Centre for Youth Mental Health - Research Publications
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ItemNo Preview AvailableIntelligence trajectories in individuals at ultra-high risk for psychosis: An 8-year longitudinal analysis(ELSEVIER, 2022-10)Cognitive impairment is a well-documented predictor of transition to a full-threshold psychotic disorder amongst individuals at ultra-high risk (UHR) for psychosis. However, less is known about whether change in cognitive functioning differs between those who do and do not transition. Studies to date have not examined trajectories in intelligence constructs (e.g., acquired knowledge and fluid intelligence), which have demonstrated marked impairments in individuals with schizophrenia. This study aimed to examine intelligence trajectories using longitudinal data spanning an average of eight years, where some participants completed assessments over three time-points. Participants (N = 139) at UHR for psychosis completed the Wechsler Abbreviated Scale of Intelligence (WASI) at each follow-up. Linear mixed-effects models mapped changes in WASI Full-Scale IQ (FSIQ) and T-scores on Vocabulary, Similarities, Block Design, and Matrix Reasoning subtests. The sample showed stable and improving trajectories for FSIQ and all subtests. There were no significant differences in trajectories between those who did and did not transition to psychosis and between individuals with good and poor functional outcomes. However, although not significant, the trajectories of the acquired knowledge subtests diverged between transitioned and non-transitioned individuals (β = -0.12, 95 % CI [-0.29, 0.05] for Vocabulary and β = -0.14, 95 % CI [-0.33, 0.05] for Similarities). Overall, there was no evidence for long-term deterioration in intelligence trajectories in this UHR sample. Future studies with a larger sample of transitioned participants may be needed to explore potential differences in intelligence trajectories between UHR transition groups and other non-psychosis outcomes.
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ItemTwelve-Month Cognitive Trajectories in Individuals at Ultra-High Risk for Psychosis: A Latent Class Analysis(Oxford University Press (OUP), 2022-01-01)Abstract Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, 6- and 12-months (N = 288). Using Growth Mixture Modeling, a single unimpaired improving trajectory class was observed for motor function, speed of processing, verbal fluency, and BACS composite. A two-class solution was observed for executive function and working memory, showing one unimpaired and a second impaired class. A three-class solution was found for verbal learning and memory: unimpaired, mildly impaired, and initially extremely impaired, but improved (“caught up”) to the level of the mildly impaired. IQ, omega-3 index, and premorbid adjustment were associated with class membership, whereas clinical variables (symptoms, substance use), including transition to psychosis, were not. Working memory and verbal learning and memory trajectory class membership was associated with functioning outcomes. These findings suggest there is no short-term progressive cognitive decline in help-seeking UHR individuals, including those who transition to psychosis. Screening of cognitive performance may be useful for identifying UHR individuals who may benefit from targeted cognitive interventions.
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ItemNo Preview AvailableImpaired olfactory ability associated with larger left hippocampus and rectus volumes at earliest stages of schizophrenia: A sign of neuroinflammation?(ELSEVIER IRELAND LTD, 2020-07)Impaired olfactory identification has been reported as a first sign of schizophrenia during the earliest stages of illness, including before illness onset. The aim of this study was to examine the relationship between volumes of these regions (amygdala, hippocampus, gyrus rectus and orbitofrontal cortex) and olfactory ability in three groups of participants: healthy control participants (Ctls), patients with first-episode schizophrenia (FE-Scz) and chronic schizophrenia patients (Scz). Exploratory analyses were performed in a sample of individuals at ultra-high risk (UHR) for psychosis in a co-submission paper (Masaoka et al., 2020). The relationship to brain structural measures was not apparent prior to psychosis onset, but was only evident following illness onset, with a different pattern of relationships apparent across illness stages (FE-Scz vs Scz). Path analysis found that lower olfactory ability was related to larger volumes of the left hippocampus and gyrus rectus in the FE-Scz group. We speculate that larger hippocampus and rectus in early schizophrenia are indicative of swelling, potentially caused by an active neurochemical or immunological process, such as inflammation or neurotoxicity, which is associated with impaired olfactory ability. The volumetric decreases in the chronic stage of Scz may be due to degeneration resulting from an active immune process and its resolution.
