Psychiatry - Research Publications
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ItemChanges in neural responses during affective and non-affective tasks and improvement of posttraumatic stress disorder symptoms following trauma-focused psychotherapy(SPRINGERNATURE, 2023-03-09)At least one-third posttraumatic stress disorder (PTSD) patients do not respond to trauma-focused psychotherapy (TF-psychotherapy), which is the treatment of choice for PTSD. To clarify the change mechanisms that may be associated with treatment response, this study examined changes in neural activations during affective and non-affective processing that occur with improvement of symptoms after TF-psychotherapy. This study assessed PTSD treatment-seeking patients (n = 27) prior to and after TF-psychotherapy using functional magnetic resonance imaging when they completed three tasks: (a) passive viewing of affective faces, (b) cognitive reappraisal of negative images, and (c) non-affective response inhibition. Patients then underwent 9 sessions of TF-psychotherapy, and were assessed on the Clinician-Administered PTSD Scale following treatment. Changes in neural responses in affect and cognitive processing regions-of-interest for each task were correlated with reduction of PTSD severity from pretreatment to posttreatment in the PTSD cohort. Data from 21 healthy controls was used for comparison. Improvement of symptoms in PTSD were associated with increased activation of left anterior insula, reductions in the left hippocampus and right posterior insula during viewing of supraliminally presented affective images, and reduced connectivity between the left hippocampus with the left amygdala and rostral anterior cingulate. Treatment response was also associated with reduced activation in the left dorsolateral prefrontal cortex during reappraisal of negative images. There were no associations between response and activation change during response inhibition. This pattern of findings indicates that improvement of PTSD symptoms following TF-psychotherapy is associated with changes in affective rather than non-affective processes. These findings accord with prevailing models that TF-psychotherapy promotes engagement and mastery of affective stimuli.Clinical Trials Registration: Trial Registration: Prospectively registered at Australian and New Zealand Clinical Trials Registry, ACTRN12612000185864 and ACTRN12609000324213. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83857.
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ItemDelineating gene-environment effects using virtual twins of patients treated with clozapine(WILEY, 2022-11-24)Studies that focus on individual covariates, while ignoring their interactions, may not be adequate for model-informed precision dosing (MIPD) in any given patient. Genetic variations that influence protein synthesis should be studied in conjunction with environmental covariates, such as cigarette smoking. The aim of this study was to build virtual twins (VTs) of real patients receiving clozapine with interacting covariates related to genetics and environment and to delineate the impact of interacting covariates on predicted clozapine plasma concentrations. Clozapine-treated patients with schizophrenia (N = 42) with observed clozapine plasma concentrations, demographic, environmental, and genotype data were used to construct VTs in Simcyp. The effect of increased covariate virtualization was assessed by performing simulations under three conditions: "low" (demographic), "medium" (demographic and environmental interaction), and "high" (demographic and environmental/genotype interaction) covariate virtualization. Increasing covariate virtualization with interaction improved the coefficient of variation (R2 ) from 0.07 in the low model to 0.391 and 0.368 in the medium and high models, respectively. Whereas R2 was similar between the medium and high models, the high covariate virtualization model had improved accuracy, with systematic bias of predicted clozapine plasma concentration improving from -138.48 ng/ml to -74.65 ng/ml. A high level of covariate virtualization (demographic, environmental, and genotype) may be required for MIPD using VTs.
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ItemGenetic and environmental influences on fruit and vegetable consumption and depression in older adults(BMC, 2023-02-03)BACKGROUND: Prior work suggests that higher fruit and vegetable consumption may protect against depression in older adults. Better understanding of the influence of genetic and environmental factors on fruit and vegetable intakes may lead to the design of more effective dietary strategies to increase intakes. In turn this may reduce the occurrence of depression in older adults. OBJECTIVES: The primary aim of this study is to estimate the genetic and environmental influences on the consumption of fruit and vegetables in older adults. The secondary aim is an exploratory analysis into possible shared genetic influences on fruit and vegetable intakes and depression. METHODS: Analysis of observational data from 374 twins (67.1% female; 208 monozygotic (MZ); 166 dizygotic (DZ)) aged ≥ 65 years drawn from the Older Australian Twins Study. Dietary data were obtained using a validated food frequency questionnaire and depressive symptoms were measured using the 15-item short form Geriatric Depression Scale. The contribution of genetic and environmental influences on fruit and vegetable intake were estimated by comparing MZ and DZ twin intakes using structural equation modelling. A tri-variate twin model was used to estimate the genetic and environmental correlation between total fruit and vegetable intakes and depression. RESULTS: In this study, vegetable intake was moderately influenced by genetics (0.39 95%CI 0.22, 0.54). Heritability was highest for brassica vegetables (0.40 95%CI 0.24, 0.54). Overall fruit intake was not significantly heritable. No significant genetic correlations were detected between fruit and vegetable intake and depressive symptoms. CONCLUSIONS: Vegetable consumption, particularly bitter tasting brassica vegetables, was significantly influenced by genetics, although environmental influences were also apparent. Consumption of fruit was only influenced by the environment, with no genetic influence detected, suggesting strategies targeting the food environment may be particularly effective for encouraging fruit consumption.
