AIM: Cognitive impairments are a core feature of first-episode psychosis (FEP) and one of the strongest predictors of long-term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support. However, there are currently no validated screening measures for young people with FEP. CogScreen is a hybrid effectiveness-implementation study which aims to evaluate the classification accuracy (relative to a neuropsychological assessment as a reference standard), test-retest reliability and acceptability of two cognitive screening tools in young people with FEP. METHODS: Participants will be 350 young people (aged 12-25) attending primary and specialist FEP treatment centres in three large metropolitan cities (Adelaide, Sydney, and Melbourne) in Australia. All participants will complete a cross-sectional assessment over two sessions including two cognitive screening tools (Screen for Cognitive Impairment in Psychiatry and Montreal Cognitive Assessment), a comprehensive neuropsychological assessment battery, psychiatric and neurodevelopmental assessments, and other supplementary clinical measures. To determine the test-retest reliability of the cognitive screening tools, a subset of 120 participants will repeat the screening measures two weeks later. RESULTS: The protocol, rationale, and hypotheses for CogScreen are presented. CONCLUSIONS: CogScreen will provide empirical evidence for the validity and reliability of two cognitive screening tools when compared to a comprehensive neuropsychological assessment. The screening measures may later be incorporated into clinical practice to assist with rapid identification and treatment of cognitive deficits commonly experienced by young people with FEP.
BACKGROUND: Young people with mental ill-health experience higher rates of high-risk sexual behaviour, have poorer sexual health outcomes, and lower satisfaction with their sexual wellbeing compared to their peers. Ensuring good sexual health in this cohort is a public health concern, but best practice intervention in the area remains under-researched. This study aimed to co-design a novel intervention to address the sexual health needs of young people with mental ill-health to test its effectiveness in a future trial undertaken in youth mental health services in Melbourne, Australia. METHODS: We followed the 2022 Medical Research Council (MRC) guidelines for developing and evaluating complex interventions. This involved synthesising evidence from the 'top down' (published evidence) and 'bottom up' (stakeholder views). We combined systematic review findings with data elicited from qualitative interviews and focus groups with young people, carers, and clinicians and identified critical cultural issues to inform the development of our intervention. RESULTS: Existing evidence in the field of sexual health in youth mental health was limited but suggested the need to address sexual wellbeing as a concept broader than an absence of negative health outcomes. The Information-Motivation-Belief (IMB) model was chosen as the theoretical Framework on which to base the intervention. Interviews/focus groups were conducted with 29 stakeholders (18 clinicians, three carers, and eight young people). Synthesis of the evidence gathered resulted in the co-design of a novel intervention consisting of an initial consultation and four 60-90-minute sessions delivered individually by a young 'sex-positive' clinician with additional training in sexual health. Barriers and supports to intervention success were also identified. CONCLUSIONS: Using the MRC Framework has guided the co-design of a potentially promising intervention that addresses the sexual health needs of young people with mental ill-health. The next step is to test the intervention in a one-arm feasibility trial.
Mental Health Services , Sexual Health , Adolescent , Humans , Mental Health , Sexual Behavior , Health Promotion
AIM: Cognitive impairments negatively impact the everyday functioning of young people with mental illness. However, no previous study has asked young people (1) how much of a priority cognitive functioning is within mental health treatment, and (2) what types of cognition-focused treatments are most appealing. The current study aimed to address these questions. METHODS: Your Mind, Your Choice was a survey-based study involving an Australian sample of young people who were receiving mental health treatment. The survey asked participants to (1) provide demographic and mental health history, (2) rate the importance of 20 recovery domains, including cognition, when receiving mental health treatment, (3) share their experiences of cognitive functioning, and (4) rate their likelihood of trying 14 different behavioural, biochemical, and physical treatments that may address cognitive functioning. RESULTS: Two-hundred and forty-three participants (Mage = 20.07, SD = 3.25, range = 15-25, 74% female) completed the survey. Participants reported that addressing cognitive functioning in mental health care was very important (M = 76.33, SD = 20.7, rated on a scale from 0 = not important to 100 = extremely important), ranking cognition among their top six treatment needs. Seventy percent of participants reported experiencing cognitive difficulties, but less than one-third had received treatment for these difficulties. Compensatory training, sleep interventions and psychoeducation were ranked as treatments that participants were most likely to try to support their cognitive functioning. CONCLUSIONS: Young people with mental ill-health commonly experience cognitive difficulties and would like this to be a focus of treatment; however, this need is often unmet and should be a focus of research and implementation.
