Ketogenictherapy in serious mental illness: emerging evidence

[Extract] We have read the recent review article on the potential application of induced ketosis in psychiatry by Morris et al. (Morris et al., 2020) with great interest and shared enthusiasm. It is quite encouraging to see that others are recognizing the exciting potential of the ketogenic diet and other ketogenic therapies in the treatment of serious mental disorders. As with all research, however, it is important to be aware of what existing evidence is already accumulated. This is particularly pertinent as such published evidence further strengthens the case for induced ketosis in psychiatry proposed as “food for thought” (Morris et al., 2020). In this Commentary, we aim to fill this gap by providing a brief overview of the published preclinical and clinical evidence that clearly supports the advancement of ketogenic therapies in a variety of psychiatric disorders, especially in psychosis (Figure 1)

The gut microbiome in psychosis from mice to men: a systematic review of preclinical and clinical studies

The gut microbiome is rapidly becoming the focus of interest as a possible factor involved in the pathophysiology of neuropsychiatric disorders. Recent understanding of the pathophysiology of schizophrenia emphasizes the role of systemic components, including immune/inflammatory and metabolic processes, which are influenced by and interacting with the gut microbiome. Here we systematically review the current literature on the gut microbiome in schizophrenia-spectrum disorders and in their animal models. We found that the gut microbiome is altered in psychosis compared to healthy controls. Furthermore, we identified potential factors related to psychosis, which may contribute to the gut microbiome alterations. However, further research is needed to establish the disease-specificity and potential causal relationships between changes of the microbiome and disease pathophysiology. This can open up the possibility of. manipulating the gut microbiome for improved symptom control and for the development of novel therapeutic approaches in schizophrenia and related psychotic disorders

Machine Learning for Stress Monitoring from Wearable Devices: A Systematic Literature Review

Introduction. The stress response has both subjective, psychological and objectively measurable, biological components. Both of them can be expressed differently from person to person, complicating the development of a generic stress measurement model. This is further compounded by the lack of large, labeled datasets that can be utilized to build machine learning models for accurately detecting periods and levels of stress. The aim of this review is to provide an overview of the current state of stress detection and monitoring using wearable devices, and where applicable, machine learning techniques utilized. Methods. This study reviewed published works contributing and/or using datasets designed for detecting stress and their associated machine learning methods, with a systematic review and meta-analysis of those that utilized wearable sensor data as stress biomarkers. The electronic databases of Google Scholar, Crossref, DOAJ and PubMed were searched for relevant articles and a total of 24 articles were identified and included in the final analysis. The reviewed works were synthesized into three categories of publicly available stress datasets, machine learning, and future research directions. Results. A wide variety of study-specific test and measurement protocols were noted in the literature. A number of public datasets were identified that are labeled for stress detection. In addition, we discuss that previous works show shortcomings in areas such as their labeling protocols, lack of statistical power, validity of stress biomarkers, and generalization ability. Conclusion. Generalization of existing machine learning models still require further study, and research in this area will continue to provide improvements as newer and more substantial datasets become available for study.Comment: 50 pages, 8 figure

Ensemble Machine Learning Model Trained on a New Synthesized Dataset Generalizes Well for Stress Prediction Using Wearable Devices

Introduction. We investigate the generalization ability of models built on datasets containing a small number of subjects, recorded in single study protocols. Next, we propose and evaluate methods combining these datasets into a single, large dataset. Finally, we propose and evaluate the use of ensemble techniques by combining gradient boosting with an artificial neural network to measure predictive power on new, unseen data. Methods. Sensor biomarker data from six public datasets were utilized in this study. To test model generalization, we developed a gradient boosting model trained on one dataset (SWELL), and tested its predictive power on two datasets previously used in other studies (WESAD, NEURO). Next, we merged four small datasets, i.e. (SWELL, NEURO, WESAD, UBFC-Phys), to provide a combined total of 99 subjects,. In addition, we utilized random sampling combined with another dataset (EXAM) to build a larger training dataset consisting of 200 synthesized subjects,. Finally, we developed an ensemble model that combines our gradient boosting model with an artificial neural network, and tested it on two additional, unseen publicly available stress datasets (WESAD and Toadstool). Results. Our method delivers a robust stress measurement system capable of achieving 85% predictive accuracy on new, unseen validation data, achieving a 25% performance improvement over single models trained on small datasets. Conclusion. Models trained on small, single study protocol datasets do not generalize well for use on new, unseen data and lack statistical power. Ma-chine learning models trained on a dataset containing a larger number of varied study subjects capture physiological variance better, resulting in more robust stress detection.Comment: 37 pages, 11 figure

Within-treatment changes in a novel addiction treatment program using traditional Amazonian medicine

