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Previous studies have demonstrated that quetiapine (QTP) may have neuroprotective properties; however, the underlying mechanisms have not been fully elucidated. In this study, we identified a novel mechanism by which QTP increased the synthesis of ATP in astrocytes and protected GABAergic neurons from aging-induced death. In 12-month-old mice, QTP significantly improved cell number of GABAegic neurons in the cortex and ameliorated anxiety-like behaviors compared to control group. Complimentary in vitro studies showed that QTP had no direct effect on the survival of aging GABAergic neurons in culture. Astrocyte-conditioned medium (ACM) pretreated with QTP (ACMQTP) for 24 h effectively protected GABAergic neurons against aging-induced spontaneous cell death. It was also found that QTP boosted the synthesis of ATP from cultured astrocytes after 24 h of treatment, which might be responsible for the protective effects on neurons. Consistent with the above findings, a Rhodamine 123 test showed that ACMQTP, not QTP itself, was able to prevent the decrease in mitochondrial membrane potential in the aging neurons. For the first time, our study has provided evidence that astrocytes may be the conduit through which QTP is able to exert its neuroprotective effects on GABAergic neurons. The neuroprotective properties of quetiapine (QTP) have not been fully understood. Here, we identify a novel mechanism by which QTP increases the synthesis of ATP in astrocytes and protects GABAergic neurons from aging-induced death in a primary cell culture model. In 12-month-old mice, QTP significantly improves cell number of GABAegic neurons and ameliorates anxiety-like behaviors. Our study indicates that astrocytes may be the conduit through which QTP exerts its neuroprotective effects on GABAergic neurons., (© 2014 International Society for Neurochemistry.)

The unpredictable chronic mild stress (UCMS) model was developed based upon the stress-diathesis hypothesis of depression. Most effects of UCMS can be reversed by antidepressants, demonstrating a strong predictive validity of this model for depression. However, the mechanisms underlying the effects induced by UCMS remain incompletely understood. Increasing evidence has shown that AMP-activated protein kinase (AMPK) regulates intracellular energy metabolism and is especially important for neurons because neurons are known to have small energy reserves. Abnormalities in the AMPK pathway disturb normal brain functions and synaptic integrity. In the present study, we first investigated the effects of UCMS on a battery of different tests measuring anxiety and depression-like behaviors in female C57BL/6N mice after 4 weeks of UCMS exposure. Stressed mice showed suppressed body weight gain, heightened anxiety, and increased immobility in the forced swim and tail suspension tests. These results are representative of some of the core symptoms of depression. Simultaneously, we observed decrease of synaptic proteins in the cortex of mice subjected to UCMS, which is associated with decreased levels of phosphorylated AMP-activated protein kinase α (AMPKα) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). Our findings suggest that AMPKα inactivation might be a mechanism by which UCMS causes anxiety/depression-like behaviors in mice., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Chronic long-term exposure to cuprizone causes severe brain demyelination in mice, which leads to changes in locomotion, working memory and anxiety. These findings suggest the importance of intact myelin for these behaviors. This study aimed to investigate the possible behavioral changes in mice with mild oligodendrocyte/myelin damage that parallels the white matter changes seen in the brains of patients with psychiatric disporders. We used the cuprizone-treated mouse model to test both tissue changes and behavioral functions (locomotor activity, anxiety status, and spatial working memory). The results showed that mice given cuprizone in their diet for 7 days had no significant myelin breakdown as evaluated by immunohistochemical staining for myelin basic protein, while the number of mature oligodendrocytes was reduced. The number and length of Caspr protein clusters, a structural marker of the node of Ranvier, did not change. The locomotor activity of the cuprizone-treated mice increased whereas their anxiety levels were lower than in normal controls; spatial working memory, however, did not change. These results, for the first time, link emotion-related behavior with mild white matter damage in cuprizone-treated mice.

Quetiapine, an atypical antipsychotic drug, is effective in treating the behavioral and psychological symptoms in Alzheimer's disease (AD). However, it is presently unclear whether quetiapine has beneficial effects on memory and whether the effects of quetiapine on psychological symptoms are associated with its effect on memory in AD. The present study was designed to examine the effect of chronic administration of quetiapine on the conditioned (generalized) anxiety that is related to learning experience of open arm exposure in the elevated T-maze (ETM) test in an amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mouse model of AD. In a 2nd experiment, the effect of quetiapine on memory per se was investigated in a Y-maze test in AD mice. Non-transgenic and transgenic mice were treated with quetiapine in drinking water from the age of 2 months. After continuous treatment with quetiapine (5 mg/kg/day) for 10 months, mice were tested for conditioned anxiety on the ETM task. After ETM testing, the expression of brain-derived neurotrophic factor (BDNF), a neuroprotective protein, was examined by immunohistochemistry in the basolateral amygdala (BLA) and hippocampus. In the 2nd experiment, the effect of quetiapine (2.5 or 5 mg/kg/day) on the short-term memory in AD mice was tested in a Y-maze test. After 10 months of administration, quetiapine prevented the decrease of conditioned anxiety and cerebral BDNF in AD mice. In addition, quetiapine also prevented memory impairment in the Y-maze test in AD mice. These findings suggest that the therapeutic mechanism of quetiapine on anxiety in AD may be associated with its beneficial effect on memory and its neuroprotective effect on cerebral BDNF expression.

