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Patients with depression and bipolar disorder have previously been shown to have impaired white matter (WM) integrity compared with healthy controls. This study aimed to investigate potential sex differences that may provide further insight into the pathophysiology of these highly debilitating mood disorders.Participants aged 17 to 30 years (168 with depression [60% females], 107 with bipolar disorder [74% females], and 61 controls [64% females]) completed clinical assessment, self-report measures, and a neuropsychological assessment battery. Participants also underwent magnetic resonance imaging from which diffusion tensor imaging data were collected among five fronto-limbic WM tracts: cingulum bundle (cingulate gyrus and hippocampus subsections), fornix, stria terminalis, and the uncinate fasciculus. Mean fractional anisotropy (FA) scores were compared between groups using analyses of variance with sex and diagnosis as fixed factors.Among the nine WM tracts analyzed, one revealed a significant interaction between sex and diagnosis, controlling for age. Male patients with bipolar disorder had significantly lower FA scores in the fornix compared with the other groups. Furthermore, partial correlations revealed a significant positive association between FA scores for the fornix and psychomotor speed.Our findings suggest that males with bipolar disorder may be at increased risk of disruptions in WM integrity, especially in the fornix, which is thought to be responsible for a range of cognitive functions. More broadly, our findings suggest that sex differences may exist in WM integrity and thereby alter our understanding of the pathophysiology of mood disorders.

Adolescence is a period of significant brain development and decreased sleep quality, making it an ideal period to investigate early indicators of anxiety disorders such as psychological distress. The amygdala and hippocampus have been implicated in the neurobiology of anxiety symptoms. Sex-based differences in anxiety symptoms and sleep quality suggest sex-specific indicators may be preferable to a “one size fits all” approach. N = 70 early adolescents (12 years) completed the Pittsburgh Sleep Quality Index (PSQI), Kessler psychological distress scale (K10) and MRI scanning. Female participants were found to be poorer sleepers and to have higher psychological distress levels. Females also had larger right amygdala and hippocampal volumes than males controlling for total brain volume. Findings of sex-based differences in amygdala and hippocampal volumes as well as sleep and psychological distress at age 12 may represent an important step in elucidating sex specific early indicators of future mental health disorders.

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.

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.

Did you know that sleep is one of the most important parts of your day? Sleep helps your body to recover from your busy day and leaves you energized and ready for the next. While sleep is critical for people of all ages, it is perhaps the most important for teenagers. Teenagers who get enough sleep are helping their brains become stronger and better connected. This helps them to get better grades at school, to make helpful decisions at home and school, to continue to grow bigger and stronger, and to feel happier. Unfortunately, online gaming before bedtime is making it hard for some teens to get the sleep they need to enjoy all of sleep’s benefits. So, put away those consoles before bed, to give your brain the best chance of making you smarter, stronger, faster, and happier!

People with an Intellectual Disability (ID) are around 4 times more likely to suffer with a mental health disorder than IQ-typical people, however previous studies have shown they may be less likel...

Background: Pulmonary and critical care medicine (PCCM) fellowship requires a high degree of medical knowledge and procedural competency. Gaps in fellowship readiness can result in significant trainee anxiety related to starting fellowship training. Objective: To improve fellowship readiness and alleviate anxiety for PCCM-bound trainees by improving confidence in procedural skills and cognitive domains. Methods: Medical educators within the American Thoracic Society developed a national resident boot camp (RBC) to provide an immersive, experiential training program for physicians entering PCCM fellowships. The RBC curriculum is a 2-day course designed to build procedural skills, medical knowledge, and clinical confidence through high-fidelity simulation and active learning methodology. Separate programs for adult and pediatric providers run concurrently to provide unique training objectives targeted to their learners’ needs. Trainee assessments include multiple-choice pre- and post-RBC knowledge tests and confidence assessments, which are scored on a four-point Likert scale, for specific PCCM-related procedural and cognitive skills. Learners also evaluate course material and educator effectiveness, which guide modifications of future RBC programs and provide feedback for individual educators, respectively. Results: The American Thoracic Society RBC was implemented in 2014 and has grown annually to include 132 trainees and more than 100 faculty members. Mean knowledge test scores for participants in the 2019 RBC adult program increased from 55% (±14% SD) on the pretest to 72% (±11% SD; P

