Longitudinal associations between resting-state, interregional theta-beta phase-amplitude coupling, psychological distress, and wellbeing in 12-15-year-old adolescents.

Cross-frequency coupling between the phase of slower oscillatory activity and the amplitude of faster oscillatory activity in the brain (phase-amplitude coupling; PAC), is a promising new biological marker for mental health. Prior research has demonstrated that PAC is associated with mental health. However, most research has focused on within-region theta-gamma PAC in adults. Our recent preliminary study found increased theta-beta PAC was associated with increased psychological distress in 12 year olds. It is important to investigate how PAC biomarkers relate to mental health and wellbeing in youth. Thus, in this study, we investigated longitudinal associations between interregional (posterior-anterior cortex) resting-state theta-beta PAC (Modulation Index [MI]), psychological distress and wellbeing in N = 99 adolescents (aged 12-15 years). In the right hemisphere, there was a significant relationship, whereby increased psychological distress was associated with decreased theta-beta PAC and psychological distress increased with increased age. In the left hemisphere, there was a significant relationship, whereby decreased wellbeing was associated with decreased theta-beta PAC and wellbeing scores decreased with increased age. This study presents novel findings demonstrating longitudinal relationships between interregional, resting-state theta-beta PAC and mental health and wellbeing in early adolescents. This EEG marker may facilitate improved early identification of emerging psychopathology.

A longitudinal study of functional connectome uniqueness and its association with psychological distress in adolescence.

Each human brain has a unique functional synchronisation pattern (functional connectome) analogous to a fingerprint that underpins brain functions and related behaviours. Here we examine functional connectome (whole-brain and 13 networks) maturation by measuring its uniqueness in adolescents who underwent brain scans longitudinally from 12 years of age every four months. The uniqueness of a functional connectome is defined as its ratio of self-similarity (from the same subject at a different time point) to the maximal similarity-to-others (from a given subject and any others at a different time point). We found that the unique whole brain connectome exists in 12 years old adolescents, with 92% individuals having a whole brain uniqueness value greater than one. The cingulo-opercular network (CON; a long-acting 'brain control network' configuring information processing) demonstrated marginal uniqueness in early adolescence with 56% of individuals showing uniqueness greater than one (i.e., more similar to her/his own CON four months later than those from any other subjects) and this increased longitudinally. Notably, the low uniqueness of the CON correlates (ß = -18.6, FDR-Q < < 0.001) with K10 levels at the subsequent time point. This association suggests that the individualisation of CON network is related to psychological distress levels. Our findings highlight the potential of longitudinal neuroimaging to capture mental health problems in young people who are undergoing profound neuroplasticity and environment sensitivity period.

Can measures of sleep quality or white matter structural integrity predict level of worry or rumination in adolescents facing stressful situations? Lessons from the COVID-19 pandemic.

INTRODUCTION: COVID-19 has resulted in major life changes to the majority of the world population, particularly adolescents, with social-distancing measures such as home-based schooling likely to impact sleep quality. Increased worry is also likely considering the substantial financial, educational and health concerns accompanying COVID-19. White matter (WM) integrity has been shown to be associated with anxiety and depression symptoms, including worry, as well being closely associated with sleep quality. This study aimed to investigate the associations between pre-COVID sleep quality, WM structural integrity and levels of worry and rumination about COVID. METHODS: N = 30 adolescent participants from Queensland, Australia, completed diffusion tensor imaging (DTI) scanning pre-COVID, the Pittsburgh Sleep Quality Index (PSQI) pre and during COVID, and 9 items designed to measure 3 constructs, perceived impact of COVID, general worry, and COVID-specific worry and rumination. RESULTS: Sleep quality (PSQI total) was significantly poorer during COVID compared with pre-COVID. Sleep onset latency measured pre-COVID was significantly associated with COVID-specific worry and rumination. While the structural integrity of a number of WM tracts (measured pre-COVID) were found to be significantly associated with COVID-specific worry and rumination. Follow-up regression analysis using a model including pre-COVID sleep onset latency, structural integrity of the posterior limb of the internal capsule (PLIC), gender and change in PSQI explained a significant 47% of the variance in COVID-specific worry and rumination. CONCLUSIONS: These findings suggest that adolescents with poor sleep quality and perturbed WM integrity may be at risk of heightened reactivity to future stressful events and interventions should focus on improving sleep onset latency.

