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Objective: This study investigates (1) the proportion of people with psychosis who are on long-acting injectable antipsychotics; (2) the difference in the demographic, clinical, substance use and adverse drug reaction profiles of people taking long-acting injectables compared to oral antipsychotics; and (3) the differences in the same profiles of those on first-generation antipsychotic versus second-generation antipsychotic long-acting injectables. Methods: Data were collected as part of the Survey of High Impact Psychosis. For this study, participants with diagnoses of schizophrenia or schizoaffective disorder who were on any antipsychotic medication were included ( N = 1049). Results: Nearly a third (31.5%) of people with psychosis were on long-acting injectables, of whom 49.7% were on first-generation antipsychotic long-acting injectables and 47.9% were on second-generation antipsychotic long-acting injectables. This contrasts with oral antipsychotics where there was a higher utilisation of second-generation antipsychotics (86.3%). Of note, compared to those on the oral formulation, people on long-acting injectables were almost four times more likely to be under a community treatment order. Furthermore, people on long-acting injectables were more likely to have a longer duration of illness, reduced degree of insight, increased cognitive impairment as well as poor personal and social functioning. They also reported more adverse drug reactions. Compared to those on first-generation antipsychotic long-acting injectables, people on SGA long-acting injectables were younger and had had a shorter duration of illness. They were also more likely to experience dizziness and increased weight, but less likely to experience muscle stiffness or tenseness. Conclusion: Long-acting injectable use in Australia is associated with higher rates of community treatment order use, as well as poorer insight, personal and social performance, and greater cognitive impairment. While long-acting injectables may have the potential to improve the prognosis of people with psychosis, a better understanding of the choices behind the utilisation of long-acting injectable treatment in Australia is urgently needed.

The predominant assay detection methodologies used for enzyme inhibitor identification during early-stage drug discovery are fluorescence-based. Each fluorophore has a characteristic fluorescence decay, known as the fluorescence lifetime, that occurs throughout a nanosecond-to-millisecond timescale. The measurement of fluorescence lifetime as a reporter for biological activity is less common than fluorescence intensity, even though the latter has numerous issues that can lead to false-positive readouts. The confirmation of hit compounds as true inhibitors requires additional assays, cost, and time to progress from hit identification to lead drug-candidate optimization. To explore whether the use of fluorescence lifetime technology (FLT) can offer comparable benefits to label-free-based approaches such as RapidFire mass spectroscopy (RF-MS) and a superior readout compared to time-resolved fluorescence resonance energy transfer (TR-FRET), three equivalent assays were developed against the clinically validated tyrosine kinase 2 (TYK2) and screened against annotated compound sets. FLT provided a marked decrease in the number of false-positive hits when compared to TR-FRET. Further cellular screening confirmed that a number of potential inhibitors directly interacted with TYK2 and inhibited the downstream phosphorylation of the signal transducer and activator of transcription 4 protein (STAT4).

Although the inclusion of individuals with lived experience is encouraged within the research process, there remains inconsistent direct involvement in many mental health fields. Within the eating disorders field specifically, there is a very strong and increasing presence of lived experience advocacy. However, due to a number of potential challenges, research undertaken in consultation or in collaboration with individuals with lived experience of an eating disorder is scarce. This paper describes the significant benefits of the inclusion of individuals with lived experience in research. The specific challenges and barriers faced in eating disorders research are also outlined. It is concluded that in addition to existing guidelines on working with lived experience collaborators in mental health research, more specific procedures are required when working with those with eating disorders.