Cognitive Dysfunction , Mental Disorders , Humans , Female , Adolescent , Young Adult , Adult , Male , Australia , Mental Disorders/therapy , Mental Disorders/psychology , Mental Health , Cognitive Dysfunction/therapy , Cognition
BACKGROUND: Hospitals are insufficiently resourced to appropriately support young people who present with suicidal crises. Digital mental health innovations have the potential to provide cost-effective models of care to address this service gap and improve care experiences for young people. However, little is currently known about whether digital innovations are feasible to integrate into complex hospital settings or how they should be introduced for sustainability. OBJECTIVE: This qualitative study explored the potential benefits, barriers, and collective action required for integrating digital therapeutics for the management of suicidal distress in youth into routine hospital practice. Addressing these knowledge gaps is a critical first step in designing digital innovations and implementation strategies that enable uptake and integration. METHODS: We conducted a series of semistructured interviews with young people who had presented to an Australian hospital for a suicide crisis in the previous 12 months and hospital staff who interacted with these young people. Participants were recruited from the community nationally via social media advertisements on the web. Interviews were conducted individually, and participants were reimbursed for their time. Using the Normalization Process Theory framework, we developed an interview guide to clarify the processes and conditions that influence whether and how an innovation becomes part of routine practice in complex health systems. RESULTS: Analysis of 29 interviews (n=17, 59% young people and n=12, 41% hospital staff) yielded 4 themes that were mapped onto 3 Normalization Process Theory constructs related to coherence building, cognitive participation, and collective action. Overall, digital innovations were seen as a beneficial complement to but not a substitute for in-person clinical services. The timing of delivery was important, with the agreement that digital therapeutics could be provided to patients while they were waiting to be assessed or shortly before discharge. Staff training to increase digital literacy was considered key to implementation, but there were mixed views on the level of staff assistance needed to support young people in engaging with digital innovations. Improving access to technological devices and internet connectivity, increasing staff motivation to facilitate the use of the digital therapeutic, and allowing patients autonomy over the use of the digital therapeutic were identified as other factors critical to integration. CONCLUSIONS: Integrating digital innovations into current models of patient care for young people presenting to hospital in acute suicide crises is challenging because of several existing resource, logistical, and technical barriers. Scoping the appropriateness of new innovations with relevant key stakeholders as early as possible in the development process should be prioritized as the best opportunity to preemptively identify and address barriers to implementation.
BACKGROUND: Depression is common during adolescence and is associated with adverse educational, employment, and health outcomes in later life. Digital programs are increasingly being implemented in schools to improve and protect adolescent mental health. Although digital depression prevention programs can be effective, there is limited knowledge about how contextual factors influence real-world delivery at scale in schools. OBJECTIVE: The purpose of this study was to examine the contextual factors that influence the implementation of the Future Proofing Program (FPP) from the perspectives of school staff. The FPP is a 2-arm hybrid type 1 effectiveness-implementation trial evaluating whether depression can be prevented at scale in schools, using an evidence-based smartphone app delivered universally to year 8 students (13-14 years of age). METHODS: Qualitative interviews were conducted with 23 staff from 20 schools in New South Wales, Australia, who assisted with the implementation of the FPP. The interviews were guided by our theory-driven logic model. Reflexive thematic analysis, using both deductive and inductive coding, was used to analyze responses. RESULTS: Staff perceived the FPP as a novel ("innovative approach") and appropriate way to address an unmet need within schools ("right place at the right time"). Active leadership and counselor involvement were critical for planning and engaging; teamwork, communication, and staff capacity were critical for execution ("ways of working within schools"). Low student engagement and staffing availability were identified as barriers for future adoption and implementation by schools ("reflecting on past experiences"). CONCLUSIONS: Four superordinate themes pertaining to the program, implementation processes, and implementation barriers were identified from qualitative responses by school staff. On the basis of our findings, we proposed a select set of recommendations for future implementation of digital prevention programs delivered at scale in schools. These recommendations were designed to facilitate an organizational change and help staff to implement digital mental health programs within their schools. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2020-042133.
