scholarly journals BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders

2019 ◽  
Vol 6 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Peiyuan Qiu ◽  
Jian Jiang ◽  
Zhen Liu ◽  
Yijun Cai ◽  
Tao Huang ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Stress Responses ◽  
Depressive Disorders ◽  
Circadian Disruption ◽  
Auditory Oddball ◽  
Light Regimen ◽  
Age Related ◽  
Major Depressive Disorders ◽  
Transcription Networks ◽  
Human Primate

AbstractCircadian disruption is a risk factor for metabolic, psychiatric and age-related disorders, and non-human primate models could help to develop therapeutic treatments. Here, we report the generation of BMAL1 knockout cynomolgus monkeys for circadian-related disorders by CRISPR/Cas9 editing of monkey embryos. These monkeys showed higher nocturnal locomotion and reduced sleep, which was further exacerbated by a constant light regimen. Physiological circadian disruption was reflected by the markedly dampened and arrhythmic blood hormonal levels. Furthermore, BMAL1-deficient monkeys exhibited anxiety and depression, consistent with their stably elevated blood cortisol, and defective sensory processing in auditory oddball tests found in schizophrenia patients. Ablation of BMAL1 up-regulated transcriptional programs toward inflammatory and stress responses, with transcription networks associated with human sleep deprivation, major depressive disorders, and aging. Thus, BMAL1 knockout monkeys are potentially useful for studying the physiological consequences of circadian disturbance, and for developing therapies for circadian and psychiatric disorders.

scholarly journals Transdiagnostic Neural Signatures in common Pediatric Psychiatric Disorders: a data-driven meta-analysis of functional neuroimaging studies

2021 ◽  
Author(s):  
Jules R Dugre ◽  
Simon Eickhoff ◽  
Stephane Potvin
Keyword(s):  
Psychiatric Disorders ◽  
Depressive Disorders ◽  
Meta Analysis ◽  
Brain Regions ◽  
Data Driven ◽  
Task Characteristics ◽  
Major Depressive ◽  
Oppositional Defiant ◽  
Major Depressive Disorders ◽  
Neural Signatures

BACKGROUND. In the last decades, neuroimaging studies have attempted to unveil the neurobiological markers underlying pediatric psychiatric disorders. However, children diagnosed with such disorders are likely to receive an additional diagnosis in the following years. Yet, the vast majority of neuroimaging studies focus on a single nosological category, which limit our understanding of the shared/specific neural correlates between these disorders. Therefore, we aimed to investigate the transdiagnostic neural signatures through a novel meta-analytical method. METHOD. A data-driven meta-analysis was carried out which grouped similar experiments topographic map together, irrespectively of nosological categories and task-characteristics. Then, activation likelihood estimation meta-analysis was performed on each group of experiments to extract spatially convergent brain regions. RESULTS. One hundred forty-seven experiments were retrieved (3199 subjects): 79 attention-deficit/hyperactivity disorder, 32 conduct/oppositional defiant disorder, 14 anxiety disorders, 22 major depressive disorders. Four significant groups of experiments were observed. Functional characterization suggested that these groups of aberrant brain regions may be implicated internally/externally directed processes, attentional control of affect, somato-motor and visual processes. Furthermore, despite that some differences in rates of studies involving major depressive disorders were noticed, nosological categories were evenly distributed between these four sets of regions. Additionally, main effects of task characteristics were observed. CONCLUSIONS. By using a data-driven meta-analytic method, we observed four significant groups of aberrant brain regions that may reflect transdiagnostic neural signature of pediatric psychiatric disorders. Overall, results of this study underscore the importance of studying pediatric psychiatric disorders simultaneously rather than independently.

scholarly journals The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD

2021 ◽  
Vol 22 (11) ◽  
pp. 5495
Author(s):  
Felipe Borges Almeida ◽  
Graziano Pinna ◽  
Helena Maria Tannhauser Barros
Keyword(s):  
Hpa Axis ◽  
Depressive Disorders ◽  
Post Traumatic Stress ◽  
Major Depressive ◽  
Physiological Adaptations ◽  
Suppression Test ◽  
Post Traumatic ◽  
Major Depressive Disorders ◽  
Cortisol Release

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.

scholarly journals Development of a Nomogram for Predicting Depression in the Elderly Using Patient Health Questionnaire-9 among a Nationwide Sample of Korean Elderly

2021 ◽  
Vol 11 (7) ◽  
pp. 645
Author(s):  
Haewon Byeon
Keyword(s):  
Depressive Disorders ◽  
The Elderly ◽  
Subjective Health ◽  
Moderate Intensity ◽  
Subjective Health Status ◽  
Major Depressive ◽  
Moderate Intensity Physical Activity ◽  
Patient Health ◽  
Intensity Physical Activity ◽  
Major Depressive Disorders

