Psychiatry - Research Publications

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    Interactive relationships of Type 2 diabetes and bipolar disorder with cognition: evidence of putative premature cognitive ageing in the UK Biobank Cohort
    Ringin, E ; Dunstan, DW ; McIntyre, RS ; Berk, M ; Owen, N ; Rossell, SL ; Van Rheenen, TE (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.
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    A preliminary investigation of the clinical and cognitive correlates of circulating vitamin D in bipolar disorder
    Van Rheenen, TE ; Ringin, E ; Karantonis, JA ; Furlong, L ; Bozaoglu, K ; Rossell, SL ; Berk, M ; Balanza-Martinez, V (ELSEVIER IRELAND LTD, 2022-12-21)
    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.
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    Increased cortical surface area but not altered cortical thickness or gyrification in bipolar disorder following stabilisation from a first episode of mania
    Van Rheenen, TE ; Cotton, SM ; Dandash, O ; Cooper, RE ; Ringin, E ; Daglas-Georgiou, R ; Allott, K ; Chye, Y ; Suo, C ; Macneil, C ; Hasty, M ; Hallam, K ; McGorry, P ; Fornito, A ; Yucel, M ; Pantelis, C ; Berk, M (PERGAMON-ELSEVIER SCIENCE LTD, 2023-03-02)
    BACKGROUND: Despite reports of altered brain morphology in established bipolar disorder (BD), there is limited understanding of when these morphological abnormalities emerge. Assessment of patients during the early course of illness can help to address this gap, but few studies have examined surface-based brain morphology in patients at this illness stage. METHODS: We completed a secondary analysis of baseline data from a randomised control trial of BD individuals stabilised after their first episode of mania (FEM). The magnetic resonance imaging scans of n = 35 FEM patients and n = 29 age-matched healthy controls were analysed. Group differences in cortical thickness, surface area and gyrification were assessed at each vertex of the cortical surface using general linear models. Significant results were identified at p < 0.05 using cluster-wise correction. RESULTS: The FEM group did not differ from healthy controls with regards to cortical thickness or gyrification. However, there were two clusters of increased surface area in the left hemisphere of FEM patients, with peak coordinates falling within the lateral occipital cortex and pars triangularis. CONCLUSIONS: Cortical thickness and gyrification appear to be intact in the aftermath of a first manic episode, whilst cortical surface area in the inferior/middle prefrontal and occipitoparietal cortex is increased compared to age-matched controls. It is possible that increased surface area in the FEM group is the outcome of abnormalities in a premorbidly occurring process. In contrast, the findings raise the hypothesis that cortical thickness reductions seen in past studies of individuals with more established BD may be more attributable to post-onset factors.
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    Brain Morphological Characteristics of Cognitive Subgroups of Schizophrenia-Spectrum Disorders and Bipolar Disorder: A Systematic Review with Narrative Synthesis
    Karantonis, JA ; Carruthers, SP ; Burdick, KE ; Pantelis, C ; Green, M ; Rossell, SL ; Hughes, ME ; Cropley, V ; Van Rheenen, TE (SPRINGER, 2022-02-22)
    Despite a growing body of research, there is yet to be a cohesive synthesis of studies examining differences in brain morphology according to patterns of cognitive function among both schizophrenia-spectrum disorder (SSD) and bipolar disorder (BD) individuals. We aimed to provide a systematic overview of the morphological differences-inclusive of grey and white matter volume, cortical thickness, and cortical surface area-between cognitive subgroups of these disorders and healthy controls, and between cognitive subgroups themselves. An initial search of PubMed and Scopus databases resulted in 1486 articles of which 20 met inclusion criteria and were reviewed in detail. The findings of this review do not provide strong evidence that cognitive subgroups of SSD or BD map to unique patterns of brain morphology. There is preliminary evidence to suggest that reductions in cortical thickness may be more strongly associated with cognitive impairment, whilst volumetric deficits may be largely tied to the presence of disease.
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    Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force.
    Miskowiak, KW ; Yalin, N ; Seeberg, I ; Burdick, KE ; Balanzá-Martínez, V ; Bonnin, CDM ; Bowie, CR ; Carvalho, AF ; Dols, A ; Douglas, K ; Gallagher, P ; Hasler, G ; Kessing, LV ; Lafer, B ; Lewandowski, KE ; López-Jaramillo, C ; Martinez-Aran, A ; McIntyre, RS ; Porter, RJ ; Purdon, SE ; Schaffer, A ; Sumiyoshi, T ; Torres, IJ ; Van Rheenen, TE ; Yatham, LN ; Young, AH ; Vieta, E ; Stokes, PRA (Wiley, 2022-09)
    BACKGROUND: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions. METHODS: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist. RESULTS: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred. CONCLUSIONS: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out-of-scanner tests.
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    Surviving the COVID-19 pandemic: An examination of adaptive coping strategies.
    Meyer, D ; Van Rheenen, TE ; Neill, E ; Phillipou, A ; Tan, EJ ; Toh, WL ; Sumner, PJ ; Rossell, SL (Elsevier BV, 2022-05)
    The mental health consequences of the COVID-19 pandemic have been significant in Australia. The aim of this study was to investigate coping strategies that individuals have adopted to assist them through this stressful period. Survey data collected in September and December 2020 as part of a larger study (the COLLATE project) were analysed. The number of adaptive coping strategies endorsed by respondents had a significant negative relationship with depression and a significant positive relationship with resilience. Females tended to use more of these strategies than men, as did people who said their mental health had improved rather than deteriorated because of the COVID-19 restrictions imposed by government. Specific adaptive coping strategies differed for those with and without a mental illness. People with a mental illness were more likely to seek professional and online help, while people without a mental illness were more likely to use self-help. Focusing on what one is grateful for and keeping oneself productively occupied ("using the time to do things around the house") were the most beneficial coping strategies in terms of alleviating depression, anxiety and stress. Public health messaging promoting adaptive coping strategies may be useful in bolstering the mental health of individuals during lockdown periods. In particular, the promotion of coping flexibility should be recommended rather than the frequent use of the same coping strategies.
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    Brain Morphological Characteristics of Cognitive Subgroups of Schizophrenia-spectrum Disorders and Bipolar Disorder: a Systematic Review with Narrative Synthesis (Feb, 10.1007/s11065-021-09533-0, 2022)
    Karantonis, JA ; Carruthers, SP ; Burdick, KE ; Pantelis, C ; Green, M ; Rossell, SL ; Hughes, ME ; Cropley, V ; Van Rheenen, TE (SPRINGER, 2022-03-28)
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    Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force
    Miskowiak, KW ; Seeberg, I ; Jensen, MB ; Balanza-Martinez, V ; Mar Bonnin, C ; Bowie, CR ; Carvalho, AF ; Dols, A ; Douglas, K ; Gallagher, P ; Hasler, G ; Lafer, B ; Lewandowski, KE ; Lopez-Jaramillo, C ; Martinez-Aran, A ; McIntyre, RS ; Porter, RJ ; Purdon, SE ; Schaffer, A ; Stokes, P ; Sumiyoshi, T ; Torres, IJ ; Van Rheenen, TE ; Yatham, LN ; Young, AH ; Kessing, L ; Burdick, KE ; Vieta, E (WILEY, 2022-02-24)
    BACKGROUND: Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations. METHODS: The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials. RESULTS: We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking. CONCLUSIONS: Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.
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    Recognising the relevance of cognitive dysfunction in the clinical management of bipolar disorder
    Van Rheenen, TE ; Miskowiak, K ; Burdick, KE (WILEY, 2021-03-02)
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