Data from four consecutive cohorts of students in Australia (2019-2022) show the impact of the COVID-19 pandemic on domestic and international university students' mental health.

INTRODUCTION: COVID-19 and related travel and social restrictions caused significant stress for university students in Australia and globally. Learning quickly moved online and many students (particularly international students) were separated from social and economic support. This study examined the impact of the pandemic from pre-pandemic (2019) to the COVID-19 Omicron wave (2022) on domestic and international students' mental health. METHODS: Participants were 1540 students (72% females, 28% international) in four first-year cohorts (2019, 2020, 2021, 2022). We screened for mental health concerns (% positive) and symptom scores for depression, anxiety and somatic distress using the PsyCheck, and general wellbeing using the Warwick-Edinburgh Mental Well-being scale. RESULTS: From pre-COVID (2019) to the first wave of COVID-19 (2020), the proportion of students screening positive for mental health problems rose in both domestic students (66-76%) and international students (46-67%). Depression symptoms and wellbeing were worse in 2020 than in 2019, 2021 and 2022. Anxiety symptoms increased from 2019 to 2020 and continued to rise in 2021 and 2022. Somatic symptoms did not show an effect of cohort. Contrary to expectations, domestic students reported higher distress and lower wellbeing than international students across cohorts. CONCLUSION: The pandemic was associated with a marked increase in psychological distress in first-year university students, not all of which settled with the easing of restrictions. Post-pandemic recovery in the Australian university sector must include university-wide access to mental health information and support for incoming students.

Optical tools for visualizing and controlling human GLP-1 receptor activation with high spatiotemporal resolution.

The glucagon-like peptide-1 receptor (GLP1R) is a broadly expressed target of peptide hormones with essential roles in energy and glucose homeostasis, as well as of the blockbuster weight-loss drugs semaglutide and liraglutide. Despite its large clinical relevance, tools to investigate the precise activation dynamics of this receptor with high spatiotemporal resolution are limited. Here, we introduce a novel genetically encoded sensor based on the engineering of a circularly permuted green fluorescent protein into the human GLP1R, named GLPLight1. We demonstrate that fluorescence signal from GLPLight1 accurately reports the expected receptor conformational activation in response to pharmacological ligands with high sensitivity (max ΔF/F0=528%) and temporal resolution (τON = 4.7 s). We further demonstrated that GLPLight1 shows comparable responses to glucagon-like peptide-1 (GLP-1) derivatives as observed for the native receptor. Using GLPLight1, we established an all-optical assay to characterize a novel photocaged GLP-1 derivative (photo-GLP1) and to demonstrate optical control of GLP1R activation. Thus, the new all-optical toolkit introduced here enhances our ability to study GLP1R activation with high spatiotemporal resolution.

Therapists who foster social identification build stronger therapeutic working alliance and have better client outcomes.

BACKGROUND: For decades we have known that therapeutic working alliance is a key contributor to client engagement and positive outcomes in therapy. However, we have made little progress in narrowing down its determinants, which is critical in supporting trainees to optimize such alliance. We make a case for the value of incorporating social psychological frameworks into models of alliance and explore the role of social identity processes in the development of therapeutic alliance. METHOD: Across two studies, over 500 psychotherapy clients completed validated measures of alliance, social identification with their therapist, positive therapy outcomes, and a range of client and therapist characteristics. FINDINGS: Social identification strongly predicted alliance in both samples, whereas client and therapist characteristics showed few such associations. Alliance mediated the relationship between social identification and positive therapy outcomes. In addition, we found evidence that (a) personal control is a key psychological resource in therapy that arises from social identification, and (b) therapists who engage in identity leadership (i.e., who represent and build a social identity that they share with clients) are more likely to foster social identification and its downstream benefits. INTERPRETATION: These data show that social identity processes are key to the emergence of working alliance. We conclude with a discussion of how recent social identity and identity leadership interventions might be adapted to train therapists in relevant identity-building skills.

A photocaged orexin-B for spatiotemporally precise control of orexin signaling.

