Monique T Jones

Rational
Ketamine has been investigated as a treatment alternative for PTSD for the last 20 years, yet there have been limited reports of biological changes or biomarker characterisation related to treatment.

Objectives
To address this significant gap, this study analysed blood samples from 25 participants with PTSD who took part in an open-label 6-week trial of low dose oral ketamine treatment.

Methods
Serum and plasma samples were quantified before and after ketamine treatment for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor A (VEGF-A), serotonin, FK506 binding protein 51 (FKBP51) and a panel of cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-12p70, IL-17 A and tumour necrosis factor alpha (TNFα)).

Results
Analysis of BDNF and VEGF-A levels from serum detected a significant positive correlation between the two biomarkers and a small but statistically significant decrease in both measures after ketamine treatment. This novel finding reinforces theories that ketamine’s effects may rely on a reciprocal interaction between BDNF and VEGF-A, offering potential insights into a biological mechanism underpinning PTSD symptom reduction. Additionally, the analysis of FKBP51 and serotonin revealed novel relationships between these biomarkers and clinical scales, before and after ketamine treatment. Finally, significant changes or relationships involving the immune cytokines were not detected, possibly because half the participants presented with low-grade inflammation while the other half did not.

Conclusions
This study represents a much-needed broad analysis of blood biomarkers before and after ketamine treatment for PTSD and reveals important biological changes and relationships related to this treatment.

The COVID-19 pandemic highlighted growing demand on mental health services and the need for scalable early interventions. Lifestyle medicine is a first-line treatment for common mental health disorders. Combining health coaching with lifestyle medicine and online delivery may improve accessibility and effectiveness. This study evaluated the EMERALD program, an 8-week online lifestyle medicine and health coaching intervention delivered as a clinical service during the pandemic. A single arm, pre–post observational design was used, with assessments completed at baseline (week 1) and post-intervention (week 8). Eighty-five adults (M_age = 46.47, SD = 15.47) completed all outcome measures; most participants identified as female (83.5%). Eligible community participants reported mild to moderate anxiety or mood symptoms (PHQ-9 < 14; GAD-7 < 14). Individuals with severe symptoms, suicide risk, or current engagement in psychological or psychiatric treatment were excluded. Depression, anxiety, wellbeing, loneliness, and functioning across life domains (e.g., occupational, social, daily responsibilities) were assessed using validated self-report measures. Significant improvements were observed across all measures, with greater wellbeing gains among those with higher baseline depression severity. These findings support the benefits of online mental health coaching and lifestyle medicine interventions for improving psychological wellbeing during periods of elevated need.

Objective
The rising prevalence of mental health symptoms brought on by the COVID19 pandemic led to the inception and development of EMERging Anxiety, Loneliness, Depression (EMERALD) well-being programme. EMERALD was designed to improve psychological well-being of the general population who had not previously sought mental health support. The programme incorporated a focus on lifestyle medicine and was underpinned by solution focused health coaching. The aim of the paper is to describe the programme according to the Template for Intervention Description and Replication (TIDieR) checklist to provide detailed reporting of the intervention's elements.
Methods
The TIDieR checklist was utilised to comprehensively describe the programme, including theoretical underpinnings, materials, procedures, providers, mode of delivery and tailoring of the programme. The Behaviour Change Technique Taxonomy v2 was used to identify the specific behaviour change techniques used within the solution focused health coaching framework.
Results
The programme was developed to align with the latest evidence-based literature in lifestyle medicine and solution focused coaching. The programme also offered allied health expertise, online educational modules and was tailored to the participants. The programme was delivered online through a telehealth platform.
Conclusion
The TIDieR checklist has enabled the provision of a detailed structure of the EMERALD program intervention. The behaviour change taxonomy has facilitated the outlining of specific techniques used in health coaching sessions. Both structures have operationalised the detail of the intervention for the purposes of replication and informing the literature.

Analysis of cognitive behavioural therapy apps for generalised anxiety disorder: Evidence-based content and user experience. Abstract Mental illness substantially contributes to the global burden of disease, with anxiety high in prevalence. The increase of mobile technology, mental health apps have potential to lessen this burden. However, within apps, the use of evidence-based interventions, such as cognitive behavioural therapy (CBT) are limited. Regardless, many commercially available mental health apps are highly rated by users, highlighting the need to understand what makes mental health apps valuable to the user. The contribution of this study was to uncover apps that support generalised anxiety disorder (GAD) and worry with a CBT basis, explore app functionality, and user experience. Firstly, by identifying apps that support GAD and worry and included CBT. Secondly, by identifying and analysing therapeutic and engagement functions within the apps, and finally, by thematically analysing user reviews. Six apps were identified to support GAD and worry that purported to be CBT-based. However, CBT therapeutic features and engagement features were minimally present in the apps. User reviews yielded 112 comments about the apps and key themes were identified about the app users' global experiences with the app, and about the combination of technological (e.g., useability, reliability) and therapeutic experiences (e.g., learning and using skills). Future development of quality apps to support GAD and worry must consider the empirical standing of both therapeutic and technology aspects, to provide efficacious and engaging interventions.

