Centre for Youth Mental Health - Research Publications
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ItemNo Preview AvailableEffects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial(SPRINGERNATURE, 2023-06-10)The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone/paliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted. A healthy control group was also recruited. A cognitive battery was administered at baseline and 6 months. Intention-to-treat analysis involved 76 patients (antipsychotic medication group: 37; 18.6Mage [2.9] years; 21 women; placebo group: 39; 18.3Mage [2.7]; 22 women); and 42 healthy controls (19.2Mage [3.0] years; 28 women). Cognitive performance predominantly remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. However, a significant group-by-time interaction was observed for immediate recall (p = 0.023), verbal learning (p = 0.024) and delayed recall (p = 0.005). The medication group declined whereas the placebo group improved on each measure (immediate recall: p = 0.024; ηp2 = 0.062; verbal learning: p = 0.015; ηp2 = 0.072 both medium effects; delayed recall: p = 0.001; ηp2 = 0.123 large effect). The rate of change for the placebo and healthy control groups was similar. Per protocol analysis (placebo n = 16, medication n = 11) produced similar findings. Risperidone/paliperidone may worsen verbal learning and memory in the early months of psychosis treatment. Replication of this finding and examination of various antipsychotic agents are needed in confirmatory trials. Antipsychotic effects should be considered in longitudinal studies of cognition in psychosis.Trial registration: Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au/ ; ACTRN12607000608460).
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ItemNo Preview AvailableThe relationship between subjective sleep disturbance and attenuated psychotic symptoms after accounting for anxiety and depressive symptoms(ELSEVIER, 2023-08)BACKGROUND AND HYPOTHESES: Sleep disturbances are increasingly recognized as cooccurring with psychotic symptoms. The potential importance of this relationship is complicated when considering the effects of anxiety and depressive symptoms which commonly present in early-stage illness states. This study aimed to investigate the relationship between self-reported sleep disturbance on the development of attenuated psychotic symptoms (APS) cross-sectionally and longitudinally while adjusting for roles of anxiety and depressive symptoms. DESIGN: Eight-hundred and two help-seeking young people aged 12 to 25 years who engaged with our Australian early intervention services were included in the study (the "Transitions" cohort). Cross sectional mediation and cross-lagged longitudinal (12-month) mediation models were developed with outcomes being different APS domains. RESULTS: Only baseline excessive daytime sleepiness predicted later APS when accounting for previous APS, anxiety and depressive symptomatology. Cross sectionally, self-reported sleep disturbance showed both direct and indirect predictive relationships with all APS domains. Partial mediation through anxiety and depression was shown for unusual thought content, perceptual abnormalities, and disorganised speech, while full mediation through depression was shown for non-bizarre ideas. CONCLUSIONS: The specificity of the relationship between self-reported sleep disturbance on APS highlights the potential for different roles in mechanistic models of psychotic symptom expression. This further indicates the need for further experimental research to illuminate potential causal pathways. Future research should continue to use continuous, symptom level approaches across a range of timeframes to more accurately model the complex dynamics present in the sleep-psychosis relationship.