Highlights • Current data characterizes the mental health and wellbeing of the Australian general. public during the initial stages of the COVID-19 pandemic. • The most prevalent concerns were about the health and wellbeing of loved ones. • There were high levels of negative emotions (depression, stress and anxiety) in the Australian general public. • Being young, female and having a mental illness diagnosis were risk factors for increased negative emotions. • Increased mental health support will be of paramount importance as the world faces the consequences of the COVID-19 pandemic., The novel coronavirus disease (COVID-19) poses mental health challenges globally; however, to date, there is limited community level data. This study reports on the COLLATE project (COvid-19 and you: mentaL heaLth in AusTralia now survEy), an ongoing study aimed at understanding the impact of the COVID-19 pandemic on Australian mental health and well-being. We addressed prevailing primary concerns related to the COVID-19 pandemic, current levels of negative emotions and risk factors predicting negative emotions. On April 1st to 4th 2020, 5158 adults from the general public completed an online survey. Participants ranked their top ten current primary concerns about COVID-19, and completed standardized measures of negative emotions. The top three primary concerns were related to health and well-being of family and loved ones. Levels of negative emotion were high. Modelling of predictors of negative emotions established several risk factors related to demographic variables, personal vulnerabilities, financial stresses, and social distancing perceptions; particularly being young, female, or having a mental illness diagnosis. The data provides important characterization of the current Australian mental health. It appears that specific groups may need special attention to ensure their mental health is protected. These results may provide direction for international researchers characterizing similar issues.

The mental health consequences of the COVID-19 pandemic have been significant in Australia. The aim of this study was to investigate coping strategies that individuals have adopted to assist them through this stressful period. Survey data collected in September and December 2020 as part of a larger study (the COLLATE project) was analysed. The number of adaptive coping strategies endorsed by respondents had a significant negative relationship with depression and a significant positive relationship with resilience. Females tended to use more of these strategies than men, as did people who said their mental health had improved rather than deteriorated because of the COVID-19 restrictions imposed by government. Specific adaptive coping strategies differed for those with and without a mental illness. People with a mental illness were more likely to seek professional and online help, while people without a mental illness were more likely to use self-help. Focusing on what one is grateful for and keeping oneself productively occupied (“using the time to do things around the house”) were the most beneficial coping strategies in terms of alleviating depression, anxiety and stress. Public health messaging promoting adaptive coping strategies may be useful in bolstering the mental health of individuals during lockdown periods. In particular, the promotion of coping flexibility should be recommended rather than the frequent use of the same coping strategies. Funding: AP and WLT are supported by National Health and Medical Research Council of Australia (NHMRC) Project Grants (CIA- GNT1159953, CIA- GNT1161609, respectively). SLR holds a Senior NHMRC Fellowship (GNT1154561), and EJT (GNT1142424) and TVR (GNT1088785) hold Early Career NHMRC Fellowships. Declaration of Interests: None to declare. Ethics Approval Statement: The COLLATE project received ethics approval from the Swinburne University Human Ethics Review Committee (approval number: 20202917-4107) and complied with the Declaration of Helsinki.

Supplemental material, sj-docx-1-anp-10.1177_00048674211009602 for Characteristics of people on long-acting injectable antipsychotics in Australia: Data from the 2010 National Survey of High Impact Psychosis by Shuichi Suetani, Dan Siskind, Andrea Phillipou, Anna Waterreus, Vera A Morgan and David Castle in Australian & New Zealand Journal of Psychiatry

Supplemental material, sj-pdf-1-jbx-10.1177_24725552211002472 for Reducing False Positives through the Application of Fluorescence Lifetime Technology: A Comparative Study Using TYK2 Kinase as a Model System by Luke A. Greenhough, Gabriella Clarke, Alexander N. Phillipou, Faith Mazani, Bhumika Karamshi, Sam Rowe, Paul Rowland, Cassie Messenger, Carl P. Haslam, Ryan P. Bingham and Peter D. Craggs in SLAS Discovery

Objective:There is ongoing debate regarding the relationship between clinical symptoms and cognition in schizophrenia spectrum disorders (SSD). The present study aimed to explore the potential relationships between symptoms, with an emphasis on negative symptoms, and social and non-social cognition.Method:Hierarchical cluster analysis with k-means optimisation was conducted to characterise clinical subgroups using the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms in n = 130 SSD participants. Emergent clusters were compared on the MATRICS Consensus Cognitive Battery, which measures non-social cognition and emotion management as well as demographic and clinical variables. Spearman’s correlations were then used to investigate potential relationships between specific negative symptoms and emotion management and non-social cognition.Results:Four distinct clinical subgroups were identified: 1. high hallucinations, 2. mixed symptoms, 3. high negative symptoms, and 4. relatively asymptomatic. The high negative symptom subgroup was found to have significantly poorer emotion management than the high hallucination and relatively asymptomatic subgroups. No further differences between subgroups were observed. Correlation analyses revealed avolition-apathy and anhedonia-asociality were negatively correlated with emotion management, but not non-social cognition. Affective flattening and alogia were not associated with either emotion management or non-social cognition.Conclusions:The present study identified associations between negative symptoms and emotion management within social cognition, but no domains of non-social cognition. This relationship may be specific to motivation, anhedonia and apathy, but not expressive deficits. This suggests that targeted interventions for social cognition may also result in parallel improvement in some specific negative symptoms.