Orexin neuropeptides carry out important neuromodulatory functions in the brain, yet tools to precisely control the activation of endogenous orexin signaling are lacking. Here, we developed a photocaged orexin-B (photo-OXB) through a C-terminal photocaging strategy. We show that photo-OXB is unable to activate its cognate receptors in the dark but releases functionally active native orexin-B upon uncaging by illumination with UV-visible (UV-vis) light (370-405 nm). We established an all-optical assay combining photo-OXB with a genetically encoded orexin biosensor and used it to characterize the efficiency and spatial profile of photo-OXB uncaging. Finally, we demonstrated that photo-OXB enables optical control over orexin signaling with fine temporal precision both in vitro and ex vivo. Thus, our photocaging strategy and photo-OXB advance the chemical biological toolkit by introducing a method for the optical control of peptide signaling and physiological function.

Lipidated Calcitonin Gene-Related Peptide (CGRP) Peptide Antagonists Retain CGRP Receptor Activity and Attenuate CGRP Action In Vivo.

Signaling through calcitonin gene-related peptide (CGRP) receptors is associated with pain, migraine, and energy expenditure. Small molecule and monoclonal antibody CGRP receptor antagonists that block endogenous CGRP action are in clinical use as anti-migraine therapies. By comparison, the potential utility of peptide antagonists has received less attention due to suboptimal pharmacokinetic properties. Lipidation is an established strategy to increase peptide half-life in vivo. This study aimed to explore the feasibility of developing lipidated CGRP peptide antagonists that retain receptor antagonist activity in vitro and attenuate endogenous CGRP action in vivo. CGRP peptide analogues based on the archetypal CGRP receptor antagonist, CGRP8-37, were palmitoylated at the N-terminus, position 24, and near the C-terminus at position 35. The antagonist activities of the lipidated peptide analogues were tested in vitro using transfected Cos-7 cells expressing either the human or mouse CGRP receptor, amylin subtype 1 (AMY1) receptor, adrenomedullin (AM) receptors, or calcitonin receptor. Antagonist activities were also evaluated in SK-N-MC cells that endogenously express the human CGRP receptor. Lipidated peptides were then tested for their ability to antagonize endogenous CGRP action in vivo using a capsaicin-induced dermal vasodilation (CIDV) model in C57/BL6J mice. All lipidated peptides except for the C-terminally modified analogue retained potent antagonist activity compared to CGRP8-37 towards the CGRP receptor. The lipidated peptides also retained, and sometimes gained, antagonist activities at AMY1, AM1 and AM2 receptors. Several lipidated peptides produced robust inhibition of CIDV in mice. This study demonstrates that selected lipidated peptide antagonists based on αCGRP8-37 retain potent antagonist activity at the CGRP receptor and are capable of inhibition of endogenous CGRP action in vivo. These findings suggest that lipidation can be applied to peptide antagonists, such as αCGRP8-37 and are a potential strategy for antagonizing CGRP action.

Groups 4 Health versus cognitive-behavioural therapy for depression and loneliness in young people: randomised phase 3 non-inferiority trial with 12-month follow-up.

BACKGROUND: Depression treatments are typically less effective for young people than for adults. However, treatments rarely target loneliness, which is a key risk factor in the onset, maintenance and development of depression. AIMS: This study evaluated the efficacy of a novel loneliness intervention, Groups 4 Health (G4H), relative to the best-practice treatment of cognitive-behavioural therapy (CBT) in reducing loneliness and depression over a 12-month period (Australian New Zealand Clinical Trial Registry: ACTRN12618000440224). METHOD: The study was a phase 3 randomised non-inferiority trial comparing G4H with dose-controlled group CBT. Participants were 174 people aged 15-25 years experiencing loneliness and clinically significant symptoms of depression, who were not in receipt of adjunct treatment. Participants were recruited from mental health services in Southeast Queensland, Australia. Randomisation was conducted using computer software. Follow-up assessments and statistical analyses were masked to allocation. Both interventions consisted of five 75 min group-based psychotherapy sessions. The primary outcomes were depression and loneliness, with a non-inferiority margin of 2.20 for depression. RESULTS: The trial enrolled 174 participants between 24 April 2018 and 25 May 2019, with 84 in the G4H condition and 90 in the CBT condition. All randomised participants were included in the intention-to-treat analyses (n = 174). The pre-post effect sizes for depression were dG4H = -0.71 and dCBT = -0.91. For loneliness, they were dG4H = -1.07 and dCBT = -0.89. At 12-month follow-up, the absolute difference between groups on depression was 1.176 (95% CI -1.94 to 4.29) and on loneliness it was -0.679 (95% CI -1.43 to 0.07). No adverse effects were observed. CONCLUSIONS: G4H was non-inferior to CBT for depression and showed a slight advantage over CBT for loneliness that emerged after treatment completion.