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ItemNo Preview AvailableA Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis The Staged Treatment in Early Psychosis (STEP) Sequential Multiple Assignment Randomized Trial(AMER MEDICAL ASSOC, 2023-09)IMPORTANCE: Clinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis. OBJECTIVE: To determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis. DESIGN, SETTING, AND PARTICIPANTS: The Staged Treatment in Early Psychosis (STEP) sequential multiple assignment randomized trial took place within the clinical program at Orygen, Melbourne, Australia. Individuals aged 12 to 25 years who were seeking treatment and met criteria for ultrahigh risk of psychosis according to the Comprehensive Assessment of At-Risk Mental States were recruited between April 2016 and January 2019. Of 1343 individuals considered, 342 were recruited. INTERVENTIONS: Step 1: 6 weeks of support and problem solving (SPS); step 2: 20 weeks of cognitive-behavioral case management (CBCM) vs SPS; and step 3: 26 weeks of CBCM with fluoxetine vs CBCM with placebo with an embedded fast-fail option of ω-3 fatty acids or low-dose antipsychotic medication. Individuals who did not remit progressed through these steps; those who remitted received SPS or monitoring for up to 12 months. MAIN OUTCOMES AND MEASURES: Global Functioning: Social and Role scales (primary outcome), Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Montgomery-Åsberg Depression Rating Scale, quality of life, transition to psychosis, and remission and relapse rates. RESULTS: The sample comprised 342 participants (198 female; mean [SD] age, 17.7 [3.1] years). Remission rates, reflecting sustained symptomatic and functional improvement, were 8.5%, 10.3%, and 11.4% at steps 1, 2, and 3, respectively. A total of 27.2% met remission criteria at any step. Relapse rates among those who remitted did not significantly differ between SPS and monitoring (step 1: 65.1% vs 58.3%; step 2: 37.7% vs 47.5%). There was no significant difference in functioning, symptoms, and transition rates between SPS and CBCM and between CBCM with fluoxetine and CBCM with placebo. Twelve-month transition rates to psychosis were 13.5% (entire sample), 3.3% (those who ever remitted), and 17.4% (those with no remission). CONCLUSIONS AND RELEVANCE: In this sequential multiple assignment randomized trial, transition rates to psychosis were moderate, and remission rates were lower than expected, partly reflecting the ambitious criteria set and challenges with real-world treatment fidelity and adherence. While all groups showed mild to moderate functional and symptomatic improvement, this was typically short of remission. While further adaptive trials that address these challenges are needed, findings confirm substantial and sustained morbidity and reveal relatively poor responsiveness to existing treatments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02751632.
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ItemNo Preview AvailableNetwork-Based Spreading of Gray Matter Changes Across Different Stages of Psychosis(American Medical Association, 2023-12)IMPORTANCE: Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown. OBJECTIVE: To test the hypothesis that brain network architecture constrains cross-sectional and longitudinal gray matter alterations across different stages of psychotic illness and to identify whether certain brain regions act as putative epicenters from which volume loss spreads. DESIGN, SETTINGS, AND PARTICIPANTS: This case-control study included 534 individuals from 4 cohorts, spanning early and late stages of psychotic illness. Early-stage cohorts included patients with antipsychotic-naive first-episode psychosis (n = 59) and a group of patients receiving medications within 3 years of psychosis onset (n = 121). Late-stage cohorts comprised 2 independent samples of people with established schizophrenia (n = 136). Each patient group had a corresponding matched control group (n = 218). A sample of healthy adults (n = 356) was used to derive representative structural and functional brain networks for modeling of network-based spreading processes. Longitudinal illness-related and antipsychotic-related gray matter changes over 3 and 12 months were examined using a triple-blind randomized placebo-control magnetic resonance imaging study of the antipsychotic-naive patients. All data were collected between April 29, 2008, and January 15, 2020, and analyses were performed between March 1, 2021, and January 14, 2023. MAIN OUTCOMES AND MEASURES: Coordinated deformation models were used to estimate the extent of gray matter volume (GMV) change in each of 332 parcellated areas by the volume changes observed in areas to which they were structurally or functionally coupled. To identify putative epicenters of volume loss, a network diffusion model was used to simulate the spread of pathology from different seed regions. Correlations between estimated and empirical spatial patterns of GMV alterations were used to quantify model performance. RESULTS: Of 534 included individuals, 354 (66.3%) were men, and the mean (SD) age was 28.4 (7.4) years. In both early and late stages of illness, spatial patterns of cross-sectional volume differences between patients and controls were more accurately estimated by coordinated deformation models constrained by structural, rather than functional, network architecture (r range, >0.46 to <0.57; P < .01). The same model also robustly estimated longitudinal volume changes related to illness (r ≥ 0.52; P < .001) and antipsychotic exposure (r ≥ 0.50; P < .004). Network diffusion modeling consistently identified, across all 4 data sets, the anterior hippocampus as a putative epicenter of pathological spread in psychosis. Epicenters of longitudinal GMV loss were apparent in posterior cortex early in the illness and shifted to the prefrontal cortex with illness progression. CONCLUSION AND RELEVANCE: These findings highlight a central role for white matter fibers as conduits for the spread of pathology across different stages of psychotic illness, mirroring findings reported in neurodegenerative conditions. The structural connectome thus represents a fundamental constraint on brain changes in psychosis, regardless of whether these changes are caused by illness or medication. Moreover, the anterior hippocampus represents a putative epicenter of early brain pathology from which dysfunction may spread to affect connected areas.
