Melbourne School of Psychological Sciences - Research Publications
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ItemEarly life stress alters pituitary growth during adolescence-A longitudinal study(PERGAMON-ELSEVIER SCIENCE LTD, 2015-03)The pituitary gland is integral in mediating the stress-response via its role in hypothalamic-pituitary-adrenal (HPA) axis function. Pituitary gland volume (PGV) is altered in stress-related psychopathology, and one study to date has shown stress to be associated with age-related PGV change during adolescence. The current study investigated the effects of a number of different types of early life (i.e., childhood and adolescent) stress (including childhood maltreatment, stressful life events, and maternal affective behavior) on PGV development from mid- to late adolescence using a longitudinal design. The influence of PGV development on depressive and anxiety symptoms was also investigated. Ninety one (49 male) adolescents took part in mother-child dyadic interaction tasks when they were approximately 12 years old, reported on childhood maltreatment and stressful life events when they were approximately 15 years old, and underwent two waves of structural magnetic resonance imaging (MRI) scans, when they were approximately 16 and 19 years old. Results revealed that childhood maltreatment predicted accelerated PGV development in females, and maternal dysphoric behavior predicted accelerated PGV development in the whole sample. PGV development was not associated with depressive or anxiety symptoms. These results suggest an effect of early life stress on altered HPA axis function across mid- to late adolescence. Further research is required to assess functional implications and whether these changes might be associated with risk for subsequent psychopathology.
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ItemNasal Resistance Is Elevated in People with Tetraplegia and Is Reduced by Topical Sympathomimetic Administration(AMER ACAD SLEEP MEDICINE, 2016)STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in individuals with tetraplegia and associated with adverse health outcomes. The causes of the high prevalence of OSA in this population are unknown, but it is important to understand as standard treatments are poorly tolerated in tetraplegia. Nasal congestion is common in tetraplegia, possibly because of unopposed parasympathetic activity. Further, nasal obstruction can induce OSA in healthy individuals. We therefore aimed to compare nasal resistance before and after topical administration of a sympathomimetic between 10 individuals with tetraplegia (T) and 9 able-bodied (AB) controls matched for OSA severity, gender, and age. METHODS: Nasal, pharyngeal, and total upper airway resistance were calculated before and every 2 minutes following delivery of ≈0.05 mL of 0.5% atomized phenylephrine to the nostrils and pharyngeal airway. The surface tension of the upper airway lining liquid was also assessed. RESULTS: At baseline, individuals with tetraplegia had elevated nasal resistance (T = 7.0 ± 1.9, AB = 3.0 ± 0.6 cm H2O/L/s), that rapidly fell after phenylephrine (T = 2.3 ± 0.4, p = 0.03 at 2 min) whereas the able-bodied did not change (AB = 2.5 ± 0.5 cm H2O/L/s, p = 0.06 at 2 min). Pharyngeal resistance was non-significantly higher in individuals with tetraplegia than controls at baseline (T = 2.6 ± 0.9, AB = 1.2 ± 0.4 cm H2O/L/s) and was not altered by phenylephrine in either group. The surface tension of the upper airway lining liquid did not differ between groups (T = 64.3 ± 1.0, AB = 62.7 ± 0.6 mN/m). CONCLUSIONS: These data suggest that the unopposed parasympathetic activity in tetraplegia increases nasal resistance, potentially contributing to the high occurrence of OSA in this population.
