• Journal of Life Science
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• v.33 no.12
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• pp.1062-1073
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• 2023

Although depression is a common psychiatric disorder that negatively affects individuals and societies, its exact pathogenesis is not well understood. Stress is a major risk factor for depression and is known to increase susceptibility by triggering inflammation. Indeed, many preclinical and clinical studies have suggested a strong link between depression and inflammation. Depression is associated with increased levels of pro-inflammatory cytokines, such as interleukin (IL-)1β, IL-6, IL-12, tumor necrosis factor-α, and interferon-γ, and decreased levels of the anti-inflammatory IL-4, IL-10, and transforming growth factor-β. Administering pro-inflammatory cytokines causes depression-like behaviors in rodents. Conversely, administering anti-inflammatory drugs appears to ameliorate depressive symptoms. Although the importance of inflammation as a mediator of depression has been demonstrated, the mechanisms by which inflammation is activated in depression remain unclear. To address this issue, recent studies have focused on the importance of stress-induced sterile inflammation. Sterile inflammation refers to the activation of inflammatory processes due to physical and/or psychological stress in the absence of pathogens. Stress promotes the release of endogenous factors known as damage-associated molecular patterns (DAMPs), thereby triggering sterile inflammation. In turn, DAMPs are recognized by pattern recognition receptors, leading to the production of pro-inflammatory cytokines. Here, we review the role of DAMPs in depression based on preclinical and clinical evidence on the dysregulation of sterile inflammation.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.277-287
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• 1996

Objective : It has been proposed that cognition and related aspects of mental functioning are decreased in depression as well as in alcoholism. The objective of the study was to compare behavioral side effects of paroxetine and amitriptyline in depressed patients accompanied by alcoholism. The focused comparisons were drug effects concerning psychomotor performance, cognitive function, sleep and daytime sleepiness during the first 2 weeks of treatment. Methods : After an alcohol detoxification period(3 weeks) and a washout period(1 week), a total of 20 male inpatients with alcohol use disorder (DSM-IV), who also had a major depressive episode(DSM-IV), were treated double-blind with paroxetine 20mg/day(n=10) or amitriptyline 25mg/day(n=10) for 2 weeks. All patients were required to have a scare of at least 18 respectively on bath the Hamilton Rating Scale far Depression(HAM-D) and Beck Depression Inventory(BDI) at pre-drug baseline. Patients randomized to paroxetine received active medication in the morning and placebo in the evening whereas those randomized to amitriptyline received active medication in the evening and placebo in the morning. All patients performed the various tasks in a test battery at baseline and at days 3, 7 and 14. The test battery included : critical flicker fusion threshold for sensory information processing capacity : choice reaction time for gross psychomotor performance : tracking accuracy and latency of response to peripheral stimulus as a measure of line sensorimotor co-ordination and divided attention : digit symbol substitution as a measure of sustained attention and concentration. To rate perceived sleep and daytime sleepiness, 10cm line Visual analogue scales were employed at baseline and at days 3, 7 and 14. The subjective rating scales were adapted far this study from Leeds sleep Evaluation Questionnaire and Epworth Sleepiness Scale. In addition a comprehensive side effect assessment, using the UKU side effect rating scale, was carried out at baseline and at days 7 and 14. The efficacy of treatment was evaluated using HAM-D, BDI and clinical global impression far severity and improvement at days 7 and 14. Results : The pattern of results indicated thai paroxetine improved performance an mast of the lest variables and also improved sleep with no effect on daytime sleepiness aver the study period. In contrast, amitriptyline produced disruption of performance on same tests and improved sleep with increased daytime sleepiness in particular at day 3. On the UKU side effect rating scale, mare side effects were registered an amitriptyline. The therapeutic efficacy was observed in favor of paroxetine early in day 7. Conclusion : These results demonstrated thai paroxetine in much better than amitriptyline for the treatment of depressed patients accompained by alcoholism at least in terms of behavioral safety and tolerability, furthermore the results may assist in explaining the therapeutic outcome of paroxetine. For example, and earlier onset of antidepressant action of paroxetine may be caused by early improved cognitive function or by contributing to good compliance with treatment.