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ItemBaseline data of a sequential multiple assignment randomized trial (STEP study)(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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ItemNo Preview AvailableUnderstanding What Drives Long-term Engagement in Digital Mental Health Interventions: Secondary Causal Analysis of the Relationship Between Social Networking and Therapy Engagement(JMIR PUBLICATIONS, INC, 2023)BACKGROUND: Low engagement rates with digital mental health interventions are a major challenge in the field. Multicomponent digital interventions aim to improve engagement by adding components such as social networks. Although social networks may be engaging, they may not be sufficient to improve clinical outcomes or lead users to engage with key therapeutic components. Therefore, we need to understand what components drive engagement with digital mental health interventions overall and what drives engagement with key therapeutic components. OBJECTIVE: Horyzons was an 18-month digital mental health intervention for young people recovering from first-episode psychosis, incorporating therapeutic content and a private social network. However, it is unclear whether use of the social network leads to subsequent use of therapeutic content or vice versa. This study aimed to determine the causal relationship between the social networking and therapeutic components of Horyzons. METHODS: Participants comprised 82 young people (16-27 years) recovering from first-episode psychosis. Multiple convergent cross mapping was used to test causality, as a secondary analysis of the Horyzons intervention. Multiple convergent cross mapping tested the direction of the relationship between each pair of social and therapeutic system usage variables on Horyzons, using longitudinal usage data. RESULTS: Results indicated that the social networking aspects of Horyzons were most engaging. Posting on the social network drove engagement with all therapeutic components (r=0.06-0.36). Reacting to social network posts drove engagement with all therapeutic components (r=0.39-0.65). Commenting on social network posts drove engagement with most therapeutic components (r=0.11-0.18). Liking social network posts drove engagement with most therapeutic components (r=0.09-0.17). However, starting a therapy pathway led to commenting on social network posts (r=0.05) and liking social network posts (r=0.06), and completing a therapy action led to commenting on social network posts (r=0.14) and liking social network posts (r=0.15). CONCLUSIONS: The online social network was a key driver of long-term engagement with the Horyzons intervention and fostered engagement with key therapeutic components and ingredients of the intervention. Online social networks can be further leveraged to engage young people with therapeutic content to ensure treatment effects are maintained and to create virtuous cycles between all intervention components to maintain engagement. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12614000009617; https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12614000009617.
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ItemCan disorders of subjective time inform the differential diagnosis of psychiatric disorders? A transdiagnostic taxonomy of time.(Wiley, 2023-03)AIM: Time is a core aspect of psychopathology with potential for clinical use and early intervention. Temporal experience, perception, judgement and processing are distorted in various psychiatric disorders such as mood (depression and mania), anxiety, autistic, impulse-control, dissociative and attention-deficit/hyperactivity disorders. Can these disorders of time be used as early diagnostic or predictive markers? To answer this question, we develop a Transdiagnostic Taxonomy of (disordered) Time (TTT) that maps on to the symptomatological, phenomenal, perceptual and functional descriptions of each underlying disorder in a 2 × 2 × 2 state space. Temporal distortions may precede functional decline, and so assist efforts at early detection and intervention in at-risk groups. METHOD: Firstly, this article integrates a psychological model of how time is processed with a subjective or phenomenological model of how time is experienced or perceived. Secondly, the integrated combined model of time is then used to heuristically map major psychiatric disorders on to the basic elements of temporal flow and integration. RESULTS: The TTT systematically describes the basic temporal nature of eight diagnostic categories of psychiatric illness. It differentiates between diagnoses primarily associated with distorted "macro-level" phenomenal temporal experiences (i.e. anxiety, dissociation/PTSD, depression, and mania) from those primarily related to distorted 'micro-level' temporal processing (i.e. psychotic, impulse-control, autistic and attention-deficit/hyperactivity disorders). CONCLUSIONS: The TTT allows differential diagnostic classification of various psychiatric disorders in terms of a possible underlying time disorder, making it useful for future diagnostic and predictive purposes using novel techniques of temporal processing, time perception, passage of time, and time perspective.
