Melbourne School of Psychological Sciences - Research Publications

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    Early life stress alters pituitary growth during adolescence-A longitudinal study
    Ganella, DE ; Allen, NB ; Simmons, JG ; Schwartz, O ; Kim, JH ; Sheeber, L ; Whittle, S (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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    Nasal Resistance Is Elevated in People with Tetraplegia and Is Reduced by Topical Sympathomimetic Administration
    Gainche, L ; Berlowitz, DJ ; LeGuen, M ; Ruehland, WR ; O'Donoghue, FJ ; Trinder, J ; Graco, M ; Schembri, R ; Eckert, DJ ; Rochford, PD ; Jordan, AS (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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    The underlying neurobiology of key functional domains in young people with mood and anxiety disorders: a systematic review
    Iorfino, F ; Hickie, IB ; Lee, RSC ; Lagopoulos, J ; Hermens, DF (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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    The Relationship between Sleep-Wake Cycle and Cognitive Functioning in Young People with Affective Disorders
    Carpenter, JS ; Robillard, R ; Lee, RSC ; Hermens, DF ; Naismith, SL ; White, D ; Whitwell, B ; Scott, EM ; Hickie, IB (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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    Neuropsychological and functional outcomes in recent-onset major depression, bipolar disorder and schizophrenia-spectrum disorders: a longitudinal cohort study
    Lee, RSC ; Hermens, DF ; Naismith, SL ; Lagopoulos, J ; Jones, A ; Scott, J ; Chitty, KM ; White, D ; Robillard, R ; Scott, EM ; Hickie, IB (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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    Neuropsychological profile according to the clinical stage of young persons presenting for mental health care.
    Hermens, DF ; Naismith, SL ; Lagopoulos, J ; Lee, RSC ; Guastella, AJ ; Scott, EM ; Hickie, IB (Springer Science and Business Media LLC, 2013)
    BACKGROUND: Clinical staging of mental disorders proposes that individuals can be assessed at various sub-syndromal and later developed phases of illness. As an adjunctive rating, it may complement traditional diagnostic silo-based approaches. In this study, we sought to determine the relationships between clinical stage and neuropsychological profile in young persons presenting to youth-focused mental health services. METHODS: Neuropsychological testing of 194 help-seeking young people (mean age 22.6 years, 52% female) and 50 healthy controls. Clinical staging rated 94 persons as having an 'attenuated syndrome' (stage 1b) and 100 with a discrete or persistent disorder (stage 2/3). RESULTS: The discrete disorder group (stage 2/3) showed the most impaired neuropsychological profile, with the earlier stage (1b) group showing an intermediate profile, compared to controls. Greatest impairments were seen in verbal memory and executive functioning. To address potential confounds created by 'diagnosis', profiles for those with a mood syndrome or disorder but not psychosis were also examined and the neuropsychological impairments for the stage 2/3 group remained. CONCLUSIONS: The degree of neuropsychological impairment in young persons with mental disorders appears to discriminate those with attenuated syndromes from those with a discrete disorder, independent of diagnostic status and current symptoms. Our findings suggest that neuropsychological assessment is a critical aspect of clinical evaluation of young patients at the early stages of a major psychiatric illness.
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    Cognitive remediation improves memory and psychosocial functioning in first-episode psychiatric out-patients.
    Lee, RSC ; Redoblado-Hodge, MA ; Naismith, SL ; Hermens, DF ; Porter, MA ; Hickie, IB (Cambridge University Press (CUP), 2013-06)
    BACKGROUND: Cognitive remediation (CR) is an effective treatment for several psychiatric disorders. To date, there have been no published studies examining solely first-episode psychiatric cohorts, despite the merits demonstrated by early intervention CR studies. The current study aimed to assess the effectiveness of CR in patients with a first-episode of either major depression or psychosis. Method Fifty-five patients (mean age = 22.8 years, s.d. = 4.3) were randomly assigned to either CR (n = 28) or treatment as usual (TAU; n = 27). CR involved once-weekly 2-h sessions for a total of 10 weeks. Patients were comprehensively assessed before and after treatment. Thirty-six patients completed the study, and analyses were conducted using an intent-to-treat (ITT) approach with all available data. RESULTS: In comparison to TAU, CR was associated with improved immediate learning and memory controlling for diagnosis and baseline differences. Similarly, CR patients demonstrated greater improvements than TAU patients in psychosocial functioning irrespective of diagnosis. Delayed learning and memory improvements mediated the effect of treatment on psychosocial functioning at a marginal level. CONCLUSIONS: CR improves memory and psychosocial outcome in first-episode psychiatric out-patients for both depression and psychosis. Memory potentially mediated the functional gains observed. Future studies need to build on the current findings in larger samples using blinded allocation and should incorporate longitudinal follow-up and assessment of potential moderators (e.g. social cognition, self-efficacy) to examine sustainability and the precise mechanisms of CR effects respectively.