Recently, we have reported that quetiapine, an atypical antipsychotic drug, prevents memory impairment and hippocampus neurodegeneration induced by global cerebral ischemia (GCI). In the present study, we examined the possible effects of quetiapine on other behavioural deficits, including the depressive and anxiolytic-like behavioural consequences of GCI. Mice were treated with quetiapine (5 or 10mg/kg/day; intraperitoneal (i.p.)) for 14 days. On Day 15, the animals were subjected to GCI. GCI resulted in a decrease of striatal tyrosine hydroxylase (TH) immunostaining and induced depressive and anxiolytic-like behavioural changes. The behavioural changes were indicated by a significant increase in the immobility duration in a tail-suspension test, and an increase in the time spent in the light box in a light/dark box test. Pre-administration of quetiapine significantly alleviated the decreased TH immunostaining and attenuated the depressive and anxiolytic-like behavioural changes induced by GCI. These results enhance our understanding about the mechanisms of quetiapine and suggest a wider perspective for the clinical use of quetiapine.

Aim: Opioid use disorder (OUD) is a leading cause of preventable mortality amongst young people worldwide. Early identification and intervention of modifiable risk factors may reduce future OUD risk. The aim of this study was to explore whether the onset of OUD is associated with preexisting mental health conditions such as anxiety and depressive disorders in young people. Methods: A retrospective, population‐based case‐control study was conducted from 31 March 2018 until 01 January 2002. Provincial administrative health data were collected from Alberta, Canada. Cases: Individuals 18–25 years on 01 April 2018, with a previous record of OUD. Controls: Individuals without OUD were matched to cases, on age/sex/index date. Conditional logistic regression analysis was used to control for additional covariates (e.g., alcohol‐related disorders, psychotropic medications, opioid analgesics, and social/material deprivation). Results: We identified N = 1848 cases and N = 7392 matched controls. After adjustment, OUD was associated with the following preexisting mental health conditions: Anxiety disorders, aOR = 2.53 (95% CI = 2.16–2.96); depressive disorders, aOR = 2.20 (95% CI = 1.80–2.70); alcohol‐related disorders, aOR = 6.08 (95% CI, 4.86–7.61); anxiety and depressive disorders, aOR = 1.94 (95% CI = 1.56–2.40); anxiety and alcohol‐related disorders, aOR = 5.22 (95% CI = 4.03–6.77); depressive and alcohol‐related disorders, aOR = 6.47 (95% CI = 4.73–8.84); anxiety, depressive and alcohol‐related disorders, aOR = 6.09 (95% CI = 4.41–8.42). Discussion: Preexisting mental health conditions such as anxiety and depressive disorders are risk factors for future OUD in young people. Preexisting alcohol‐related disorders showed the strongest association with future OUD and demonstrated an additive risk when concurrent with anxiety/depression. As not all plausible risk factors could be examined, more research is still needed. [ABSTRACT FROM AUTHOR]

Background: This study reports on the changes in stress, anxiety, and depressive symptoms of subscribers after 3 months using Text4Hope, a supportive text messaging program designed to provide support during the pandemic. Methods: Standardized self-report measures were used to evaluate perceived stress (measured with the Perceived Stress Scale-10 [PSS-10]), anxiety (measured with the General Anxiety Disorder Scale 7 [GAD-7]), and depressive symptoms (measured with the Patient Health Questionnaire [PHQ-9]), at baseline and 3rd month (n = 373). Results: After 3 months of using Text4Hope, subscribers' self-reports revealed significant (p< 0.001) mean score reductions compared with baseline on: the GAD-7 by 22.7%, PHQ-9 by 10.3%, and PSS-10 scores by 5.7%. Reductions in inferred prevalence rates for moderate to high symptoms were also observed, with anxiety demonstrating the largest reduction (15.7%). Conclusions: Observed Text4Hope-related reductions in psychological distress during COVID-19 indicate that Text4Hope is an effective, convenient, and accessible means of implementing a population-level psychological intervention. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to assess prevalence of major depressive disorder (MDD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) in students of Keyano College 18 months after a wildfire and to determine the predictors of likely MDD, GAD, and PTSD in the respondents. Methods: A quantitative cross-sectional survey was used to collect data through self-administered, paper-based questionnaires to determine likely MDD, GAD, and PTSD using the PHQ 9, GAD-7, and the PTSD Checklist for DSM 5, Part 3, respectively. Data were analyzed with SPSS version 20 (IBM Corp, Armonk, NY) using univariate analysis with chi-square tests. Results: Eighteen months after the wildfire, the 1-month prevalence rates for MDD, GAD, and PTSD among the college students were 23.4%, 18.7%, and 11.0%, respectively. There were statistically significant associations between multiple sociodemographic variables and the likelihood respondents presented with MDD, GAD, and PTSD 18 months after the wildfire. There were also associations between the likely MDD, GAD, and PTSD and abuse/dependence on alcohol and substances in respondents at 18 months. Conclusion: Our study has established prevalence rates for MDD, GAD, and PTDS among college students 18 months after the Fort McMurray wildfires. Further studies are needed to explore the impact of college-based mental health interventions on the long-term mental health effects of the wildfires. [ABSTRACT FROM AUTHOR]