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Item"They may be confronting but they are good questions to be asking" young people's experiences of completing a trauma and PTSD screening tool in an early psychosis program(WILEY, 2022-12)BACKGROUND: There is a history of inadequate enquiry about, and assessment of, trauma in young people within Early Psychosis services and even when screening does occur there is little known about how young people experience this process. AIMS: This study aimed to explore young people's experiences of completing a trauma and PTSD screening tool when receiving a service in an Early Psychosis Program. METHOD: Semi-structured interviews were conducted with 10 young people, aged 18-24 years, to explore their subjective experience of this process. Transcripts were analysed via interpretative phenomenological analysis. RESULTS: Four super-ordinate themes were identified: (i) an emotional experience, (ii) the importance of the relationship with the clinician, (iii) an opportunity to reflect on past experiences, and (iv) the ability to be able to provide honest responses. Results from this study indicated that young people expected to be asked about their trauma experiences, acknowledged that this was challenging for them but found that this was made easier due to the relationship they had built with the clinician, the timing of the screening and also, possibly, by the written style format of the questionnaires. CONCLUSIONS: Young people in this study accepted the need for screening for traumatic histories, and expected to be asked about their traumatic experiences, despite the possibility of a short-term increase in distress. The support offered by a trusted clinician, whom the young person had built a relationship with, appeared to be an important component to the willingness and the ability of the young person to complete the questionnaires. This reinforces the fact that screening for trauma in an early psychosis service can be conducted in a way that is safe and acceptable to young people.
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ItemNo Preview AvailableHas improved treatment contributed to the declining rate of transition to psychosis in ultra-high-risk cohorts?(ELSEVIER, 2022-05)BACKGROUND: The factors contributing to declining psychotic disorder transition rates in ultra-high-risk populations remain unclear. We examined the contribution of longitudinal changes in standard clinical treatment ('treatment as usual') to this decline. METHOD: An audit was conducted on 105 clinical files of patients who received standard care at a specialised ultra-high-risk service. The session notes of these files were quantified, allowing examination of treatment quantity, targets, psychotherapy, and medication. Differences in these aspects across patients' year of clinic entry were assessed. Variables with significant differences across years were examined using cox regression to assess their contribution to psychosis transition rates. RESULTS: Findings were that, as a function of patients' year of clinic entry, there were increases in: patients' number of sessions, cognitive behavioural therapy (CBT), problem and solving therapy. There was a relationship between baseline year cohort and psychosis transition rate, with lower rates observed in more recent cohorts. When changes in treatment between cohorts were adjusted for, the relationship between baseline year cohort and transition rate disappeared. The relationship between baseline year and transition rate was attenuated most by increases in CBT. CONCLUSION: Changes in standard treatment, particularly increases in CBT, may have contributed to the decline in psychosis risk observed in recent ultra-high-risk cohorts, although these variables do not fully explain this trend. Implications for clinical practice, prediction and intervention research are discussed. Future ultra-high-risk research should investigate the impact of other treatment factors, such as therapeutic alliance.
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ItemYoung migrants to Australia identified as being at ultra-high risk for psychosis: Pathways to care and clinical characteristics(ELSEVIER, 2022-03)INTRODUCTION: Despite the established finding that migrants are at higher risk of developing a first-episode psychosis, they are under-represented in cohorts of young people identified as being at ultra-high risk for psychosis (UHR). Therefore, in order to determine the reasons for these conflicting findings, this study examined the pathways to care and clinical presentation of migrants attending an At-Risk Mental State clinic. METHODOLOGY: This study included consecutive UHR cases identified over five years attending the PACE clinic in Melbourne, Australia. The CAARMS was used to assess the severity of attenuated psychotic symptoms. Depressive symptoms and functioning were measured using the PHQ9 and GAF, respectively. RESULTS: Over the five-year study period, 461 UHR young people attended the PACE clinic and 13.7% were first-generation migrants. A higher proportion of migrants were referred by community health services, such as general practitioners, than other referral sources. Australian born UHR patients were more likely to be referred via another mental health service. There was no difference in the type or severity of attenuated psychotic symptoms based on migrant status, except that there was a trend for young African migrants to have more severe unusual thought content. Depressive symptoms and poor functioning were highly prevalent across the total cohort and did not differ according to migrant status. CONCLUSIONS: It is not yet understood why migrants are under-represented in UHR cohorts. Qualitative interviews of migrants, who are not typically identified in the UHR stage, could provide insights into the barriers to accessing care.