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ItemHigh polygenic risk score for exceptional longevity is associated with a healthy metabolic profile(SPRINGER, 2022-08-16)Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual's polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40-69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55-85 years), Older Australian Twins Study (n = 539, 65-90 years) and Sydney Memory and Ageing Study (n = 925, 70-90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (n = 2273, 70-93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22-30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (OR = 0.94, p = 1.84 × 10-42) and its components (p < 2.30 × 10-8). Meta-analyses of the replication cohorts showed nominal associations with MetS (p = 0.028) and 3 MetS components (p < 0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity.
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ItemA comparison of the functional connectome in mild traumatic brain injury and post-traumatic stress disorder(WILEY, 2022-10-07)Post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) often co-occur in the context of threat to one's life. These conditions also have an overlapping symptomatology and include symptoms of anxiety, poor concentration and memory problems. A major challenge has been articulating the underlying neurobiology of these overlapping conditions. The primary aim of this study was to compare intrinsic functional connectivity between mTBI (without PTSD) and PTSD (without mTBI). The study included functional MRI data from 176 participants: 42 participants with mTBI, 67 with PTSD and a comparison group of 66 age and sex-matched healthy controls. We used network-based statistical analyses for connectome-wide comparisons of intrinsic functional connectivity between mTBI relative to PTSD and controls. Our results showed no connectivity differences between mTBI and PTSD groups. However, we did find that mTBI had significantly reduced connectivity relative to healthy controls within an extensive network of regions including default mode, executive control, visual and auditory networks. The mTBI group also displayed hyperconnectivity between dorsal and ventral attention networks and perceptual regions. The PTSD group also demonstrated abnormal connectivity within these networks relative to controls. Connectivity alterations were not associated with severity of PTSD or post-concussive symptoms in either clinical group. Taken together, the similar profiles of intrinsic connectivity alterations in these two conditions provide neural evidence that can explain, in part, the overlapping symptomatology between mTBI and PTSD.
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ItemCost-effectiveness of media reporting guidelines for the prevention of suicide(WILEY, 2022-09-15)INTRODUCTION: Media guidelines for the responsible reporting of suicide are a recognized universal suicide prevention intervention. While implemented in numerous countries, including Australia, little is known about whether they are cost-effective. We aimed to determine the cost-effectiveness of Mindframe, the national initiative implementing media guidelines in Australia. METHOD: We conducted a modelled economic evaluation (5-year time-horizon) incorporating two types of economic analysis: (i) return-on-investment (ROI) comparing estimated cost savings from the intervention to the total intervention cost, and (ii) cost-effectiveness analysis comparing the net intervention costs to health outcomes: suicide deaths prevented and quality-adjusted life-years (QALYs). We also included uncertainty analyses to propagate parameter uncertainty and sensitivity analyses to test the robustness of the model outputs to changes in input parameters and assumptions. RESULTS: The estimated ROI ratio for the main analysis was 94:1 (95% uncertainty interval [UI]: 37 to 170). The intervention was associated with cost savings of A$596M (95% UI: A$228M to A$1,081M), 139 (95% UI: 55 to 252) suicides prevented and 107 (95% UI: 42 to 192) QALYs gained. The intervention was dominant, or cost-saving, compared with no intervention with results being robust to sensitivity analysis but varying based on the conservativeness of the parameters entered. CONCLUSION: Mindframe was found to be cost-saving, and therefore, worthy of investment and inclusion as part of national suicide prevention strategies.