Predicting therapeutic response to oral ketamine for chronic suicidal ideation: a Bayesian network for clinical decision support.

BACKGROUND: The glutamatergic modulator ketamine has been shown to result in rapid reductions in both suicidal ideation (SI) and depressive symptoms in clinical trials. There is a practical need for identification of pre-treatment predictors of ketamine response. Previous studies indicate links between treatment response and body mass index (BMI), depression symptoms and previous suicide attempts. Our aim was to explore the use of clinical and demographic factors to predict response to serial doses of oral ketamine for chronic suicidal ideation. METHODS: Thirty-two participants completed the Oral Ketamine Trial on Suicidality (OKTOS). Data for the current study were drawn from pre-treatment and follow-up time-points of OKTOS. Only clinical and sociodemographic variables were included in this analysis. Data were used to create a proof of concept Bayesian network (BN) model of variables predicting prolonged response to oral ketamine, as defined by the Beck Scale for Suicide Ideation (BSS). RESULTS: The network of potential predictors of response was evaluated using receiver operating characteristic (ROC) curve analyses. A combination of nine demographic and clinical variables predicted prolonged ketamine response, with strong contributions from BMI, Social and Occupational Functioning Assessment Scale (SOFAS), Montgomery-Asberg Depression Rating Scale (MADRS), number of suicide attempts, employment status and age. We evaluated and optimised the proposed network to increase the area under the ROC curve (AUC). The performance evaluation demonstrated that the BN predicted prolonged ketamine response with 97% accuracy, and AUC = 0.87. CONCLUSIONS: At present, validated tools to facilitate risk assessment are infrequently used in psychiatric practice. Pre-treatment assessment of individuals' likelihood of response to oral ketamine for chronic suicidal ideation could be beneficial in making more informed decisions about likelihood of success for this treatment course. Clinical trials registration number ACTRN12618001412224, retrospectively registered 23/8/2018.

Investigating the association between sleep quality and diffusion-derived structural integrity of white matter in early adolescence.

INTRODUCTION: Poor sleep quality has been linked to reduced neural connectivity through decreased white matter (WM) structural integrity. WM tract development has been shown to continue throughout adolescence with studies reporting positive correlations between diffusion-derived estimates of structural integrity and reduced sleep quality in adult samples. Few studies have investigated this relationship exclusively within a sample of young adolescents. METHODS: N = 51 participants aged 12 years (M = 151.5 months, SD = 4 months) completed a self-report questionnaire which included the Pittsburgh Sleep Quality Index (PSQI) and underwent Diffusion Tensor Imaging (DTI) as part of their baseline assessment in the Longitudinal Adolescent Brain Study (LABS) being undertaken in Queensland, Australia. Fractional anisotropy (FA) were extracted using Tract-Based Spatial Statistics (TBSS) to investigate associations between sleep quality and WM integrity across the brain. RESULTS: Significant correlations were found between the posterior limb of the internal capsule and the PSQI total sleep quality and sleep latency scores. There was also a significant difference in sleep duration between male and female participants. CONCLUSION: These findings provide an important insight of the impact that sleep may have on early adolescent WM development. Ongoing longitudinal assessment of sleep on WM development across adolescence is likely to provide further important information about how WM maturation relates to variations in sleep quality as circadian rhythm changes occur during middle and late adolescence.

Incidence of Discharge Against Medical Advice in Queensland Hospital Emergency Departments Among Indigenous Patients from 2016 to 2021.