Oral ketamine has shown to be a rapid-acting antidepressant and a potential treatment option for suicidality, however, repeated doses are often required. Objective markers of prolonged treatment response are needed to help individuals and clinicians make informed treatment decisions. This secondary analysis sought to identify objective electrophysiological predictors of both prolonged response and dose sensitivity to low-dose oral ketamine in people with chronic suicidality. Individuals with a Beck Scale for Suicide Ideation total score (BSS) ≥ 6 (N = 29) completed a six-week ketamine treatment, pre-treatment electroencephalography and follow-up assessment of suicidality (four weeks from the final ketamine dose). Prolonged response was observed in 52% of participants (follow-up BSS reduced by 50% or ≤6); nearly half were prolonged non-responders. There was decisive evidence for a predictive Bayesian linear regression model with follow-up BSS score as the response variable and pre-treatment auditory evoked power bands as predictors (theta, alpha and beta frequencies, BF10 = 17,948, R2 = 0.70). A Bayesian one-way ANOVA indicated strong evidence for a model of positive association between auditory evoked power and ketamine dose sensitivity (theta-alpha BF+0 = 108, effect size δ = 1.3, 95% CI 0.5–2.1; high-beta BF+0 = 7.4, δ = 0.8, 95% CI 0.1–1.6). Given auditory evoked power may index serotonin neurotransmission, these results suggest that a prolonged response to ketamine may, in part, be mediated by pre-treatment serotonergic functioning. In addition, the observed beta power differences may arise from GABAergic functioning. These suicidality phenotypes, identifiable by pre-treatment electrophysiology, may aid diagnosis, treatment selection and prediction of prolonged treatment outcome.

Research of clinical patients with a pre-existing psychological disorder involved in a disaster is limited. This study investigated relationships between pre-and post-earthquake psychopathology (i.e., anxiety, depression, and posttraumatic stress), peritraumatic distress, work and social impairment, perceived support post-earthquake, and personality dimensions in an outpatient, anxiety disorder population. Thirty-seven patients with pre-existing anxiety disorders completed standard clinical assessments pre-earthquake. They then completed a second set of questionnaires 3 months after exposure to the 2010 Christchurch, Aotearoa New Zealand, earthquake. Bivariate correlations on the variables determined what relationships were present, and paired samples t-tests assessed differences in pre-and post-earthquake anxiety, depression, and alcohol and drug consumption as well as relationships with peritraumatic distress, posttraumatic stress, and personality variables. Significant relationships were found between pre-earthquake psychopathology, peritraumatic distress, post-earthquake psychopathology, and impairment. Paired samples t-tests demonstrated anxiety and depression scores were significantly lower post-earthquake. However, prior anxiety and depression, as well as peritraumatic distress, were significantly associated with post-earthquake psychopathology, including posttraumatic stress and impaired work and social functioning. There were no differences between pre-and post-event alcohol and drug consumption. The personality dimensions of harm avoidance, self-directedness, and persistence significantly associated with post-disaster anxiety and depression. Promisingly, post-earthquake perceived support was significantly negatively correlated with depression and posttraumatic stress.

Background:
Stress is prevalent in people experiencing suicidality and is a major contributor to the development of mental disorders. Evidence suggests ketamine shows capacity to reverse stress-induced brain changes. Though stress and ketamine have been explored individually for suicidality, this study is the first to examine ketamine treatment for self-reported stress in adults with chronic suicidality, building on pre-clinical evidence of ketamine's capacity to normalize stress-induced responses and contributing to our understanding of oral ketamine in clinical populations.

Methods:
Thirty two adult participants (22–72 years; 17 female) with chronic suicidality completed 6 weeks of active treatment, receiving low (0.5 mg/kg – 3.0 mg/kg) doses of oral ketamine once per week, with a 4-week follow-up phase, to assess the effect of ketamine on their perceived stress. Stress was measured via self-report utilizing the Depression Anxiety Stress Scale-21(DASS-21), and analysed at pre-treatment (week 0), post-treatment (week 6) and at follow-up (week 10).

