Trace amine associated receptor 1: predicted effects of single nucleotide variants on structure-function in geographically diverse populations.

Trace Amine Associated Receptor 1 (TAAR1) is a novel pharmaceutical target under investigation for the treatment of several neuropsychiatric conditions. TAAR1 single nucleotide variants (SNV) have been found in patients with schizophrenia and metabolic disorders. However, the frequency of variants in geographically diverse populations and the functional effects of such variants are unknown. In this study, we aimed to characterise the distribution of TAAR1 SNVs in five different WHO regions using the Database of Genotypes and Phenotypes (dbGaP) and conducted a critical computational analysis using available TAAR1 structural data to identify SNVs affecting ligand binding and/or functional regions. Our analysis shows 19 orthosteric, 9 signalling and 16 micro-switch SNVs hypothesised to critically influence the agonist induced TAAR1 activation. These SNVs may non-proportionally influence populations from discrete regions and differentially influence the activity of TAAR1-targeting therapeutics in genetically and geographically diverse populations. Notably, our dataset presented with orthosteric SNVs D1033.32N (found only in the South-East Asian Region and Western Pacific Region) and T1945.42A (found only in South-East Asian Region), and 2 signalling SNVs (V1253.54A/T2526.36A, found in African Region and commonly, respectively), all of which have previously demonstrated to influence ligand induced functions of TAAR1. Furthermore, bioinformatics analysis using SIFT4G, MutationTaster 2, PROVEAN and MutationAssessor predicted all 16 micro-switch SNVs are damaging and may further influence the agonist activation of TAAR1, thereby possibly impacting upon clinical outcomes. Understanding the genetic basis of TAAR1 function and the impact of common mutations within clinical populations is important for the safe and effective utilisation of novel and existing pharmacotherapies.

Seven decades of antipsychotic drugs: Why is the life of Australians with schizophrenia still so suboptimal?

The advent of dopamine (D2) receptor-blocking medications over 70 years ago, ushered in a new era of biological treatment for schizophrenia. However, we argue that little subsequent progress has been made in translating this into fulfilled and fulfilling lives for people with schizophrenia. This Viewpoint asks why this is the case, and suggests ways forward for capitalising on extant and emerging new treatments for psychotic disorders, to the betterment of the lives of people living with schizophrenia.

Practical psychiatry: On therapeutic equipoise - Principles of a balanced approach to psychiatric treatments.

OBJECTIVE: There are many burgeoning treatments, and a large range of therapeutic options for 21st century psychiatry. This paper briefly comments upon considerations for balancing treatment to suit the patient, their illness, and their milieu. CONCLUSIONS: Therapeutic equipoise, for psychiatric care, is an aspiration rather than a position easily achieved. In day-to-day clinical practice, there will be unexpected demands and barriers that cannot always be accommodated or surmounted. Psychiatrists can work collaboratively with patients, carers, and colleagues in conceptualising and care-planning to avoid extremes of therapeutic hubris and despair, and to adapt evidence-based care more effectively so that it is suited to the patient and their circumstances.

Unpeeling the onion: Digital triage and monitoring of general practice, private psychiatry, and psychology.

OBJECTIVE: The Australian federal government is considering a 'digital front door' to mental healthcare. The Brain and Mind Centre at the University of Sydney has published a discussion paper advocating that the government should adopt a comprehensive model of digital triage and monitoring (DTM) based on a government-funded initiative Project Synergy ($30 million). We critically examine the final report on Project Synergy, which is now available under a Freedom of Information request. CONCLUSION: The DTM model is disruptive. Non-government organisations would replace general practitioners as care coordinators. Patients, private psychiatrists, and psychologists would be subjected to additional layers of administration, assessment, and digital compliance, which may decrease efficiency, and lengthen the duration of untreated illness. Only one patient was deemed eligible for DTM, however, during the 8-month regional trial of Project Synergy (recruitment rate = 1/500,000 across the region). Instead of an unproven DTM model, the proposed 'digital front door' to Australian mental healthcare should emphasise technology-enabled shared care (general practitioners and mental health professionals) for the treatment of moderate-to-severe illness.

The 2024-2025 Commonwealth Budget for Mental Health: Funding unproven initiatives and stings in the tail.