BACKGROUND: The incidence of discharge against medical advice (DAMA) in emergency departments (EDs) among Indigenous people is a growing concern in Australia. This study aimed to determine the incidence of ED DAMA in public hospitals in Queensland (QLD) from 2016 to 2021 and investigate the disparities in ED DAMA between Indigenous and non-Indigenous patients. The study also assessed the impact of the COVID-19 pandemic on the incidence of ED DAMA. METHODS: A descriptive epidemiological study was conducted using aggregated data from QLD public hospital EDs. The data was retrieved from Clinical Excellence QLD, Healthcare Improvement Unit, in the QLD Health Open Data Portal for the period 1 January 2016 to 31 December 2021. Incidence rates and unadjusted odds ratios were calculated and compared using the chi-square test to identify differences between Indigenous and non-Indigenous patients. RESULTS: The annual incidence of DAMA in EDs was 7.7% among Indigenous patients, compared to 4.8% among non-Indigenous patients, with the highest rate (8.9%) reported in 2021 among Indigenous patients. The incidence of ED DAMA was higher for Indigenous patients in major cities (20.0%) than in very remote areas (7.4%). Patients in triage categories 4 (10.0%) and 3 (7.3%) accounted for the vast majority of ED DAMA events among Indigenous patients. The acute group A hospitals had the highest incidence of ED DAMA (10.9% for Indigenous patients and 6.5% for non-Indigenous patients). The COVID-19 pandemic had no impact on the incidence of ED DAMA. CONCLUSION: Indigenous patients experience a disparity in ED DAMA incidence. Addressing this issue requires collaborative efforts from healthcare providers, policymakers, and community organizations.

Electrophysiological phenotypes of suicidality predict prolonged response to oral ketamine treatment.

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.

clusterBMA: Bayesian model averaging for clustering.

Various methods have been developed to combine inference across multiple sets of results for unsupervised clustering, within the ensemble clustering literature. The approach of reporting results from one 'best' model out of several candidate clustering models generally ignores the uncertainty that arises from model selection, and results in inferences that are sensitive to the particular model and parameters chosen. Bayesian model averaging (BMA) is a popular approach for combining results across multiple models that offers some attractive benefits in this setting, including probabilistic interpretation of the combined cluster structure and quantification of model-based uncertainty. In this work we introduce clusterBMA, a method that enables weighted model averaging across results from multiple unsupervised clustering algorithms. We use clustering internal validation criteria to develop an approximation of the posterior model probability, used for weighting the results from each model. From a combined posterior similarity matrix representing a weighted average of the clustering solutions across models, we apply symmetric simplex matrix factorisation to calculate final probabilistic cluster allocations. In addition to outperforming other ensemble clustering methods on simulated data, clusterBMA offers unique features including probabilistic allocation to averaged clusters, combining allocation probabilities from 'hard' and 'soft' clustering algorithms, and measuring model-based uncertainty in averaged cluster allocation. This method is implemented in an accompanying R package of the same name. We use simulated datasets to explore the ability of the proposed technique to identify robust integrated clusters with varying levels of separation between subgroups, and with varying numbers of clusters between models. Benchmarking accuracy against four other ensemble methods previously demonstrated to be highly effective in the literature, clusterBMA matches or exceeds the performance of competing approaches under various conditions of dimensionality and cluster separation. clusterBMA substantially outperformed other ensemble methods for high dimensional simulated data with low cluster separation, with 1.16 to 7.12 times better performance as measured by the Adjusted Rand Index. We also explore the performance of this approach through a case study that aims to identify probabilistic clusters of individuals based on electroencephalography (EEG) data. In applied settings for clustering individuals based on health data, the features of probabilistic allocation and measurement of model-based uncertainty in averaged clusters are useful for clinical relevance and statistical communication.

The effect of mindfulness training on resting-state networks in pre-adolescent children with sub-clinical anxiety related attention impairments.

