Divergence in depressive symptom severity and vascular dysfunction with gender in rats with unpredictable chronic mild stress (680.20)

The presence of chronic, unresolvable stresses leads to negative health outcomes, including development of clinical depression/depressive disorders, with outcome severity being correlated with depressive symptom severity. One of the major outcomes associated with chronic stress and depression is the development of cardiovascular disease (CVD) and an elevated CVD risk profile. However, in epidemiological research, sex disparities are evident, with premenopausal women suffering from depressive symptoms more acutely than men, but also demonstrating a relative protection from the onset of CVD. Given this, we investigated the differential effect of sex on conduit artery and resistance arteriolar function in male and female mice following 8 wk of an unpredictable chronic mild stress (UCMS) protocol. In males, plasma cortisol and depressive symptom severity (e.g., coat status, anhedonia, delayed grooming) were elevated by UCMS. Endothelium-dependent dilation to methacholine/acetylcholine was impaired in conduit arteries and skeletal muscle arterioles, suggesting a severe loss of nitric oxide bioavailability and increased production of thromboxane A2 vs. prostaglandin I2 associated with elevated reactive oxygen species (ROS) and an increased level of systemic inflammation. Endothelium-independent dilation was intact. In females, depressive symptoms and plasma cortisol increases were more severe than in males, although alterations to vascular reactivity were blunted, including the effects of elevated ROS and inflammation on dilator responses. These results suggest that compared with males, female rats are more susceptible to chronic stress in terms of the severity of depressive behaviors, but that the subsequent development of vasculopathy is blunted owing to an improved ability to tolerate elevated ROS and systemic inflammatory stress.

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Protection from vascular dysfunction in female rats with chronic stress and depressive symptoms

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00647.2017 ◽

2018 ◽

Vol 314 (5) ◽

pp. H1070-H1084 ◽

Cited By ~ 12

Author(s):

Steven D. Brooks ◽

Stanley M. Hileman ◽

Paul D. Chantler ◽

Samantha A. Milde ◽

Kent A. Lemaster ◽

...

Keyword(s):

Depressive Symptoms ◽

Depressive Symptom ◽

Chronic Stress ◽

Symptom Severity ◽

Vascular Reactivity ◽

Vascular Dysfunction ◽

Sex Hormone ◽

Female Rats ◽

Depressive Symptom Severity ◽

Female Subjects

The increasing prevalence and severity of clinical depression are strongly correlated with vascular disease risk, creating a comorbid condition with poor outcomes but demonstrating a sexual disparity whereby female subjects are at lower risk than male subjects for subsequent cardiovascular events. To determine the potential mechanisms responsible for this protection against stress/depression-induced vasculopathy in female subjects, we exposed male, intact female, and ovariectomized (OVX) female lean Zucker rats to the unpredictable chronic mild stress (UCMS) model for 8 wk and determined depressive symptom severity, vascular reactivity in ex vivo aortic rings and middle cerebral arteries (MCA), and the profile of major metabolites regulating vascular tone. While all groups exhibited severe depressive behaviors from UCMS, severity was significantly greater in female rats than male or OVX female rats. In all groups, endothelium-dependent dilation was depressed in aortic rings and MCAs, although myogenic activation and vascular (MCA) stiffness were not impacted. Higher-resolution results from pharmacological and biochemical assays suggested that vasoactive metabolite profiles were better maintained in female rats with normal gonadal sex steroids than male or OVX female rats, despite increased depressive symptom severity (i.e., higher nitric oxide and prostacyclin and lower H2O2and thromboxane A2levels). These results suggest that female rats exhibit more severe depressive behaviors with UCMS but are partially protected from the vasculopathy that afflicts male rats and female rats lacking normal sex hormone profiles. Determining how female sex hormones afford partial vascular protection from chronic stress and depression is a necessary step for addressing the burden of these conditions on cardiovascular health.NEW & NOTEWORTHY This study used a translationally relevant model for chronic stress and elevated depressive symptoms to determine how these factors impact conduit and resistance arteriolar function in otherwise healthy rats. While chronic stress leads to an impaired vascular reactivity associated with elevated oxidant stress, inflammation, and reduced metabolite levels, we demonstrated partial protection from vascular dysfunction in female rats with normal sex hormone profiles compared with male or ovariectomized female rats.

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N-acetylcysteine as an adjunctive treatment to reduce depressive symptom severity when C-reactive protein levels are increased

10.26226/morressier.5971be83d462b80290b52f0e ◽

2017 ◽

Author(s):

Sandra Odebrecht Vargas Nunes

Keyword(s):

Depressive Symptom ◽

Symptom Severity ◽

Adjunctive Treatment ◽

C Reactive Protein ◽

Protein Levels ◽

Reactive Protein ◽

Depressive Symptom Severity

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The contribution of depressive ‘disorder characteristics’ to determinations of prognosis for adults with depression: an individual patient data meta-analysis

Psychological Medicine ◽

10.1017/s0033291721001367 ◽

2021 ◽

pp. 1-14

Author(s):

Joshua E. J. Buckman ◽

Rob Saunders ◽

Zachary D. Cohen ◽

Phoebe Barnett ◽

Katherine Clarke ◽

...

