.88, partial η2 = 0.06. Comparing the high and low trauma BP groups, high trauma was related to lower auditory and visual memory factor scores (p < .05). As compared to controls, the BP high trauma group had lower scores on six of eight factors (all p < .01), while the BP low trauma group had lower scores on four of eight factors (all p < .01). LIMITATIONS: Analyses of factor score do not address which aspect of the memory process is affected and biomarkers may help guide interventions addressing underlying biological process. CONCLUSIONS: Adults diagnosed with BP with higher childhood trauma have worse memory functioning, beyond the lower childhood trauma BP group, highlighting the importance of understanding the long-term cognitive outcomes of childhood trauma.