Results:
Repeated measures ANOVA showed a significant reduction in stress (p<.001) post-treatment and Reliable Change Index calculations confirmed this to be clinically significant. Furthermore, those classified as ‘prolonged responders’ demonstrated a sustained reduction in stress at follow-up (i.e. after 4 weeks of nil ketamine).

Limitations:
Small sample size, open label design, expectancy, secondary analysis

Conclusions:
Ketamine showed the capacity to produce a robust and sustained improvement in stress symptoms, in people with chronic suicidality. Future larger, controlled studies examining treatment suitability in a range of stress related disorders are warranted.

Recovery of functioning is integral to successful treatment outcomes in depressive illness. Optimal antidepressant treatment results in both symptomatic remission and functional recovery. Oral ketamine rapidly reduces suicidality and depression; however, reports of functional and wellbeing outcomes are lacking. This study examines participants’ social and occupational functioning and wellbeing outcomes in the Oral Ketamine Trial on Suicidality (OKTOS). Thirty adults with chronic suicidality participated in the trial over 10 weeks. Functional recovery and wellbeing were assessed using the Social and Occupational Functioning Scale (SOFAS) and World Health Organization Well-Being Index (WHO-5). Suicidality and depressive symptoms were assessed using the Beck Scale for Suicidal ideation (BSS) and Montgomery-Asberg Depression Rating Scale (MADRS). Relationships between the four treatment outcomes were analysed. Forty-three percent of participants achieved healthy function (SOFAS ≥80) and 27% reported healthy wellbeing (WHO-5 >60%) at the four-week post-treatment follow-up. Wellbeing was revealed as the data-derived treatment endpoint for the sample. Effect sizes for functioning and wellbeing outcomes were smaller than for suicidality and depression outcomes. Results suggest that reduction in depressive symptoms and suicidal ideation may be necessary but not sufficient for full resto-ration of function and wellbeing in antisuicidal and antidepressant therapy, including clinical trials.

Recently, low-dose ketamine has been proposed as a rapid-acting treatment option for suicidality. The majority of studies to date have utilised intravenous (IV) ketamine, however, this route of administration has limitations. On the other hand, oral ketamine can be administered in a range of settings, which is important in treating suicidality, although studies as to safety and feasibility are lacking.
n
 = 32 adults (aged 22–72 years; 53% female) with chronic suicidal thoughts participated in the Oral Ketamine Trial on Suicidality (OKTOS), an open-label trial of sub-anaesthetic doses of oral ketamine over 6 weeks. Participants commenced with 0.5 mg/kg of ketamine, which was titrated to a maximum 3.0 mg/kg. Follow-up assessments occurred at 4 weeks after the final dose. The primary outcome measure was the Beck Scale for Suicide Ideation (BSS) and secondary measures included scales for suicidality and depressive symptoms, and measures of functioning and well-being. Mean BSS scores significantly reduced from a high level of suicidal ideation at the pre-ketamine (week 0) timepoint to below the clinical threshold at the post-ketamine (week 6) timepoint. The proportion of participants that achieved clinical improvement within the first 6 weeks was 69%, whereas 50% achieved a significant improvement by the follow-up (week 10) timepoint. Six weeks of oral ketamine treatment in participants with chronic suicidality led to significant reduction in suicidal ideation. The response observed in this study is consistent with IV ketamine trials, suggesting that oral administration is a feasible and tolerable alternative treatment for chronic suicidality.

Social anxiety disorder (SAD) is a prevalent chronic condition with a large demand for treatment. This community outpatient study examined the effectiveness of a group intervention version of the established one-to-one cognitive therapy derived from the Clark and Wells model for SAD. Questionnaires were completed pre-treatment and post-treatment for SAD symptoms (Social Phobia Scale, Social Interaction Anxiety Scale), depressive symptoms (BDI-II), self-focused attention, safety behaviours (Social Phobia Weekly Summary Scale and Subtle Avoidance Frequency Examination), and impaired functioning (Work and Social Adjustment Scale). From an initial sample of 159 participants, 101 completed at least seven of the nine weekly group sessions (Mage = 34.1 years, SDage = 10.8 years, 53% female). Significant improvements were demonstrated on all measures. Large effect sizes were found for social anxiety symptoms and safety behaviour use. Self-focused attention, depressive symptoms, and impaired functioning had moderate effect sizes. Effect sizes for anxiety (d = 1.00 and 1.32) and mood measures (d = 0.71) were as high, or in some cases, higher than previous group treatment studies. Results suggest group cognitive therapy for SAD based on the Clark and Wells model is effective in a clinical setting for individuals with moderate/severe and treatment-resistant social anxiety.