Aminovinyl Cysteine Containing Peptides: A Unique Motif That Imparts Key Biological Activity.

Natural products that contain distinctive chemical functionality can serve as useful starting points to develop Nature's compounds into viable therapeutics. Peptide natural products, an under-represented class of medicines, such as ribosomally synthesized and post-translationally modified peptides (RiPPs), often contain noncanonical amino acids and structural motifs that give rise to potent biological activity. However, these motifs can be difficult to obtain synthetically, thereby limiting the transition of RiPPs to the clinic. Aminovinyl cysteine containing peptides, which display potent antimicrobial or anticancer activity, possess an intricate C-terminal ring that is critical for bioactivity. To date, successful methods for the total chemical synthesis of such peptides are yet to be realized, although several advancements have been achieved. In this perspective, we review this burgeoning class of aminovinyl cysteine peptides and critically evaluate the chemical strategies to install the distinct aminovinyl cysteine motif.

Groups 4 Health protects against unanticipated threats to mental health: Evaluating two interventions during COVID-19 lockdown among young people with a history of depression and loneliness.

BACKGROUND: Decades of research indicate that when social connectedness is threatened, mental health is at risk. However, extant interventions to tackle loneliness have had only modest success, and none have been trialled under conditions of such threat. METHOD: 174 young people with depression and loneliness were randomised to one of two evidence-based treatments: cognitive behaviour therapy (CBT) or Groups 4 Health (G4H), an intervention designed to increase social group belonging. Depression, loneliness, and well-being outcomes were evaluated at one-year follow-up; COVID-19 lockdown restrictions were imposed partway through follow-up assessments. This provided a quasi-experimental test of the utility of each intervention in the presence (lockdown group) and absence (control group) of a threat to social connectedness. RESULTS: At one-year follow-up, participants in lockdown reported significantly poorer wellbeing than controls who completed follow-up before lockdown, t(152)=2.41, p=.017. Although both CBT and G4H led to symptom improvement, the benefits of G4H were more robust following an unanticipated threat to social connectedness for depression (χ2(16)=31.35, p=.001), loneliness (χ2(8)=21.622, p=.006), and wellbeing (χ2(8)=22.938, p=.003). LIMITATIONS: Because the COVID-19 lockdown was unanticipated, this analysis represents an opportunistic use of available data. As a result, we could not measure the specific impact of restrictions on participants, such as reduced income, degree of isolation, or health-related anxieties. CONCLUSIONS: G4H delivered one year prior to COVID-19 lockdown offered greater protection than CBT against relapse of loneliness and depression symptoms. Implications are discussed with a focus on how these benefits might be extended to other life stressors and transitions.

When trust goes wrong: A social identity model of risk taking.

Risk taking is typically viewed through a lens of individual deficits (e.g., impulsivity) or normative influence (e.g., peer pressure). An unexplored possibility is that shared group membership, and the trust that flows from it, may play a role in reducing risk perceptions and promoting risky behavior. We propose and test a Social Identity Model of Risk Taking in eight studies (total N = 4,708) that use multiple methods including minimal group paradigms, correlational, longitudinal, and experimental designs to investigate the effect of shared social identity across diverse risk contexts. Studies 1 and 2 provided evidence for the basic premise of the model, showing that ingroup members were perceived as posing lower risk and inspired greater risk taking behavior than outgroup members. Study 3 found that social identification was a moderator, such that effect of shared group membership was strongest among high identifiers. Studies 4 and 5 among festival attendees showed correlational and longitudinal evidence for the model and further that risk-taking was mediated by trust, not disgust. Study 6 manipulated the mediator and found that untrustworthy faces were trusted more and perceived as less risky when they were ingroup compared with outgroup members. Studies 7 and 8 identified integrity as the subcomponent of trust that consistently promotes greater risk taking in the presence of ingroup members. The findings reveal that a potent source of risk discounting is the group memberships we share with others. Ironically, this means the people we trust the most may sometimes pose the greatest risk. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Enhancing mental health recovery by joining arts-based groups: a role for the social cure approach.