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ItemMotion Extrapolation for Eye Movements Predicts Perceived Motion-Induced Position Shifts(SOC NEUROSCIENCE, 2018-09-19)Transmission delays in the nervous system pose challenges for the accurate localization of moving objects as the brain must rely on outdated information to determine their position in space. Acting effectively in the present requires that the brain compensates not only for the time lost in the transmission and processing of sensory information, but also for the expected time that will be spent preparing and executing motor programs. Failure to account for these delays will result in the mislocalization and mistargeting of moving objects. In the visuomotor system, where sensory and motor processes are tightly coupled, this predicts that the perceived position of an object should be related to the latency of saccadic eye movements aimed at it. Here we use the flash-grab effect, a mislocalization of briefly flashed stimuli in the direction of a reversing moving background, to induce shifts of perceived visual position in human observers (male and female). We find a linear relationship between saccade latency and perceived position shift, challenging the classic dissociation between "vision for action" and "vision for perception" for tasks of this kind and showing that oculomotor position representations are either shared with or tightly coupled to perceptual position representations. Altogether, we show that the visual system uses both the spatial and temporal characteristics of an upcoming saccade to localize visual objects for both action and perception.SIGNIFICANCE STATEMENT Accurately localizing moving objects is a computational challenge for the brain due to the inevitable delays that result from neural transmission. To solve this, the brain might implement motion extrapolation, predicting where an object ought to be at the present moment. Here, we use the flash-grab effect to induce perceptual position shifts and show that the latency of imminent saccades predicts the perceived position of the objects they target. This counterintuitive finding is important because it not only shows that motion extrapolation mechanisms indeed work to reduce the behavioral impact of neural transmission delays in the human brain, but also that these mechanisms are closely matched in the perceptual and oculomotor systems.
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ItemClinical, neurocognitive and demographic factors associated with functional impairment in the Australian Brain and Mind Youth Cohort Study (2008-2016)(BMJ PUBLISHING GROUP, 2018-12)OBJECTIVES: We sought to determine the unique and shared contributions of clinical, neurocognitive and demographic factors to functional impairment in a large, transdiagnostic, clinical cohort of adolescents and young adults. DESIGN: Cross-sectional baseline data from a prospective, cohort study. SETTING: Help-seeking youth referred from outpatient services were recruited to the Brain and Mind Youth Cohort (2008-2016) in Sydney, Australia. PARTICIPANTS: In total, 1003 outpatients were recruited, aged between 12 and 36 years (mean= 20.4 years, 54% female), with baseline diagnoses of affective, psychotic, developmental or behavioural disorders. INTERVENTIONS: Treatment as usual. PRIMARY OUTCOME MEASURES: Social and occupational functioning was used to index level of functional impairment. Structural equation modelling was used to examine associations between neurocognition, core clinical symptoms and alcohol and substance use, and clinician-rated and researcher-rated functional impairment. Moderator analyses were conducted to determine the potential influence of demographic and clinical factors (eg, medication exposure). RESULTS: Independent of diagnosis, we found that neurocognitive impairments, and depressive, anxiety and negative symptoms, were significantly associated with functioning. The association of neurocognition with social and occupational functioning remained significant even when constraining for age (15-25-year-olds only) or diagnosis (affective disorders only) in the final model. CONCLUSIONS: This study demonstrated that, in a clinically representative sample of youth, the key determinants of functioning may not be disorder specific. Further, evidence of neurocognitive dysfunction suggests that interventions that target cognition and functioning should not necessarily be reserved just for older adults with established illness.
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ItemThe underlying neurobiology of key functional domains in young people with mood and anxiety disorders: a systematic review(BMC, 2016-05-23)BACKGROUND: Mood and anxiety disorders are leading causes of disability and mortality, due largely to their onset during adolescence and young adulthood and broader impact on functioning. Key factors that are associated with disability and these disorders in young people are social and economic participation (e.g. education, employment), physical health, suicide and self-harm behaviours, and alcohol and substance use. A better understanding of the objective markers (i.e. neurobiological parameters) associated with these factors is important for the development of effective early interventions that reduce the impact of disability and illness persistence. METHODS: We systematically reviewed the literature for neurobiological parameters (i.e. neuropsychology, neuroimaging, sleep-wake and circadian biology, neurophysiology and metabolic measures) associated with functional domains in young people (12 to 30 years) with mood and/or anxiety disorders. RESULTS: Of the one hundred and thirty-four studies selected, 7.6 % investigated social and economic participation, 2.1 % physical health, 15.3 % suicide and self-harm behaviours, 6.9 % alcohol and substance use, whereas the majority (68.1 %) focussed on clinical syndrome. CONCLUSIONS: Despite the predominance of studies that solely examine the clinical syndrome of young people the literature also provides evidence of distinct associations among objective measures (indexing various aspects of brain circuitry) and other functional domains. We suggest that a shift in focus towards characterising the mechanisms that underlie and/or mediate multiple functional domains will optimise personalised interventions and improve illness trajectories.
