Psychiatry - 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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    Genetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks
    Fornito, A ; Zalesky, A ; Bassett, DS ; Meunier, D ; Ellison-Wright, I ; Yuecel, M ; Wood, SJ ; Shaw, K ; O'Connor, J ; Nertney, D ; Mowry, BJ ; Pantelis, C ; Bullmore, ET (SOC NEUROSCIENCE, 2011-03-02)
    The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09-0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization.
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    The relationship between Hippocampal asymmetry and working memory processing in combat-related PTSD - a monozygotic twin study
    Hall, T ; Galletly, C ; Clark, CR ; Veltmeyer, M ; Metzger, LJ ; Gilbertson, MW ; Orr, SP ; Pitman, RK ; McFarlane, A (BMC, 2012-12)
    BACKGROUND: PTSD is associated with reduction in hippocampal volume and abnormalities in hippocampal function. Hippocampal asymmetry has received less attention, but potentially could indicate lateralised differences in vulnerability to trauma. The P300 event-related potential component reflects the immediate processing of significant environmental stimuli and has generators in several brain regions including the hippocampus. P300 amplitude is generally reduced in people with PTSD. METHODS: Our study examined hippocampal volume asymmetry and the relationship between hippocampal asymmetry and P300 amplitude in male monozygotic twins discordant for Vietnam combat exposure. Lateralised hippocampal volume and P300 data were obtained from 70 male participants, of whom 12 had PTSD. We were able to compare (1) combat veterans with current PTSD; (2) their non-combat-exposed co-twins; (3) combat veterans without current PTSD and (4) their non-combat-exposed co-twins. RESULTS: There were no significant differences between groups in hippocampal asymmetry. There were no group differences in performance of an auditory oddball target detection task or in P300 amplitude. There was a significant positive correlation between P300 amplitude and the magnitude of hippocampal asymmetry in participants with PTSD. CONCLUSIONS: These findings suggest that greater hippocampal asymmetry in PTSD is associated with a need to allocate more attentional resources when processing significant environmental stimuli.
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    Characterization of the ATP4 ion pump in Toxoplasma gondii
    Lehane, AM ; Dennis, ASM ; Bray, KO ; Li, D ; Rajendran, E ; McCoy, JM ; McArthur, HM ; Winterberg, M ; Rahimi, F ; Tonkin, CJ ; Kirk, K ; van Dooren, GG (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2019-04-05)
    The Plasmodium falciparum ATPase PfATP4 is the target of a diverse range of antimalarial compounds, including the clinical drug candidate cipargamin. PfATP4 was originally annotated as a Ca2+ transporter, but recent evidence suggests that it is a Na+ efflux pump, extruding Na+ in exchange for H+ Here we demonstrate that ATP4 proteins belong to a clade of P-type ATPases that are restricted to apicomplexans and their closest relatives. We employed a variety of genetic and physiological approaches to investigate the ATP4 protein of the apicomplexan Toxoplasma gondii, TgATP4. We show that TgATP4 is a plasma membrane protein. Knockdown of TgATP4 had no effect on resting pH or Ca2+ but rendered parasites unable to regulate their cytosolic Na+ concentration ([Na+]cyt). PfATP4 inhibitors caused an increase in [Na+]cyt and a cytosolic alkalinization in WT but not TgATP4 knockdown parasites. Parasites in which TgATP4 was knocked down or disrupted exhibited a growth defect, attributable to reduced viability of extracellular parasites. Parasites in which TgATP4 had been disrupted showed reduced virulence in mice. These results provide evidence for ATP4 proteins playing a key conserved role in Na+ regulation in apicomplexan parasites.