Aims: The therapeutic use of psychedelics is regaining scientific momentum, but similarly psychoactive ethnobotanical substances have a long history of medical (and other) uses in indigenous contexts. Here we aimed to evaluate patient outcomes in a residential addiction treatment center that employs a novel combination of Western and traditional Amazonian methods. Methods: The study was observational, with repeated measures applied throughout treatment. All tests were administered in the center, which is located in Tarapoto, Peru. Data were collected between 2014 and 2015, and the study sample consisted of 36 male inpatients who were motivated to seek treatment and who entered into treatment voluntarily. Around 58% of the sample was from South America, 28% from Europe, and the remaining 14% from North America. We primarily employed repeated measures on a psychological test battery administered throughout treatment, measuring perceived stress, craving frequency, mental illness symptoms, spiritual well-being, and physical and emotional health. Addiction severity was measured on intake, and neuropsychological performance was assessed in a subsample from intake to at least 2 months into treatment. Results: Statistically significant and clinically positive changes were found across all repeated measures. These changes appeared early in the treatment and were maintained over time. Significant improvements were also found for neuropsychological functioning. Conclusion: These results provide evidence for treatment safety in a highly novel addiction treatment setting, while also suggesting positive therapeutic effects

Childhood adversity, allostatic load, and adult mental health: Study protocol using the Avon Longitudinal Study of Parents and Children birth cohort

Introduction: The cumulative burden of chronic stress and life events has been termed allostatic load. Elevated allostatic load indices are associated with different mental health conditions in adulthood. To date, however, the association between elevated allostatic load in childhood and later development of mental health conditions has not been investigated. Methods: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we will calculate allostatic load indices using biomarkers representing the cardiovascular, metabolic, immune, and neuroendocrine systems, at the ages of 9 and 17 years. Bivariate and multivariable logistic regression models will be used to investigate the association between allostatic load and psychiatric disorders in adulthood. Furthermore, the role of adverse childhood experiences as a modifier will be investigated. Discussion: This protocol describes a strategy for investigating the association between elevated allostatic load indices in childhood at the age of 9 years old and psychiatric disorders in adulthood at 24 years old

Allostatic load is associated with positive symptoms in schizophrenia and first-episode psychosis and decreases with antipsychotic therapy

Background: Current pathophysiological models of schizophrenia suggest that stress contributes to the etiology and trajectory of the disorder. We investigated whether cumulative exposure to stress, quantified by allostatic load (AL), an integrative index of immune, metabolic, and neuroendocrine dysregulation, is elevated in patients with schizophrenia (SCZ) and first-episode psychosis (FEP) and related to psychotic symptoms and social and occupational functioning and assessed the temporal dynamics of AL in response to treatment with second-generation antipsychotics. Methods: We assessed AL in a naturalistic study of unmedicated patients with SCZ (n = 28), FEP (n = 28), and healthy controls matched for age and gender (n = 53) at baseline and 6 and 12 weeks after commencement of antipsychotic therapy. Biomarkers for the AL index were selected based on (1) representation of several physiological systems including the cardiovascular, neuroendocrine, immune, and metabolic systems; (2) use in previous AL research; and (3) associations with disease risk. We adopted a scaled AL algorithm whereby each marker proportionally contributes to the overall AL index. Unadjusted and adjusted differences between patients with SCZ, FEP, and controls in AL were tested with ANCOVA, and partial correlations were used to test associations of AL with psychometric variables. Results: AL was higher in patients with SCZ compared to controls (4.91 ± 1.89 vs. 2.87 ± 1.62, P < .001), patients with FEP compared to controls (3.80 ± 1.66 vs. 2.87 ± 1.62, P = .020) but not different between patients with SCZ and patients with FEP (P = .302). Adjusting for age and smoking, we found that positive symptoms were positively correlated with AL across all patients with a psychotic disorder (adjusted R = .520, P < .001) and Global Assessment of Functioning (GAF) scores were negatively correlated with AL at trend level (adjusted R = −.251, P = .070). No significant associations were found for negative symptoms (P = .582). AL decreased after treatment with olanzapine, risperidone, or quetiapine was commenced in patients with SCZ and FEP between the baseline assessment and the 6- and 12-week follow-up. Conclusion: Our data provide evidence for cumulative physiological dysregulation in patients with SCZ and FEP that is linked to the experience of current positive psychotic symptoms. AL could be a useful model that takes stress, long-term adaptation, and its failures into account to further understand the pathophysiology of schizophrenia

A Cross-Sectional Study Investigating Canadian and Australian Adolescents' Perceived Experiences of COVID-19: Gender Differences and Mental Health Implications

The coronavirus (COVID-19) disease pandemic has been associated with adverse psychological outcomes. This cross-cultural study (N = 1326, 71% female) aimed to investigate Canadian and Australian adolescents’ subjective experiences of COVID-19, gender differences, and psychological implications. Mixed-methods analyses were used to examine differences in COVID-19 experiences and mental health outcomes between country and gender in a Canadian (N = 913, 78% fe-male) and an Australian sample (N = 413, 57% female) of adolescents. Canadian adolescents reported increased COVID-19 discussions and more concerns related to their COVID-19 experiences compared to Australian adolescents. Girls consistently reported more concerns related to COVID-19 and poorer psychological outcomes compared to boys. School lockdown for the Canadian sample may have played a role in these country differences. Further, girls might be at significantly more risk for mental health concerns during COVID-19, which should be considered in adolescent mental health initiatives during the pandemic. Although school disruption and separation of peers due to the pandemic likely have a role in adolescent perceived stressors and mental health, the differences between Canadian and Australian adolescents were less clear and future investigations comparing more objective pre-COVID-19 data to current data are needed