We discuss the ramifications of the Commonwealth of Australia Budget allocations for mental healthcare for 2024-2025. There is funding for population-based mental health initiatives for milder anxiety and depression but no direct funding of services for the most severe and disabling forms of mental illness, other than pre-existing state/territory disbursements from the Commonwealth for state-based health services. There are substantial concerns that the Commonwealth funding has potentially been misallocated to ineffective interventions that are unlikely to reduce the population prevalence of mild anxiety and depression in Australia. Funds may have been better allocated to provide effective care for those with the most severe and disabling illnesses including schizophrenia, bipolar disorder and severe depression.

Practical psychiatry: Taking gaming seriously - a primer for psychiatrists on gamers and gaming culture.

OBJECTIVE: Up to three billion, of the eight billion people in the world, play videogames. Gaming is a significant global sociocultural influence. This primer will aid psychiatrists in understanding sociocultural milieux of gamers, who include patients and their communities. METHOD: A rapid narrative review. RESULTS: Benefits include expression of personality, identity and culture through social aspects of gaming. Improved physical health, neurocognition, self-efficacy and quality of life are associated with gaming in those with certain mental health disorders including schizophrenia. Harms may include in-game discrimination, disordered gaming, as well as encouragement of online gambling. There is no longitudinal association between violent games and youth aggression. CONCLUSIONS: Psychiatrists should enquire about gaming as part of the sociocultural milieux of patients' lives, and the perceived mental health benefits and harms of gaming.

Behind the curtain of Australasian Psychiatry: The practice of a medical journal and a call for reviewers.

The process of medical scientific journal publishing merits further explanation for authors and readers. Prospective authors need to understand the scope of the journal and the article types that are published. We give an overview of the editorial process, including selection of reviewers, peer review and decisions regarding revision, acceptance and rejection of papers for Australasian Psychiatry. We encourage authors and readers to submit papers, and volunteer as peer reviewers, working together with the journal editorial team.

Healthcare provider data breaches - framework for crisis communication and support of patients and healthcare workers in mental healthcare.

Increasing numbers of healthcare data breaches highlight the need for structured organisational responses to protect patients, trainees and psychiatrists against identity theft and blackmail. Evidence-based guidance that is informed by the COVID-19 pandemic response includes: timely and reliable information tailored to users' safety, encouragement to take protective action, and access to practical and psychological support. For healthcare organisations which have suffered a data breach, insurance essentially improves access to funded cyber security responses, risk communication and public relations. Patients, trainees and psychiatrists need specific advice on protective measures. Healthcare data security legislative reform is urgently needed.

The RANZCP Workforce Report: Action is needed, now.

OBJECTIVE: The RANZCP conducted an anonymous survey of 7200 members (trainees and psychiatrists) in December 2023, receiving 1269 responses, representing the views of roughly 1 in 6 members, and of the respondents, three quarters reported experiencing burnout in the last 3 years. We provide a commentary, citing evidence from relevant previous research, discussing the implications and proposing potential interventions. CONCLUSIONS: Members of the RANZCP reported worsening workforce shortages, with 9 in 10 respondents stating that these negatively impacted patient care, and 7 in 10 experiencing symptoms of burnout. Eighty per cent identified workforce shortages as the top contributing factor to such burnout. The aetiology of workforce shortages and burnout is likely due to operational and structural shortfalls in psychiatric services. However, public and private sector employment information was not included in the report. There are a range of strategic, evidence-based interventions to address the psychiatrist and trainee workforce challenges, comprising general healthcare service as well as specific initiatives. Based on the findings of the report, such interventions are needed, now.

Psychiatric electronic health records in the era of data breaches - What are the ramifications for patients, psychiatrists and healthcare systems?

OBJECTIVE: To update psychiatrists and trainees on the realised risks of electronic health record data breaches. METHODS: This is a selective narrative review and commentary regarding electronic health record data breaches. RESULTS: Recent events such as the Medibank and Australian Clinical Labs data breaches demonstrate the realised risks for electronic health records. If stolen identity data is publicly released, patients and doctors may be subject to blackmail, fraud, identity theft and targeted scams. Medical diagnoses of psychiatric illness and substance use disorder may be released in blackmail attempts. CONCLUSIONS: Psychiatrists, trainees and their patients need to understand the inevitability of electronic health record data breaches. This understanding should inform a minimised collection of personal information in the health record to avoid exposure of confidential information and identity theft. Governmental regulation of electronic health record privacy and security is needed.