Mindfulness training has been associated with improved attention and affect regulation in preadolescent children with anxiety related attention impairments, however little is known about the underlying neurobiology. This study sought to investigate the impact of mindfulness training on functional connectivity of attention and limbic brain networks in pre-adolescents. A total of 47 children with anxiety and/or attention issues (aged 9-11 years) participated in a 10-week mindfulness intervention. Anxiety and attention measures and resting-state fMRI were completed at pre- and post-intervention. Sustained attention was measured using the Conners Continuous Performance Test, while the anxiety levels were measured using the Spence Children's Anxiety Scale. Functional networks were estimated using independent-component analysis, and voxel-based analysis was used to determine the difference between the time-points to identify the effect of the intervention on the functional connectivity. There was a significant decrease in anxiety symptoms and improvement in attention scores following the intervention. From a network perspective, the results showed increased functional connectivity post intervention in the salience and fronto-parietal networks as well as the medial-inferior temporal component of the default mode network. Positive correlations were identified in the fronto-parietal network with Hit Response Time and the Spence Children's Anxiety Scale total and between the default mode network and Hit Response Time. A 10-week mindfulness intervention in children was associated with a reduction in anxiety related attention impairments, which corresponded with concomitant changes in functional connectivity.

Social Connectedness, Cyberbullying, and Well-Being: Preliminary Findings from the Longitudinal Adolescent Brain Study.

Social connectedness is well established as an important aspect of adolescence, with higher levels typically resulting in positive mental health and well-being. Cyberbullying is a prevalent concern during adolescence and is a significant contributor to poor mental health outcomes during this important phase of life. Research shows that social connectedness may act as a protective factor for mental health and well-being when young people experience cyberbullying. However, further research is required to elucidate associations between social connectedness, well-being, and cyberbullying over time. This article outlines preliminary findings from the Longitudinal Adolescent Brain Study (LABS). Data are reported from N = 64 LABS participants recruited at age 12 and assessed at four timepoints over a 12-month period, with a total of 204 completed assessments. Structural equation modeling revealed a mediating effect of social connectedness on the relationship between cyberbullying and well-being. In other words, the negative influences of cyberbullying and cybervictimization on well-being scores over time are influenced by levels of social connectedness. The present findings highlight that increased social connectedness in young people is vital to promoting positive well-being over time and can protect well-being in those experiencing cyberbullying and/or cybervictimization. Findings can inform cyberbullying education programs, health care practitioners, parents, and educators on the importance of young people remaining socially connected when experiencing cyberbullying and/or cybervictimization.

Basal ganglia correlates of wellbeing in early adolescence.

It has been suggested that biological markers that define mental health are different to those that define mental illness. The basal ganglia changes dramatically over adolescence and has been linked to wellbeing and mental health disorders in young people. However, there remains a paucity of research on wellbeing and brain structure in early adolescence. This cross-sectional study examined relationships between grey matter volume (GMV) of basal ganglia regions (caudate, putamen, pallidum and nucleus accumbens) and self-reported wellbeing (COMPAS-W), in a sample of Australian adolescents aged 12 years (N = 49, M = 12.6, 46.9% female). Significant negative associations were found between left hemisphere caudate GMV and scores on 'total wellbeing', 'composure' and 'positivity'. The results of this study indicate that smaller caudate GMV at age 12 is linked to increased subjective wellbeing. While seemingly counter-intuitive, our finding is consistent with previous research of decreased GMV in the pons and increased COMPAS-W scores in adults. Our results suggest that protective neurobiological factors may be identifiable early in adolescence and be linked to specific types of wellbeing (such as positive affect and optimism). This has implications for interventions targeted at building resilience against mental health disorders in young people.

Oral ketamine reduces the experience of stress in people with chronic suicidality.

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.

Dataset of brain functional connectome and its maturation in adolescents.