This cross-sectional study developed a nomogram that could allow medical professionals in the primary care setting to easily and visually confirm high-risk groups of depression. This study analyzed 4011 elderly people (≥60 years old) who completed a health survey, blood pressure, physical measurement, blood test, and a standardized depression screening test. A major depressive disorder was measured using the Korean version of the Patient Health Questionnaire (PHQ-9). This study built a model for predicting major depressive disorders using logistic regression analysis to understand the relationship of each variable with major depressive disorders. In the result, the prevalence of depression measured by PHQ-9 was 6.8%. The results of multiple logistic regression analysis revealed that the major depressive disorder of the elderly living alone was significantly (p < 0.05) related to monthly mean household income, the mean frequency of having breakfast per week for the past year, moderate-intensity physical activity, subjective level of stress awareness, and subjective health status. The results of this study implied that it would be necessary to continuously monitor these complex risk factors such as household income, skipping breakfast, moderate-intensity physical activity, subjective stress, and subjective health status to prevent depression among older adults living in the community.

scholarly journals Systematic review and meta-analysis of the prevalence of depressive symptoms, dysthymia and major depressive disorders among homeless people

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040061
Author(s):  
Getinet Ayano ◽  
Asmare Belete ◽  
Bereket Duko ◽  
Light Tsegay ◽  
Berihun Assefa Dachew
Keyword(s):  
Systematic Review ◽  
Depressive Symptoms ◽  
Depressive Disorders ◽  
Meta Analysis ◽  
Random Effect ◽  
Homeless People ◽  
Sensitivity Analyses ◽  
Prevalence Rates ◽  
Major Depressive ◽  
Major Depressive Disorders

ObjectivesTo assess the global prevalence estimates of depressive symptoms, dysthymia and major depressive disorders (MDDs) among homeless people.DesignSystematic review and meta-analysis.Data sourcesDatabases including PubMed, Scopus and Web of Science were systematically searched up to February 2020 to identify relevant studies that have reported data on the prevalence of depressive symptoms, dysthymia and MDDs among homeless people.Eligibility criteriaOriginal epidemiological studies written in English that addressed the prevalence of depressive problems among homeless people.Data extraction and synthesisA random-effect meta-analysis was performed to pool the prevalence estimated from individual studies. Subgroup and sensitivity analyses were employed to compare the prevalence across the groups as well as to identify the source of heterogeneities. The Joanna Briggs Institute’s quality assessment checklist was used to measure the study quality. Cochran’s Q and the I2 test were used to assess heterogeneity between the studies.ResultsForty publications, including 17 215 participants, were included in the final analysis. This meta-analysis demonstrated considerably higher prevalence rates of depressive symptoms 46.72% (95% CI 37.77% to 55.90%), dysthymia 8.25% (95% CI 4.79% to 11.86%), as well as MDDs 26.24% (95% CI 21.02% to 32.22%) among homeless people. Our subgroup analysis showed that the prevalence of depressive symptoms was high among younger homeless people (<25 years of age), whereas the prevalence of MDD was high among older homeless people (>50 years of age) when compared with adults (25–50 years).ConclusionThis review showed that nearly half, one-fourth and one-tenth of homeless people are suffering from depressive symptoms, dysthymia and MDDs, respectively, which are notably higher than the reported prevalence rates in the general population. The findings suggest the need for appropriate mental health prevention and treatment strategies for this population group.

scholarly journals Preliminary Pharmacogenetic Study to Explore Putative Dopaminergic Mechanisms of Antidepressant Action

2021 ◽  
Vol 11 (8) ◽  
pp. 731
Author(s):  
Taichi Ochi ◽  
Natalya M. Vyalova ◽  
Innokentiy S. Losenkov ◽  
Diana Z. Paderina ◽  
Ivan V. Pozhidaev ◽  
...  
Keyword(s):  
Depressive Disorders ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Sufficient Evidence ◽  
Therapeutic Effects ◽  
Pharmacogenetic Study ◽  
Dopaminergic Mechanisms ◽  
Major Depressive Disorders ◽  
Related Proteins ◽  
Antidepressant Action

Background: There is sufficient evidence that interference of dopaminergic neurotransmission contributes to the therapeutic effects of antidepressants in unipolar and bipolar depression. Methods: Hamilton depression rating scale (HAMD 17) scores of 163 at least moderately ill patients with major depressive disorders were used to establish treatment response. HAMD 17 score status was measured before initiation, after two weeks, and after four weeks of treatment with various antidepressants. The possible association between response and genotype in a total of 14 variants of dopamine neurotransmission-related proteins was investigated. Results: DRD4 rs11246226 CA heterozygous patients were found with a greater improvement of HAMD 17 score when compared to homozygous C patients during 0–2 weeks and 0–4 weeks. Patients with MAOB rs1799836 heterozygous GA and homozygous A also demonstrated improved scores during 2–4 weeks and 0–4 weeks. Conclusions: The results are preliminary due to the limited population size and the small number of variants. Further research into the involvement of habenular dopamine D4 receptors in the antidepressant response is desirable.

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