Comparison of the out-of-pocket costs of Medicare-funded telepsychiatry and face-to-face consultations: A descriptive study.

OBJECTIVE: Telepsychiatry items in the Australian Medicare Benefits Schedule (MBS) were expanded following the COVID-19 pandemic. However, their out-of-pocket costs have not been examined. We describe and compare patient out-of-pocket payments for face-to-face and telepsychiatry (videoconferencing and telephone) MBS items for outpatient psychiatric services to understand the differential out-of-pocket cost burden for patients across these modalities. METHODS: out-of-pocket cost information was obtained from the Medical Costs Finder website, which extracted data from Services Australia's Medicare claims data in 2021-2022. Cost information for corresponding face-to-face, video, and telephone MBS items for outpatient psychiatric services was compared, including (1) Median specialist fees; (2) Median out-of-pocket payments; (3) Medicare reimbursement amounts; and (4) Proportions of patients subject to out-of-pocket fees. RESULTS: Medicare reimbursements are identical for all comparable face-to-face and telepsychiatry items. Specialist fees for comparable items varied across face-to-face to telehealth options, with resulting differences in out-of-pocket costs. For video items, higher proportions of patients were not bulk-billed, with greater out-of-pocket costs than face-to-face items. However, the opposite was true for telephone items compared with face-to-face items. CONCLUSIONS: Initial cost analyses of MBS telepsychiatry items indicate that telephone consultations incur the lowest out-of-pocket costs, followed by face-to-face and video consultations.

Comparing the trends of MBS telepsychiatry and consultant physician telehealth services from 2017 to 2022: A retrospective study.

OBJECTIVE: The Medicare Benefit Schedule (MBS) telehealth items were expanded in March 2020 during the COVID-19 pandemic. We measured the use of MBS telepsychiatry items compared to consultant physician telehealth items within the context of these item changes, to understand differences in telepsychiatry and physician telehealth utilisation. METHODS: Monthly counts of face-to-face and telehealth (videoconferencing and telephone) MBS items for psychiatrists and physicians from January 2017 to December 2022 were compiled from Services Australia MBS Item Reports. Usage levels were compared before and after telehealth item expansion. Usage trends for MBS telepsychiatry and physician telehealth items were compared in time-series plots. RESULTS: Telehealth item expansion resulted in a greater rise of telepsychiatry services from 3.8% beforehand to 43.8% of total services subsequently, compared with physician telehealth services (from 0.6% to 20.0%). More physician telehealth services were by telephone compared with telepsychiatry services. Time-series of both telehealth services displayed similar patterns until mid-2022, when physician telehealth services declined as telephone items were restricted. Telepsychiatry services consistently comprised a greater proportion of total services than physician telehealth services. CONCLUSIONS: MBS psychiatrist services showed a more substantial and persistent shift to telehealth than physician services, suggesting a greater preference and use of telepsychiatry.

The changing psychiatry workforce in Australia: Still lacking in rural and remote regions.

INTRODUCTION: There is a long standing and worsening shortage of psychiatrists in Australia particularly in rural areas. The majority of psychiatrists work in major cities. OBJECTIVE: To identify recent trends in the Australian rural psychiatrist workforce compared with the metropolitan workforce. DESIGN: We descriptively analysed population-level data from the National Health Workforce Data Set (NHWDS), the Australian Institute of Health and Welfare (AIHW) and the Australian Bureau of Statistics (ABS). A descriptive analysis of the numbers (count) and gender of psychiatrists from 1995 to 2022 working in Australia was conducted. For the period 2013 to 2022, we analysed for rurality, gender, years' experience, hours worked, Medicare-subsidised services provided and proportions of Specialist International Medical Graduates (SIMG) by sex, with a focus on the rural workforce. For international comparison, psychiatrist numbers were obtained for other OECD countries. The number of psychiatrists working in Australia, as per NHWDS and AIHW, was quantified. We analysed trends in demographics, hours worked and rurality of psychiatrists working in Australia in a serial cross-sectional design. FINDINGS: Most psychiatrists are maldistributed to major cities, while outer regional and remote areas have few resident psychiatrists. Outer regional New South Wales (NSW) and South Australia (SA) have the lowest numbers of psychiatrists per capita. The full-time equivalent (FTE) of psychiatrists per 100 000 has increased from 12.6 in 2000 to 15.2 in 2022. However, the average hours worked by psychiatrists has declined. In total, available psychiatrist hours worked per 100 000 population has increased by 6.1% since the beginning of the millennium. DISCUSSION: Rural areas in NSW and SA have the greatest shortage of psychiatrists. Specialist International Medical Graduates and females (43% of the overall workforce) are the predominant workforce in rural areas. Although Medicare-subsidised services per 1000 people have increased in rural areas, they remain lower than for those living in major cities. CONCLUSION: There remains an acute shortage of psychiatrists in many regional and remote areas of Australia, with an increasing proportion of SIMGs and females working in these areas, in the context of future increased demand.

