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The Role of Chronic Stress in Anxious Depression.

ABSTRACT: Depression is a heterogeneous disease with many different subtypes. Patients with the anxious depression-a common subtype of major depression-are at an increased risk for treatment-resistance to standard antidepressants, with resultant increases in morbidity. However, the underlying pathophysiology of anxious depression remains unknown. Without such knowledge, the development of targeted treatments towards this specific depression subtype will likely remain elusive. One method by which research into the neurobiology of anxious depression may prove fruitful is with the research domain criteria (RDoC). RDoC provides a framework for investigation into the underlying pathophysiology of mental illness. By studying disorders in terms of RDoC constructs-such as the sustained threat construct of the negative valence system-new insights may be gained into neurobiological mechanisms of disease. These mechanisms may be useful for the development of novel antidepressants that are based on specific brain targets. Specifically, we review the impact that sustained threat-or chronic stress-has on the eventual development of depression (especially anxious depression) through pathological changes to molecules, cells, neurocircuitry, physiology, and behavior.

SUBMITTER: Ross RA

PROVIDER: S-EPMC7219927 | biostudies-literature | 2017 Jan-Dec

REPOSITORIES: biostudies-literature

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The Role of Chronic Stress in Anxious Depression.

Ross Rachel A RA Foster Simmie L SL Ionescu Dawn F DF

Chronic stress (Thousand Oaks, Calif.) 20170101

Depression is a heterogeneous disease with many different subtypes. Patients with the anxious depression-a common subtype of major depression-are at an increased risk for treatment-resistance to standard antidepressants, with resultant increases in morbidity. However, the underlying pathophysiology of anxious depression remains unknown. Without such knowledge, the development of targeted treatments towards this specific depression subtype will likely remain elusive. One method by which research ...[more]

PMID: 32440578

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Project description:BackgroundThe microbiota-gut-brain axis plays a critical role in neuropsychiatric disorders, particularly anxious depression, and attracts more attention gradually. Zhi Zi Chi decoction (ZZCD) consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a classic formula in clinic and widely applied in anxiety and depression treatment. However, the underlying mechanisms of regulating microbiota-gut-brain axis in the treatment of anxious depression by oral administration of ZZCD remain elusive.Materials and methodsIn this project, we clarified the origin and preparation methods of the Gardenia jasminoides J. Ellis and Glycine max (L.) Merr and examined the chemical ingredients of ZZCD by liquid chromatograph mass spectrometer. Then, corticosterone combined with chronic restraint stress was applied to establish an anxious depression model. After treated with ZZCD standard decoction, based on enzyme-linked immunosorbent assay (ELISA), 16S rRNA technology, high-throughput sequencing, quantitative RT-PCR and fecal microbiota transplantation (FMT), the multiple associations between nucleus accumbens and intestinal flora in anxious depression mice were determined to clarify the mechanism of ZZCD in the treatment of anxiety and depression disorder.ResultsWe found various substances with antidepressant and antianxiety properties in ZZCD such as rosiridin and oleanolic acid. ZZCD could alleviate depressive and anxiety behaviors in anxious depression mice via regulating the disturbance of gut microbiota. Meanwhile, the bioactive compounds of ZZCD might directly active on neurodevelopment and neuroimmune-related genes. Furthermore, the secretion of prolactin and estrogen, and interfering with mitogen-activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were mainly involved in the multi-target therapeutic effects of ZZCD against anxiety and depression.ConclusionsThese findings suggested that ZZCD exerts antidepressant effects pleiotropically through modulating the microbiota-gut-brain.

Dataset Information

The Role of Chronic Stress in Anxious Depression.

Publications

The Role of Chronic Stress in Anxious Depression.

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