Resting-state EEG correlates of sustained attention in healthy ageing: Cross-sectional findings from the LEISURE study.

While structural and biochemical brain changes are well-documented in ageing, functional neuronal network differences, as indicated by electrophysiological markers, are less clear. Moreover, age-related changes in sustained attention and their associated electrophysiological correlates are still poorly understood. To address this, we analysed cross-sectional baseline electroencephalography (EEG) and cognitive data from the Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE). Participants were 96 healthy older adults, aged 50-84. We examined resting-state EEG periodic (individual alpha frequency [IAF], aperiodic-adjusted individual alpha power [aIAP]) and aperiodic (exponent and offset) activity, and their associations with age and sustained attention. Results showed associations between older age and slower IAF, but not aIAP or global aperiodic exponent and offset. Additionally, hierarchical linear regression revealed that after controlling for demographic variables, faster IAF was associated with better Sustained Attention to Response Task performance, and mediation analysis confirmed IAF as a mediator between age and sustained attention performance. These findings indicate that IAF may be an important marker of ageing, and a slower IAF may signal diminished cognitive processing capacity for sustained attention in older adults.

Structural brain correlates of sustained attention in healthy ageing: Cross-sectional findings from the LEISURE study.

Sustained attention is important for maintaining cognitive function and autonomy during ageing, yet older people often show reductions in this domain. The role of the underlying neurobiology is not yet well understood, with most neuroimaging studies primarily focused on fMRI. Here, we utilise sMRI to investigate the relationships between age, structural brain volumes and sustained attention performance. Eighty-nine healthy older adults (50-84 years, Mage 65.5 (SD=8.4) years, 74 f) underwent MRI brain scanning and completed two sustained attention tasks: a rapid visual information processing (RVP) task and sustained attention to response task (SART). Independent hierarchical linear regressions demonstrated that greater volumes of white matter hyperintensities (WMH) were associated with worse RVP_A' performance, whereas greater grey matter volumes were associated with better RVP_A' performance. Further, greater cerebral white matter volumes were associated with better SART_d' performance. Importantly, mediation analyses revealed that both grey and white matter volumes completely mediated the relationship between ageing and sustained attention. These results explain disparate attentional findings in older adults, highlighting the intervening role of brain structure.

Prevalence of mental disorders among family members of individuals on the autism spectrum: systematic review and meta-analysis.

Parenting a child on the autism spectrum presents particular challenges that can lead to increased stress, anxiety, and depression among family members. Therefore, we aimed to investigate the prevalence of mental disorders in first-degree relatives of individuals on the autism spectrum. This article adheres to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) guidelines, including studies indexed in PubMed/Medline, Embase, PsycINFO, Biblioteca Virtual em Saúde (BVS), and SciELO. Nineteen articles met eligibility criteria for the systematic review. Using a random-effects model (N = 93,876), we found a pooled prevalence of affective disorders of 13% in mothers of people on the autism spectrum (95% CI 7-21%; I2 = 99%, p < 0.01). Additionally, another random-effects model pointed out that first-degree relatives of people on the autism spectrum (N = 93,263) were more likely to present affective disorders than relatives of people with neurotypical development (N = 152,455) (pooled OR: 2.17; 95% CI 1.81-2.61). Careful assessment for mental disorders in parents and siblings of individuals on the autism spectrum is crucial to ensure appropriate treatment for these family members. This approach can also contribute to optimizing care for the individuals on the autism spectrum.

Appearance-related cyberbullying and its association with the desire to alter physical appearance among adolescent females.

