Centre for Youth Mental Health - Research Publications

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    Perceptual abnormalities in an ultra-high risk for psychosis population relationship to trauma and co-morbid disorder
    O' Connor, K ; Nelson, B ; Cannon, M ; Yung, A ; Thompson, A ; Ghose, P (WILEY, 2019-04)
    AIMS: The aims of this study were 3-fold. We wished to investigate whether at baseline entry to an ultra-high risk (UHR) clinic whether: (1) perceptual abnormalities are more prevalent in those young people with co-morbid psychiatric diagnoses, (2) perceptual abnormalities are more prevalent in those young people with histories of childhood adversity (childhood trauma, bullying) and (3) perceptual abnormality type is associated with co-morbid psychiatric diagnoses or histories of childhood adversity. METHODS: In a sample of 118 UHR patients we investigated the relationship between perceptual abnormalities and non-psychotic diagnoses and adverse life events at entry to a UHR clinic. RESULTS: Depressive disorder at baseline was associated with increased odds of experiencing perceptual abnormalities (OR 3.59, P = .004), particularly visual perceptual abnormalities (OR 2.36, P = .02). Borderline personality disorder at baseline was associated with increased odds of any auditory perceptual abnormalities (OR 3.44, P = .04) and specifically second person perceptual abnormalities (OR 2.69, P = .04). A history of childhood trauma and childhood bullying were both associated with increased odds of experiencing perceptual abnormalities at baseline (trauma OR 6.30, P < .001; bullying OR 5.00, P = .01). CONCLUSIONS: Our findings suggest that in the UHR population, certain types of perceptual abnormalities index risk for co-morbid non-psychotic disorder and indicate prior experience of childhood trauma. The use of detailed phenomenology of psychotic symptoms can help to shape our understanding of risk in UHR patients.
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    Staged treatment and acceptability guidelines in early psychosis study (STAGES): A randomized placebo controlled trial of intensive psychosocial treatment plus or minus antipsychotic medication for first-episode psychosis with low-risk of self-harm or aggression. Study protocol and baseline characteristics of participants
    O'Donoghue, B ; Francey, SM ; Nelson, B ; Ratheesh, A ; Allott, K ; Grahann, J ; Baldwin, L ; Alvarez-Jinnenez, M ; Thonnpson, A ; Fornito, A ; Polari, A ; Berk, M ; Macneil, C ; Crisp, K ; Pantelis, C ; Yuen, HP ; Harrigan, S ; McGorry, P (WILEY, 2019-08)
    AIM: It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented. METHODS: This study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM-IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans. RESULTS: Ninety participants have been recruited and baseline characteristics are presented. CONCLUSIONS: Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines.
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    Does reason for referral to an ultra-high risk clinic predict transition to psychosis?
    Rice, S ; Polari, A ; Thompson, A ; Hartmann, J ; McGorry, P ; Nelson, B (WILEY, 2019-04)
    AIM: To examine reasons for referral to a specialist ultra-high risk (UHR) for psychosis clinic and whether these reasons are associated with risk for subsequent transition to psychosis. METHODS: Data for 127 patients referred to the Personal Assessment and Crisis Evaluation clinic were collected by medical record audit. Time to transition to psychosis was calculated from date of referral to time at which the young person was judged by their treating team to be experiencing onset of first episode psychosis. RESULTS: Patients were primarily referred due to attenuated psychotic symptoms and depression (40.2%). There was an association with transition, with those in the attenuated psychotic-symptom-only category being more likely to transition. CONCLUSION: As well as attenuated psychotic symptoms, depression and anxiety were also important reasons for referral indicating that there is a broad clinical phenotype of young people presenting to UHR clinics. Clinical reason for referral may index level of risk for subsequent transition to psychosis.
