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

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

Testing self-report time-use diaries against objective instruments in real time

This study provides a new test of time-use diary methodology, comparing diaries with a pair of objective criterion measures: wearable cameras and accelerometers. A volunteer sample of respondents (n = 148) completed conventional self-report paper time-use diaries using the standard UK Harmonised European Time Use Study (HETUS) instrument. On the diary day, respondents wore a camera that continuously recorded images of their activities during waking hours (approximately 1,500–2,000 images/day) and also an accelerometer that tracked their physical activity continuously throughout the 24-hour period covered by the diary. Of the initial 148 participants recruited, 131 returned usable diary and camera records, of whom 124 also provided a usable whole-day accelerometer record. The comparison of the diary data with the camera and accelerometer records strongly supports the use of diary methodology at both the aggregate (sample) and individual levels. It provides evidence that time-use data could be used to complement physical activity questionnaires for providing population-level estimates of physical activity. It also implies new opportunities for investigating techniques for calibrating metabolic equivalent of task (MET) attributions to daily activities using large-scale, population-representative time-use diary studies

Sex and gender role differences on stress, depression, and anxiety symptoms in response to the COVID-19 pandemic over time

IntroductionStress, depression, and anxiety symptoms have been reported during the pandemic, with important inter-individual differences. Past cross-sectional studies have found that sex and gender roles may contribute to the modulation of one's vulnerability to develop such symptoms. This longitudinal study aimed to examine the interaction of sex and psychological gender roles on stress, depression, and anxiety symptoms in adults during the COVID-19 pandemic.MethodsFollowing the confinement measures in March 2020 in Montreal, stress, depression, and anxiety symptoms were assessed every 3 months (from June 2020 to March 2021) with the Depression, Anxiety and Stress Scale among 103 females and 50 males. Femininity and masculinity scores were assessed with the Bem Sex Role Inventory before the pandemic and were added as predictors along with time, sex, and the interactions between these variables using linear mixed models.ResultsWe observed similar levels of depressive symptoms between males and females, but higher levels of stress and anxious symptoms in females. No effects of sex and gender roles on depressive symptoms were found. For stress and anxiety, an interaction between time, femininity, and sex was found. At the beginning of the pandemic, females with high femininity had more stress symptoms than males with high femininity, whereas females with low femininity had more anxiety symptoms 1 year after the confinement measures compared to males with low femininity.DiscussionThese findings suggest that sex differences and psychological gender roles contribute to heterogeneous patterns of stress and anxiety symptoms over time in response to the COVID-19 pandemic

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

IntroductionThe 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.MethodsUsing 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.DiscussionThis 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

A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress–disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental healt

A clinical allostatic load index detects stress-related problems in older adults and workers

Allostatic load (AL) refers to biological wear and tear caused by chronic psychosocial stress. The AL model proposes that by measuring the multi-systemic interactions among sub-clinically relevant biomarkers, biomedical advances can be made in the detection of individuals at high risk of developing stress-related diseases. By incorporating an AL index encompassing neuroendocrine, immune, metabolic, and cardiovascular biomarkers, a growing body of literature has demonstrated augmented prediction of numerous deleterious outcomes. As it stands, however, the AL index is a research tool that has not been standardized for use by healthcare providers. Using a new AL index based on clinical reference ranges, we investigated physical and psychological outcomes in two studies. In Study 1, 85 older adults were followed longitudinally over six years, while Study 2 included a separate cross-section of 30 younger workers. We hypothesized that increased AL indices based on 7 and 15 biomarkers respectively would relate to increased levels of psychological distress, dysregulated diurnal and reactive stress hormone levels, subjective memory and physical complaints, objective memory impairments, and finally symptoms of depression and burnout. Our results support our hypotheses at different ages. For older adults, higher AL predicted greater depressive symptoms three years in advance with subsequent cognitive complaints and impairments. For younger workers, higher AL was manifested physiologically and symptomatically as a pre-burnout condition without cognitive and physical complaints. These findings provide preliminary support for the utility of a new clinical AL index sensitive to specific stress-related problems throughout the life span that is easily accessible to healthcare providers.La charge allostatique (CA) est la dégradation biologique causée par le stress chronique. Le modèle de la CA propose qu'en mesurant les interactions multi-systémiques de biomarqueurs qui sont sous-cliniquement significatifs, des avancées biomédicales seront possibles afin de détecter les individus à risque de développer différentes maladies. La littérature démontre qu'en utilisant un indice de CA qui inclut des biomarqueurs neuroendocriniens, immunitaires, métaboliques et cardiovasculaires, il est possible de mieux prédire de nombreuses conséquences négatives. Par contre, à ce jour, l'indice de la CA n'est qu'un outil de recherche et n'a pas encore été validé pour l'utilisation médicale. En utilisant un nouvel indice de la CA basé sur des distributions cliniques, nous avons investigué les conséquences physiques et psychologiques du stress chronique dans le cadre de deux études. Dans l'étude 1, 85 adultes âgés ont été suivis longitudinalement pendant six ans, alors que l'étude 2 a été réalisée à une reprise auprès de 30 travailleurs de divers domaines. Notre hypothèse était que des indices élevés de la CA seraient reliés à des niveaux plus élevés de stress psychologique, des niveaux dérégulés de cortisol basal et réactif, des plaintes subjectives de troubles de mémoire et de fonctionnement physique, des déficits de mémoire, et finalement des symptômes de dépression et d'épuisement professionnel. Nos résultats supportent nos hypothèses, mais diffèrent selon l'âge de l'échantillon étudié. Pour les adultes âgés, une CA plus élevée prédisait des symptômes de dépression trois ans en avance ainsi que des plaintes subjectives de mémoire et des déficits cognitifs. Pour les travailleurs plus jeunes, une CA plus élevée se manifestait physiologiquement et symptomatiquement par une condition ressemblant à l'épuisement professionnel sans trouble cognitif ou physique. Ces résultats sont une évidence