Cyberbullying is associated with various mental health concerns in adolescents, including body dissatisfaction and disordered eating behaviours. However, there is a significant research gap concerning the unique effects of appearance-related cyberbullying (ARC) on adolescent mental health. This study examined the prevalence and psychological consequences of ARC among middle to late adolescent females (aged 14-19 years, Mage = 15.98, N = 336). Participants completed an online survey regarding their experiences of ARC, body image variables, and eating disorder symptomology. Findings indicate the widespread occurrence of ARC among adolescent females, with body shape and size emerging as predominant targets. Experiences of ARC-victimisation positively correlated with increased concerns about body shape, body shame, and eating disorder symptomology. Conversely, experiences of ARC-victimisation were negatively correlated with body esteem and body appreciation. Finally, appearance-related cybervictimisation was significantly associated with adolescent females' desire to pursue appearance alterations through methods such as dieting and exercising, altering self-presentation, and undergoing cosmetic procedures due to perceived experiences of ARC. These findings highlight the urgent need for preventative measures, such as age-appropriate social media policies and health promotion programs that encourage positive online behaviour, and strategies to address the impacts of ARC to protect the mental well-being of adolescent females.

Cyberbullying directed towards appearance is a serious problem for many adolescent females. Our study examined how often this type of cyberbullying happens online and its impact on females aged 14­19. We found that many adolescent females experience appearance-related cyberbullying, where they are teased or insulted about their body shape, weight, or physical features. These experiences make them more likely to feel bad about their bodies, leading to harmful behaviours like extreme dieting or considering cosmetic surgery. These findings highlight the urgent need for action from schools, parents, and social media platforms to prevent this form of cyberbullying and support those affected.

Oral ketamine effects on dynamics of functional network connectivity in patients treated for chronic suicidality.

The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning.

Chronotype and subjective sleep quality predict white matter integrity in young people with emerging mental disorders.

Protecting brain health is a goal of early intervention. We explored whether sleep quality or chronotype could predict white matter (WM) integrity in emerging mental disorders. Young people (N = 364) accessing early-intervention clinics underwent assessments for chronotype, subjective sleep quality, and diffusion tensor imaging. Using machine learning, we examined whether chronotype or sleep quality (alongside diagnostic and demographic factors) could predict four measures of WM integrity: fractional anisotropy (FA), and radial, axial, and mean diffusivities (RD, AD and MD). We prioritised tracts that showed a univariate association with sleep quality or chronotype and considered predictors identified by ≥80% of machine learning (ML) models as 'important'. The most important predictors of WM integrity were demographics (age, sex and education) and diagnosis (depressive and bipolar disorders). Subjective sleep quality only predicted FA in the perihippocampal cingulum tract, whereas chronotype had limited predictive importance for WM integrity. To further examine links with mood disorders, we conducted a subgroup analysis. In youth with depressive and bipolar disorders, chronotype emerged as an important (often top-ranking) feature, predicting FA in the cingulum (cingulate gyrus), AD in the anterior corona radiata and genu of the corpus callosum, and RD in the corona radiata, anterior corona radiata, and genu of corpus callosum. Subjective quality was not important in this subgroup analysis. In summary, chronotype predicted altered WM integrity in the corona radiata and corpus callosum, whereas subjective sleep quality had a less significant role, suggesting that circadian factors may play a more prominent role in WM integrity in emerging mood disorders.

A short-interval longitudinal study of associations between psychological distress and hippocampal grey matter in early adolescence.

This study of Australian adolescents (N = 88, 12-13-years-old) investigated the relationship between hippocampal grey matter volume (GMV) and self-reported psychological distress (K10) at four timepoints, across 12 months. Participants were divided into two groups; those who had K10 scores between 10 and 15 for all four timepoints were categorised as "low distress" (i.e., control group; n = 38), while participants who had K10 scores of 16 or higher at least once over the year were categorised as "moderate-high distress" (n = 50). Associations were tested by GEE fitting of GMV and K10 measures at the same time point, and in the preceding and subsequent timepoints. Analyses revealed smaller preceding left GMV and larger preceding right GMV were associated with higher subsequent K10 scores in the "moderate-high distress" group. This was not observed in the control group. In contrast, the control group showed significant co-occurring associations (i.e., at the same TP) between GMV and K10 scores. The "moderate-high distress" group experienced greater variability in distress. These results suggest that GMV development in early adolescence is differently associated with psychological distress for those who experience "moderate-high distress" at some point over the year, compared to controls. These findings offer a novel way to utilise short-interval, multiple time-point longitudinal data to explore changes in volume and experience of psychological distress in early adolescents. The results suggest hippocampal volume in early adolescence may be linked to fluctuations in psychological distress.

