A brief intervention to increase uptake and adherence of an internet-based program for depression and anxiety (Enhancing Engagement with Psychosocial Interventions): Randomized controlled trial

Background: Psychosocial, self-guided, internet-based programs are effective in treating depression and anxiety. However, the community uptake of these programs is poor. Recent approaches to increasing engagement (defined as both uptake and adherence) in internet-based programs include brief engagement facilitation interventions (EFIs). However, these programs require evaluation to assess their efficacy. Objective: The aims of this hybrid implementation effectiveness trial are to examine the effects of a brief internet-based EFI presented before an internet-based cognitive behavioral therapy self-help program (myCompass 2) in improving engagement (uptake and adherence) with that program (primary aim), assess the relative efficacy of the myCompass 2 program, and determine whether greater engagement was associated with improved efficacy (greater reduction in depression or anxiety symptoms) relative to the control (secondary aim). Methods: A 3-arm randomized controlled trial (N=849; recruited via social media) assessed the independent efficacy of the EFI and myCompass 2. The myCompass 2 program was delivered with or without the EFI; both conditions were compared with an attention control condition. The EFI comprised brief (5 minutes), tailored audio-visual content on a series of click-through linear webpages. Results: Uptake was high in all groups; 82.8% (703/849) of participants clicked through the intervention following the pretest survey. However, the difference in uptake between the EFI + myCompass 2 condition (234/280, 83.6%) and the myCompass 2 alone condition (222/285, 77.9%) was not significant (n=565; χ21=29.2; P=.09). In addition, there was no significant difference in the proportion of participants who started any number of modules (1-14 modules) versus those who started none between the EFI + myCompass 2 (214/565, 37.9%) and the myCompass 2 alone (210/565, 37.2%) conditions (n=565; χ21<0.1; P=.87). Finally, there was no significant difference between the EFI + myCompass 2 and the myCompass 2 alone conditions in the number of modules started (U=39366.50; z=−0.32; P=.75) or completed (U=39494.0; z=−0.29; P=.77). The myCompass 2 program was not found to be efficacious over time for symptoms of depression (F4,349.97=1.16; P=.33) or anxiety (F4,445.99=0.12; P=.98). However, planned contrasts suggested that myCompass 2 may have been effective for participants with elevated generalized anxiety disorder symptoms (F4,332.80=3.50; P=.01). Conclusions: This brief internet-based EFI did not increase the uptake of or adherence to an existing internet-based program for depression and anxiety. Individuals' motivation to initiate and complete internet-based self-guided interventions is complex and remains a significant challenge for self-guided interventions.This project was supported by a National Health and Medical Research Fund grant (grant 1138713). The lead author can disseminate the results of this trial without the express permission of the funder. PJB is supported by National Health and Medical Research Council (NHMRC) fellowship 1158707; ALC is supported by NHMRC fellowships 1122544 and 1173146; FKL is supported by NHMRC fellowship 1110371. LMF is supported by the ARC DECRA DE190101382. HC is supported by the NHMRC fellowship 1056964

Effects of previous exposure to psychotherapeutic strategies on depression and anxiety symptoms during the COVID-19 pandemic

Background The COVID-19 pandemic has seen an increase in depression and anxiety among those with and without a history of mental illness. Commonly used forms of psychological therapy improve mental health by teaching psychotherapeutic strategies that assist people to better manage their symptoms and cope with life stressors. Minimal research to date has explored their application or value in managing mental health during significant broad-scale public health crises. Aims To determine which psychotherapeutic strategies people who have previously received therapy use to manage their distress during the COVID-19 pandemic, and whether the use and perceived helpfulness of these strategies has an effect on symptoms of depression and anxiety. Method Data (N = 857) was drawn from multiple waves of a representative longitudinal study of the effects of COVID-19 on the mental health of Australian adults, which includes measures of anxiety, depression and experiences with psychotherapy and psychotherapeutic strategies. Results Previous engagement in therapy with psychotherapeutic strategies had a protective effect on depressive but not anxiety symptoms. Common and helpful strategies used by respondents were exercise, mindfulness and breathing exercises. Using mindfulness and perceiving it to be helpful was associated with lower levels of depression and anxiety symptoms. No other strategies were associated with improved mental health. Conclusions Prior knowledge of psychotherapeutic strategies may play a role in managing mental health during unprecedented public health events such as a global pandemic. There may be value in promoting these techniques more widely in the community to manage general distress during such times.This study was funded by a Crisis Research Seed Funding COVID-19 grant from the Australian National University (ANU) College of Health and Medicine, and funding from the ANU Research School of Psychology and the ANU Research School of Population Healt

Trajectories of depression and anxiety symptoms during the COVID‐19 pandemic in a representative Australian adult cohort