Keyword(s):

Primary Care ◽

Depressive Symptoms ◽

Depressive Symptom ◽

Panic Disorder ◽

Symptom Severity ◽

Individual Patient Data ◽

Antidepressant Treatment ◽

Patient Data ◽

History Of ◽

Depressive Symptom Severity

Abstract Background This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care. Methods We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted. Results Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions. Conclusions When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.

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Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression

Pharmaceuticals ◽

10.3390/ph14070659 ◽

2021 ◽

Vol 14 (7) ◽

pp. 659

Author(s):

Juthamart Maneenet ◽

Orawan Monthakantirat ◽

Supawadee Daodee ◽

Chantana Boonyarat ◽

Yutthana Chotritthirong ◽

...

Keyword(s):

Mrna Expression ◽

Chronic Mild Stress ◽

Antidepressant Activity ◽

Piper Nigrum ◽

Psychiatric Disease ◽

Mild Stress ◽

Herbal Formula ◽

Necrosis Factor Alpha ◽

Unpredictable Chronic Mild Stress

Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.

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EFFECTIVENESS OF COGNITIVE BEHAVIORAL THERAPY FOR INSOMNIA: INFLUENCE OF SLIGHT-TO-MODERATE DEPRESSIVE SYMPTOM SEVERITY AND WORRYING

Depression and Anxiety ◽

10.1002/da.22258 ◽

2014 ◽

Vol 31 (8) ◽

pp. 662-668 ◽

Cited By ~ 8

Author(s):

Astrid B. H. Hamoen ◽

Else M. Redlich ◽

Al W. de Weerd

Keyword(s):

Depressive Symptom ◽

Cognitive Behavioral Therapy ◽

Symptom Severity ◽

Behavioral Therapy ◽

Cognitive Behavioral ◽

Depressive Symptom Severity

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Improvement of penile neurogenic and endothelial relaxant responses by chronic administration of resveratrol in rabbits exposed to unpredictable chronic mild stress

International Journal of Impotence Research ◽

10.1038/s41443-018-0016-8 ◽

2018 ◽

Vol 30 (4) ◽

pp. 163-170 ◽

Cited By ~ 2

Author(s):

Yusufhan Yazir ◽

Tijen Utkan ◽

Tuğçe Demirtaş Şahin ◽

Semil Selcen Gocmez

Keyword(s):

Chronic Mild Stress ◽

Chronic Administration ◽

Mild Stress ◽

Unpredictable Chronic Mild Stress

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Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis

Psychopharmacology ◽

10.1007/s00213-017-4720-8 ◽

2017 ◽

Vol 234 (22) ◽

pp. 3385-3394 ◽

Cited By ~ 34

Author(s):

Hong-Yan Li ◽

Ying-Hua Zhao ◽

Min-Jie Zeng ◽

Fang Fang ◽

Min Li ◽

...

Keyword(s):

Hpa Axis ◽

Chronic Mild Stress ◽

Hippocampal Neurogenesis ◽

Mild Stress ◽

Unpredictable Chronic Mild Stress

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Patient-reported outcomes before and after treatment of major depressive disorder

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2014.16.2/rcohen ◽

2014 ◽

Vol 16 (2) ◽

pp. 171-183 ◽

Cited By ~ 5

Keyword(s):

Depressive Symptom ◽

Symptom Severity ◽

Patient Reported Outcomes ◽

Burden Of Illness ◽

Major Depressive ◽

Patient Reported ◽

Before And After ◽

Depressive Symptom Severity ◽

The Impact ◽

Level 2

Patient reported outcomes (PROs) of quality of life (QoL), functioning, and depressive symptom severity are important in assessing the burden of illness of major depressive disorder (MDD) and to evaluate the impact of treatment. We sought to provide a detailed analysis of PROs before and after treatment of MDD from the large Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. This analysis examines PROs before and after treatment in the second level of STAR*D. The complete data on QoL, functioning, and depressive symptom severity, were analyzed for each STAR*D level 2 treatment. PROs of QoL, functioning, and depressive symptom severity showed substantial impairments after failing a selective serotonin reuptake inhibitor trial using citalopram (level 1). The seven therapeutic options in level 2 had positive statistically (P values) and clinically (Cohen's standardized differences [Cohen's d]) significant impact on QoL, functioning, depressive symptom severity, and reduction in calculated burden of illness. There were no statistically significant differences between the interventions. However, a substantial proportion of patients still suffered from patient-reported QoL and functioning impairment after treatment, an effect that was more pronounced in nonremitters. PROs are crucial in understanding the impact of MDD and in examining the effects of treatment interventions, both in research and clinical settings.

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