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ItemDivergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis(CAMBRIDGE UNIV PRESS, 2015-02)BACKGROUND: Whether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses. METHOD: Cortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined. RESULTS: The effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms. CONCLUSIONS: Our results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness.
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ItemDeterioration of visuospatial associative memory following a first psychotic episode: a long-term follow-up study(CAMBRIDGE UNIV PRESS, 2018-01)BACKGROUND: Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset. METHODS: In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5-11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised. RESULTS: Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up. CONCLUSIONS: Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.
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ItemNo Preview AvailableThe Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample(OXFORD UNIV PRESS, 2012-03)Cannabis use is highly prevalent among people with schizophrenia, and coupled with impaired cognition, is thought to heighten the risk of illness onset. However, while heavy cannabis use has been associated with cognitive deficits in long-term users, studies among patients with schizophrenia have been contradictory. This article consists of 2 studies. In Study I, a meta-analysis of 10 studies comprising 572 patients with established schizophrenia (with and without comorbid cannabis use) was conducted. Patients with a history of cannabis use were found to have superior neuropsychological functioning. This finding was largely driven by studies that included patients with a lifetime history of cannabis use rather than current or recent use. In Study II, we examined the neuropsychological performance of 85 patients with first-episode psychosis (FEP) and 43 healthy nonusing controls. Relative to controls, FEP patients with a history of cannabis use (FEP + CANN; n = 59) displayed only selective neuropsychological impairments while those without a history (FEP - CANN; n = 26) displayed generalized deficits. When directly compared, FEP + CANN patients performed better on tests of visual memory, working memory, and executive functioning. Patients with early onset cannabis use had less neuropsychological impairment than patients with later onset use. Together, these findings suggest that patients with schizophrenia or FEP with a history of cannabis use have superior neuropsychological functioning compared with nonusing patients. This association between better cognitive performance and cannabis use in schizophrenia may be driven by a subgroup of "neurocognitively less impaired" patients, who only developed psychosis after a relatively early initiation into cannabis use.
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ItemNeurocognitive predictors of transition to psychosis: medium- to long-term findings from a sample at ultra-high risk for psychosis(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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ItemNo Preview AvailablePhenylthiocarbamide (PTC) perception in ultra-high risk for psychosis participants who develop schizophrenia: Testing the evidence for an endophenotypic marker(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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ItemOlfactory identification dysfunction, aggression and impulsivity in war veterans with post-traumatic stress disorder(CAMBRIDGE UNIV PRESS, 2008-04)BACKGROUND: Due to neuropsychological conceptualizations of orbitoprefrontal cortex (OFC) dysfunction underpinning impulsive aggression and the incidence of such behaviour in post-traumatic stress disorder (PTSD), this study aimed to explore olfactory identification (OI) ability in war veterans with PTSD as a probe of putative OFC dysfunction; and to explore the utility of OI ability in predicting aggressive and impulsive behavior in this clinical population. METHOD: Participants comprised 31 out-patient male war veterans with PTSD (mean=58.23 years, s.d.=2.56) recruited from a Melbourne Veterans Psychiatry Unit, and 31 healthy age- and gender-matched controls (mean=56.84 years, s.d.=7.24). All participants were assessed on clinical measures of PTSD, depression, anxiety, and alcohol misuse; olfactory identification; neurocognitive measures of dorsolateral prefrontal, lateral prefrontal and mesial temporal functioning; and self-report measures of aggression and impulsivity. RESULTS: War veterans with PTSD exhibited significant OI deficits (OIDs) compared to controls, despite uncompromised performance on cognitive measures. OIDs remained after covaring for IQ, anxiety, depression and alcohol misuse, and were significant predictors of aggression and impulsivity. CONCLUSIONS: This research contributes to emerging evidence of orbitoprefrontal dysfunction in the pathophysiology underlying PTSD. This is the first study to report OIDs as a predictor of aggression and impulsivity in this clinical population. It prompts further exploration of the potential diagnostic utility of OIDs in the assessment of PTSD. Such measures may help delineate the clinical complexity of PTSD, and support more targeted interventions for individuals with a greater susceptibility to aggressive and impulsive behaviors.