Exercise Interventions as the Primary Treatment for Depression: Evidence from a Narrative Review.
Md Zemberi Nur Fatin Nabilah,Ismail Muhammad Mokhzani,Abdullah Mohammad Farris Iman Leong
The Malaysian journal of medical sciences : MJMS
There is an increasing evidence supporting the efficacy of exercise interventions in the treatment of depression, which is a growing global health concern. However, data on the efficacy of exercise as the primary treatment for depression are scarce. This narrative review explored the efficacy of exercise interventions as the primary treatment for depressive disorders. A comprehensive search for English-language literature published between January 1965 and November 2019 was conducted via PubMed, Google Scholar, Scopus, Web of Science, PsycINFO, EMBASE, Cochrane database and Medline. Thirteen randomised control trials (RCTs) were included in the final analysis. Their results indicated that supervised aerobic exercise and high-intensity progressive resistance training (PRT) were effective in ameliorating depressive symptoms as the primary treatment compared with control groups, but they were not superior to other active treatments, such as antidepressants and cognitive behavioural therapy. Aerobic exercise and high-intensity PRT may be a promising primary treatment for depression as they may induce biopsychosocial effects (effects on neurotrophic factor, pro-inflammatory cytokines, monoamine, the hypothalamic-pituitary-adrenal axis, self-efficacy, mastery experience, adaptive coping and social interaction), which may ameliorate the severity of depressive symptoms. However, future RCTs with more comprehensive and well-designed methodologies are warranted to confirm our findings.
Role of glucocorticoid- and monoamine-metabolizing enzymes in stress-related psychopathological processes.
Tseilikman Vadim,Dremencov Eliyahu,Tseilikman Olga,Pavlovicova Michaela,Lacinova Lubica,Jezova Daniela
Stress (Amsterdam, Netherlands)
Glucocorticoid signaling is fundamental in healthy stress coping and in the pathophysiology of stress-related diseases, such as post-traumatic stress disorder (PTSD). Glucocorticoids are metabolized by cytochrome P450 (CYP) as well as 11-β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 2 (11βHSD2). Acute stress-induced increase in glucocorticoid concentrations stimulates the expression of several CYP sub-types. CYP is primarily responsible for glucocorticoid metabolism and its increased activity can result in decreased circulating glucocorticoids in response to repeated stress stimuli. In addition, repeated stress-induced glucocorticoid release can promote 11βHSD1 activation and 11βHSD2 inhibition, and the 11βHSD2 suppression can lead to apparent mineralocorticoid excess. The activation of CYP and 11βHSD1 and the suppression of 11βHSD2 may at least partly contribute to development of the blunted glucocorticoid response to stressors characteristic in high trait anxiety, PTSD, and other stress-related disorders. Glucocorticoids and glucocorticoid-metabolizing enzymes interact closely with other biomolecules such as inflammatory cytokines, monoamines, and some monoamine-metabolizing enzymes, namely the monoamine oxidase type A (MAO-A) and B (MAO-B). Glucocorticoids boost MAO activity and this decreases monoamine levels and induces oxidative tissue damage which then activates inflammatory cytokines. The inflammatory cytokines suppress CYP expression and activity. This dynamic cross-talk between glucocorticoids, monoamines, and their metabolizing enzymes could be a critical factor in the pathophysiology of stress-related disorders.Glucocorticoids, which are produced and released under the control by brain regulatory centers, are fundamental in the stress response. This review emphasizes the importance of glucocorticoid metabolism and particularly the interaction between the brain and the liver as the major metabolic organ in the body. The activity of enzymes involved in glucocorticoid metabolism is proposed to play not only an important role in positive, healthy glucocorticoid effects, but also to contribute to the development and course of stress-related diseases.
Systemic low-grade inflammation in post-traumatic stress disorder: a systematic review.
Speer Kathryn,Upton Dominic,Semple Stuart,McKune Andrew
Journal of inflammation research
Studies examining post-traumatic stress disorder (PTSD) have either emphasized a relationship between PTSD and a systemically pro-inflammatory state or identified a link between PTSD and chronic disease. The aim of this study was to evaluate the evidence for a relationship between individuals with PTSD and systemic low-grade inflammation that has been proposed to underlie chronic disease development in this population. The authors conducted a systematic review of the literature (January 2006 to April 2017) in accordance with the PRISMA statement in the following four databases: PubMed, MEDLINE, PsycINFO, and SPORTDiscus with Full Text. The search strategy was limited to articles published in peer-reviewed journals and to human studies. Nine studies measuring systemic inflammation and discussing its role in chronic disease development were selected for inclusion in this review. The association between markers of systemic inflammation and PTSD was evaluated by the measurement of a variety of systemic inflammatory markers including acute-phase proteins, complement proteins, pro- and anti-inflammatory cytokines, natural killer cells, and white blood cells. In general, systemic inflammatory biomarkers were elevated across the studies in the PTSD groups. There is evidence that PTSD is underpinned by the presence of a systemic low-grade inflammatory state. This inflammation may be the mechanism associated with increased risk for chronic disease in the PTSD population. From this, future research should focus on interventions that help to reduce inflammation, such as exercise.
Exercise activates vagal induction of dopamine and attenuates systemic inflammation.