Binding of SEP-363856 within TAAR1 and the 5HT1A receptor: implications for the design of novel antipsychotic drugs.

Current medications for schizophrenia typically modulate dopaminergic neurotransmission. While affecting positive symptoms, antipsychotic drugs have little clinical effect on negative symptoms and cognitive impairment. Moreover, newer 'atypical' antipsychotic drugs also have significant metabolic adverse-effects. The recent positive clinical trial of the novel drug candidate SEP-363856, which targets non-dopamine receptors (trace amine-associated receptor and the 5HT1A receptor), is a potentially promising development for the management of schizophrenia. In this perspective, we briefly overview the role of TAAR1 and the 5HT1A receptor in schizophrenia and explore the specific binding characteristics of SEP-363856 at these receptors. Molecular dynamics simulations (MDS) indicate that SEP-363856 interacts with a small, common set of conserved residues within the TAAR1 and 5HT1A ligand-binding domain. The primary interaction of SEP-363856 involves binding to the negatively charged aspartate residue (Asp1033.32, TAAR1; Asp1163.32, 5HT1A). In general, the binding of SEP-363856 within TAAR1 involves a greater number of aromatic contacts compared to 5HT1A. MDS provides important insights into the molecular basis of binding site interactions of SEP-363856 with TAAR1 and the 5HT1A receptor, which will be beneficial for understanding the pharmacological uniqueness of SEP-363856 and for the design of novel drug candidates for these newly targeted receptors in the treatment of schizophrenia and related disorders.

Minimum and optimal numbers of psychiatric beds: expert consensus using a Delphi process.

The required minimum number of psychiatric inpatient beds is highly debated and has substantial resource implications. The present study used the Delphi method to try to reach a global consensus on the minimum and optimal psychiatric bed numbers. An international board of scientific advisors nominated the Delphi panel members. In the first round, the expert panel provided responses exploring estimate ranges for a minimum to optimal numbers of psychiatric beds and three levels of shortage. In a second round, the panel reconsidered their responses using the input from the total group to achieve consensus. The Delphi panel comprised 65 experts (42% women, 54% based in low- and middle-income countries) from 40 countries in the six regions of the World Health Organization. Sixty psychiatric beds per 100 000 population were considered optimal and 30 the minimum, whilst 25-30 was regarded as mild, 15-25 as moderate, and less than 15 as severe shortage. This is the first expert consensus on minimum and optimal bed numbers involving experts from HICs and LMICs. Many high-income countries have psychiatric bed numbers that fall within the recommended range. In contrast, the number of beds in many LMIC is below the minimum recommended rate.

Effects of the antipsychotic quetiapine on sleep and breathing: a review of clinical findings and potential mechanisms.

Quetiapine is an antipsychotic medication indicated for schizophrenia and bipolar disorder. However, quetiapine also has hypnotic properties and as such is increasingly being prescribed at low doses 'off-label' in people with insomnia symptoms. Pharmacologically, in addition to its dopaminergic properties, quetiapine also modulates multiple other transmitter systems involved in sleep/wake modulation and potentially breathing. However, very little is known about the impact of quetiapine on obstructive sleep apnoea (OSA), OSA endotypes including chemosensitivity, and control of breathing. Given that many people with insomnia also have undiagnosed OSA, it is important to understand the effects of quetiapine on OSA and its mechanisms. Accordingly, this concise review covers the existing knowledge on the effects of quetiapine on sleep and breathing. Further, we highlight the pharmacodynamics of quetiapine and its potential to alter key OSA endotypes to provide potential mechanistic insight. Finally, an agenda for future research priorities is proposed to fill the current key knowledge gaps.