For people living with psychosis, cognitive impairment is common and can have significant impacts for functional recovery, impacting engagement with treatment and quality of life more broadly. There is now strong evidence for the effectiveness of cognition-focused treatments, such as cognitive remediation to improve clinical and functional outcomes for people with psychosis. However, engagement with treatment has been a long-standing issue in mental health care, including for people with psychosis, who often experience difficulties with motivation. While research on clinical effectiveness of cognition-focused treatment is growing, to date there has been little research focused on the implementation of such treatments and it is not clear how best to support uptake and engagement across diverse mental health settings. Implementation science is the study of methods and strategies to promote the adoption, application, and maintenance of evidence-based practices in routine care. To integrate cognition-focused treatments into routine practice, and improve engagement with treatment and the quality and effectiveness of care for people with psychosis, researchers need to embrace implementation science and research. This paper provides a succinct overview of the field of implementation science, current evidence for implementation of cognition-focused treatments for psychosis and practical guidance for using implementation science in clinical research. The future of psychosis research includes multidisciplinary teams of clinical researchers and implementation scientists, working together with providers and consumers to build the evidence that can improve the implementation of cognition-focused treatments.
Cognitive Dysfunction , Psychotic Disorders , Humans , Implementation Science , Quality of Life , Psychotic Disorders/complications , Psychotic Disorders/therapy , Mental Health , Cognitive Dysfunction/etiology , Cognitive Dysfunction/therapy
BACKGROUND: Climate change represents a serious threat to human health, including mental health, due to both the traumatizing effects of extreme climate events and the psychological effect of worry about climate change. OBJECTIVES: This scoping review aims to search the literature for original research investigating mental health and climate-related negative emotions in young people. Findings will help to understand the current landscape, gaps in the literature, and provide recommendations for future youth mental health research and practice. METHODS: A scoping review of the literature examining negative emotions associated with climate change in young people was undertaken. Studies published prior to March 2022 were included if they examined mental ill-health (e.g., symptoms of depression or anxiety) or negative emotions (e.g., distress, worry, concern) associated with the threat of climate change. RESULTS: Of 3939 articles screened, 26 met the inclusion criteria. Together, studies show that young people are worried about climate change. Negative emotions about climate change were correlated with symptoms of mental ill-health. Studies also explored coping strategies young people use to manage their distress caused by climate change. DISCUSSION: The limited literature in this area indicates a key gap in youth mental health research. While available evidence suggests that young people are concerned about climate change, more research is needed on the relationship between climate-related negative emotions and mental ill-health. Clinicians should assess for and address climate-related negative emotions in young people. Mental health leaders are urged to advocate for actions to mitigate the mental health impact of climate change.
