Psychiatry - Research Publications

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    Assessment of conditioned fear extinction in male and female adolescent rats
    Perry, CJ ; Ganella, DE ; Ly, DN ; Du, X ; Drummond, KD ; Whittle, S ; Pang, TY ; Kim, JH (PERGAMON-ELSEVIER SCIENCE LTD, 2020-06)
    Pavlovian fear conditioning and extinction have been widely studied across many species to understand emotional learning and memory. Importantly, it is becoming clear that these processes are affected by sex and age. In adult rodents and humans, sex differences are evident in extinction, with estradiol playing a significant role. In adolescence, an extinction deficit has been reported in rodents and humans. However, the influence of sex on extinction during adolescence is unknown. This is surprising, since adolescence coincides with the onset of hormone cycling, and therefore it might be expected that hormones fluctuations exert a more profound effect at this time. Therefore, we examined Pavlovian fear conditioning and extinction in adolescent male and female rats. In experiment 1, 35-day-old male and female rats were exposed to 6 pairings of a conditioned stimulus (CS, a tone) with an aversive unconditioned stimulus (US, a footshock). The next day they were extinguished in a contextually distinct chamber, via 60 presentations of the CS without the US. Extinction recall was tested 24 hours later in the extinction context. Estrous phase was monitored by cytology on vaginal smears taken 1 hour after each behavioral session. In experiment 2, male and female rats were given sham surgery or gonadectomy at 21 days of age. They were then trained and tested as for experiment 1. We observed that females in proestrus or met/diestrus during extinction showed delayed extinction and impaired extinction recall the next day compared to males. Ovariectomy enhanced extinction for female rats, but orchidectomy delayed extinction for males. Plasma analyses showed that met/di/proestrus phases were associated with high estradiol levels. These findings suggest that high plasma estradiol levels impair extinction for adolescent females. These results contradict what is reported in adult animals, suggesting that hormonal influences on extinction are dependent on age. Given that impaired extinction is widely used as a model to understand resistance to exposure-based therapies, our findings have important implications for understanding mental health treatments in adolescents.
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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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    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 multisite longitudinal evaluation of patient characteristics associated with a poor response to non-surgical multidisciplinary management of low back pain in an advanced practice physiotherapist-led tertiary service.
    O'Leary, S ; Raymer, M ; Window, P ; Swete Kelly, P ; Lee, D ; Garsden, L ; Tweedy, R ; Phillips, B ; O'Sullivan, W ; Wake, A ; Smith, A ; Pahor, S ; Pearce, L ; McLean, R ; Thompson, D ; Williams, E ; Nolan, D ; Anning, J ; Seels, I ; Wickins, D ; Marks, D ; Diplock, B ; Parravicini, V ; Parnwell, L ; Vicenzino, B ; Comans, T ; Cottrell, M ; Khan, A ; McPhail, S (Springer Science and Business Media LLC, 2020-12-03)
    BACKGROUND: Non-surgical multidisciplinary management is often the first pathway of care for patients with chronic low back pain (LBP). This study explores if patient characteristics recorded at the initial service examination have an association with a poor response to this pathway of care in an advanced practice physiotherapist-led tertiary service. METHODS: Two hundred and forty nine patients undergoing non-surgical multidisciplinary management for their LBP across 8 tertiary public hospitals in Queensland, Australia participated in this prospective longitudinal study. Generalised linear models (logistic family) examined the relationship between patient characteristics and a poor response at 6 months follow-up using a Global Rating of Change measure. RESULTS: Overall 79 of the 178 (44%) patients completing the Global Rating of Change measure (28.5% loss to follow-up) reported a poor outcome. Patient characteristics retained in the final model associated with a poor response included lower Formal Education Level (ie did not complete school) (Odds Ratio (OR (95% confidence interval)) (2.67 (1.17-6.09), p = 0.02) and higher self-reported back disability (measured with the Oswestry Disability Index) (OR 1.33 (1.01-1.77) per 10/100 point score increase, p = 0.046). CONCLUSIONS: A low level of formal education and high level of self-reported back disability may be associated with a poor response to non-surgical multidisciplinary management of LBP in tertiary care. Patients with these characteristics may need greater assistance with regard to their comprehension of health information, and judicious monitoring of their response to facilitate timely alternative care if no benefits are attained.