Anorexia nervosa (AN) is associated with poor sleep and altered circadian rhythms. Evidence is unclear as to whether these features relate to ongoing psychiatric symptoms of AN, or are merely concomitant with low weight. In this study, we sought to evaluate subjective sleep quality and sleep–wake preferences in a sample of individuals with lifetime AN. Furthermore, we aimed to examine whether sleep quality would significantly predict AN symptom severity, after accounting for demographic features and negative emotions (depression, anxiety and stress). Adults with a lifetime diagnosis of AN (n = 96) or no lifetime psychiatric diagnoses (NC; n = 246) completed an online survey assessing demographics, sleep quality, circadian sleep–wake preferences, eating disorder symptoms, and negative emotions. AN participants reported significantly poorer sleep quality overall, including increased sleep disturbances, use of sleep medications, and daytime dysfunction, as compared to NC participants. Groups did not differ significantly in circadian sleep–wake preferences. Regression analysis showed that among AN participants, sleep quality and negative emotions significantly predicted AN symptom severity, while sex and body mass index (BMI) did not. The findings demonstrate that poor sleep quality was associated with more severe symptoms of AN, even when accounting for negative emotions and BMI. Future research should investigate causal interactions between sleep quality and AN symptom severity longitudinally and across different recovery stages. Level III—Cohort and case–control analytic studies.

There are currently no validated biomarkers for anorexia nervosa (AN), though recent literature suggests an increased research interest in this area. Biomarkers are objective, measurable indicators of illness that can be used to assist with diagnosis, risk assessment, and tracking of illness state. Related to biomarkers are endophenotypes, which are quantifiable phenomena that are distinct from symptoms and which link genes to manifest illness. In this scoping review, we sought to provide a summary of recent research conducted in the pursuit of biomarkers and endophenotypes for AN. The findings indicate that a number of possible biomarkers which can assess the presence or severity of AN independently of weight status, including psychophysical (e.g., eye-tracking) and biological (e.g., immune, endocrine, metabolomic, neurobiological) markers, are currently under investigation. However, this research is still in early phases and lacking in replication studies. Endophenotype research has largely been confined to the study of several neurocognitive features, with mixed evidence to support their classification as possible endophenotypes for the disorder. The study of biomarkers and endophenotypes in AN involves significant challenges due to confounding factors of illness-related sequalae, such as starvation. Future research in these areas must prioritise direct evaluation of the sensitivity, specificity and test-retest reliability of proposed biomarkers and enhanced control of confounding physical consequences of AN in the study of biomarkers and endophenotypes.

Life satisfaction is a core aspect of an individual's wellbeing and describes the subjective assessment of their quality of life. Reduced life satisfaction is frequently reported in anorexia nervosa (AN), but the factors contributing to this are still unclear. This study sought to extend previous work by examining 12 potential correlates of AN life satisfaction. One hundred and five female AN patients were administered questionnaires assessing life satisfaction, depression, anxiety, stress, employment status, marital status, body mass index, eating disorder symptomatology, perceived disability and readiness for change. A stepwise linear regression revealed that only depression, perceived disability and employment status were significantly associated with AN life satisfaction. The findings thus highlight prevailing mood and personal functioning as critical foci for clinical management strategies in people with AN. Addressing depressive symptoms and perceived disability while bettering employment prospects could facilitate improved AN life satisfaction.

