Psychiatry - 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 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(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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ItemCognitive ability and metabolic physical health in first-episode psychosis(ELSEVIER, 2021-06)Cognitive impairments are a core feature of first-episode psychosis (FEP), arising before illness onset and antipsychotic exposure. Individuals with chronic psychosis experience poorer physical health while taking antipsychotic medication, but health disparities may be evident at FEP onset, prior to antipsychotic exposure. Given the links between cognition and physical health in healthy populations, the aim was to explore whether cognition and physical health are associated in FEP, which could inform early physical health interventions for cognition in FEP. Participants were aged 15 to 25 and included 86 individuals experiencing FEP with limited antipsychotic exposure and duration of untreated psychosis of ≤six months, and 43 age- and sex-matched controls. Individuals with FEP performed significantly poorer than controls in most cognitive domains (Cohen's d = 0.38 to 1.59). Groups were similar in metabolic health measures, excluding a significantly faster heart rate in FEP (d = 0.68). Through hierarchical regression analyses, we found that in the overall sample, BMI was negatively related to current IQ after controlling for education and group (FEP/control). Relationships between BMI and cognition were consistent across the FEP and healthy control groups. In FEP, current IQ and working memory were negatively correlated with lipid profiles. Findings suggest that in FEP, impaired cognition is exhibited earlier than physical health problems, and that compared to controls, similar relationships with cognition are demonstrated. Causal pathways and trajectories of relationships between health and cognition in FEP require investigation, especially as antipsychotic medications are introduced. The findings have implications for cognitive and health interventions.
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ItemPsychosocial Intervention With or Without Antipsychotic Medication for First-Episode Psychosis: A Randomized Noninferiority Clinical Trial(Oxford University Press (OUP), 2020-01-01)Abstract This triple-blind (participants, clinicians, and researchers) randomized controlled noninferiority trial examined whether intensive psychosocial intervention (cognitive-behavioral case management, CBCM) for first-episode psychosis (FEP) in 15–25 year-olds managed in a specialized early intervention for psychosis service was noninferior to usual treatment of antipsychotic medication plus CBCM delivered during the first 6 months of treatment. To maximize safety, participants were required to have low levels of suicidality and aggression, a duration of untreated psychosis (DUP) of less than 6 months, and be living in stable accommodation with social support. The primary outcome was level of functioning as assessed by the Social and Occupational Functioning Scale (SOFAS) at 6 months. Ninety young people were randomized by computer, 46 to placebo, and 44 antipsychotic medication and 33% of those who commenced trial medication completed the entire 6-month trial period. On the SOFAS, both groups improved, and group differences were small and clinically trivial, indicating that treatment with placebo medication was no less effective than conventional antipsychotic treatment (mean difference = −0.2, 2-sided 95% confidence interval = −7.5 to 7.0, t = 0.060, P = .95). Within the context of a specialized early intervention service, and with a short DUP, the immediate introduction of antipsychotic medication may not be required for all cases of FEP in order to see functional improvement. However, this finding can only be generalized to a very small proportion of FEP cases at this stage, and a larger trial is required to clarify whether antipsychotic-free treatment can be recommended for specific subgroups of those with FEP. Trial Registration: ACTRN12607000608460 (www.anzctr.org.au).
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ItemENACT: a protocol for a randomised placebo-controlled trial investigating the efficacy and mechanisms of action of adjunctive N-acetylcysteine for first-episode psychosis(BMC, 2019-11-28)BACKGROUND: First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness; however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N-acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2 g/day for 26 weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups. METHODS/DESIGN: ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15-25 years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration. DISCUSSION: Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ID: ACTRN12618000413224. Registered on 21 March 2018.
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ItemBiomarkers and clinical staging in psychiatry(WILEY, 2014-10)Personalized medicine is rapidly becoming a reality in today's physical medicine. However, as yet this is largely an aspirational goal in psychiatry, despite significant advances in our understanding of the biochemical, genetic and neurobiological processes underlying major mental disorders. Preventive medicine relies on the availability of predictive tools; in psychiatry we still largely lack these. Furthermore, our current diagnostic systems, with their focus on well-established, largely chronic illness, do not support a pre-emptive, let alone a preventive, approach, since it is during the early stages of a disorder that interventions have the potential to offer the greatest benefit. Here, we present a clinical staging model for severe mental disorders and discuss examples of biological markers that have already undergone some systematic evaluation and that could be integrated into such a framework. The advantage of this model is that it explicitly considers the evolution of psychopathology during the development of a mental illness and emphasizes that progression of illness is by no means inevitable, but can be altered by providing appropriate interventions that target individual modifiable risk and protective factors. The specific goals of therapeutic intervention are therefore broadened to include the prevention of illness onset or progression, and to minimize the risk of harm associated with more complex treatment regimens. The staging model also facilitates the integration of new data on the biological, social and environmental factors that influence mental illness into our clinical and diagnostic infrastructure, which will provide a major step forward in the development of a truly pre-emptive psychiatry.
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ItemMedial temporal lobe glutathione concentration in first episode psychosis: A 1H-MRS investigation(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2009-03)Glutathione (GSH) is implicated in the pathophysiology of schizophrenia. Previous brain spectroscopy studies, however, have been inconsistent, and there is little data available from first episode psychosis patients. This study compared brain GSH in a first episode cohort (n=30) to controls (n=18), using magnetic resonance spectroscopy (MRS), examining a temporal lobe voxel. Short-echo (TE 30 ms) acquisition proton MRS was performed on a 3T clinical magnetic resonance scanner. Comparison of the first-episode and control groups' GSH concentrations revealed a significant main effect of group (F(1,46)=4.7, p=0.035), but no main effect of hemisphere (F(1,46)=2.3, p=0.137) or group-by-side interactions (F(1,46)=0.4, p=0.513). Medial temporal lobe GSH concentrations in the first episode group were 22% higher than those in the control group. This study provides further evidence of significant perturbations in brain GSH in first episode psychosis, and supports a broader involvement of GSH in the pathophysiology of schizophrenia.