Understanding Wellbeing Profiles According to White Matter Structural Connectivity Sub-types in Early Adolescents: The First Hundred Brains Cohort from the Longitudinal Adolescent Brain Study.

Wellbeing is protective against the emergence of psychopathology. Neurobiological markers associated with mental wellbeing during adolescence are important to understand. Limited research has examined neural networks (white matter tracts) and mental wellbeing in early adolescence specifically. A cross-sectional diffusion tensor imaging analysis approach was conducted, from the Longitudinal Adolescent Brain study, First Hundred Brains cohort (N = 99; 46.5% female; Mage = 13.01, SD = 0.55). Participants completed self-report measures including wellbeing, quality-of-life, and psychological distress. Potential neurobiological profiles using fractional anisotropy, axial, and radial diffusivity were determined via a whole brain voxel-wise approach, and hierarchical cluster analysis of fractional anisotropy values, obtained from 21 major white matter tracts. Three cluster groups with significantly different neurobiological profiles were distinguished. No significant differences were found between the three cluster groups and measures of wellbeing, but two left lateralized significant associations between white matter tracts and wellbeing measures were found. These results provide preliminary evidence for potential neurobiological markers of mental health and wellbeing in early adolescence and should be tracked longitudinally to provide more detailed and robust findings.

Hippocampal subfield volumes predict treatment response to oral ketamine in people with suicidality.

Ongoing stress results in hippocampal neuro-structural alterations which produce pathological consequences, including depression and suicidality. Ketamine may ameliorate stress related illnesses, including suicidality, via neuroplasticity processes. This novel study sought to determine whether oral ketamine treatment specifically affects hippocampal (whole and subfield) volumes in patients with chronic suicidality and MDD. It was hypothesised that oral ketamine treatment would differentially alter hippocampal volumes in trial participants categorised as ketamine responders, versus those who were non-responders. Twenty-eight participants received 6 single, weekly doses of oral ketamine (0.5-3 mg/kg) and underwent MRI scans at pre-ketamine (week 0), post-ketamine (week 6), and follow up (week 10). Hippocampal subfield volumes were extracted using the longitudinal pipeline in FreeSurfer. Participants were grouped according to ketamine response status and then compared in terms of grey matter volume (GMV) changes, among 10 hippocampal regions, over 6 and 10 weeks. Mixed ANOVAs were used to analyse interactions between time and group. Post treatment analysis revealed a significant main effect of group for three left hippocampal GMVs as well in the left and right whole hippocampus. Ketamine acute responders (Week 6) showed increased GMVs in both left and right whole hippocampus and in three subfields compared to acute non-responders, across all three timepoints, suggesting that pre-treatment increased hippocampal GMVs (particularly left hemisphere) may be predictive biomarkers of acute treatment response. Future studies should further investigate the potential of hippocampal volumes as a biomarker of ketamine treatment response.

The Addition of Fish Oil to Cognitive Behavioral Case Management for Youth Depression: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial.

BACKGROUND: Clinical trials suggest that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) may reduce depressive symptoms in adults with major depressive disorder. Therefore, n-3 PUFAs may be a potential treatment for depression in youth. METHODS: Participants were 15- to-25 year-old individuals with major depressive disorder who sought care in one of three government-funded mental health services for young people in metropolitan Melbourne, Perth, or Sydney, Australia. Participants were randomly assigned in a double-blind, parallel-arm design to receive either fish oil (840 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid) or placebo capsules as adjunct to cognitive behavioral case management. All participants were offered 50-minute cognitive behavioral case management sessions every 2 weeks delivered by qualified therapists (treatment as usual) at the study sites during the intervention period. The primary outcome was change in the interviewer-rated Quick Inventory of Depressive Symptomatology, Adolescent Version, score at 12 weeks. Erythrocyte n-3 PUFA levels were assessed pre-post intervention. RESULTS: A total of 233 young people were randomized to the treatment arms: 115 participants to the n-3 PUFA group and 118 to the placebo group. Mean change from baseline in the Quick Inventory of Depressive Symptomatology score was -5.8 in the n-3 PUFA group and -5.6 in the placebo group (mean difference, 0.2; 95% CI, -1.1 to 1.5; p = .75). Erythrocyte PUFA levels were not associated with depression severity at any time point. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial and biomarker analysis found no evidence to support the use of fish oil for treatment in young people with major depressive disorder.