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    Relationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial
    Berger, M ; Nelson, B ; Markulev, C ; Yuen, HP ; Schafer, MR ; Mossaheb, N ; Schloegelhofer, M ; Smesny, S ; Hickie, IB ; Berger, GE ; Chen, EYH ; de Haan, L ; Nieman, DH ; Nordentoft, M ; Riecher-Rossler, A ; Verma, S ; Thompson, A ; Yung, AR ; McGorry, PD ; Amminger, GP (FRONTIERS MEDIA SA, 2019-06-06)
    Background: Deficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we investigated associations of membrane PUFA with clinical symptoms and functioning in a large sample of individuals at ultra-high risk (UHR) for psychosis. Methods: A total of 285 participants of the NEURAPRO clinical trial were investigated for erythrocyte PUFA levels, including the n-3 index, n-6/n-3 PUFA ratio, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Severity of general psychopathology [Brief Psychiatric Rating Scale (BPRS)], psychotic symptoms (BPRS psychosis subscale), negative symptoms [Scale for the Assessment of Negative Symptoms (SANS)], manic symptoms [Young Mania Rating Scale (YMRS)], depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS)], and functioning [Social and Occupational Functioning Scale (SOFAS), Global Functioning Social (GF-S) and Role (GF-R) scales] were assessed concurrently. Partial correlation taking into account the effects of gender, age, and smoking was used to examine the relationship between PUFAs and symptoms severity. Results: The n-3 index negatively correlated with the severity of general psychopathology, psychotic symptoms, depressive symptoms, and manic symptoms. The n-6/n-3 PUFA ratio positively correlated with severity of psychotic and depressive symptoms. The n-3 PUFA DHA negatively correlated with the severity of general psychopathology, positive, manic, and depressive symptoms. EPA negatively correlated with manic symptoms. Nervonic acid, an n-9 monounsaturated fatty acid, positively correlated with general psychopathology, positive and negative symptoms, depressive symptoms, and manic symptoms. The long-chain saturated fatty acid tetracosanoic acid positively correlated with general psychopathology, positive, manic, and depressive symptoms. Conclusions: Partially consistent with a previous study, psychotic symptoms, depressive symptoms, and symptoms of mania were associated with several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in the UHR for psychosis group. Clinical Trial Registration: ANZCTR, identifier: 12608000475347.
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    NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders-medium-term follow-up and clinical course.
    Nelson, B ; Amminger, GP ; Yuen, HP ; Markulev, C ; Lavoie, S ; Schäfer, MR ; Hartmann, JA ; Mossaheb, N ; Schlögelhofer, M ; Smesny, S ; Hickie, IB ; Berger, G ; Chen, EYH ; de Haan, L ; Nieman, DH ; Nordentoft, M ; Riecher-Rössler, A ; Verma, S ; Thompson, A ; Yung, AR ; McGorry, PD (Springer Science and Business Media LLC, 2018-06-25)
    This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6-12. Mean time to follow-up was 3.4 (median = 3.3; SD = 0.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11-13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.
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    Longitudinal determinants of client treatment satisfaction in an intensive first-episode psychosis treatment programme
    Cruz, LN ; Kline, E ; Seidman, LJ ; Minor, KS ; Meyer, EC ; Iati, C ; Zimmet, SV ; Friedman-Yakoobian, M (WILEY, 2017-08)
    AIM: Previous evidence demonstrates that higher treatment satisfaction is strongly associated with improved clinical outcomes and functioning. The aim of the current study is to explore potential associations between clinical and demographic attributes, as well as changes in role, social and cognitive functioning occurring over the course of treatment, on self-reported treatment satisfaction within the context of an intensive first-episode psychosis intervention programme. METHODS: Forty-four young adults attending a first-episode psychosis treatment programme completed a battery of clinical and neuropsychological measures at intake to the programme and again after 6 months of treatment. A modified version of the Client Satisfaction Questionnaire was administered at 6 months. Baseline, 6-month and change scores across the clinical and demographic measures were examined relative to the satisfaction questionnaire to evaluate determinants of treatment satisfaction. RESULTS: Better premorbid adjustment during childhood and early adolescence was associated with higher treatment satisfaction, as did positive changes in clients' cognitive performance and their use of humour as a coping strategy. Clients' use of emotional support as a coping strategy at 6 months was also positively associated with treatment satisfaction. Although clients' social and role functioning improved significantly during the 6-month treatment window, changes in functional outcomes were not significantly associated with treatment satisfaction. CONCLUSIONS: The current study highlights the role of premorbid adjustment and changes in coping and neurocognition as factors influencing treatment satisfaction. Future research designs might be able to more specifically ascertain causal relationships between patient characteristics, treatment components, client satisfaction and clinical effects.
