Psychiatry - Research Publications
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ItemNo Preview AvailableCortical and Subcortical Neuroanatomical Signatures of Schizotypy in 2,952 Individuals Assessed in a Worldwide ENIGMA Study(ELSEVIER SCIENCE INC, 2021-05-01)
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ItemCortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study(SPRINGERNATURE, 2022-02)Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.
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ItemCerebrovascular disease, Alzheimer's disease biomarkers and longitudinal cognitive decline(WILEY-BLACKWELL, 2016-06)
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ItemNo Preview AvailablePersonality disorder among youth with first episode psychotic mania: An important target for specific treatment?(WILEY, 2022-03)AIM: Personality disorder is a common co-occurrence ('comorbidity') among patients with bipolar disorder and appears to affect outcome negatively. However, there is little knowledge about the impact of this comorbidity in the early phases of bipolar disorder. We examined the prevalence and effect of personality disorder co-occurrence on outcome in a cohort of youth with first episode mania with psychotic features. METHODS: Seventy-one first episode mania patients, aged 15-29, were assessed at baseline, 6, 12, and 18 months as part of a randomized controlled trial of olanzapine and chlorpromazine as add-on to lithium in first episode mania with psychotic features. The current study involved secondary analysis of trial data. RESULTS: A co-occurring clinical personality disorder diagnosis was present in 16.9% of patients. Antisocial and narcissistic personality disorders were the most common diagnoses. Patients with co-occurring personality disorder had higher rates of readmission to hospital, lower rates of symptomatic recovery and poorer functional levels at 6 months, but these differences disappeared after 12 and 18 months. CONCLUSIONS: In the early phase of bipolar disorder, patients with personality disorder comorbidity display delayed symptomatic and functional recovery and increased likelihood to need hospital readmissions. These observations suggest that routine assessment for personality disorder and specific interventions are important in order to improve short-term treatment efficacy in this subgroup.
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ItemGenome-wide association study of circulating interleukin 6 levels identifies novel loci(OXFORD UNIV PRESS, 2021-03-01)Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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ItemPsychosocial recovery after serious injury(TAYLOR & FRANCIS LTD, 2014)BACKGROUND: The 2010 iteration of the Global Burden of Disease statistics (Murray et al., 2012) points to the growing impact of injury and highlights the mounting burden of psychiatric disorder. It is essential to examine the intersection between these two contributors to disease burden. METHODS: The Australian Injury Vulnerability Study collected data of over 1,000 injury patients from their initial hospitalization to 6 years post-injury. Structured clinical interviews were used to diagnose psychiatric disorder and self-report measures for disability and symptom severity. RESULTS: A wide range of psychiatric disorders developed following injury, which included posttraumatic stress disorder, agoraphobia, depression, and substance use disorders (Bryant, O'Donnell, Creamer, Silove, & McFarlane, 2010). Although prevalence rates for these disorders were generally consistent over time, examination of trajectory data showed that different people had the disorders at different times. Importantly, the data showed that early anxiety, depression, and PTSD symptoms played a significant role in the development of long term disability after injury (Carty, O'Donnell, Evans, Kazantzis, & Creamer, 2011; O'Donnell et al., 2013). CONCLUSIONS: These data support the view that transdiagnostic models for early intervention may be required to address the complex psychiatric disorder trajectories that develop after injury.
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ItemNo Preview AvailablePhysical therapy as an environmental modulator of genetic determinism in HD: The FIT-HD study(IOS Press, 2013)HD has long been viewed as the quintessential example of genetic determinism. However, research has demonstrated that environmental factors play a signifi cant role in modulating the disease process, including the age of onset. In transgenic mouse models of HD, co-author Hannan’s laboratory has demonstrated that environmental enrichment (enhanced motor, cognitive and sensory stimulation) delays onset and progression of motor symptoms and neural degeneration. Introducing an exercise wheel to young HD mice delays onset and progression of motor symptoms, and reverses reduction of brain derived neurotrophic factor in the striatum and hippocampus. Such stimulation has also ameliorated defi cits in learning and memory, as well as depressive behaviours in HD mice. Physical activity (PA) has been found to have benefi cial neural effects in older adults, with increases in hippocampal volume and cognition, apparent even when exercise is limited to later life. We have found that PA improved cognitive function in those at risk of Alzheimer’s disease (AD), and are conducting randomized controlled trials (RCT) investigating this PA program in AD patients, older adults at risk of AD with vascular risk factors or sedentary lifestyle, and in older care recipients and carers. The role of exercise as a potential modifi er is receiving increasing attention in HD. Avoiding passivity was found to be a potential benefi cial modulator in HD, and a PA program improved in motor function in HD patients. However, evidence from RCTs is lacking. AIMS of this study are to: 1) examine the feasibility of our PA program in FIT-HD (by measuring adherence, acceptability, benefi ts, risks); 2) improve physical and mental health and quality of life in HD carriers. HYPOTHESES. Participants randomised to the PA program will: 1) increase PA and adhere to the protocol; have 2) improved quality of life and fi tness, 3) improved sleep, 4) less motor and cognitive decline, 5) improved resting brain state, and 6) have less depressive symptoms, as compared to participants randomised to usual care. Methods: RCT of a validated 24-week PA intervention in HD in Australia. Participants are randomly allocated to an education/usual care group or to a 24-week home-based PA program. Results: PA should be more promoted in the HD community due to multiple health benefi ts. Should our RCT be completed successfully and our hypotheses supported then this could change clinical care of HD.