Anxiety , Mental Health , Adolescent , Humans , Emotions , Adaptation, Psychological , Anxiety Disorders
Globally, mental illness and substance use disorders are the leading cause of disability and disease burden for young people. Orygen is an Australian youth mental health organisation with a mission to reduce the impact of mental ill health on young people, families and society, through research, clinical services, advocacy, and the design and delivery of youth mental health workforce and service development initiatives. Orygen is one of only a few known research and clinical centres with a dedicated knowledge translation division, which concentrates on growing the capacity of the systems, services, and professionals who support young people experiencing mental ill health. This paper provides a case study of the workforce development team within the Orygen knowledge translation, outlining how implementation science informs their work and how the division has adapted its model in the face of COVID-19. Since 2017, the team has delivered training to more than 4000 youth mental health workers across Australia, on the topics of trauma, psychosis, mood and anxiety disorders, brief interventions, cognition and other areas of youth mental health. The COVID-19 pandemic generated abrupt and dramatic changes to the delivery of workforce and service development initiatives in Australia due to significant restrictions to travel and in-person events. It also placed major delivery demands on youth mental health services. This paper outlines how the team at Orygen adapted their approach to youth mental health workforce development in response to COVID-19, offering reflections and future directions for implementation science that can support flexible models of support in a changing system.
Cognitive impairments in psychosis negatively impact functional recovery and quality of life. Existing interventions for improving cognitive impairment in recent-onset psychosis show inconsistent treatment efficacy, small effects, suboptimal engagement and limited generalizability to daily life functioning. In this perspective we explore how digital technology has the potential to address these limitations in order to improve cognitive and functional outcomes in recent-onset psychosis. Computer programs can be used for standardized, automated delivery of cognitive remediation training. Virtual reality provides the opportunity for learning and practicing cognitive skills in real-world scenarios within a virtual environment. Smartphone apps could be used for notification reminders for everyday tasks to compensate for cognitive difficulties. Internet-based technologies can offer psychoeducation and training materials for enhancing cognitive skills. Early findings indicate some forms of digital interventions for cognitive enhancement can be effective, with well-established evidence for human-supported computer-based cognitive remediation in recent-onset psychosis. Emerging evidence regarding virtual reality is favorable for improving social cognition. Overall, blending digital interventions with human support improves engagement and effectiveness. Despite the potential of digital interventions for enhancing cognition in recent-onset psychosis, few studies have been conducted to date. Implementation challenges affecting application of digital technologies for cognitive impairment in recent-onset psychosis are sustained engagement, clinical integration, and lack of quality in the commercial marketplace. Future opportunities lie in including motivational frameworks and behavioral change interventions, increasing service engagement in young people and lived experience involvement in digital intervention development.
Cognitive impairments associated with advanced age involve alterations in the hippocampus that changes with experience throughout life. The hippocampus is critical for cognitive flexibility involved with extinction and reinstatement of conditioned fear. It is widely accepted that regular exercise can be beneficial for hippocampal function. Therefore, we asked whether chronic voluntary exercise in middle-aged mice can improve extinction and/or reinstatement of conditioned fear compared with standard-housing. Eight-month-old male and female C57Bl/6J mice had access to a running wheel or remained in standard-housing until 11 months of age. Alongside control standard-housed young adult (3-month-old) mice, they received tone-footshock pairings, which were subsequently extinguished with tone-alone presentations the next day. Half of the mice then received a reminder in the form of a single footshock. Male and female 11-month-old mice housed in standard conditions exhibited impaired reinstatement compared with young adult mice. However, for males that had access to a running wheel from 8 months of age, the reminder treatment rescued reinstatement ability. This was not observed in females. Additionally, exercise during middle age in both sexes increased expression of brain-derived neurotrophic factor (Bdnf) mRNA in the hippocampus, specifically exon 4 mRNA. These results show that, at least for males, physical exercise is beneficial for reducing age-related decline in cognitive abilities. Despite not affecting reinstatement, exercise also increased Bdnf gene expression in the female hippocampus, which could potentially benefit other forms of hippocampus-dependent cognition.