Examining the Longitudinal Relationship Between Metacognitive Beliefs and Psychological Distress in an Adolescent Population: A Preliminary Analysis.

Adolescence is a period marked by significant vulnerability to the onset of mental health concerns. Within adults, the metacognitive model of psychological disorders advocates for the involvement of metacognitive beliefs in the onset, and maintenance, of psychopathology. The current study aimed to assess the applicability of the metacognitive model in adolescence by exploring the relationship, as well as the trajectory, between metacognitive beliefs and psychological distress. The longitudinal prospective cohort study investigated data from a community-based sample of participants aged 12 to 13. Self-report assessment measures of metacognitive beliefs, psychological distress, and somatic distress are reported across four time-points. Baseline assessments are reported for 70 participants, which reduced to 53 participants at time-point four. Correlational analyses demonstrated a significant relationship between overall metacognition, as well as negative metacognitive beliefs, and psychological distress at each of the four time-points. Generalised Estimating Equations found a significant association between metacognitive predictors and psychological distress over the four time-points. These results indicate that negative metacognitive beliefs, positive metacognitive beliefs, metacognitive beliefs related to superstition, punishment, and responsibility, low perceived levels of cognitive confidence and cognitive self-consciousness predict psychological distress over 12 months in adolescents aged 12 to 13. The strongest longitudinal correlational structure was found for the model of negative metacognitive beliefs and psychological distress. These findings provide preliminary evidence for the positive linear relationship between metacognitive beliefs and psychological distress in adolescence. The study provides an important contribution to understanding the role of metacognitive beliefs in the aetiology and perpetuation of psychological distress in adolescence.

EMPOWERED trial: protocol for a randomised control trial of digitally supported, highly personalised and measurement-based care to improve functional outcomes in young people with mood disorders.

OBJECTIVES: Many adolescents and young adults with emerging mood disorders do not achieve substantial improvements in education, employment, or social function after receiving standard youth mental health care. We have developed a new model of care referred to as 'highly personalised and measurement-based care' (HP&MBC). HP&MBC involves repeated assessment of multidimensional domains of morbidity to enable continuous and personalised clinical decision-making. Although measurement-based care is common in medical disease management, it is not a standard practice in mental health. This clinical effectiveness trial tests whether HP&MBC, supported by continuous digital feedback, delivers better functional improvements than standard care and digital support. METHOD AND ANALYSIS: This controlled implementation trial is a PROBE study (Prospective, Randomised, Open, Blinded End-point) that comprises a multisite 24-month, assessor-blinded, follow-up study of 1500 individuals aged 15-25 years who present for mental health treatment. Eligible participants will be individually randomised (1:1) to 12 months of HP&MBC or standardised clinical care. The primary outcome measure is social and occupational functioning 12 months after trial entry, assessed by the Social and Occupational Functioning Assessment Scale. Clinical and social outcomes for all participants will be monitored for a further 12 months after cessation of active care. ETHICS AND DISSEMINATION: This clinical trial has been reviewed and approved by the Human Research Ethics Committee of the Sydney Local Health District (HREC Approval Number: X22-0042 & 2022/ETH00725, Protocol ID: BMC-YMH-003-2018, protocol version: V.3, 03/08/2022). Research findings will be disseminated through peer-reviewed journals, presentations at scientific conferences, and to user and advocacy groups. Participant data will be deidentified. TRIAL REGISTRATION NUMBER: ACTRN12622000882729.

The Study of Ketamine for Youth Depression (SKY-D): study protocol for a randomised controlled trial of low-dose ketamine for young people with major depressive disorder.