Contemporary drug discovery typically quantifies the effect of a molecule on a biological target using the equilibrium-derived measurements of IC50, EC50, or KD. Kinetic descriptors of drug binding are frequently linked with the effectiveness of a molecule in modulating a disease phenotype; however, these parameters are yet to be fully adopted in early drug discovery. Nanoluciferase bioluminescence resonance energy transfer (NanoBRET) can be used to measure interactions between fluorophore-conjugated probes and luciferase fused target proteins. Here, we describe an intracellular NanoBRET competition assay that can be used to quantify cellular kinetic rates of compound binding to nanoluciferase-fused bromodomain and extra-terminal (BET) proteins. Comparative rates are generated using a cell-free NanoBRET assay and by utilizing orthogonal recombinant protein-based methodologies. A screen of known pan-BET inhibitors is used to demonstrate the value of this approach in the investigation of kinetic selectivity between closely related proteins.

Highlights • The mental health status of individuals with mood disorder during COVID-19 is unclear. • Our data indicates that psychological distress in these individuals is heightened. • The distress is linked to adverse lifestyle changes occurring in response to COVID-19. • Current concerns relate to loved one's health, and access to appropriate medical care., Background Physical-distancing strategies during the coronavirus (COVID-19) pandemic may be particularly detrimental to the mental health of individuals with a pre-existing mood disorder. Data on the mental health status of these individuals during the current pandemic is sparse, and their current mental health needs unclear. Method We characterised COVID-19 related lifestyle changes, primary concerns and psychological distress in n=1292 respondents self-reporting a mood disorder (either bipolar disorder or depressive disorder) and n=3167 respondents without any reported mental disorder from the COLLATE (COvid-19 and you: mentaL heaLth in AusTralia now survEy) project; an Australian national survey launched on April 1st 2020. Results Psychological distress was heightened in the mood disorder group compared to the group with no mental disorder, with stress and depression further elevated in respondents with bipolar disorder compared to those with depressive disorder; and men with bipolar disorder having even higher levels of depression than women with bipolar disorder. Respondents with bipolar disorder were particularly concerned about financial issues associated with COVID-19 compared to those with depressive disorder and those with no mental disorder. Adverse changes to lifestyle behaviours were more prevalent in respondents with a mood disorder and linked to higher levels of distress. Limitations Mood disorder was self-reported and was not clinically verified. Conclusions Current psychological distress levels are elevated in individuals with mood disorder and are associated with maladaptive situational and lifestyle changes occurring in response to COVID-19.

During this unprecedented novel coronavirus (COVID-19) pandemic, there is an urgent need for empirical data to characterise its impact on the mental health and well-being of Australians. In this viewpoint, we outline a number of considerations for research on this topic, highlighting areas necessitating special attention, consideration of particular vulnerable groups and the need for longitudinal studies to track mental health fluctuations in the general population. We conclude by introducing the COLLATE (COvid-19 and you: mentaL heaLth in AusTralia now survEy) project, outlining its aims, addressing some considerations raised herein and detailing avenues for future research. Since the World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 (WHO, 2020), the COVID-19 pandemic has caused major upheaval both in Australia and globally. While the search for a vaccine continues, current efforts towards tackling the virus and limiting contagion in several nations have focused on social distancing and the shutdown of non-essential services. In Australia, the first case was reported on 13 January 2020 (COVID-19 National Incident Room Surveillance Team, 2020), the first death occurred on 24 February and a spate of progressive restrictions were enforced throughout the 2 weeks leading up to 31 March 2020 (COVID-19 National Incident Room Surveillance Team, 2020a).

Objective Emerging evidence suggests that the coronavirus (COVID‐19) pandemic may be negatively impacting mental health. The impact on eating and exercise behaviors is, however, currently unknown. This study aimed to identify changes in eating and exercise behaviors in an Australian sample among individuals with an eating disorder, and the general population, amidst the COVID‐19 pandemic outbreak. Method A total of 5,469 participants, 180 of whom self‐reported an eating disorder history, completed questions relating to changes in eating and exercise behaviors since the emergence of the pandemic, as part of the COLLATE (COvid‐19 and you: mentaL heaLth in AusTralia now survEy) project; a national survey launched in Australia on April 1, 2020. Results In the eating disorders group, increased restricting, binge eating, purging, and exercise behaviors were found. In the general population, both increased restricting and binge eating behaviors were reported; however, respondents reported less exercise relative to before the pandemic. Discussion The findings have important implications for providing greater monitoring and support for eating disorder patients during the COVID‐19 pandemic. In addition, the mental and physical health impacts of changed eating and exercise behaviors in the general population need to be acknowledged and monitored for potential long‐term consequences.

Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to non-bromodomain and extra terminal domain (non-BET) bromodomains through displacement of a normally conserved network of four water molecules. Starting from an initial hit molecule, we report its divergent optimization toward the ATPase family AAA domain containing 2 (ATAD2) and cat eye syndrome chromosome region, candidate 2 (CECR2) domains. This work concludes with the identification of (R)-55 (GSK232), a highly selective, cellularly penetrant CECR2 inhibitor with excellent physicochemical properties.

Objective Differences in saccadic eye movements are widely reported in mental illnesses, and can indirectly inform our understanding of neurobiological and cognitive underpinnings of psychiatric conditions, including anorexia nervosa (AN). Preliminary research has suggested that individuals with AN may show specific eye movement abnormalities; whether these deficits are representative of state or trait effects is, however, unclear. The aim of this study was to identify whether there are demonstrable differences in performance on saccadic eye movement tasks in individuals with current AN (c-AN), those who are weight-restored from AN (wr-AN), biological sisters of individuals with AN (AN-sis), and healthy controls (HC). Methods Eighty participants took part in the study (n = 20/group). A set of saccadic eye movement tasks was administered, including prosaccade, antisaccade, memory-guided saccade, and visual scanpath tasks. Results The c-AN group showed an increased rate of inhibitory errors to 10° targets on the memory-guided saccade task. Discussion The results are discussed in terms of the potential role of the superior colliculus in AN, and that the findings may reflect a state measure of AN.

ER aminopeptidase 1 (ERAP1) is an intracellular enzyme that generates antigenic peptides and is an emerging target for cancer immunotherapy and the control of autoimmunity. ERAP1 inhibitors described previously target the active site and are limited in selectivity, minimizing their clinical potential. To address this, we targeted the regulatory site of ERAP1 using a high-throughput screen and discovered a small molecule hit that is highly selective for ERAP1. (4aR,5S,6R,8S,8aR)-5-(2-(Furan-3-yl)ethyl)-8-hydroxy-5,6,8a-trimethyl-3,4,4a,5,6,7,8,8a-octahydronaphthalene-1-carboxylic acid is a natural product found in Dodonaea viscosa that constitutes a submicromolar, highly selective, and cell-active modulator of ERAP1. Although the compound activates hydrolysis of small model substrates, it is a competitive inhibitor for physiologically relevant longer peptides. Crystallographic analysis confirmed that the compound targets the regulatory site of the enzyme that normally binds the C-terminus of the peptide substrate. Our findings constitute a novel starting point for the development of selective ERAP1 modulators that have potential for further clinical development.

Background After receiving intensive medical treatment; individuals with eating disorders often require ongoing care to maintain their recovery, build social networks, and reduce risk of relapse. Methods To address this important transition period, a six-month peer mentoring program was developed and piloted in Melbourne, Australia. Twelve adults with a past history of an eating disorder (mentors) were paired with 14 individuals with a current eating disorder (mentees). Pairs met for thirteen mentoring sessions in community settings. Throughout the program mentees and mentors completed reflective questions online. Upon completion of the program, qualitative interviews were conducted. Both online reflections and interviews explored themes relating to perceived benefits and challenges of participation in the peer mentoring program, and the differences between mentoring and traditional treatment. Results Thematic analysis identified several benefits for mentees; including hope, reconnection with others, and re-engaging with the world. The majority of mentees described their mentor as uniquely supportive due to their past experience of an eating disorder. Mentors reported experiencing benefits such as increased connection with self and others, and indicated that the experience helped them positively reframe their past experience of an eating disorder. Ending the relationship at the completion of the program was a significant challenge for both groups, and managing boundaries was deemed a main challenge by mentors. Conclusions Overall, results indicated that this mode of informal support may be worthy of further investigation as an adjunct to clinical treatment programs for this population. Trial registration Australian and New Zealand Clinical Trials registration number - ACTRN12617001412325 - Date of registration – 05/10/2017 (Retrospectively registered)

Additional file 1: Appendix A. Online Reflection Questions.

Additional file 2: Appendix B. Interview Schedule.