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ItemReach and perceived effectiveness of a community-led active outreach postvention intervention for people bereaved by suicide(FRONTIERS MEDIA SA, 2022-12-22)BACKGROUND: Postvention is a core component of suicide prevention strategies, internationally. However, the types of supports provided to people impacted by suicide vary widely. This study examines the perceived effectiveness of the Primary Care Navigator (PCN) model for people bereaved by suicide. The PCN model was implemented in response to a suicide cluster. It is an active outreach postvention intervention, initiated by police in response to a suspected suicide and links individuals to support in the immediate aftermath of their loss. METHODS: A retrospective cross-sectional mixed methods approach was used to (1) identify the reach of the PCN model, (2) describe the type of support provided to people bereaved by a suspected suicide and (3) identify the perceived effectiveness of the PCN model from the perspective of WA police, postvention stakeholders and individuals bereaved by suicide. Quantitative data was used to examine the characteristics of suicide in the region, the characteristics of people who received bereavement support, and the types of support that were provided. Interviews with police, postvention stakeholders, and people bereaved by a suspected suicide were conducted to identify the perceived effectiveness of the intervention. RESULTS: Between 1 January 2019 and 31 March 2021 there were 80 suspected suicides. Active outreach was provided to 347 bereaved individuals via the PCN model. Just under half of those who were offered outreach accepted further support (N = 164) in the form of suicide bereavement information (98%), mental health or clinical support (49.6%), specialized postvention counseling (38.4%), financial assistance (16%) and assistance with meals (16%), followed by housing assistance (14%) and referral to community services (11%). Police, stakeholders, and people with lived experience of a suspected suicide perceived the PCN model to be effective at connecting them to the community, linking people to support, and preventing suicide. CONCLUSION: The results provide evidence supporting the perceived effectiveness of an active outreach approach to postvention that provides acute support to people bereaved by suicide. Findings highlight important practical areas of support such as providing referral pathways and information on grief and suicide loss in the immediate aftermath of a suicide loss.
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ItemGradual changes in microarchitectural properties of cortex and juxtacortical white matter: Observed by anatomical and diffusion MRI(WILEY, 2022-08-31)PURPOSE: Characterization of cerebral cortex is challenged by the complexity and heterogeneity of its cyto- and myeloarchitecture. This study evaluates quantitative MRI metrics, measured across two cortical depths and in subcortical white matter (WM) adjacent to cortex (juxtacortical WM), indicative of myelin content, neurite density, and diffusion microenvironment, for a comprehensive characterization of cortical microarchitecture. METHODS: High-quality structural and diffusion MRI data (N = 30) from the Human Connectome Project were processed to compute myelin index, neurite density index, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity from superficial cortex, deep cortex, and juxtacortical WM. The distributional patterns of these metrics were analyzed individually, correlated to one another, and were compared to established parcellations. RESULTS: Our results supported that myeloarchitectonic and the coexisting cytoarchitectonic structures influence the diffusion properties of water molecules residing in cortex. Full cortical thickness showed myelination patterns similar to those previously observed in humans. Higher myelin indices with similar distributional patterns were observed in deep cortex whereas lower myelin indices were observed in superficial cortex. Neurite density index and other diffusion MRI derived parameters provided complementary information to myelination. Reliable and reproducible correlations were identified among the cortical microarchitectural properties and fiber distributional patterns in proximal WM structures. CONCLUSION: We demonstrated gradual changes across the cortical sheath by assessing depth-specific cortical micro-architecture using anatomical and diffusion MRI. Mutually independent but coexisting features of cortical layers and juxtacortical WM provided new insights towards structural organizational units and variabilities across cortical regions and through depth.
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ItemConvenient consumption: a critical qualitative inquiry into the gambling practices of younger women in Australia.(Oxford University Press (OUP), 2022-12-01)There are a range of stereotypes and assumptions associated with women's gambling behaviours. While researchers have demonstrated that the practices associated with women's gambling are changing and becoming increasingly normalized, there is a limited understanding of how younger women ascribe meanings to these practices. This study explored the gambling practices of younger women. Forty-one women (20-40 years) participated in qualitative telephone interviews. Participants were asked open-ended questions about personal engagement in gambling, including experiences of gambling, gambling engagement, and experiences with different gambling products and environments. Data interpretation was guided by reflexive thematic analysis. Three themes were constructed from the data: (i) gambling infrastructures, including both products and the embedding of gambling in community environments, contributed to the convenient and regular consumption of gambling, with gambling easy to access and engage with; (ii) social networks and intergenerational gambling practices impacted the perceived social value and competencies related to gambling; and (iii) technology facilitated new gambling practices, routinizing gambling behaviours through automation and building perceived competencies with a range of gambling products. Gambling regulation and public health responses to gambling often focus on either individual behaviours or product characteristics. This study suggests that this focus is too narrow and excludes important influences on younger women's gambling practices, which include the infrastructure that supports the provision and consumption of gambling products. Public health research, policy and practice must consider the full range of determinants that may contribute to the initiation and continuation of gambling in younger women.
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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.