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    Social cognition deficits and psychopathic traits in young people seeking mental health treatment.
    van Zwieten, A ; Meyer, J ; Hermens, DF ; Hickie, IB ; Hawes, DJ ; Glozier, N ; Naismith, SL ; Scott, EM ; Lee, RSC ; Guastella, AJ ; García, AV (Public Library of Science (PLoS), 2013)
    Antisocial behaviours and psychopathic traits place an individual at risk for criminality, mental illness, substance dependence, and psychosocial dysfunction. Social cognition deficits appear to be associated with psychopathic traits and are believed to contribute to interpersonal dysfunction. Most research investigating the relationship of these traits with social cognition has been conducted either in children or adult forensic settings. We investigated whether psychopathic traits were associated with social cognition in 91 young people presenting for mental healthcare (aged between 15 and 25 years). Participants completed symptom severity measures, neuropsychological tests, the Reading the Mind in the Eyes Test of social cognition (RMET), and the Antisocial Process Screening Device (APSD) to assess psychopathic personality traits. Correlation analyses showed poorer social cognition was associated with greater psychopathic traits (r = -.36, p = .01). Interestingly, social cognition performance predicted unique variance in concurrent psychopathic personality traits above gender, IQ sustained attention, and working memory performance. These findings suggest that social cognitive impairments are associated with psychopathic tendencies in young people presenting for community mental healthcare. Research is needed to establish the directionality of this relationship and to determine whether social cognition training is an effective treatment amongst young people with psychopathic tendencies.
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    Neuropsychological and socio-occupational functioning in young psychiatric outpatients: a longitudinal investigation.
    Lee, RSC ; Hermens, DF ; Redoblado-Hodge, MA ; Naismith, SL ; Porter, MA ; Kaur, M ; White, D ; Scott, EM ; Hickie, IB ; Clelland, JD (Public Library of Science (PLoS), 2013)
    BACKGROUND: Clinical symptoms and neuropsychological deficits are longitudinally associated with functional outcome in chronic psychiatric cohorts. The current study extended these findings to young and early-course psychiatric outpatients, with the aim of identifying cognitive markers that predict later socio-occupational functioning. METHODS: At baseline, 183 young psychiatric outpatients were assessed. Ninety-three returned for follow-up (M = 21.6 years old; SD = 4.5) with an average re-assessment interval of 21.6 months (SD = 7.0), and primary diagnoses of major depressive disorder (n = 34), bipolar disorder (n = 29), or psychosis (n = 30). The primary outcome measure was cross-validated with various other functional measures and structural equation modelling was used to map out the interrelationships between predictors and later functional outcome. RESULTS: Good socio-occupational functioning at follow-up was associated with better quality of life, less disability, current employment and being in a romantic relationship. The final structural equation model explained 47.5% of the variability in functional outcome at follow-up, with baseline neuropsychological functioning (a composite of memory, working memory and attentional switching) the best independent predictor of later functional outcome. Notably, depressive and negative symptoms were only associated with functioning cross-sectionally. Diagnosis at follow-up was not associated with functional outcome. CONCLUSIONS: Neuropsychological functioning was the single best predictor of later socio-occupational outcome among young psychiatric outpatients. Therefore, framing psychiatric disorders along a neuropsychological continuum is likely to be more useful in predicting functional trajectory than traditional symptom-based classification systems. The current findings also have implications for early intervention utilising cognitive remediation approaches.
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    Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk
    Elwood, PC ; Morgan, G ; Galante, J ; Chia, JWK ; Dolwani, S ; Graziano, JM ; Kelson, M ; Lanas, A ; Longley, M ; Phillips, CJ ; Pickering, J ; Roberts, SE ; Soon, SS ; Steward, W ; Morris, D ; Weightmanm, AL ; Fukumoto, Y (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.