Indigenous suicide rates in the United States, Australia and New Zealand between 2006 and 2019.

OBJECTIVE: Indigenous suicide prevention is an important focus for national health policies. Indigenous suicide rates in formerly colonial English-speaking countries such as the United States, Australia and New Zealand are considerably higher than the general population, particularly in young males. Given the similarities in their sociocultural history, a time series analysis was conducted to assess recent sex and age trends of suicide in the Indigenous and general populations in the United States, Australia and New Zealand. METHODS: Using the number of deaths by intentional self-harm and estimated resident population, suicide incidence rates were calculated for the years 2006-2019 and stratified by Indigenous status, year, time period, sex and age group (above 15 years). Incidence rates were plotted. Using the Poisson regression model, calculated suicide incidence rate ratios were used to make comparisons for sex and age. RESULTS: Across all countries studied, Indigenous suicide rates have increased over time, with Indigenous males having higher suicide rates than Indigenous females. However, the increase in Indigenous female suicides was greater than that for Indigenous males in Australia and New Zealand. Indigenous males aged 15-44 years have the highest suicide rates across all countries. CONCLUSION: Indigenous suicide rates have remained consistently high in the United States, Australia and New Zealand, with Indigenous males aged 15-44 years showing the highest rate. However, suicide rates for Indigenous females in Australia and New Zealand are increasing more rapidly than males. Given this, it is critical that further research is dedicated to understanding and addressing the issues driving this problem, particularly in youth.

Remaining on course, online: Reflections and recommendations on more effective psychiatrist participation in online chat forums in the context of social media dynamics.

OBJECTIVE: To provide a synthesis of psychiatrist experience, online resources, and peer-reviewed literature to document benefits and challenges, and thus derive recommendations on participating in professional psychiatrist online chat forums. CONCLUSIONS: Psychiatrists should carefully consider and curate their participation in online chat forums. Convivial discourse, including shared interests, knowledge, and skills are benefits. However, social media dynamics influence online roles and behaviour. There is a performative aspect to chat forums and social media, through depiction of a participant's persona, which can be understood through social avatar theory. Even on well-moderated chat forums, there remain the risks of subtle forms of negative social media roles and behaviour (e.g. cyberbullying, online abuse, and trolling). Furthermore, there are potential risks to professional identity and reputation from posting material as well as others commenting upon psychiatrists' posts. A single unprofessional post can have a devastating impact on reputation. There are also opportunity costs from the time, attentional and emotional costs of following a forum, which can also lead to harms from anxiety and depression due to excessive social media use. We provide practical recommendations on e-professionalism for more effective participation online.

Clinical update and commentary on psychiatric care for patients experiencing workplace bullying.

OBJECTIVE: To provide a brief clinical research update and commentary advice on the practical psychiatric care of patients suffering workplace bullying. CONCLUSIONS: While there is empirical research on the prevalence and impacts of workplace bullying, there is a relative dearth of clinical research into psychiatric patient care. Accordingly, we provide commentary on practical considerations that assist in psychiatric care planning and delivery.

Considering patient narrative-based and medico-scientific epistemologies in framing psychiatric care.

OBJECTIVE: Personal narratives of lived experience with psychiatric illness and distress remain central in the epistemology of mental illness. We provide a commentary on this potential bridging of patient narrative-based epistemology, and medico-scientific epistemology used by psychiatrists used for diagnosis, formulation, prognosis and treatment. CONCLUSION: Discussion and planning of psychiatric care can be framed by understanding the narrative-based epistemology of a patient's illness as highlighted by five key questions to explore the patient's illness explanatory models. We propose five key questions for the psychiatrist's complementary consideration of medico-scientific epistemology that frame conceptual models of aetiology, pathophysiology, diagnosis, formulation, prognosis and treatment, which are embedded in the predominant socio-cultural environment. These questions assist in bridging patient narrative and medico-scientific explanatory models to facilitate more effective collaborative care planning.