-
1.
Microbiota-gut-brain axis mechanisms in the complex network of bipolar disorders: potential clinical implications and translational opportunities.
Ortega, MA, Álvarez-Mon, MA, García-Montero, C, Fraile-Martínez, Ó, Monserrat, J, Martinez-Rozas, L, Rodríguez-Jiménez, R, Álvarez-Mon, M, Lahera, G
Molecular psychiatry. 2023;(7):2645-2673
-
-
Free full text
-
Abstract
Bipolar disorders (BD) represent a severe leading disabling mental condition worldwide characterized by episodic and often progressive mood fluctuations with manic and depressive stages. The biological mechanisms underlying the pathophysiology of BD remain incompletely understood, but it seems that there is a complex picture of genetic and environmental factors implicated. Nowadays, gut microbiota is in the spotlight of new research related to this kind of psychiatric disorder, as it can be consistently related to several pathophysiological events observed in BD. In the context of the so-called microbiota-gut-brain (MGB) axis, it is shown to have a strong influence on host neuromodulation and endocrine functions (i.e., controlling the synthesis of neurotransmitters like serotonin or mediating the activation of the hypothalamic-pituitary-adrenal axis), as well as in modulation of host immune responses, critically regulating intestinal, systemic and brain inflammation (neuroinflammation). The present review aims to elucidate pathophysiological mechanisms derived from the MGB axis disruption and possible therapeutic approaches mainly focusing on gut microbiota in the complex network of BD. Understanding the mechanisms of gut microbiota and its bidirectional communication with the immune and other systems can shed light on the discovery of new therapies for improving the clinical management of these patients. Besides, the effect of psychiatric drugs on gut microbiota currently used in BD patients, together with new therapeutical approaches targeting this ecosystem (dietary patterns, probiotics, prebiotics, and other novelties) will also be contemplated.
-
2.
Understanding the basis of major depressive disorder in oncological patients: Biological links, clinical management, challenges, and lifestyle medicine.
Fraile-Martinez, O, Alvarez-Mon, MA, Garcia-Montero, C, Pekarek, L, Guijarro, LG, Lahera, G, Saez, MA, Monserrat, J, Motogo, D, Quintero, J, et al
Frontiers in oncology. 2022;:956923
Abstract
In recent years, the incidence of different types of cancer and patient survival have been rising, as well as their prevalence. The increase in survival in recent years exposes the patients to a set of stressful factors such as more rigorous follow-up and more aggressive therapeutic regimens that, added to the diagnosis of the disease itself, cause an increase in the incidence of depressive disorders. These alterations have important consequences for the patients, reducing their average survival and quality of life, and for these reasons, special emphasis has been placed on developing numerous screening tests and early recognition of depressive symptoms. Despite that cancer and major depressive disorder are complex and heterogeneous entities, they also share many critical pathophysiological mechanisms, aiding to explain this complex relationship from a biological perspective. Moreover, a growing body of evidence is supporting the relevant role of lifestyle habits in the prevention and management of both depression and cancer. Therefore, the present study aims to perform a thorough review of the intricate relationship between depression and cancer, with a special focus on its biological links, clinical management, challenges, and the central role of lifestyle medicine as adjunctive and preventive approaches to improve the quality of life of these patients.
-
3.
Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection.
Ortega, MA, Fraile-Martínez, Ó, García-Montero, C, Alvarez-Mon, MA, Lahera, G, Monserrat, J, Llavero-Valero, M, Mora, F, Rodríguez-Jiménez, R, Fernandez-Rojo, S, et al
Frontiers in nutrition. 2022;:867150
Abstract
Major depressive disorder (MDD) is a complex, multifactorial disorder of rising prevalence and incidence worldwide. Nearly, 280 million of people suffer from this leading cause of disability in the world. Moreover, patients with this condition are frequently co-affected by essential nutrient deficiency. The typical scene with stress and hustle in developed countries tends to be accompanied by eating disorders implying overnutrition from high-carbohydrates and high-fat diets with low micronutrients intake. In fact, currently, coronavirus disease 2019 (COVID-19) pandemic has drawn more attention to this underdiagnosed condition, besides the importance of the nutritional status in shaping immunomodulation, in which minerals, vitamins, or omega 3 polyunsaturated fatty acids (ω-3 PUFA) play an important role. The awareness of nutritional assessment is greater and greater in the patients with depression since antidepressant treatments have such a significant probability of failing. As diet is considered a crucial environmental factor, underlying epigenetic mechanisms that experience an adaptation or consequence on their signaling and expression mechanisms are reviewed. In this study, we included metabolic changes derived from an impairment in cellular processes due to lacking some essential nutrients in diet and therefore in the organism. Finally, aspects related to nutritional interventions and recommendations are also addressed.