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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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    Effectiveness of a peer-refugee delivered psychological intervention to reduce psychological distress among adult Syrian refugees in the Netherlands: study protocol
    de Graaff, AM ; Cuijpers, P ; Acarturk, C ; Bryant, R ; Burchert, S ; Fuhr, DC ; Huizink, AC ; de Jong, J ; Kieft, B ; Knaevelsrud, C ; McDaid, D ; Morina, N ; Park, A-L ; Uppendahl, J ; Ventevogel, P ; Whitney, C ; Wiedemann, N ; Woodward, A ; Sijbrandij, M (TAYLOR & FRANCIS LTD, 2020)
    Background: Syrian refugees face multiple hardships and adversities which put them at risk for the development of mental health problems. However, access to adequate mental health care in host countries is limited. The WHO has developed Problem Management Plus (PM+), a brief, scalable psychological intervention, delivered by non-specialist helpers, that addresses common mental disorders in people affected by adversity. This study is part of the STRENGTHS project, that aims to evaluate peer-refugee delivered psychological interventions for Syrian refugees in Europe and the Middle East. Objective: To evaluate the effectiveness and cost-effectiveness of the peer-refugee delivered PM+ intervention among Syrian refugees with elevated levels of psychological distress in the Netherlands. Methods: PM+ will be tested in a randomized controlled trial (RCT) among Arabic-speaking Syrian refugees in the Netherlands aged 18 years and above with self-reported psychological distress (Kessler Psychological Distress Scale; K10 >15) and impaired daily functioning (WHO Disability Assessment Schedule; WHODAS 2.0 >16). Participants (N = 380) will be randomized into care as usual with PM+ (CAU/PM+, n = 190) or CAU only (CAU, n = 190). Baseline, 1-week post-intervention, and 3-month and 12-month follow-up assessments will be conducted. Primary outcomes are symptoms of depression and anxiety. Secondary outcomes are functional impairment, posttraumatic stress disorder symptoms, self-identified problems, anger, health and productivity costs, and hair cortisol concentrations. A process evaluation will be carried out to evaluate treatment dose, protocol fidelity and stakeholder views on barriers and facilitators to implementing PM+. Results and Conclusions: PM+ has proved effectiveness in other populations and settings. After positive evaluation, the adapted manual and training materials for individual PM+ will be made available through the WHO to encourage further replication and scaling up. Trial registration: Trial registration Dutch Trial Registry, NL7552, registered prospectively on March 1, 2019. Medical Ethics Review Committee VU Medical Center Protocol ID 2017.320, 7 September 2017.
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    Protocol for a randomized controlled trial: peer-to-peer Group Problem Management Plus (PM+) for adult Syrian refugees in Turkey.
    Uygun, E ; Ilkkursun, Z ; Sijbrandij, M ; Aker, AT ; Bryant, R ; Cuijpers, P ; Fuhr, DC ; de Graaff, AM ; de Jong, J ; McDaid, D ; Morina, N ; Park, A-L ; Roberts, B ; Ventevogel, P ; Yurtbakan, T ; Acarturk, C ; STRENGHTS consortium, (Springer Science and Business Media LLC, 2020-03-20)
    BACKGROUND: A large proportion of Syrians have been exposed to potentially traumatic events, multiple losses, and breakdown of supportive social networks and many of them have sought refuge in host countries where they also face post-migration living difficulties such as discrimination or integration problems or both. These adversities may put Syrian refugees at high risk for common mental disorders. In response to this, the World Health Organization (WHO) developed a trans-diagnostic scalable psychological intervention called Problem Management Plus (PM+) to reduce psychological distress among populations exposed to adversities. PM+ has been adapted for Syrian refugees and can be delivered by non-specialist peer lay persons in the community. METHODS: A randomized controlled trial (RCT) will be conducted with 380 Syrian refugees in Turkey. After providing informed consent, participants with high levels of psychological distress (scoring above 15 on the Kessler-10 Psychological Distress Scale (K10)) and functional impairment (scoring above 16 on the WHO Disability Assessment Schedule 2.0, or WHODAS 2.0) will be randomly assigned to Group PM+/enhanced care as usual (Group PM+/E-CAU) (n = 190) or E-CAU (n = 190). Outcome assessments will take place 1 week after the fifth session (post-assessment), 3 months after the fifth session and 12 months after baseline assessment. The primary outcome is psychological distress as measured by the Hopkins Symptom Checklist (HSCL-25). Secondary outcomes include functional impairment, post-traumatic stress symptoms, self-identified problems, and health system and productivity costs. A process evaluation will be conducted to explore the feasibility, challenges and success of the intervention with 25 participants, including participants, facilitators, policy makers and mental health professionals. DISCUSSION: The treatment manual of the Syrian-Arabic Group PM+ and training materials will be made available through the WHO once the effectiveness and cost-effectiveness of Group PM+ have been established. TRIAL REGISTRATION: Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03960892. Unique protocol ID: 10/2017. Prospectively registered on 21 May 2019.
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    Thinking of attachment figures blocks differential fear conditioning
    Toumbelekis, M ; Liddell, BJ ; Bryant, RA (OXFORD UNIV PRESS, 2018-09)
    Thinking of attachment figures can potentially impact acquisition and extinction of fear memories. In this study, 50 participants underwent a fear conditioning and extinction paradigm. Half the participants thought about a supportive attachment figure and half thought about a non-attachment positive experience prior to the fear conditioning. All participants then underwent a differential fear conditioning and fear extinction paradigm, and returned 2 days later for an extinction recall task. Fear-potentiated startle and subjective expectancy of shock ratings were measured as the primary indicators of fear learning across trials. The attachment prime significantly reduced the acquisition of fear-potentiated startle, and this lower level of fear was maintained at the extinction recall task. These results demonstrate that attachment primes can modulate the acquisition of conditioned fear. These findings provide preliminary evidence for the protective nature of attachment relationships at times that are characterized by fear learning.