BACKGROUND: . Even though emerging evidence suggests that participation in arts-based group programs are helpful in supporting mental health, the field lacks an established theorical framework. This study explored the extent to which participants' experiences of singing or creative writing groups aligned with theorising proposed by the social cure approach. METHODS: . Semi-structured interviews were conducted with 25 choir members, and 23 creative writing group members with chronic mental health conditions at two time points. Transcripts of the interviews were examined by four coders using thematic analysis. RESULTS: . Consistent with social cure theorising, participation in the choir and creative writing group facilitated meeting participants' needs for belonging, support, self-efficacy, purpose, and positive emotions. CONCLUSIONS: . This study demonstrated the psychosocial mechanisms by which participation in arts-based groups can enhance mental health. We conclude that engagement with the social cure framework may be useful to structure practice in this field.

The connecting adolescents to reduce relapse (CARR) trial: study protocol for a randomized controlled trial comparing the efficacy of Groups 4 Health and cognitive behaviour therapy in young people.

BACKGROUND: Depression is the leading cause of disability in young people (aged 15-25) globally. Loneliness is a major factor in the development and relapse of depression in young people, yet few interventions directly address loneliness. Groups 4 Health (G4H) - a novel, theoretically derived group psychotherapy intervention - may address this disconnect. Previous trials (Phase I and Phase II) have found G4H to be efficacious in reducing symptoms of depression. However, the efficacy of G4H compared to current evidence-based treatments (Phase III) has not been investigated. This protocol details the design and methodology of the Connecting Adolescents to Reduce Relapse (CARR) trial, a randomised control trial assessing the efficacy of G4H in young people relative to cognitive behavioural therapy (CBT). METHODS: The CARR trial is a two-arm non-inferiority randomised controlled trial that will compare the efficacy of G4H to the most widely used evidence-based treatment for depression, CBT, at program completion and 6- and 12-month follow up. Participants will be 200 young people (aged 15-25) with symptoms of depression and/or loneliness recruited from community and university mental health services. We hypothesise that the interventions will be comparable in reducing depression symptoms, but that G4H will be superior in reducing loneliness. Because loneliness is a primary risk factor for depression relapse in young people, we therefore expect the benefits of Groups 4 Health to be particularly apparent at 12-month follow up. DISCUSSION: This trial will be the first to evaluate an intervention that targets loneliness, in comparison to the current gold standard treatment approach - CBT. If found to be effective, this program offers a new approach to treatment and relapse prevention of depression among young people. TRIAL REGISTRATION: Trial prospectively registered on ANZCTR ( ACTRN12618000440224 ), registered on 27/03/2018.

Ageing well in a foreign land as a process of successful social identity change.

PURPOSE: Over and above the risks associated with ageing, older migrants are also at risk of social isolation. The social identity approach, and the Social Identity Model of Identity Change (SIMIC) in particular, provides a theoretical basis from which to understand the factors contributing to social isolation and how this then impacts on older migrants' capacity to age well in a foreign land. Building on the recognition that migration involves a major life change, we explore this transition qualitatively focusing specifically on social connectedness and adjustment. METHODS: In semi-structured interviews with 29 older migrants in Australia, we examined participants' experiences of migration and perceptions of identity and identity change. We also considered in more detail experiences of the most and least socially isolated individuals to understand adjustment trajectories. RESULTS: We found evidence supporting the key processes described in SIMIC (relating to social identity continuity, social identity gain, and perceived identity compatibility), suggesting that where adjustment was positive it was experienced as a process of successfully adapting to identity change. CONCLUSION: We emphasise the importance of identity resources as substantial and concrete assets that can enhance the well-being among older adults aging in a foreign land.

A systematic review of mental health and wellbeing outcomes of group singing for adults with a mental health condition.