Background: Tailoring implementation strategies to local contexts is a promising approach to supporting implementation and sustainment of evidence-based practices in health settings. While there is increasing research on tailored implementation of mental health interventions, implementation research on suicide prevention interventions is limited. This study aimed to evaluate implementation and subsequently develop a tailored action plan to support sustainment of an evidence-based suicide prevention intervention; Collaborative Assessment and Management of Suicidality (CAMS) in an Australian public mental health service. Methods: Approximately 150 mental health staff working within a regional and remote Local Health District in Australia were trained in CAMS. Semi-structured interviews and focus groups with frontline staff and clinical leaders were conducted to examine barriers and facilitators to using CAMS. Data were analysed using a reflexive thematic analysis approach and mapped to the Exploration, Preparation, Implementation and Sustainment (EPIS) framework and followed by stakeholder engagement to design a tailored implementation action plan based on a 'tailored blueprint' methodology. Results: A total of 22 barriers to implementing CAMS were identified. Based on the perceived impact on implementation fidelity and the feasibility of addressing identified barriers, six barriers were prioritised for addressing through an implementation action plan. These barriers were mapped to evidence-based implementation strategies and, in collaboration with local health district staff, goals and actionable steps for each strategy were generated. This information was combined into a tailored implementation plan to support the sustainable use of CAMS as part of routine care within this mental health service. Conclusions: This study provides an example of a collaborative approach to tailoring strategies for implementation on a large scale. Novel insights were obtained into the challenges of evaluating the implementation process and barriers to implementing an evidence-based suicide prevention treatment approach within a geographically large and varied mental health service in Australia. Plain language abstract: This study outlines the process of using a collaborative stakeholder engagement approach to develop tailored implementation plans. Using the Exploration Preparation Implementation Sustainment Framework, findings identify the barriers to and strategies for implementing a clinical suicide prevention intervention in an Australian community mental health setting. This is the first known study to use an implementation science framework to investigate the implementation of the clinical suicide prevention intervention (Collaborative Assessment and Management of Suicidality) within a community mental health setting. This work highlights the challenges of conducting implementation research in a dynamic public health service.
INTRODUCTION: Process evaluations provide insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the protocol for a process evaluation embedded in a cluster randomised trial of a digital depression prevention intervention delivered to secondary school students (the Future Proofing Study). The purpose is to describe the methods that will be used to capture process evaluation data within this trial. METHODS AND ANALYSIS: Using a hybrid type 1 design, a mixed-methods approach will be used with data collected in the intervention arm of the Future Proofing Study. Data collection methods will include semistructured interviews with school staff and study facilitators, automatically collected intervention usage data and participant questionnaires (completed by school staff, school counsellors, study facilitators and students). Information will be collected about: (1) how the intervention was implemented in schools, including fidelity; (2) school contextual factors and their association with intervention reach, uptake and acceptability; (3) how school staff, study facilitators and students responded to delivering or completing the intervention. How these factors relate to trial effectiveness outcomes will also be assessed. Overall synthesis of the data will provide school cluster-level and individual-level process outcomes. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of New South Wales (NSW) Human Research Ethics Committee (HC180836; 21st January 2019) and the NSW Government State Education Research Applications Process (SERAP 2019201; 19th August 2019). Results will be submitted for publication in peer-reviewed journals and discussed at conferences. Our process evaluation will contextualise the trial findings with respect to how the intervention may have worked in some schools but not in others. This evaluation will inform the development of a model for rolling out digital interventions for the prevention of mental illness in schools. TRIAL REGISTRATION NUMBER: ANZCTRN12619000855123; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377664&isReview=true.
Depression , School Health Services , Adolescent , Depression/prevention & control , Educational Status , Humans , Randomized Controlled Trials as Topic , Schools , Students
Adolescence marks a particularly vulnerable period to developing substance use disorders, and people who start using drugs in adolescence are more likely to relapse. A limited number of studies have investigated age difference in relapse following re-exposure to the drug after a period of abstinence. Using a cocaine self-administration paradigm, we showed no age difference in acquisition or extinction of self-administration. Interestingly, adolescent rats displayed impaired cocaine-primed reinstatement of cocaine seeking. Using the same dose as that self-administered in the first experiment, we then investigated age differences in acquisition and extinction of conditioned place preference, as well as locomotor sensitization. While there were no differences in locomotor activity or acquisition of preference, adolescents failed to extinguish their preference, even when the number of extinction sessions was doubled from what adults received. Taken together, these results suggest that while cocaine has similar rewarding and reinforcing effects regardless of age, adolescents may attribute stronger salience to the drug-associated context. In addition, re-exposure to cocaine itself may not be a strong relapse trigger in adolescence. Overall, these findings suggest that we should focus more on alleviating drug-context salience compared to re-exposure to substance in order to reduce relapse of drug seeking in adolescents.