Shimojo Guilherme,Joseph Biju,Shah Roshan,Consolim-Colombo Fernanda M,De Angelis Kátia,Ulloa Luis
Brain, behavior, and immunity
Physical exercise is one of the most important factors improving quality of life, but it is not feasible for patients with morbidity or limited mobility. Most previous studies focused on high-intensity or long-term exercise that causes metabolic stress or physiological adaption, respectively. Here, we studied how moderate-intensity swimming affects systemic inflammation in 6-8 week old C57BL/6J male mice during endotoxemia. One-hour swimming prevented hypokalemia, hypocalcemia, attenuated serum levels of inflammatory cytokines, increased anti-inflammatory cytokines but affected neither IL6 nor glycemia before or after the endotoxic challenge. Exercise attenuated serum TNF levels by inhibiting its production in the spleen through a mechanism mediated by the subdiaphragmatic vagus nerve but independent of the splenic nerve. Exercise increased serum levels of dopamine, and adrenalectomy prevented the potential of exercise to induce dopamine and to attenuate serum TNF levels. Dopaminergic agonist type-1, fenoldopam, inhibited TNF production in splenocytes. Conversely, dopaminergic antagonist type-1, butaclamol, attenuated exercise control of serum TNF levels. These results suggest that vagal induction of dopamine may contribute to the anti-inflammatory potential of physical exercise.
Exercise and the Regulation of Inflammatory Responses.
Allen Jacob,Sun Yi,Woods Jeffrey A
Progress in molecular biology and translational science
Exercise initiates a cascade of inflammatory events, which ultimately lead to long-term effects on human health. During and after acute exercise in skeletal muscle, interactions between immune cells, cytokines, and other intracellular components, create an inflammatory milieu responsible for the recovery and adaption from an exercise bout. In the systemic circulation, cytokines released from muscle (myokines) mediate metabolic and inflammatory processes. Moderate exercise training results in improvements in systemic inflammation, evident by reductions in acute phase proteins. The anti-inflammatory effects of regular exercise include actions dependent and independent of changes in adipose tissue mass. Future research should encompass approaches, which attempt to integrate other, less-recognized physiological processes with acute and long-term inflammatory changes. This will include investigation into metabolic, endocrine, and immune components of various tissues and organs.
Co-treatment of piracetam with risperidone rescued extinction deficits in experimental paradigms of post-traumatic stress disorder by restoring the physiological alterations in cortex and hippocampus.
Uniyal Ankit,Singh Raghunath,Akhtar Ansab,Bansal Yashika,Kuhad Anurag,Sah Sangeeta Pilkhwal
Pharmacology, biochemistry, and behavior
Pharmacotherapy and cognitive behavioral therapy, both fail to treat post-traumatic stress disorder (PTSD) in a considerable number of populations. The persistence of traumatic memories and deficit in extinction contributes to the failure of exposure therapy in PTSD. With the objective to enhance the outcomes of exposure therapy by targeting the extinction window using pharmacological agents in PTSD, the present study was aimed to explore the effect of piracetam, risperidone and their combinations in experimentally-induced PTSD-like phenotype in rats. Male SD rats were exposed to single prolonged stress model (SPS) for induction of PTSD-like behavioral changes. Piracetam, risperidone and their combination were used as therapeutic interventions while sertraline was used as a standard treatment for 14 days along with extinction training. Induction of PTSD-like behaviors were assessed in behavioral tests such as fear conditioning, elevated plus maze, social interaction test, and the marble burying test. Neurotransmitters (dopamine and serotonin and their metabolites), BDNF, proinflammatory cytokines (TNF-α, IL-6), caspase-3, and markers for oxidative stress were assessed in the hippocampus and cortex while corticosterone and nitrite levels were estimated in plasma. Our result indicated that the SPS paradigm efficiently induced PTSD-like phenotype in rats. Risperidone and piracetam were found to be effective alone, while their high dose combination, produced potentiating effect in reversing the extinction deficit, behavioral alterations, altered cortical and hippocampal BDNF, IL-6, TNF-α, caspase-3, oxidative stress markers, and neurotransmitter levels. Plasma corticosterone and nitrite levels were also found to be reversed in the combination treated groups. Our preliminary study suggests that piracetam, risperidone and their combination restored the physiological cascades in cortex and hippocampus along with successful suppression of fear memory and a symptom cluster of PTSD-like phenotype in rats. Hence they could be used as an effective adjunct to enhance the outcome of exposure therapy for the management of PTSD.
Neuroinflammation and cognition across psychiatric conditions.
Fourrier Célia,Singhal Gaurav,Baune Bernhard T
Cognitive impairments reported across psychiatric conditions (ie, major depressive disorder, bipolar disorder, schizophrenia, and posttraumatic stress disorder) strongly impair the quality of life of patients and the recovery of those conditions. There is therefore a great need for consideration for cognitive dysfunction in the management of psychiatric disorders. The redundant pattern of cognitive impairments across such conditions suggests possible shared mechanisms potentially leading to their development. Here, we review for the first time the possible role of inflammation in cognitive dysfunctions across psychiatric disorders. Raised inflammatory processes (microglia activation and elevated cytokine levels) across diagnoses could therefore disrupt neurobiological mechanisms regulating cognition, including Hebbian and homeostatic plasticity, neurogenesis, neurotrophic factor, the HPA axis, and the kynurenine pathway. This redundant association between elevated inflammation and cognitive alterations across psychiatric disorders hence suggests that a cross-disorder approach using pharmacological and nonpharmacological (ie, physical activity and nutrition) anti-inflammatory/immunomodulatory strategies should be considered in the management of cognition in psychiatry.