Background: A growing body of research has found that participating in choir singing can increase positive emotions, reduce anxiety and enhance social bonding. Consequently, group singing has been proposed as a social intervention for people diagnosed with mental health problems. However, it is unclear if group singing is a suitable and effective adjunct to mental health treatment. The current paper systematically reviews the burgeoning empirical research on the efficacy of group singing as a mental health intervention. Methods: The literature searched uncovered 709 articles that were screened. Thirteen articles representing data from 667 participants were identified which measured mental health and/or wellbeing outcomes of group singing for people living with a mental health condition in a community setting. Results: The findings of seven longitudinal studies, showed that while people with mental health conditions participated in choir singing, their mental health and wellbeing significantly improved with moderate to large effect sizes. Moreover, six qualitative studies had converging themes, indicating that group singing can provide enjoyment, improve emotional states, develop a sense of belonging and enhance self-confidence in participants. Conclusion: The current results indicate that group singing could be a promising social intervention for people with mental health conditions. However, these studies had moderate to high risk of bias. Therefore, these findings remain inconclusive and more rigorous research is needed.

Chemical Synthesis of Bioactive Naturally Derived Cyclic Peptides Containing Ene-Like Rigidifying Motifs.

The development of synthetic methods to prepare conformationally constrained peptides and peptide-polyketide hybrids remain an important chemical challenge. It is known that structural rigidity correlates with the specificity, bioactivity, and stability of these peptide systems, thus rigid systems are particularly attractive leads for development of potent biopharmaceuticals. Herein we provide an overview of recent developments in the syntheses of naturally derived constrained peptides and peptide-polyketide hybrids, with a particular emphasis on those systems containing an ene-like bond.

Solid-Phase Thiol-Ene Lipidation of Peptides for the Synthesis of a Potent CGRP Receptor Antagonist.

We report a new method herein coined SP-CLipPA (solid-phase cysteine lipidation of a peptide or amino acid) for the synthesis of mono-S-lipidated peptides. This technique utilizes thiol-ene chemistry for conjugation of a vinyl ester to a free thiol of a semiprotected, resin-bound peptide. Advantages of SP-CLipPA include: ease of handling, conversions of up to 91 %, by-product removal by simple filtration, and a single purification step. Additionally, the desired lipidated products show high chromatographic separation from impurities, thus facilitating RP-HPLC purification. To showcase the utility of SP-CLipPA, we synthesized a potent calcitonin gene-related peptide (CGRP) receptor antagonist peptide in excellent yield and purity. This peptide, selected from a series of lipidated analogues of CGRP8-37 and CGRP7-37 , has potential for the treatment of migraine.

Choir singing and creative writing enhance emotion regulation in adults with chronic mental health conditions.

OBJECTIVES: Adults with mental health conditions commonly experience difficulties with emotion regulation which affect their social functioning. Arts-based groups provide opportunities for shared emotional experiences and emotion regulation. This study explores emotion regulation strategies and the emotional effects of arts-based group participation in adults with mental health problems and in controls. DESIGN AND METHOD: The 62 participants included 39 adults with chronic mental health problems who were members of arts-based groups (ABG) and 23 comparison choir (CC) members who were not specifically experiencing mental health problems. The repeated measures design included self-reports of emotion upon waking (T1), the hour before group (T2), end of the group (T3), and evening (T4), as well as participant notes to explain their emotion ratings at each time. They also completed measures of individual and interpersonal emotion regulation. RESULTS: The ABG participants engaged marginally more in affect worsening strategies than CC (p = .057 and .08), but there were no other group differences. All participants reported a significant increase in positive emotions, F (3, 180) = 28.044, p < .001, np2 = .319; and a decrease in negative emotions during the arts-based activity: F (2.637, 155.597) = 21.09, p < .001, np2 = .263. The influence on positive emotions was short-lived, while the effect on negative emotions lasted until evening. CONCLUSION: Findings show that participation in arts-based groups benefits the emotions of both healthy adults and those experiencing mental health conditions through individual and interpersonal processes. PRACTITIONER POINTS: Individuals with chronic mental health conditions often experience difficulties in emotion processing Participation in arts-based groups was associated with significant increases in positive emotions although these were short-lived Negative emotion was significantly decreased during arts-based group activities, and sustained to the evening assessment Adults with chronic mental health conditions were equally able to derive emotional benefits as healthy adults.