Psychiatry - Research Publications
Permanent URI for this collection
Search Results
1 - 6 of 6
-
Item
-
ItemInteractive relationships of Type 2 diabetes and bipolar disorder with cognition: evidence of putative premature cognitive ageing in the UK Biobank Cohort(SPRINGERNATURE, 2023-01-01)Type 2 diabetes (T2D) is disproportionately prevalent in bipolar disorder (BD) and is associated with cognitive deficits in psychiatrically healthy cohorts. Whether there is an interaction effect between T2D and BD on cognition remains unclear. Using the UK Biobank, we explored interactions between T2D, BD and cognition during mid and later life; and examined age-related cognitive performance effects in BD as a function of T2D. Data were available for 1511 participants with BD (85 T2D), and 81,162 psychiatrically healthy comparisons (HC) (3430 T2D). BD and T2D status were determined by validated measures created specifically for the UK Biobank. Diagnostic and age-related associations between T2D status and cognition were tested using analyses of covariance or logistic regression. There was a negative association of T2D with visuospatial memory that was specific to BD. Processing speed and prospective memory performance were negatively associated with T2D, irrespective of BD diagnosis. Cognitive deficits were evident in BD patients with T2D compared to those without, with scores either remaining the same (processing speed) or improving (visuospatial memory) as a function of participant age. In contrast, cognitive performance in BD patients without T2D was worse as participant age increased, although the age-related trajectory remained broadly equivalent to the HC group. BD and T2D associated with cognitive performance deficits across the mid-life period; indicating comorbid T2D as a potential risk factor for cognitive dysfunction in BD. In comparison to BD participants without T2D and HCs, age-independent cognitive impairments in BD participants with comorbid T2D suggest a potential premature deterioration of cognitive functioning compared to what would normally be expected.
-
ItemN-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms(OXFORD UNIV PRESS, 2022-11-18)BACKGROUND AND HYPOTHESIS: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of individuals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N-acetylcysteine (NAC). STUDY DESIGN: A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks. STUDY RESULTS: NAC did not significantly improve negative symptoms (P = .62), overall cognition (P = .71) or quality of life (Manchester quality of life: P = .11; Assessment of quality of life: P = .57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P = .26). CONCLUSIONS: NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with "Australian and New Zealand Clinical Trials" on the 30 May, 2016 (Registration Number: ACTRN12615001273572).
-
ItemNo Preview AvailableA preliminary investigation of the clinical and cognitive correlates of circulating vitamin D in bipolar disorder(ELSEVIER IRELAND LTD, 2023-02)The role that vitamin D plays in the cognitive and clinical characteristics of bipolar disorder (BD) is unclear. We examined differences in the levels and deficiency status of vitamin D in an Australian sample of BD patients compared to healthy controls; and determined the extent to which vitamin D is associated with clinical variables and cognitive function in the sample. 22 healthy controls and 55 stable outpatients with a diagnosis of BD and low-grade mood symptomatology provided a sample of blood and completed cognitive tests and clinical measures. Plasma concentrations of 25-hydroxyvitamin D (vitamin D) were assayed and used to segregate participants into subgroups with sufficient or deficient levels of vitamin D. Subgroups were then compared in terms of global cognition and a range of sociodemographic and clinical factors (number of past mood episodes, illness duration, seasonal mood pattern, mood symptom severity), while mean levels of vitamin D were compared between patients and controls. Although almost 27% of the current sample were vitamin D deficient, no significant differences in mean vitamin D levels or the prevalence of vitamin D deficiency were evident between BD patients and controls. Vitamin D was not associated with global cognition in either patients or controls, nor any of the clinical measures assessed in the study. In conclusion, we observed no difference in the vitamin D levels and deficiency status of an Australian sample of healthy individuals and BD patients with low grade mood symptomatology compared to controls. Clinical symptoms and global cognition also appear to be independent of vitamin D levels in BD.
-
ItemNo Preview AvailableGenetics of methamphetamine use disorder: A systematic review and meta-analyses of gene association studies(PERGAMON-ELSEVIER SCIENCE LTD, 2021-01)Genetic susceptibility to methamphetamine use disorder is poorly understood. No twin or adequately powered genome-wide association studies (GWASs) have been conducted. However, there are a large number of hypothesis-driven candidate gene association studies, which were systematically reviewed herein. Seventy-six studies were identified, investigating markers of 75 different genes. Allele frequencies, odds ratios, 95 % confidence intervals and power were calculated. Risk of bias was also assessed as a quality measure. Meta-analyses were conducted for gene markers if three or more studies were available. Eleven markers from adequately powered studies were significantly associated with methamphetamine use disorder, with Fatty Acid Amide Hydrolase (FAAH) and Brain Derived Neurotrophic Factor (BDNF) representing promising targets. Limitations of these studies include unclear rationale for candidate gene selection, low power and high risk of bias. Future research should include replications to enable more meta-analyses, well-powered GWASs or whole exome or genome sequencing, as well as twin and family studies to further complement the findings of this review to uncover genetic contributions toward methamphetamine use disorder.
-
ItemN-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms(BMC, 2016-09-15)BACKGROUND: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60 % of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered 'clozapine resistant'. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ. METHODS: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2 g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes. DISCUSSION: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a 'go to' adjunct in patients that are only partly responsive to clozapine. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registration Number: Current Randomised Controlled Trial ACTRN12615001273572 . The date of registration 23 November 2015.