Objectives: To assess the likely prevalence rates of Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD) and Post-Traumatic Stress Disorder (PTSD) in staff of Fort McMurray School Districts eighteen months after a May 2016 wildfire, and to determine possible predictors. Methods: A quantitative cross-sectional survey was used to collect data through self-administered online questionnaires to determine likely MDD, GAD and PTSD using well validated self-report questionnaires. Results: Of 1,446 staff who were sent the online survey link in an e-mail, 197 completed the survey, of which there were 168 females (85%) and 29 males (15%). The one-month prevalence rates for likely MDD, GAD and PTSD among the school staff were 18.3, 15.7 and 10.2% respectively. There were statistically significant associations between multiple socio-demographic and clinical variables likely MDD, GAD and PTSD among respondents. Conclusion: Knowledge of key factors for MDD, GAD and PTSD may be helpful for policy makers when formulating population level social and clinical programs, to mitigate the mental health effects of future natural disasters. [ABSTRACT FROM AUTHOR]

Anxiety disorders are among the most common mental health disorders in the middle aged and older population. Because older individuals are more likely to have multiple comorbidities or increased frailty, the impact of anxiety disorders on their overall well-being is exacerbated. Early identification of anxiety disorders using machine learning (ML) can potentially mitigate the adverse consequences associated with these disorders. We applied ML to the data from the Canadian Longitudinal Study on Aging (CLSA) to predict the onset of anxiety disorders approximately three years in the future. We used Shapley value-based methods to determine the top factor for prediction. We also investigated whether anxiety onset can be predicted by baseline depression-related predictors alone. Our model was able to predict anxiety onset accurately (Area under the Receiver Operating Characteristic Curve or AUC = 0.814 ± 0.016 (mean ± standard deviation), balanced accuracy = 0.741 ± 0.016, sensitivity = 0.743 ± 0.033, and specificity = 0.738 ± 0.010). The top predictive factors included prior depression or mood disorder diagnosis, high frailty, anxious personality, and low emotional stability. Depression and mood disorders are well known comorbidity of anxiety; however a prior depression or mood disorder diagnosis could not predict anxiety onset without other factors. While our findings underscore the importance of a prior depression diagnosis in predicting anxiety, they also highlight that it alone is inadequate, signifying the necessity to incorporate additional predictors for improved prediction accuracy. Our study showcases promising prospects for using machine learning to develop personalized prediction models for anxiety onset in middle-aged and older adults using easy-to-access survey data. • Machine learning predicts anxiety onset with an AUC of 0.814 ± 0.016. • Top predictors for anxiety onset include prior depression and/or mood disorder diagnosis, high frailty, anxious personality, and low emotional stability. • Baseline depression and/or mood disorder alone is not sufficient to predict anxiety onset. [ABSTRACT FROM AUTHOR]

Abstract: We have demonstrated that the atypical antipsychotic drugs prevent cell death in PC12 cells induced by various cytotoxins and have protective effects on methamphetamine-induced neurotoxcity in rats. The present study was designed to examine the possible effects of chronic administration of quetiapine, an atypical antipsychotic drug, on the anxiety-like behavioural consequences of a neurotoxic regimen of dl-amphetamine. Rats were treated with quetiapine (10mg/kg/day; i.p.) for 33 days. During days 15–19 of this period, the animals were given dl-amphetamine (20mg/kg/day; s.c.) 1h after the administration of quetiapine. The repeated administration of dl-amphetamine resulted in a decrease of tyrosine hydroxylase (TH) immunostaining in the caudate putamen, hyperthermia, and anxiety-like behavioural changes. The behavioural changes were indicated by a significant increase in the time spent in the light box in the light/dark box test, an increase in the ratios of ambulation distance inside the inner circle over the total ambulation distance and rearings inside the inner circle over the total rearings in the open field test, and an increase in the time spent in open arms in the elevated plus-maze test. Chronic administration of quetiapine significantly attenuated the dl-amphetamine-induced hyperthermia, and the anxiety-like behavioural changes in the light/dark box and in the open field tests. These results suggest that quetiapine can normalize the dl-amphetamine-induced anxiety-like behavioural changes, and might be helpful in the treatment for amphetamine-induced emotional changes. [Copyright &y& Elsevier]