Improved sperm freezing in the endangered African wild dog (Lycaon pictus) using a two-step dilution TRIS-egg yolk extender containing Equex STM

Development of assisted breeding techniques can aid conservation and management of the endangered African wild dog (Lycaon pictus). Previous attempts to freeze sperm from this species has proven unsuccessful with sperm motility dropping to nearly 0% within 2 h of thawing. The aim of this study was to improve the freezing success of African wild dog sperm by testing two routinely used canine cryopreservation protocols. Sperm was frozen from n=3 captive African wild dog males housed at Albuquerque BioPark (Albuquerque, NM, USA) and Binder Park Zoo (Battle Creek, MI, USA) during the breeding season (Aug-Sept 2014). Freshly collected semen samples were evaluated for volume, colour, pH, motility, viability, morphology, sperm number, acrosome status and DNA integrity. Each sample was split and frozen using two different protocols. Protocol 1: semen was diluted with a Tris-egg yolk extender containing 8% glycerol and 20% egg yolk, and slowly cooled from 37°C to 4°C over 2.5 h. The sample was then loaded into 0.25 mL straws, suspended 4 cm over liquid nitrogen vapour for 10 min, then plunged in liquid nitrogen. Protocol 2: semen was first diluted with a Tris-egg yolk extender containing only 3% glycerol and 20% egg yolk, followed by a second extender (same composition) now containing 7% glycerol and 1% Equex STM, added after the 2.5 h refrigeration period. The freezing procedure was the same as Protocol 1. Straws from both protocols were thawed in a 37ᵒC water bath, but Protocol 2 straws were further diluted by with a thawing solution which that consisted of the initial extender solution without glycerol and egg yolk. Sperm were incubated at 37 ᵒC and motility evaluated at 5 min and every 2 h for 8 h after thawing. Viability, morphology and acrosome integrity was evaluated over 6 h and DNA integrity was evaluated immediately post-thaw. Sperm motility declined significantly for both protocols immediately after thawing (fresh 78.9 ± 2.6%; Protocol 1 24.4 ± 5.0%; Protocol 2 36.7 ± 4.2%; P ≤ 0.05). Motility was significantly higher for Protocol 2 from 2 h after thawing (Protocol 1 1.0 ± 0.8%; Protocol 2 30.8 ± 1.9%; P ≤ 0.05) and sperm remained motile for up to 8 h. Sperm frozen with Protocol 2 also had significantly higher viability (Protocol 1 37.0 ± 5.7%; Protocol 2 65.3 ± 9.9%; P ≤ 0.05) and acrosome integrity (Protocol 1 22.8 ± 8.2%; Protocol 2 69.3 ± 8.8%; P ≤ 0.05) immediately after thawing. There was no difference in the proportion of normal morphology or DNA fragmentation between both protocols. Our results demonstrate that using a two-step dilution with TRIS-egg yolk extender containing Equex STM yields greatly improved post-thaw quality and longevity in African wild dog sperm; making it suitable for use in artificial insemination

Hair cortisol, allostatic load, and depressive symptoms in Australian Aboriginal and Torres Strait Islander people

Chronic stress and adversity are associated with poor mental health and are thought to contribute to the existing mental health gap between Aboriginal and Torres Strait Islander people and other Australians. Hair cortisol and allostatic load (AL) are indices of sustained stress and may be mediators of the effects of stress on health. The aim of this study was to examine the relationship between hair cortisol, AL, and depressive symptoms. This cross-sectional study comprised 329 Aboriginal and Torres Strait Islander adolescents and adults recruited at two health screening programs operating in three communities in north Queensland. We measured hair cortisol and calculated an AL index from 10 biomarkers. We assessed depressive symptoms with a version of the Patient Health Questionnaire-9 adapted for Aboriginal and Torres Strait Islander people (aPHQ-9). We found differences in cortisol and AL between the screening programs and communities, which were not explained by depressive symptoms. Overall aPHQ-9 scores were unrelated to hair cortisol (p = .25 and p = .94) and AL (p = .30 and p = .88) when age, gender and smoking were taken into account. However, anhedonia (p = .007) and insomnia (p = .006) sub-scores were each significantly associated with AL in one study site. Our present data did not demonstrate overall associations of stress biomarkers and multisystem dysregulation with depressive symptoms, which suggests that the relationship between cumulative stress and depression may be better explained by other factors in this population. The specific association between anhedonia and insomnia with AL indicates that chronic multisystem dysregulation plays a role in these features of depression in this population