-
4.
Gut Microbiota Metabolites in Major Depressive Disorder-Deep Insights into Their Pathophysiological Role and Potential Translational Applications.
Ortega, MA, Alvarez-Mon, MA, García-Montero, C, Fraile-Martinez, O, Guijarro, LG, Lahera, G, Monserrat, J, Valls, P, Mora, F, Rodríguez-Jiménez, R, et al
Metabolites. 2022;(1)
Abstract
The gut microbiota is a complex and dynamic ecosystem essential for the proper functioning of the organism, affecting the health and disease status of the individuals. There is continuous and bidirectional communication between gut microbiota and the host, conforming to a unique entity known as "holobiont". Among these crosstalk mechanisms, the gut microbiota synthesizes a broad spectrum of bioactive compounds or metabolites which exert pleiotropic effects on the human organism. Many of these microbial metabolites can cross the blood-brain barrier (BBB) or have significant effects on the brain, playing a key role in the so-called microbiota-gut-brain axis. An altered microbiota-gut-brain (MGB) axis is a major characteristic of many neuropsychiatric disorders, including major depressive disorder (MDD). Significative differences between gut eubiosis and dysbiosis in mental disorders like MDD with their different metabolite composition and concentrations are being discussed. In the present review, the main microbial metabolites (short-chain fatty acids -SCFAs-, bile acids, amino acids, tryptophan -trp- derivatives, and more), their signaling pathways and functions will be summarized to explain part of MDD pathophysiology. Conclusions from promising translational approaches related to microbial metabolome will be addressed in more depth to discuss their possible clinical value in the management of MDD patients.
-
5.
The Problem of Malnutrition Associated with Major Depressive Disorder from a Sex-Gender Perspective.
García-Montero, C, Ortega, MA, Alvarez-Mon, MA, Fraile-Martinez, O, Romero-Bazán, A, Lahera, G, Montes-Rodríguez, JM, Molina-Ruiz, RM, Mora, F, Rodriguez-Jimenez, R, et al
Nutrients. 2022;(5)
Abstract
Major depressive disorder (MDD) is an incapacitating condition characterized by loss of interest, anhedonia and low mood, which affects almost 4% of people worldwide. With rising prevalence, it is considered a public health issue that affects economic productivity and heavily increases health costs alone or as a comorbidity for other pandemic non-communicable diseases (such as obesity, cardiovascular disease, diabetes, inflammatory bowel diseases, etc.). What is even more noteworthy is the double number of women suffering from MDD compared to men. In fact, this sex-related ratio has been contemplated since men and women have different sexual hormone oscillations, where women meet significant changes depending on the age range and moment of life (menstruation, premenstruation, pregnancy, postpartum, menopause…), which seem to be associated with susceptibility to depressive symptoms. For instance, a decreased estrogen level promotes decreased activation of serotonin transporters. Nevertheless, sexual hormones are not the only triggers that alter neurotransmission of monoamines and other neuropeptides. Actually, different dietary habits and/or nutritional requirements for specific moments of life severely affect MDD pathophysiology in women. In this context, the present review aims to descriptively collect information regarding the role of malnutrition in MDD onset and course, focusing on female patient and especially macro- and micronutrient deficiencies (amino acids, ω3 polyunsaturated fatty acids (ω3 PUFAs), folate, vitamin B12, vitamin D, minerals…), besides providing evidence for future nutritional intervention programs with a sex-gender perspective that hopefully improves mental health and quality of life in women.