Cocaine , Pharmaceutical Preparations , Animals , Conditioning, Classical , Extinction, Psychological , Rats , Self Administration
BACKGROUND: Internet-based Cognitive Behavioural Therapy (iCBT) is found effective in treating common mental disorders. However, the use of these interventions in routine care is limited. The international ImpleMentAll study is funded by the European Union's Horizon 2020 programme. It is concerned with studying and improving methods for implementing evidence-based iCBT services for common mental disorders in routine mental health care. A digitally accessible implementation toolkit (ItFits-toolkit) will be introduced to mental health care organizations with the aim to facilitate the ongoing implementation of iCBT services within local contexts. This study investigates the effectiveness of the ItFits-toolkit by comparing it to implementation-as-usual activities. METHODS: A stepped wedge cluster randomized controlled trial (SWT) design will be applied. Over a trial period of 30 months, the ItFits-toolkit will be introduced sequentially in twelve routine mental health care organizations in primary and specialist care across nine countries in Europe and Australia. Repeated measures are applied to assess change over time in the outcome variables. The effectiveness of the ItFits-toolkit will be assessed in terms of the degree of normalization of the use of the iCBT services. Several exploratory outcomes including uptake of the iCBT services will be measured to feed the interpretation of the primary outcome. Data will be collected via a centralized data collection system and analysed using generalized linear mixed modelling. A qualitative process evaluation of routine implementation activities and the use of the ItFits-toolkit will be conducted within this study. DISCUSSION: The ImpleMentAll study is a large-scale international research project designed to study the effectiveness of tailored implementation. Using a SWT design that allows to examine change over time, this study will investigate the effect of tailored implementation on the normalization of the use of iCBT services and their uptake. It will provide a better understanding of the process and methods of tailoring implementation strategies. If found effective, the ItFits-toolkit will be made accessible for mental health care service providers, to help them overcome their context-specific implementation challenges. TRIAL REGISTRATION: ClinicalTrials.gov NCT03652883 . Retrospectively registered on 29 August 2018.
Cognitive Behavioral Therapy , Mental Health Services , Australia , Europe , Humans , Internet , Randomized Controlled Trials as Topic
This paper reviews process evaluations associated with multilevel suicide prevention research trials. Process evaluations can provide important information about how multilevel suicide prevention models are implemented, their mechanisms of impact, and the context and elements of implementation that mediate effectiveness. Out of 42 papers identified, only four met selection criteria for including a process evaluation. Of these four, there was large variation in the level of detail provided, and only two studies specifically focused on the process of implementing a multilevelsuicide prevention model. Future trials should include targeted process evaluation, which can benefit a range of knowledge users.
