Centre for Youth Mental Health - Research Publications

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End date: 2013 × Type: Journal Article × Author: Yung, Alison × Author: Nelson, Christopher ×

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    Effects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis
    Bousman, CA ; Yung, AR ; Pantelis, C ; Ellis, JA ; Chavez, RA ; Nelson, B ; Lin, A ; Wood, SJ ; Amminger, GP ; Velakoulis, D ; McGorry, PD ; Everall, IP ; Foley, DL (NATURE PUBLISHING GROUP, 2013-04)
    Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis. In a prospective cohort (follow-up=2.4-14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis. Two NRG1 htSNPs (rs12155594 and rs4281084) predicted transition to psychosis. Carriers of the rs12155594 T/T or T/C genotype had a 2.34 (95% confidence interval (CI)=1.37-4.00) times greater risk of transition compared with C/C carriers. For every rs4281084 A-allele the risk of transition increased by 1.55 (95% CI=1.05-2.27). For every additional rs4281084-A and/or rs12155594-T allele carried the risk increased ∼1.5-fold, with 71.4% of those carrying a combination of 3 of these alleles transitioning to psychosis. None of the assessed DAOA htSNPs were associated with transition. Our findings suggest NRG1 genetic variation may improve our ability to identify UHR individuals at risk for transition to psychosis.
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    Neurocognitive predictors of transition to psychosis: medium- to long-term findings from a sample at ultra-high risk for psychosis
    Lin, A ; Yung, AR ; Nelson, B ; Brewer, WJ ; Riley, R ; Simmons, M ; Pantelis, C ; Wood, SJ (CAMBRIDGE UNIV PRESS, 2013-11)
    BACKGROUND: Individuals at ultra-high risk (UHR) for psychosis show reduced neurocognitive performance across domains but it is unclear which reductions are associated with transition to frank psychosis. The aim of this study was to investigate differences in baseline neurocognitive performance between UHR participants with (UHR-P) and without transition to psychosis (UHR-NP) and a healthy control (HC) group and examine neurocognitive predictors of transition over the medium to long term. METHOD: A sample of 325 UHR participants recruited consecutively from the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne and 66 HCs completed a neurocognitive assessment at baseline. The UHR group was followed up between 2.39 and 14.86 (median = 6.45) years later. Cox regression was used to investigate candidate neurocognitive predictors of psychosis onset. RESULTS: The UHR group performed more poorly than the HC group across a range of neurocognitive domains but only performance on digit symbol coding and picture completion differed between the groups. The risk of transition was only significantly associated with poorer performance on visual reproduction [hazard ratio (HR) 0.919, 95% confidence interval (CI) 0.876-0.965, p = 0.001] and matrix reasoning (HR 0.938, 95% CI 0.883-0.996, p = 0.037). These remained significant even after controlling for psychopathology at baseline. CONCLUSIONS: This study is the longest follow-up of an UHR sample to date. UHR status was associated with poorer neurocognitive performance compared to HCs on some tasks. Cognition at identification as UHR was not a strong predictor of risk for transition to psychosis. The results suggests the need to include more experimental paradigms that isolate discrete cognitive processes to better understand neurocognition at this early stage of illness.
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    Phenylthiocarbamide (PTC) perception in ultra-high risk for psychosis participants who develop schizophrenia: Testing the evidence for an endophenotypic marker
    Brewer, WJ ; Lin, A ; Moberg, PJ ; Smutzer, G ; Nelson, B ; Yung, AR ; Pantelis, C ; McGorry, PD ; Turetsky, BI ; Wood, SJ (ELSEVIER IRELAND LTD, 2012-08-30)
    Reports suggesting that schizophrenia participants are more likely to be phenylthiocarbamide (PTC) non-tasters when compared to controls have recently been controversial. If supported, a genetic-based phenotypic variation in PTC taster status is implicated, suggesting a greater illness risk for those participants with recessive alleles for the TAS2R38 receptor. Should PTC insensitivity be a schizophrenia endophenotype, then it would be expected in follow-up of ultra high-risk for psychosis participants who later develop schizophrenia (UHR-S). UHR-S was hypothesised to show reduced PTC sensitivity compared to those who were previously at risk, but did not transition (UHR-NP). PTC perception was assessed in 219 UHR participants at long-term follow-up, of whom 53 had transitioned to psychosis (UHR-P) during the follow-up period. Fifteen of the 219 participants were diagnosed with schizophrenia. Seventy-eight had a family history of psychotic disorder. No differences in PTC taster status were found in UHR participants based upon transition to psychosis status, schizophrenia diagnosis, or family history of schizophrenia. This report indicates that schizophrenia development among UHR participants is not associated with PTC tasting deficits and fails to support previous findings that inability to detect the bitter taste of PTC is a schizophrenia endophenotype.
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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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    Dynamic Association Between Interpersonal Functioning and Positive Symptom Dimensions of Psychosis Over Time: A Longitudinal Study of Healthy Adolescents
    Collip, D ; Wigman, JTW ; Lin, A ; Nelson, B ; Oorschot, M ; Vollebergh, WAM ; Ryan, J ; Baksheev, G ; Wichers, M ; van Os, J ; Myin-Germeys, I ; Yung, AR (OXFORD UNIV PRESS, 2013-01)
    BACKGROUND: Cross-sectional studies have indicated that alterations in social functioning, particularly interpersonal functioning, are associated with the occurrence of psychotic symptoms and experiences at different levels of the extended psychosis phenotype (ranging from population psychometric expression of liability to overt psychotic disorder). However, more research is needed on the development of this association over time. METHODS: Cross-lagged path modeling was used to analyze bidirectional, longitudinal associations between 4 dimensions of subclinical psychotic experiences (persecutory ideation, bizarre experiences, perceptual abnormalities, and magical thinking) and interpersonal functioning in an adolescent general population sample (N = 881 at T1, N = 652 at T2, and N = 512 at T3) assessed 3 times in 3 years. RESULTS: All symptom dimensions showed some association with interpersonal functioning over time, but only bizarre experiences and persecutory ideation were consistently and longitudinally associated with interpersonal functioning. Poorer interpersonal functioning predicted higher levels of bizarre experiences and persecutory ideation at later measurement points (both T1 to T2 and T2 to T3). CONCLUSIONS: Poor interpersonal functioning in adolescence may reflect the earliest expression of neurodevelopmental alterations preceding expression of psychotic experiences in a symptom-specific fashion.
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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).