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    The association between major depressive disorder, use of antidepressants and bone mineral density (BMD) in men
    Rauma, PH ; Pasco, JA ; Berk, M ; Stuart, AL ; Koivumaa-Honkanen, H ; Honkanen, RJ ; Hodge, JM ; Williams, LJ (JMNI, 2015-06)
    OBJECTIVE: Both depression and use of antidepressants have been negatively associated with bone mineral density (BMD) but mainly in studies among postmenopausal women. Therefore, the aim of this study was to investigate these relationships in men. METHODS: Between 2006 and 2011, 928 men (aged 24-98 years) from the Geelong Osteoporosis Study completed a comprehensive questionnaire, clinical measurements and had BMD assessments at the forearm, spine, total hip and total body. Major depressive disorder (MDD) was identified using a structured clinical interview (SCID-I/NP). The cross-sectional associations between BMD and both MDD and antidepressant use were analyzed using multivariable linear regression. RESULTS: Of the study population, 84 (9.1%) men had a single MDD episode, 50 (5.4%) had recurrent episodes and 65 (7.0%) were using antidepressants at the time of assessment. Following adjustments, recurrent MDD was associated with lower BMD at the forearm and total body (-6.5%, P=0.033 and -2.5%, P=0.033, respectively compared to men with no history of MDD), while single MDD episodes were associated with higher BMD at the total hip (+3.4%, P=0.030). Antidepressant use was associated with lower BMD only in lower-weight men (<75-110 kg depending on bone site). CONCLUSIONS: Both depression and use of antidepressants should be taken into account as possible risk factors for osteoporosis in men.
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    Stakeholder input into the implementation of a new music therapy program in a mental health service
    Bibb, J ; Castle, D ; McFerran, KS (Emerald, 2018-01-01)
    Purpose: Music therapy programs are increasingly common and necessary in mental health services. However, there is little knowledge of the key factors which influence the successful implementation of new therapeutic programs. The purpose of this paper is to explore how stakeholder input influenced the implementation and sustainability of a new music therapy program in four services within a large government funded mental health department in Melbourne, Australia. Design/methodology/approach: For a period of 12 months, two cycles of assessment, action and evaluation were conducted where data were collected through interviews with staff members, feedback from consumers and attendance in sessions. Findings: A number of influential factors were identified as important in the successful implementation and future sustainability of the music therapy program. These included: the degree of staff support received; how the program was structured and facilitated; promotion of the program within the service; evaluation of the program; and congruence with the existing therapeutic program. Research limitations/implications: Results suggest that successful implementation and future sustainability of a music therapy program is dependent on the flexibility of the program to the context and culture of the existing setting. Originality/value: This is the first study to incorporate contributions from stakeholders in the implementation of a new music therapy program in a mental health service.
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    An examination of children's eating behaviours as mediators of the relationship between parents' feeding practices and early childhood body mass index z-scores
    Boswell, N ; Byrne, R ; Davies, PSW (WILEY, 2019-04)
    OBJECTIVE: Parent's use of restrictive feeding practices is associated with child weight. Similarly, the literature shows that children's eating behaviours are also associated with child weight. Given this interrelationship between children's eating behaviours, restrictive feeding practices and child weight, examination of possible mediator relationships is warranted. This study aimed to examine the relationships between overt restriction and covert restriction with child body mass index z-scores (BMIz) and determine if children's eating behaviours (satiety responsiveness and food responsiveness) act as mediators. METHOD: Parents of Australian children (n = 977) 2.0-5.0 years of age (49.4% male) provided data in an online survey on child eating behaviours, parent's restrictive feeding practices and child anthropometrics (modified z-scores were created to screen for biologically implausible values). Correlation analysis was used to determine variables to include in mediation models. Hayes' PROCESS macros in spss was used to examine mediation, controlling for covariates of child BMIz. RESULTS: Overt restriction was the only parent feeding practice related to child BMIz (B = 0.132, P = 0.04). Mediation analysis showed that the indirect effect of overt restriction on child BMIz (controlling for child age, gender, parent BMI and income) became non-significant when controlling for food responsiveness, thus suggesting full mediation, explaining 5.75% of the relation. CONCLUSION: Overt restriction and covert restriction have distinctly different relationships with children's eating behaviours. Food responsiveness appears an important intermediary in the relationship between overt restriction and child BMIz.
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    Family food environment factors associated with obesity outcomes in early childhood.