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    Sexual Trauma Increases the Risk of Developing Psychosis in an Ultra High-Risk "Prodromal" Population
    Thompson, AD ; Nelson, B ; Yuen, HP ; Lin, A ; Amminger, GP ; McGorry, PD ; Wood, SJ ; Yung, AR (OXFORD UNIV PRESS, 2014-05)
    Studies indicate a high prevalence of childhood trauma in patient cohorts with established psychotic disorder and in those at risk of developing psychosis. A causal link between childhood trauma and development of psychosis has been proposed. We aimed to examine the association between experience of childhood trauma and the development of a psychotic disorder in a large "Ultra High Risk" (UHR) for psychosis cohort. The data were collected as part of a longitudinal cohort study of all UHR patients recruited to research studies at the Personal Assessment and Clinical Evaluation clinic between 1993 and 2006. Baseline data were collected at recruitment to these studies. The participants completed a comprehensive follow-up assessment battery (mean time to follow-up 7.5 years, range 2.4-14.9 years), which included the Childhood Trauma Questionnaire (CTQ), a self-report questionnaire that assesses experience of childhood trauma. The outcome of interest was transition to a psychotic disorder during the follow-up period. Data were available on 233 individuals. Total CTQ trauma score was not associated with transition to psychosis. Of the individual trauma types, only sexual abuse was associated with transition to psychosis (P = .02). The association remained when adjusting for potential confounding factors. Those with high sexual abuse scores were estimated to have a transition risk 2-4 times that of those with low scores. The findings suggest that sexual trauma may be an important contributing factor in development of psychosis for some individuals.
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    Basic Self-Disturbance Predicts Psychosis Onset in the Ultra High Risk for Psychosis "Prodromal" Population
    Nelson, B ; Thompson, A ; Yung, AR (OXFORD UNIV PRESS, 2012-11)
    INTRODUCTION: Phenomenological research indicates that disturbance of the basic sense of self may be a core phenotypic marker of schizophrenia spectrum disorders. Basic self-disturbance refers to a disruption of the sense of ownership of experience and agency of action and is associated with a variety of anomalous subjective experiences. In this study, we investigated the presence of basic self-disturbance in an "ultra high risk" (UHR) for psychosis sample compared with a healthy control sample and whether it predicted transition to psychotic disorder. METHODS: Forty-nine UHR patients and 52 matched healthy control participants were recruited to the study. Participants were assessed for basic self-disturbance using the Examination of Anomalous Self-Experience (EASE) instrument. UHR participants were followed for a mean of 569 days. RESULTS: Levels of self-disturbance were significantly higher in the UHR sample compared with the healthy control sample (P < .001). Cox regression indicated that total EASE score significantly predicted time to transition (P < .05) when other significant predictors were controlled for. Exploratory analyses indicated that basic self-disturbance scores were higher in schizophrenia spectrum cases, irrespective of transition to psychosis, than nonschizophrenia spectrum cases. DISCUSSION: The results indicate that identifying basic self-disturbance in the UHR population may provide a means of further "closing in" on individuals truly at high risk of psychotic disorder, particularly of schizophrenia spectrum disorders. This may be of practical value by reducing inclusion of "false positive" cases in UHR samples and of theoretical value by shedding light on core phenotypic features of schizophrenia spectrum pathology.
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    Omega-3 Fatty Acid Supplementation in Adolescents With Borderline Personality Disorder and Ultra-High Risk Criteria for Psychosis: A Post Hoc Subgroup Analysis of a Double-Blind, Randomized Controlled Trial
    Amminger, GP ; Chanen, AM ; Ohmann, S ; Klier, CM ; Mossaheb, N ; Bechdolf, A ; Nelson, B ; Thompson, A ; McGorry, PD ; Yung, AR ; Schaefer, MR (CANADIAN PSYCHIATRIC ASSOC, 2013-07)
    OBJECTIVE: To investigate whether long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs) improve functioning and psychiatric symptoms in young people with borderline personality disorder (BPD) who also meet ultra-high risk criteria for psychosis. METHODS: We conducted a post hoc subgroup analysis of a double-blind, randomized controlled trial. Fifteen adolescents with BPD (mean age 16.2 years, [SD 2.1]) were randomized to either 1.2 g/day n-3 PUFAs or placebo. The intervention period was 12 weeks. Study measures included the Positive and Negative Syndrome Scale, the Montgomery-Åsberg Depression Rating Scale, and the Global Assessment of Functioning. Side effects were documented with the Udvalg for Kliniske Undersøgelser. Fatty acids in erythrocytes were analyzed using capillary gas chromatography. RESULTS: At baseline, erythrocyte n-3 PUFA levels correlated positively with psychosocial functioning and negatively with psychopathology. By the end of the intervention, n-3 PUFAs significantly improved functioning and reduced psychiatric symptoms, compared with placebo. Side effects did not differ between the treatment groups. CONCLUSIONS: Long-chain n-3 PUFAs should be further explored as a viable treatment strategy with minimal associated risk in young people with BPD. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00396643).