BackgroundAdolescence is an important period for developing one’s sense of self. Social connectedness has been linked to a sense of self which in turn has links to resilience in mental disorders. Adolescence is also a period of increased risk of chronic sleep deprivation during a time of ongoing white matter (WM) maturation. The complex relationship between these variables and their relationship with the onset on mental disorders during adolescence remains largely unexplored.MethodsN = 64 participants aged 12 years (M = 12.6) completed the Pittsburgh Sleep Quality Index (PSQI), Social connectedness scale (SCS) and a diffusion weighted Magnetic Resonance Imaging (MRI) scan to investigate the relationship of these variables to predict psychological distress via the Kessler psychological distress scale (K10) in early adolescents. Multiple regression analysis was used with K10 entered as the dependent variable and SCS, PSQI, and values of white matter integrity as the predictor variables.ResultsResults showed that while all four variables collectively accounted for a significant proportion of the variance in K10 (41.1%), SCS and PSQI were the only predictors that accounted for a significant proportion of variance uniquely.ConclusionsThese findings suggest interventions aimed at increasing levels of social connectedness and sleep quality during adolescence may reduce psychological distress. Future longitudinal reporting of this combination of variables is suggested.

Background: Although numerous studies have reported an association between sleep quality and mental health, few have focused on this association exclusively in early adolescence. Targeting this age group is vital as many mental illnesses first emerge during adolescence and remain a significant burden throughout life. Method: In the current study n = 60 participants aged 12 years completed the Pittsburgh Sleep Quality Index (PSQI) and Kessler Psychological Distress Scale (K10). Results: Consistent with previous findings, bivariate correlations revealed significant positive linear relationships between K10 total score and (i) PSQI total score; (ii) sleep quality; (iii) daytime dysfunction; and (iv) sleep disturbance. However, contrary to previous findings, there was no significant correlation between K10 scores and sleep duration. Conclusion: The association between sleep quality and psychological distress in early adolescents provides some important clues about the role that sleep may play in predicting the onset of anxiety and depressive disorders. Longitudinal studies should be undertaken to investigate age-related changes in sleep and psychological distress.

Background The pervasiveness of subclinical anxiety in children, highlights the need to identify its neurobiological underpinnings to better inform interventions. Given the now well-established link between aberrant emotion processing and anxiety disorders and yet limited neurobiologically-informed research in this area, this study examined the neural correlates of emotion recognition (ER) in children with sub-clinical anxiety. Method Ninety children (aged 9–11 years) with sub-clinical anxiety, completed an emotion recognition task whilst undergoing functional magnetic resonance imaging. The ER task required participants to match shapes and match emotional faces in the context of shape distractors. Participants also completed the Spence Children's Anxiety Scale (SCAS). Results Greater blood oxygenation level dependent (BOLD) changes associated with ER were observed in the lateral occipital cortex, middle frontal gyrus, superior middle frontal gyrus, inferior frontal gyrus, superior parietal lobule, inferior parietal lobule, superior temporal gyrus, and middle temporal gyrus symmetrically. The clusters also included posterior cingulate cortex, insula, hippocampus, amygdala and cerebellum during matching emotions than those matching shapes. Females showed greater BOLD changes associated with ER than males in the right middle frontal gyrus. The BOLD changes associated with ER in the right middle frontal gyrus and right insula were greater in children with SCAS subscale (physical injury fear) scores in the normal range than those with elevated scores. Discussion The findings in this study implicate the right middle frontal gyrus and insula as key regions in the neurobiological underpinnings of sub-clinical anxiety as they relate to attention impairments in anxious children. Conclusion The results of this study indicate there are gender differences in young participants during emotion processing and provides a neurobiological target for attention impairments in anxious children.

In a series of cognitive and neuroimaging studies we investigated the relationships between adolescent sleep quality, white matter (WM) microstructural integrity and psychological distress. Collectively these studies showed that during early adolescence (12-14 years of age), sleep quality and psychological distress are significantly related. Sleep quality and the microstructure of the posterior limb of the internal capsule (PLIC), a WM tract that provides important connectivity between the cortex, thalamus and brain stem, were also shown to be significantly correlated as too were social connectedness and psychological distress. Longitudinally the uncinate fasciculus (UF), a WM tract that provides bidirectional connectivity between the amygdala and executive control centers in the Prefrontal cortex (PFC), was observed to be undergoing continued development during this period and sleep quality was shown to impact this development. Sleep latency was also shown to be a significant predictor of worry endured by early adolescents during future stressful situations. The current review places these findings within the broader literature and proposes an empirically supported model based in a theoretical framework. This model focuses on how fronto-limbic top-down control (or lack thereof) explains how poor sleep quality during early adolescence plays a crucial role in the initial development of anxiety disorders, and possibly in the reduced ability of anxiety disorder sufferers to benefit from cognitive reappraisal based therapies. While the findings outlined in these studies highlight the importance of sleep quality for WM development and in mitigating psychological distress, further research is required to further explicate the associations proposed within the model to allow causal inferences to be made.