    Boswell, N ; Byrne, R ; Davies, PSW (Springer Science and Business Media LLC, 2019)
    BACKGROUND: In attempting to gain understanding of the family food environment (FFE), as a central context for the development of obesity and obesogenic eating behaviours during early childhood, attention has largely focused on the relationships of individual variables. This fails to capture the complex combinations of variables children are exposed to. To more authentically reflect the impact of the FFE on the development of obesity and obesogenic eating behaviours during early childhood, this study aims to derive composites of FFE variables using factor analysis. METHODS: FFE and eating behaviour data were available from 757 Australian children (2.0-5.0 years) via a parent-completed online survey. Children were categorised as normal weight, overweight or obese, based on parent-reported anthropometry (underweight children were excluded). RESULTS: Eight FFE factors were derived. Scores for factors 'Negative Feeding Strategies' and 'Negative Nutrition Related Beliefs' increased with child BMI category, while 'Use of TV and devices' and 'Parent's Nutrition Knowledge' decreased. The FFE factor 'Negative Feeding Strategies' was positively associated with food fussiness, food responsiveness and slowness in eating, and negatively associated with parent body mass index (BMI) score. The FFE factor 'Negative Nutrition Related Beliefs' was positively associated with food responsiveness, as well as positively with parent BMI, male children, breastfeeding less than 6 months, and low-income status. The FFE factor 'Television (TV) and devices' was only positively associated with residing in a capital city. The FFE factor 'Parent's Nutrition Knowledge' was negatively associated with slowness in eating, breastfeeding less than 6 months and low-income status, and positively with parent stress and residing in a capital city. CONCLUSION: Consideration of the composite effect of FFE on child's eating behaviours and obesity outcomes is important in guiding future research and obesity prevention initiatives by providing a more authentic picture of the FFE children are exposed to. Examining factors of FFE variables in conjunction with psycho-social variables, further articulates the reciprocal influence of these variables on environmental constructs thus assisting in understanding of inequitable distribution of obesity risk. *KEYWORDS: childhood obesity, eating behaviours, early childhood, Family Food Environment, Factor Analysis.
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    A latent profile analysis of moral injury appraisals in refugees
    Hoffman, J ; Liddell, B ; Bryant, RA ; Nickerson, A (TAYLOR & FRANCIS LTD, 2019-01-01)
    Background: Refugees often exhibit reactions to traumatic events that may be conceptualized as moral injury (i.e. the impact of events that violate important moral values). There have been two types of moral injury appraisals found in refugees: transgressions by others and transgressions by oneself. Objective: To examine whether these types of moral injury appraisals co-occur or whether one form is usually predominant. Additionally, to investigate what types of events (trauma, living difficulties) and outcomes (PTSD, depression, anger, suicidality) were associated with each moral injury appraisal profile. Method: Participants included 221 refugees and asylum seekers residing in Australia. Data was collected online, and via pen and paper. A latent profile analysis was used to identify profiles of moral injury appraisals. Results: Results indicated a three-profile solution: Moral Injury-Other (MI-O; 37.8%), Moral Injury Other + Self (MI-OS; 35.2%), and no moral injury (No-MI; 26.9%). MI-O and MI-OS were predicted by both trauma experience and living difficulties. MI-O and MI-OS were also associated with greater psychopathology across all outcome variables compared to No-MI. MI-OS was also associated with greater anger and depression, compared to the MI-O profile. Conclusions: The association between the moral injury appraisal profiles and traumatic events, living difficulties and psychopathology, will have important clinical implications.
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    Predictors of treatment response for cognitive behaviour therapy for prolonged grief disorder.
    Bryant, RA ; Kenny, L ; Joscelyne, A ; Rawson, N ; Maccallum, F ; Cahill, C ; Hopwood, S (Informa UK Limited, 2017)
    Background: Prolonged grief disorder (PGD) causes significant impairment in approximately 7% of bereaved people. Although cognitive behaviour therapy (CBT) has been shown to effectively treat PGD, there is a need to identify predictors of treatment non-response. Methods: PGD patients (N = 80) were randomly allocated to receive 10 weekly two-hour group CBT sessions and (a) four individual sessions of exposure therapy or (b) CBT without exposure. PGD was assessed by self-report measures at baseline, post-treatment (N = 61), and six-months (N = 56) after treatment. Results: Post-treatment assessments indicated that greater reduction in grief severity relative to pretreatment levels was associated with being in the CBT/Exposure condition, and lower baseline levels of self-blame and avoidance. At follow-up, greater grief symptom reduction was associated with being in the CBT/Exposure condition and lower levels of avoidance. Conclusions: These patterns suggest that strategies that target excessive self-blame and avoidance during treatment may enhance response to grief-focused cognitive behaviour therapy.