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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    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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    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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    Effectiveness of Group Problem Management Plus (Group-PM+) for adults affected by humanitarian crises in Nepal: study protocol for a cluster randomized controlled trial.
    Van't Hof, E ; Sangraula, M ; Luitel, NP ; Turner, EL ; Marahatta, K ; van Ommeren, M ; Shrestha, P ; Bryant, R ; Kohrt, BA ; Jordans, MJD (Springer Science and Business Media LLC, 2020-04-19)
    BACKGROUND: Globally, the lack of availability of psychological services for people exposed to adversities has led to the development of a range of scalable psychological interventions with features that enable better scale-up. Problem Management Plus (PM+) is a brief intervention of five sessions that can be delivered by non-specialists. It is designed for people in communities in low- and middle-income countries (LMIC) affected by any kind of adversity. Two recent randomized controlled trials in Pakistan and Kenya demonstrated the effectiveness of individually delivered PM+. A group version of PM+ has been developed to make the intervention more scalable and acceptable. This paper describes the protocol for a cluster randomized controlled trial (c-RCT) on locally adapted Group PM+ in Nepal. METHODS/DESIGN: This c-RCT will compare Group PM+ to enhanced usual care (EUC) in participants with high levels of psychological distress recruited from the community. The study is designed as a two-arm, single-blind c-RCT that will be conducted in a community-based setting in Morang, a flood affected district in Eastern Nepal. Randomization will occur at ward level, the smallest administrative level in Nepal, with 72 enrolled wards allocated to Group PM+ or to EUC (ratio 1:1). Group PM+ consists of five approximately 2.5-h sessions, in which participants are taught techniques to manage their stressors and problems, and is delivered by trained and supervised community psychosocial workers (CPSWs). EUC consists of a family meeting with (a) basic information on adversity and mental health, (b) benefits of getting support, (c) information on seeking services from local health facilities with mhGAP-trained staff. The primary outcome measure is levels of individual psychological distress at endline (equivalent to 20 ± 1 weeks after baseline), measured by the General Health Questionnaire (GHQ-12). Secondary outcome measures include levels of functioning, depressive symptoms, post-traumatic stress disorder symptoms, levels of social support, somatic symptoms, and ways of coping. We hypothesize that skills acquired will mediate any impact of the intervention. DISCUSSION: This c-RCT will contribute to the growing evidence-base for transdiagnostic psychological interventions delivered by non-specialists for people in communities affected by adversity. If Group PM+ is proven effective, the intervention manual will be released for use, giving the opportunity for further adaptation and implementation of the intervention in diverse settings with communities that require better access to psychological interventions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03747055.
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    Valid ICD-11 PGD Scales and Structured Clinical Interviews Needed.
    O'Connor, M ; Larsen, L ; Joensen, BV ; Boelen, PA ; Maccallum, F ; Komischke-Konnerup, K ; Bryant, RA (Frontiers Media SA, 2020)
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    Feasibility of Group Problem Management Plus (PM plus ) to improve mental health and functioning of adults in earthquake-affected communities in Nepal
    Sangraula, M ; Turner, EL ; Luitel, NP ; van 't Hof, E ; Shrestha, P ; Ghimire, R ; Bryant, R ; Marahatta, K ; van Ommeren, M ; Kohrt, BA ; Jordans, MJD (CAMBRIDGE UNIV PRESS, 2020)
    AIMS: Psychological interventions that are brief, acceptable, effective and can be delivered by non-specialists are especially necessary in low- and middle-income countries, where mental health systems are unable to address the high level of psychosocial needs. Problem Management Plus (PM+) is a five-session intervention designed for those impaired by psychological distress while living in communities affected by adversity. Individual PM+ has demonstrated effectiveness in reducing distress in Kenya and Pakistan, and a group version of PM+ (Group PM+) was effective for conflict-affected women in Pakistan. This paper describes a feasibility and acceptability trial of locally adapted Group PM+ for women and men in an earthquake-affected region of rural Nepal. METHODS: In this feasibility cluster randomised controlled trial, participants in the experimental