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ItemThe Relationship between Sleep-Wake Cycle and Cognitive Functioning in Young People with Affective Disorders(PUBLIC LIBRARY SCIENCE, 2015-04-21)Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in young adults early in the course of affective illness.
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ItemNeuropsychological and functional outcomes in recent-onset major depression, bipolar disorder and schizophrenia-spectrum disorders: a longitudinal cohort study(NATURE PUBLISHING GROUP, 2015-04-28)Functional disability is the lead contributor to burden of mental illness. Cognitive deficits frequently limit functional recovery, although whether changes in cognition and disability are longitudinally associated in recent-onset individuals remains unclear. Using a prospective, cohort design, 311 patients were recruited and assessed at baseline. One hundred and sixty-seven patients met eligibility criteria (M=21.5 years old, s.d.=4.8) and returned for follow-up (M=20.6 months later, s.d.=7.8). Two-hundred and thirty participants were included in the final analysis, comprising clinically stable patients with major depression (n=71), bipolar disorder (BD; n=61), schizophrenia-spectrum disorders (n=35) and 63 healthy controls. Neuropsychological functioning and self-rated functional disability were examined using mixed-design, repeated-measures analysis, across diagnoses and cognitive clusters, covarying for relevant confounds. Clinical, neuropsychological and functional changes did not differ between diagnoses (all P>0.05). Three reliable neuropsychological subgroups emerged through cluster analysis, characterized by psychomotor slowing, improved sustained attention, and improved verbal memory. Controlling for diagnosis and changes in residual symptoms, clusters with improved neuropsychological functioning observed greater reductions in functional disability than the psychomotor slowing cluster, which instead demonstrated a worsening in disability (P<0.01). Improved sustained attention was independently associated with greater likelihood of follow-up employment (P<0.01). Diagnosis of BD uniquely predicted both follow-up employment and independent living. Neuropsychological course appears to be independently predictive of subjective and objective functional outcomes. Importantly, cognitive phenotypes may reflect distinct pathophysiologies shared across major psychiatric conditions, and be ideal targets for personalized early intervention.
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ItemSystematic review update of observational studies further supports aspirin role in cancer treatment: Time to share evidence and decision-making with patients?(PUBLIC LIBRARY SCIENCE, 2018-09-25)BACKGROUND: Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer. METHODS: Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted. RESULTS: Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64-0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53-0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73-1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95). CONCLUSION: Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers?
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ItemSystematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk(PUBLIC LIBRARY SCIENCE, 2016-11-15)BACKGROUND: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. METHODS: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. RESULTS: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). CONCLUSIONS: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.
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ItemPsychological interventions for people with psychotic experiences: protocol for a updates systematic review and meta-analysis(BMC, 2019-05-23)BACKGROUND: Many people who have common mental disorders, such as depression and anxiety, also have some psychotic experiences. These experiences are associated with higher clinical complexity, poor treatment response, and negative clinical outcomes. Psychological interventions have the potential to improve outcomes for people with psychotic experiences. The aims of this systematic review are to (1) synthesise the evidence on the effectiveness and cost-effectiveness of psychological interventions to reduce psychotic experiences and their associated distress and (2) identify key components of effective interventions. METHODS: Our search strategy will combine terms for (1) psychological interventions, (2) psychotic experiences, and (3) symptoms associated with psychotic experiences. We will search the following online databases: MEDLINE, Embase, PsycINFO, all Cochrane databases, British Nursing Index (BNI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Health Management Information Consortium (HMIC), Education Resources Information Center (ERIC), and EconLit. Our primary outcome is the proportion of people who recovered or remitted from psychotic experiences after the intervention. Our secondary outcomes are changes in positive psychotic symptoms, negative psychotic symptoms, depression, anxiety, functioning (including social, occupational, and academic), quality of life, and cost-effectiveness. Two independent reviewers will judge each study against pre-specified inclusion and exclusion criteria and will extract study characteristics, outcome data, and intervention components. Risk of bias and methodological quality will be assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies and the Drummond Checklist. Results will be synthesised using random-effects meta-analysis and narrative synthesis. DISCUSSION: The identification of effective psychological interventions and of specific components associated with intervention effectiveness will augment existing evidence that can inform the development of a new, tailored intervention to improve outcomes related to psychotic symptoms, anxiety and depression, distress, functioning, and quality of life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033869.