BACKGROUND: Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD). METHODS: SKY-D is a double-masked, randomised controlled trial funded by the Australian Government's National Health and Medical Research Council (NHMRC). Participants aged between 16 and 25 years (inclusive) with moderate-to-severe MDD will be randomised to receive either low-dose ketamine (intervention) or midazolam (active control) via subcutaneous injection once per week for 4 weeks. The primary outcome is change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment. Further follow-up assessment will occur at 8 and 26 weeks from treatment commencement to determine whether treatment effects are sustained and to investigate safety outcomes. DISCUSSION: Results from this trial will be important in determining whether low-dose subcutaneous ketamine is an effective treatment for young people with moderate-to-severe MDD. This will be the largest randomised trial to investigate the effects of ketamine to treat depression in young people. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ID: ACTRN12619000683134. Registered on May 7, 2019. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377513 .

Oral ketamine may offer a solution to the ketamine conundrum.

Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with additional concerns regarding long-term safety and abuse potential. Attempts to produce a similar drug to ketamine, without the psychotomimetic side effects, have proved elusive. Orally administered ketamine has a different pharmacological profile to parentally administered ketamine, suggesting it may be a viable alternative. Emerging evidence regarding the efficacy and tolerability of oral ketamine suggests that it may be a favourable route of administration, as it appears to obtain similarly beneficial treatment effects, but without the cost and medical resources required in parenteral dosing. The pharmacological effects may be due to the active metabolite norketamine, which has been found to be at substantially higher levels via oral dosing, most likely due to first-pass clearance. Despite bioavailability and peak plasma concentrations both being lower than when administered parenterally, evidence suggests that low-dose oral ketamine is clinically effective in treating pain. This may also be due to the actions of norketamine and therefore, its relevance to the mental health context is explored in this narrative review.

The temporal dependencies between social, emotional and physical health factors in young people receiving mental healthcare: a dynamic Bayesian network analysis.

AIMS: The needs of young people attending mental healthcare can be complex and often span multiple domains (e.g., social, emotional and physical health factors). These factors often complicate treatment approaches and contribute to poorer outcomes in youth mental health. We aimed to identify how these factors interact over time by modelling the temporal dependencies between these transdiagnostic social, emotional and physical health factors among young people presenting for youth mental healthcare. METHODS: Dynamic Bayesian networks were used to examine the relationship between mental health factors across multiple domains (social and occupational function, self-harm and suicidality, alcohol and substance use, physical health and psychiatric syndromes) in a longitudinal cohort of 2663 young people accessing youth mental health services. Two networks were developed: (1) 'initial network', that shows the conditional dependencies between factors at first presentation, and a (2) 'transition network', how factors are dependent longitudinally. RESULTS: The 'initial network' identified that childhood disorders tend to precede adolescent depression which itself was associated with three distinct pathways or illness trajectories; (1) anxiety disorder; (2) bipolar disorder, manic-like experiences, circadian disturbances and psychosis-like experiences; (3) self-harm and suicidality to alcohol and substance use or functioning. The 'transition network' identified that over time social and occupational function had the largest effect on self-harm and suicidality, with direct effects on ideation (relative risk [RR], 1.79; CI, 1.59-1.99) and self-harm (RR, 1.32; CI, 1.22-1.41), and an indirect effect on attempts (RR, 2.10; CI, 1.69-2.50). Suicide ideation had a direct effect on future suicide attempts (RR, 4.37; CI, 3.28-5.43) and self-harm (RR, 2.78; CI, 2.55-3.01). Alcohol and substance use, physical health and psychiatric syndromes (e.g., depression and anxiety, at-risk mental states) were independent domains whereby all direct effects remained within each domain over time. CONCLUSIONS: This study identified probable temporal dependencies between domains, which has causal interpretations, and therefore can provide insight into their differential role over the course of illness. This work identified social, emotional and physical health factors that may be important early intervention and prevention targets. Improving social and occupational function may be a critical target due to its impacts longitudinally on self-harm and suicidality. The conditional independence of alcohol and substance use supports the need for specific interventions to target these comorbidities.

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.

Excitatory and inhibitory neurometabolites in anorexia nervosa: A systematic review of proton magnetic resonance spectroscopy studies.