Objectives To estimate initial levels of symptoms of depression and anxiety, and their changes during the early months of the COVID-19 pandemic in Australia; to identify trajectories of symptoms of depression and anxiety; to identify factors associated with these trajectories. Design, setting, participants Longitudinal cohort study; seven fortnightly online surveys of a representative sample of 1296 Australian adults from the beginning of COVID-19-related restrictions in late March 2020 to mid-June 2020. Main outcome measures Symptoms of depression and anxiety, measured with the Patient Health Questionnaire (PHQ-9) depression and Generalised Anxiety Disorder (GAD-7) scales; trajectories of symptom change. Results Younger age, being female, greater COVID-19-related work and social impairment, COVID-19-related financial distress, having a neurological or mental illness diagnosis, and recent adversity were each significantly associated with higher baseline depression and anxiety scores. Growth mixture models identified three latent trajectories for depression symptoms (low throughout the study, 81% of participants; moderate throughout the study, 10%; initially severe then declining, 9%) and four for anxiety symptoms (low throughout the study, 77%; initially moderate then increasing, 10%; initially moderate then declining, 5%; initially mild then increasing before again declining, 8%). Factors statistically associated with not having a low symptom trajectory included mental disorder diagnoses, COVID-19-related financial distress and social and work impairment, and bushfire exposure. Conclusion Our longitudinal data enabled identification of distinct symptom trajectories during the first three months of the COVID-19 pandemic in Australia. Early intervention to ensure that vulnerable people are clinically and socially supported during a pandemic should be a priority

α-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra

The protein α-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal α-synuclein burden. Here, feasibility and safety of α-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA) directed against α-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of α-synuclein mRNA and protein in the infused (left) vs. untreated (right) hemisphere and revealed a significant 40–50% suppression of α-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in α-synuclein. Infusion with α-synuclein siRNA, while lowering α-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i) the number and phenotype of nigral dopaminergic neurons, and (ii) the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-α-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics

Corrigendum: The Effect of COVID-19 on Mental Health and Wellbeing in a Representative Sample of Australian Adults

In the original article, there was an error in Table 3 as published. The prevalence of depression and generalized anxiety in our sample appeared in the wrong rows. The main text of the original article did however report the prevalence rates correctly, i.e., the statement “Overall, 20.3% and 16.4% of our sample scored above the clinical cut-offs on our depression (PHQ-9) and anxiety (GAD-7) measures respectively.” (p. 4 of original article) is correct. The corrected Table 3 appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. The original article: by Dawel, A., Shou, Y., Smithson, M., Cherbuin, N., Banfield, M., Calear, A. L., et al. (2020). Front. Psychiatry 11:579985. doi: 10.3389/fpsyt.2020.57998

Involvement of the Intrinsic/Default System in Movement-Related Self Recognition

The question of how people recognize themselves and separate themselves from the environment and others has long intrigued philosophers and scientists. Recent findings have linked regions of the ‘default brain’ or ‘intrinsic system’ to self-related processing. We used a paradigm in which subjects had to rely on subtle sensory-motor synchronization differences to determine whether a viewed movement belonged to them or to another person, while stimuli and task demands associated with the “responded self” and “responded other” conditions were precisely matched. Self recognition was associated with enhanced brain activity in several ROIs of the intrinsic system, whereas no differences emerged within the extrinsic system. This self-related effect was found even in cases where the sensory-motor aspects were precisely matched. Control conditions ruled out task difficulty as the source of the differential self-related effects. The findings shed light on the neural systems underlying bodily self recognition

Neuroimaging the consciousness of self: Review, and conceptual-methodological framework

We review neuroimaging research investigating self-referential processing (SRP), that is, how we respond to stimuli that reference ourselves, prefaced by a lexical-thematic analysis of words indicative of “self-feelings”. We consider SRP as occurring verbally (V-SRP) and non-verbally (NV-SRP), both in the controlled, “top-down” form of introspective and interoceptive tasks, respectively, as well as in the “bottom-up” spontaneous or automatic form of “mind wandering” and “body wandering” that occurs during resting state. Our review leads us to outline a conceptual and methodological framework for future SRP research that we briefly apply toward understanding certain psychological and neurological disorders symptomatically associated with abnormal SRP. Our discussion is partly guided by William James’ original writings on the consciousness of self

Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual participant data

BACKGROUND: Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom. METHODS: We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683. FINDINGS: We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1·83 [95% credible interval (CrI) -2·90 to -0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. INTERPRETATION: The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package. FUNDING: Japan Society for the Promotion of Science.Japan Society for the Promotion of Science

Neural substrates of self-referential processing in Chinese Buddhists

Our recent work showed that self-trait judgment is associated with increased activity in the ventral medial prefrontal cortex (VMPFC) in non-religious Chinese, but in the dorsal medial prefrontal cortex (DMPFC) in Chinese Christians. The current work further investigated neural substrates of self-referential processing in Chinese Buddhists. Using functional magnetic resonance imaging, we scanned 14 Chinese Buddhists, while they conducted trait judgments of the self, Zhu Rongji (the former Chinese premier), Sakyamuni (the Buddhist leader) and Jesus (the Christian leader). We found that, relative to Zhu Rongji judgment, self-judgment in Buddhist participants failed to generate increased activation in the VMPFC but induced increased activations in the DMPFC/rostral anterior cingulate cortex, midcingulate and the left frontal/insular cortex. Self-judgment was also associated with decreased functional connectivity between the DMPFC and posterior parietal cortex compared with Zhu Rongji judgment. The results suggest that Buddhist doctrine of No-self results in weakened neural coding of stimulus self-relatedness in the VMPFC, but enhanced evaluative processes of self-referential stimuli in the DMPFC. Moreover, self-referential processing in Buddhists is characterized by monitoring the conflict between the doctrine of No-self and self-focus thinking during self-trait judgment