arm were offered five sessions of Group PM+ and participants in the control arm received enhanced usual care (EUC), which entailed brief psycho-education and providing referral options to primary care services with health workers trained in the mental health Gap Action Programme Intervention Guide (mhGAP-IG). A mixed-methods design was used to assess the feasibility and acceptability of Group PM+. Feasibility was assessed with criteria including fidelity and retention of participants. Acceptability was assessed through in-depth interviews with participants, family members, programme staff and other stakeholders. The primary clinical outcome was depression symptoms assessed using the Patient Health Questionnaire (PHQ-9) administered at baseline and 8-8.5 weeks post-baseline (i.e. after completion of Group PM+ or EUC). RESULTS: We recruited 121 participants (83% women and 17% men), with equal allocation to the Group PM+ and EUC arms (1:1). Group PM+ was delivered over five 2.5-3 hour sessions by trained and supervised gender-matched local non-specialists, with an average attendance of four out of five sessions. The quantitative and qualitative results demonstrated feasibility and acceptability for non-specialists to deliver Group PM+. Though the study was not powered to assess for effectiveness, for all five key outcome measures, including the primary clinical outcome, the estimated mean improvement was larger in the Group PM+ arm than the EUC arm. CONCLUSION: The intervention and trial procedures were acceptable to participants, family members, and programme staff. The communities and participants found the intervention to be beneficial. Because feasibility and acceptability were established in this trial, a fully powered randomised controlled trial will be conducted for larger scale implementation to determine the effectiveness of the intervention in Nepal.
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    Evaluating a screener to quantify PTSD risk using emergency care information: a proof of concept study.
    van der Mei, WF ; Barbano, AC ; Ratanatharathorn, A ; Bryant, RA ; Delahanty, DL ; deRoon-Cassini, TA ; Lai, BS ; Lowe, SR ; Matsuoka, YJ ; Olff, M ; Qi, W ; Schnyder, U ; Seedat, S ; Kessler, RC ; Koenen, KC ; Shalev, AY ; International Consortium to Predict PTSD, (Springer Science and Business Media LLC, 2020-03-02)
    BACKGROUND: Previous work has indicated that post-traumatic stress disorder (PTSD) symptoms, measured by the Clinician-Administered PTSD Scale (CAPS) within 60 days of trauma exposure, can reliably produce likelihood estimates of chronic PTSD among trauma survivors admitted to acute care centers. Administering the CAPS is burdensome, requires skilled professionals, and relies on symptoms that are not fully expressed upon acute care admission. Predicting chronic PTSD from peritraumatic responses, which are obtainable upon acute care admission, has yielded conflicting results, hence the rationale for a stepwise screening-and-prediction practice. This work explores the ability of peritraumatic responses to produce risk likelihood estimates of early CAPS-based PTSD symptoms indicative of chronic PTSD risk. It specifically evaluates the Peritraumatic Dissociative Experiences Questionnaire (PDEQ) as a risk-likelihood estimator. METHODS: We used individual participant data (IPD) from five acute care studies that used both the PDEQ and the CAPS (n = 647). Logistic regression calculated the probability of having CAPS scores ≥ 40 between 30 and 60 days after trauma exposure across the range of initial PDEQ scores, and evaluated the added contribution of age, sex, trauma type, and prior trauma exposure. Brier scores, area under the receiver-operating characteristic curve (AUC), and the mean slope of the calibration line evaluated the accuracy and precision of the predicted probabilities. RESULTS: Twenty percent of the sample had CAPS ≥ 40. PDEQ severity significantly predicted having CAPS ≥ 40 symptoms (p < 0.001). Incremental PDEQ scores produced a reliable estimator of CAPS ≥ 40 likelihood. An individual risk estimation tool incorporating PDEQ and other significant risk indicators is provided. CONCLUSION: Peritraumatic reactions, measured here by the PDEQ, can reliably quantify the likelihood of acute PTSD symptoms predictive of chronic PTSD and requiring clinical attention. Using them as a screener in a stepwise chronic PTSD prediction strategy may reduce the burden of later CAPS-based assessments. Other peritraumatic metrics may perform similarly and their use requires similar validation. TRIAL REGISTRATION: Jerusalem Trauma Outreach and Prevention Study (J-TOPS): NCT00146900.
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    Group problem management plus (gPM+) in the treatment of common mental disorders in Syrian refugees in a Jordanian camp: study protocol for a randomized controlled trial.