Chronic suicidality has been associated with neuronal atrophy in cortico-striato-limbic regions and is thought to be mediated via a glutamatergic imbalance. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been posited to exert anti-suicidal effects by promoting neurogenesis via modulation of glutamatergic transmission. This voxel-based morphometry study examined the effect of ketamine on whole brain grey matter in adults with chronic suicidality. Grey matter in the periaqueductal grey, nucleus accumbens, putamen, caudate, and thalamus was significantly increased following 6 weeks of low dose oral ketamine treatment. These results support the notion that ketamine rapidly enhances synaptic plasticity within striato-limbic regions.

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.

The importance of sleep for mental health has been known for some time. Although it was initially suggested that mental health conditions negatively impact sleep, it is now widely understood that this association is bidirectional. Adolescence is a period where people are at an increased risk of being sleep deprived largely due to a late shift in the circadian rhythm around puberty combined with early school start times. This combination may lead to adolescents being at an increased risk of mental health problems. Adolescence is also a period of continued brain development with white matter maturation continuing in the frontal brain regions throughout adolescence and into early adulthood. White matter development involves myelination of axons that link areas of grey matter and is integral for communication speed and efficiency. Studies have demonstrated that sufficient sleep is required for myelination to occur. The uncinate fasciculus (UF) is one of the last white matter tracts to be myelinated with this process occurring throughout adolescence and running between the amygdala in the limbic system and the orbitofrontal (OFC) and medial prefrontal cortices (mPFC). Recent studies have shown that connectivity between the amygdala and OFC is important for an individual's ability to exert top-down executive control over amygdala based automatic emotional responses to experiences perceived as threatening. The current literature review provides an overview of these mechanisms and concludes by proposing a model of adolescent sleep deprivation leading to potential life-long mental health issues through the moderating impact of reduced UF development.

Missed Parkinson's disease (PD) medications when patients are admitted to hospital are associated with increased ­morbidity and mortality. Swallowing difficulties in hospitalised PD patients are common and should prompt clinicians to ­consider conversion of a patient's PD medications to a non-oral form – this is, however, recognised as a challenging area with potential for error. Northumbria Healthcare NHS Foundation Trust's PD service set out to address this patient safety issue through the development of an innovative online medication ­calculator (pdmedcalc.co.uk). This article summarises the development process underpinning the calculator, presents numerical data on the usage of the calculator and presents survey data ­relating to user experiences of the calculator. Lastly, we highlight how user feedback has been used to refine subsequent iterations of the calculator and how use of the calculator has rapidly spread beyond our trust because of it being freely accessible online.

Multiple fires in quick succession can cause an abrupt switch from forest to non-forest vegetation in some biomes. A prime example of such type conversion concerns alpine ash forests (Eucalyptus delegatensis subsp. delegatensis), which are endemic to the Australian Alps bioregion. These forests are long lived and can only regenerate following fire disturbance through the release of seed from the tree canopy, but complete regeneration failure of the eucalypt overstorey can occur if immature stands are subsequently reburnt. Wildfires in 2003, 2007 and 2009 burnt over 87% of the Alpine ash forest in Victoria, with some areas being burnt a second or third time within a decade by the 2013 Harrietville-Alpine Bushfire. Using aerial and field surveys we demonstrated that an area burnt two or three times in the Alpine National Park in Victoria would have resulted in loss of alpine ash forest were it not for an aerial sowing program. This sowing program used reduced sowing rates compared to those typically used in forestry silviculture operations in Victoria. Seedling establishment during the first year was lower on sown than natural seedfall areas but fell within the range of acceptable silvicultural stocking rates. Analysis of cohorts of seedlings over their first summer showed mortality was highest in the 2–3 months following emergence, especially during hot dry periods, but there was no difference in mortality rates between artificially and naturally sown areas. While the aerial sowing intervention established a cohort of alpine ash seedlings, the challenge for land managers is to protect these seedlings from wildfires for the next two decades to avoid loss of these forests.

The C14,15-dihydro-C22,25-epi north unit of cephalostatin 1 has been synthesized in 11 operations from commercially available hecogenin acetate via multiple reductions and oxidations. The key transformations include (i) Cr(VI)-catalyzed E-ring opening, (ii) C17 hydroxylation, and (iii) a base-triggered cyclization cascade.