Suicide Prevention , Humans , Program Evaluation
BACKGROUND: Despite increasing investment in suicide prevention, Australian suicide rates have increased steadily in the past decade. In response to growing evidence for multicomponent intervention models for reducing suicide, the LifeSpan model has been developed as the first multicomponent, evidence-based, system-wide approach to suicide prevention in Australia. The LifeSpan model consists of nine evidence-based strategies. These include indicated, selective and universal interventions which are delivered simultaneously to community and healthcare systems over a 2-year implementation period. This study will evaluate the effectiveness of the LifeSpan model in reducing suicide attempts and suicide deaths in four geographically defined regions in New South Wales, Australia. METHODS: We outline the protocol for a stepped-wedge, cluster randomized controlled trial. Following a 6-month transition phase, the trial sites will move to the 2-year active implementation phase in 4-monthly intervals with evaluation extending a minimum of 24 months after establishment of the full active period. Analysis will be undertaken of the change attributable to the invention across the four sites. The primary outcome for the study is the rate of attempted suicide in the regions involved. Rate of suicide deaths within each site is a secondary outcome. DISCUSSION: If proven effective, the LifeSpan model for suicide prevention could be more widely delivered in Australian communities, providing a valuable new approach to tackle rising suicide rates. LifeSpan has the potential to significantly contribute to the mental health of Australians by improving help-seeking for suicide, facilitating early detection, and improving aftercare to reduce re-attempts. The findings from this research should also contribute to the evidence base for multilevel suicide prevention programs internationally. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Register, ID: ACTRN12617000457347. Prospectively registered on 28 March 2017. https://www.anzctr.org.au/TrialSearch.aspx#&&conditionCode=&dateOfRegistrationFrom=&interventionDescription=&interventionCodeOperator=OR&primarySponsorType=&gender=&distance=&postcode=&pageSize=20&ageGroup=&recruitmentCountryOperator=OR Protocol Version: 1.0, 31 May 2019.
Mental Health/standards , Residence Characteristics/statistics & numerical data , Suicide, Attempted/prevention & control , Suicide, Attempted/psychology , Australia/epidemiology , Cluster Analysis , Early Diagnosis , Humans , Longevity , New South Wales/epidemiology , Research Design , Risk Factors , Suicide, Attempted/statistics & numerical data
Cue-associated learning is vital to guiding behaviour for survival. Adolescence represents a key developmental stage for perturbations in cue-related learning, including a characteristic deficit in cue extinction learning. The present review summarizes evidence from animal and human literature that cue extinction is critically mediated by prefrontal dopamine, a system that undergoes dramatic reorganization during adolescence. We propose that extinction learning and memory is governed by a developmentally dynamic balance of dopamine receptors in the prefrontal cortex, which changes across adolescence into adulthood. This is contrary to the previous idea that extinction deficits during adolescence reflect inefficiency in the same neural circuitry as adults. This leads to proposal of the novel theory that cue extinction involves divergent prefrontal dopaminergic mechanisms depending on the age of extinction.
Association , Dopamine/metabolism , Extinction, Psychological/physiology , Prefrontal Cortex/growth & development , Prefrontal Cortex/metabolism , Animals , Cues , Extinction, Psychological/drug effects , Fear/drug effects , Fear/physiology , Humans , Models, Neurological , Prefrontal Cortex/drug effects , Sexual Maturation
Anxiety disorders are the most common type of mental disorder during adolescence, which is at least partly due to the resistance to extinction exhibited at this age. The dopaminergic system is known to be dysregulated during adolescence; therefore, we aimed to facilitate extinction in adolescent rats using the dopamine receptor 2 partial agonist aripiprazole (Abilify™), and examine the behavioral and neural outcomes. Adolescent rats were conditioned to fear a tone. The next day, rats received extinction 30 min after a systemic injection of either 5 mg/kg aripiprazole or vehicle, and then were tested the following day. For the immunohistochemistry experiment, naïve and "no extinction" conditions were added and rats were perfused either on the extinction day or test day. To assess the activation of neurons receiving dopaminergic input, c-Fos, and dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) labeled neurons were quantified in the amygdala and the medial prefrontal cortex (mPFC). Systemic treatment with aripiprazole at the time of extinction significantly reduced freezing at test the next day. This effect was not observed in rats that were fear conditioned but did not receive any extinction. Aripiprazole's facilitation of extinction was accompanied by increased activation of neurons in the mPFC. Taken together, aripiprazole represents a novel pharmacological adjunct to exposure therapy worthy of further examination. The effect of aripiprazole is related to enhanced activation of mPFC neurons receiving dopaminergic innervation.