    Akhtar, A ; Giardinelli, L ; Bawaneh, A ; Awwad, M ; Naser, H ; Whitney, C ; Jordans, MJD ; Sijbrandij, M ; Bryant, RA ; STRENGTHS Consortium, (Springer Science and Business Media LLC, 2020-03-26)
    BACKGROUND: Accessing quality mental health care poses significant challenges for persons affected by adversity, especially in low- and middle-income countries where resources are scarce. To mitigate this, the World Health Organization has developed group problem management plus (gPM+), a low-intensity psychological intervention for adults experiencing psychological distress. gPM+ is a group-based intervention consisting of five-sessions, and can be delivered by non-specialist providers. This paper outlines the study protocol for a trial of gPM+ in Jordan. METHODS: We will conduct a single-blind, two-arm, randomized controlled trial in a Syrian refugee camp in Jordan. We aim to enrol 480 adults into the trial. Participants will be eligible for the trial if they screen positive for levels of psychological distress. Following screening, those eligible will be randomly assigned to receive the gPM+ intervention or enhanced treatment as usual. The primary outcome is reduction in levels of psychological distress at 3-months post-treatment. Secondary outcomes include anxiety, depression, prodromal psychotic symptoms, posttraumatic stress disorder, prolonged grief, daily functioning, economic effectiveness, and change in parenting behaviour. Secondary outcomes also include the reduction in psychological distress of the participant's child. DISCUSSION: The trial aims to deliver a template for affordable and scalable psychosocial interventions that can readily be implemented in refugee settings, and that can benefit both the participant and their child. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619001386123. Registered prospectively on 10/10/2019.
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    Improving mental health and psychosocial wellbeing in humanitarian settings: reflections on research funded through R2HC.
    Tol, WA ; Ager, A ; Bizouerne, C ; Bryant, R ; El Chammay, R ; Colebunders, R ; García-Moreno, C ; Hamdani, SU ; James, LE ; Jansen, SCJ ; Leku, MR ; Likindikoki, S ; Panter-Brick, C ; Pluess, M ; Robinson, C ; Ruttenberg, L ; Savage, K ; Welton-Mitchell, C ; Hall, BJ ; Harper Shehadeh, M ; Harmer, A ; van Ommeren, M (Springer Science and Business Media LLC, 2020-10-30)
    Major knowledge gaps remain concerning the most effective ways to address mental health and psychosocial needs of populations affected by humanitarian crises. The Research for Health in Humanitarian Crisis (R2HC) program aims to strengthen humanitarian health practice and policy through research. As a significant portion of R2HC's research has focused on mental health and psychosocial support interventions, the program has been interested in strengthening a community of practice in this field. Following a meeting between grantees, we set out to provide an overview of the R2HC portfolio, and draw lessons learned. In this paper, we discuss the mental health and psychosocial support-focused research projects funded by R2HC; review the implications of initial findings from this research portfolio; and highlight four remaining knowledge gaps in this field. Between 2014 and 2019, R2HC funded 18 academic-practitioner partnerships focused on mental health and psychosocial support, comprising 38% of the overall portfolio (18 of 48 projects) at a value of approximately 7.2 million GBP. All projects have focused on evaluating the impact of interventions. In line with consensus-based recommendations to consider a wide range of mental health and psychosocial needs in humanitarian settings, research projects have evaluated diverse interventions. Findings so far have both challenged and confirmed widely-held assumptions about the effectiveness of mental health and psychosocial interventions in humanitarian settings. They point to the importance of building effective, sustained, and diverse partnerships between scholars, humanitarian practitioners, and funders, to ensure long-term program improvements and appropriate evidence-informed decision making. Further research needs to fill knowledge gaps regarding how to: scale-up interventions that have been found to be effective (e.g., questions related to integration across sectors, adaptation of interventions across different contexts, and optimal care systems); address neglected mental health conditions and populations (e.g., elderly, people with disabilities, sexual minorities, people with severe, pre-existing mental disorders); build on available local resources and supports (e.g., how to build on traditional, religious healing and community-wide social support practices); and ensure equity, quality, fidelity, and sustainability for interventions in real-world contexts (e.g., answering questions about how interventions from controlled studies can be transferred to more representative humanitarian contexts).