We provided the dataset of brain connectome matrices, their similarities measures to self and others longitudinally, and Kessler's psychological distress scales (K10) including the response to each question. The dataset can be used to replicate the results of the manuscript titled "A longitudinal study of functional connectome uniqueness and its association with psychological distress in adolescence". The functional connectome (whole-brain and 13 networks) matrices were calculated from the resting-state functional MRIs (rs-fMRIs). We collected rs-fMRI and Kessler's psychological distress scale (K10) in 77 adolescents longitudinally up to 9 times from 12 years of age every four months. After removal of data with excessive motion, 262 functional connectome matrices were provided with this paper. The 300 regions of interest (ROIs) were defined using the Greene lab brain atlas. The functional connectome matrices were calculated as correlations between time series from any pair of ROIs extracted from pre-processed fMRIs. This dataset could be potentially used to1.Understand developmental changes in the functional brain connectivity,2.As a normal control database of functional connectome matrices,3.Develop and validate connectome and network-related analysing methods.

EEG-based clusters differentiate psychological distress, sleep quality and cognitive function in adolescents.

INTRODUCTION: To better understand the relationships between neurophysiology, cognitive function and psychopathology risk in adolescence there is value in identifying data-driven subgroups based on measurements of brain activity and function, and then comparing cognition and mental health between such subgroups. METHODS: We developed a flexible and scaleable multi-stage analysis pipeline to identify data-driven clusters of 12-year-olds (M = 12.64, SD = 0.32) based on frequency characteristics calculated from resting state, eyes-closed electroencephalography (EEG) recordings. For this preliminary cross-sectional study, EEG data was collected from 59 individuals in the Longitudinal Adolescent Brain Study (LABS) being undertaken in Queensland, Australia. Applying multiple unsupervised clustering algorithms to these EEG features, we identified well-separated subgroups of individuals. To study patterns of difference in cognitive function and mental health symptoms between clusters, we applied Bayesian regression models to probabilistically identify differences in these measures between clusters. RESULTS: We identified 5 core clusters associated with distinct subtypes of resting state EEG frequency content. Bayesian models demonstrated substantial differences in psychological distress, sleep quality and cognitive function between clusters. By examining associations between neurophysiology and health measures across clusters, we have identified preliminary risk and protective profiles linked to EEG characteristics. CONCLUSION: This method provides the potential to identify neurophysiological subgroups of adolescents in the general population based on resting state EEG, and associated patterns of health and cognition that are not observed at the whole group level. This approach offers potential utility in clinical risk prediction for mental and cognitive health outcomes throughout adolescent development.

Phase-Amplitude Coupling, Mental Health and Cognition: Implications for Adolescence.

Identifying biomarkers of developing mental disorder is crucial to improving early identification and treatment-a key strategy for reducing the burden of mental disorders. Cross-frequency coupling between two different frequencies of neural oscillations is one such promising measure, believed to reflect synchronization between local and global networks in the brain. Specifically, in adults phase-amplitude coupling (PAC) has been shown to be involved in a range of cognitive processes, including working and long-term memory, attention, language, and fluid intelligence. Evidence suggests that increased PAC mediates both temporary and lasting improvements in working memory elicited by transcranial direct-current stimulation and reductions in depressive symptoms after transcranial magnetic stimulation. Moreover, research has shown that abnormal patterns of PAC are associated with depression and schizophrenia in adults. PAC is believed to be closely related to cortico-cortico white matter (WM) microstructure, which is well established in the literature as a structural mechanism underlying mental health. Some cognitive findings have been replicated in adolescents and abnormal patterns of PAC have also been linked to ADHD in young people. However, currently most research has focused on cross-sectional adult samples. Whereas initial hypotheses suggested that PAC was a state-based measure due to an early focus on cognitive, task-based research, current evidence suggests that PAC has both state-based and stable components. Future longitudinal research focusing on PAC throughout adolescent development could further our understanding of the relationship between mental health and cognition and facilitate the development of new methods for the identification and treatment of youth mental health.

A novel, complex systems approach to modelling risk of psychological distress in young adolescents.