The dysregulation of excitatory and inhibitory neurotransmission is considered a pathological marker of Anorexia Nervosa (AN), however, no systematic evaluation of the proton Magnetic Resonance Spectroscopy (1H-MRS) literature has been conducted to date. Accordingly, we conducted a systematic review of neurometabolite differences between individuals with AN and healthy controls (HC). A comprehensive database search (until June 2023) identified seven studies meeting inclusion criteria. Samples included adolescents and adults with similar mean age (AN: 22.20 HC: 22.60), and female percentages (AN: 98%; HC: 94%). The review found a considerable need for improving study design and the reporting of MRS sequence parameters and analysis. Reduced glutamate concentrations in the ACC and OCC, and reduced Glx concentrations in the ACC were reported by one and two studies, respectively. Lastly, only one study to date has quantified GABA concentrations, with no significant differences found. In conclusion, there is currently insufficient evidence of excitatory and inhibitory neurometabolites changes in AN. As the 1H-MRS literature in AN increases, the key questions herein proposed must be revisited.

The LEISURE Study: A Longitudinal Randomized Controlled Trial Protocol for a Multi-Modal Lifestyle Intervention Study to Reduce Dementia Risk in Healthy Older Adults.

Dementia is understood to arise from a mixed etiology, enveloping chronic inflammatory and vascular impacts on the brain, driven by a constellation of modifiable risk factors which are largely mediated by lifestyle-related behaviors. These risk factors manifest over a prolonged preclinical period and account for up to 40% of the population attributable risk for dementia, representing viable targets for early interventions aimed at abating disease onset and progression. Here we outline the protocol for a 12-week randomized control trial (RCT) of a multimodal Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE), with longitudinal follow-up at 6-months and 24-months post-intervention. This trial integrates exercise, diet, sleep, and mindfulness to simultaneously target multiple different etiopathogenetic mechanisms and their interplay in a healthy older adult population (aged 50-85 years), and assesses dementia risk reduction as the primary endpoint. The LEISURE study is located in the Sunshine Coast region of Australia, which has one of the nation's highest proportions of adults aged over 50 years (36.4%), and corresponding dementia prevalence. This trial is novel in its inclusion of mindfulness and sleep as multidomain lifestyle targets, and in its comprehensive suite of secondary outcomes (based on psychological, physical health, sleep activity, and cognitive data) as well as exploratory neuroimaging (magnetic resonance imaging and electroencephalography) and molecular biology measures. These measures will provide greater insights into the brain-behavioral underpinnings of dementia prevention, as well as the predictors and impacts of the proposed lifestyle intervention. The LEISURE study was prospectively registered (ACTRN12620000054910) on 19 January 2020.

Dynamic modelling of chronotype and hypo/manic and depressive symptoms in young people with emerging mental disorders.

There is significant interest in the possible influence of chronotype on clinical states in young people with emerging mental disorders. We apply a dynamic approach (bivariate latent change score modelling) to examine the possible prospective influence of chronotype on depressive and hypo/manic symptoms in a youth cohort with predominantly depressive, bipolar, and psychotic disorders (N = 118; 14-30-years), who completed a baseline and follow-up assessment of these constructs (mean interval = 1.8-years). Our primary hypotheses were that greater baseline eveningness would predict increases in depressive but not hypo/manic symptoms. We found moderate to strong autoregressive effects for chronotype (ß = -0.447 to -0.448, p < 0.001), depressive (ß = -0.650, p < 0.001) and hypo/manic symptoms (ß = -0.819, p < 0.001). Against our predictions, baseline chronotypes did not predict change in depressive (ß = -0.016, p = 0.810) or hypo/manic symptoms (ß = 0.077, p = 0.104). Similarly, the change in chronotype did not correlate with the change in depressive symptoms (ß = -0.096, p = 0.295) nor did the change in chronotype and the change in hypo/manic symptoms (ß = -0.166, p = 0.070). These data suggest that chronotypes may have low utility for predicting future hypo/manic and depressive symptoms in the short term, or that more frequent assessments over longer periods are needed to observe these associations. Future studies should test whether other circadian phenotypes (e.g. sleep-wake variability) are better indicators of illness course.