Adolescence is a period of significant anatomical and functional brain changes, and complex interactions occur between mental health risk factors. The Longitudinal Adolescent Brain Study commenced in 2018, to monitor environmental and psychosocial factors influencing mental health in 500 adolescents, for 5 years. Participants are recruited at age 12 from the community in Australia's Sunshine Coast region. In this baseline, cross-sectional study of N = 64 participants, we draw on the network perspective, conceptualising mental disorders as causal systems of interacting entities, to propose a Bayesian network (BN) model of lifestyle and psychosocial variables influencing chances of individuals being psychologically well or experiencing psychological distress. Sensitivity analysis of network priors revealed that psychological distress (Kessler-10) was most affected by eating behaviour. Unhealthy eating increased the chance of moderate psychological distress by 600%. Low social connectedness increased the chance of severe psychological disorder by 200%. Certainty for psychological wellness required 33% decrease in unhealthy eating behaviours, 11% decrease in low social connectedness, and 9% reduction in less physical activity. BN can augment clinician judgement in mental disorders as probabilistic decision support systems. The full potential of BN methodology in a complex systems approach to psychopathology has yet to be realised.

Short strides to important findings: A short interval longitudinal study of sleep quality, psychological distress and microstructure changes to the uncinate fasciculus in early adolescents.

BACKGROUND: Developmental studies have shown adolescence is a period of ongoing white matter (WM) development, reduced sleep quality and the onset of many mental disorders. Findings indicate the WM development of the uncinate fasciculus (UF), a WM tract suggested to play a key role in mental disorders, continues throughout adolescence. While these studies provide valuable information, they are limited by long intervals between scans (1 to 4 years) leaving researchers and clinicians to infer what may be occurring between time-points. To allow inferences to be made regarding the impact that sleep quality may be having on WM development, longitudinal studies with much shorter between-scan intervals are required. METHODS: The current study reports longitudinal data of self-reported sleep quality (PSQI), diffusion tensor imaging (DTI) measures of WM development and psychological distress (K10) for n = 64 early adolescents spanning the first twelve months (four time-points; Baseline, 4, 8, & 12 months) of the Longitudinal Adolescent Brain Study (LABS) study currently underway at the Thompson Institute. RESULTS: Generalised Estimating Equation analysis showed a significant relationship between sleep quality and psychological distress over the four time-points. Reduced radial diffusivity and increased fractional anisotropy of the UF is also reported with increasing age suggesting that ongoing myelination is occurring. Adding sleep quality to the model, however, negatively impacted this myelination process. CONCLUSION: These findings represent an important step towards elucidating how sleep, psychological distress and maturation of the UF may co-develop during early adolescence.

Relationships between reduction in symptoms and restoration of function and wellbeing: Outcomes of the Oral Ketamine Trial on Suicidality (OKTOS).

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 restoration of function and wellbeing in antisuicidal and antidepressant therapy, including clinical trials.

Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study.

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.

Using measures of intrinsic homeostasis and extrinsic modulation to evaluate mental health in adolescents: Preliminary results from the longitudinal adolescent brain study (LABS).

Adolescence is a period when complex interactions occur between mental health risk factors. The Longitudinal Adolescent Brain Study (LABS) commenced in 2018, to monitor environmental and psychosocial factors thought to influence mental health in 500 young people. Participants commence at 12 years of age, via a community-based recruitment model, and data is collected at 15 time-points over five years. This study examines demographic and psychosocial self-report data from time-point 1, for the first 50 participants. Here we investigate associations between environmental and psychosocial factors, considered as measures of intrinsic homeostasis and extrinsic modulation. Numerous strong correlations were found. Findings indicate that sleep dysfunction and social connectedness were strongly associated external modulators of intrinsic homeostasis in this sample of 12-year old participants. To successfully address the increase in mental health problems in young people, comprehensive evaluation of lifestyle and environmental risk factors is recommended in addition to medicalised approaches. Interventions to promote mental health wellbeing in young adolescents should include a focus on sleep quality and patterns and the positive and negative aspects of social connectedness.