-
6.
Exploring the Role of Nutraceuticals in Major Depressive Disorder (MDD): Rationale, State of the Art and Future Prospects.
Alvarez-Mon, MA, Ortega, MA, García-Montero, C, Fraile-Martinez, O, Monserrat, J, Lahera, G, Mora, F, Rodriguez-Quiroga, A, Fernandez-Rojo, S, Quintero, J, et al
Pharmaceuticals (Basel, Switzerland). 2021;(8)
Abstract
Major depressive disorder (MDD) is a complex and common disorder, with many factors involved in its onset and development. The clinical management of this condition is frequently based on the use of some pharmacological antidepressant agents, together with psychotherapy and other alternatives in most severe cases. However, an important percentage of depressed patients fail to respond to the use of conventional therapies. This has created the urgency of finding novel approaches to help in the clinical management of those individuals. Nutraceuticals are natural compounds contained in food with proven benefits either in health promotion or disease prevention and therapy. A growing interest and economical sources are being placed in the development and understanding of multiple nutraceutical products. Here, we summarize some of the most relevant nutraceutical agents evaluated in preclinical and clinical models of depression. In addition, we will also explore less frequent but interest nutraceutical products which are starting to be tested, also evaluating future roads to cover in order to maximize the benefits of nutraceuticals in MDD.
-
7.
Nutritional Components in Western Diet Versus Mediterranean Diet at the Gut Microbiota-Immune System Interplay. Implications for Health and Disease.
García-Montero, C, Fraile-Martínez, O, Gómez-Lahoz, AM, Pekarek, L, Castellanos, AJ, Noguerales-Fraguas, F, Coca, S, Guijarro, LG, García-Honduvilla, N, Asúnsolo, A, et al
Nutrients. 2021;(2)
Abstract
The most prevalent diseases of our time, non-communicable diseases (NCDs) (including obesity, type 2 diabetes, cardiovascular diseases and some types of cancer) are rising worldwide. All of them share the condition of an "inflammatory disorder", with impaired immune functions frequently caused or accompanied by alterations in gut microbiota. These multifactorial maladies also have in common malnutrition related to physiopathology. In this context, diet is the greatest modulator of immune system-microbiota crosstalk, and much interest, and new challenges, are arising in the area of precision nutrition as a way towards treatment and prevention. It is a fact that the westernized diet (WD) is partly responsible for the increased prevalence of NCDs, negatively affecting both gut microbiota and the immune system. Conversely, other nutritional approaches, such as Mediterranean diet (MD), positively influence immune system and gut microbiota, and is proposed not only as a potential tool in the clinical management of different disease conditions, but also for prevention and health promotion globally. Thus, the purpose of this review is to determine the regulatory role of nutritional components of WD and MD in the gut microbiota and immune system interplay, in order to understand, and create awareness of, the influence of diet over both key components.
-
8.
Areas of Interest and Attitudes Toward Antiobesity Drugs: Thematic and Quantitative Analysis Using Twitter.
Alvarez-Mon, MA, Llavero-Valero, M, Asunsolo Del Barco, A, Zaragozá, C, Ortega, MA, Lahera, G, Quintero, J, Alvarez-Mon, M
Journal of medical Internet research. 2021;(10):e24336
Abstract
BACKGROUND Antiobesity drugs are prescribed for the treatment of obesity in conjunction with healthy eating, physical activity, and behavior modification. However, poor adherence rates have been reported. Attitudes or beliefs toward medications are important to ascertain because they may be associated with patient behavior. The analysis of tweets has become a tool for health research. OBJECTIVE The aim of this study is to investigate the content and key metrics of tweets referring to antiobesity drugs. METHODS In this observational quantitative and qualitative study, we focused on tweets containing hashtags related to antiobesity drugs between September 20, 2019, and October 31, 2019. Tweets were first classified according to whether they described medical issues or not. Tweets with medical content were classified according to the topic they referred to: side effects, efficacy, or adherence. We additionally rated it as positive or negative. Furthermore, we classified any links included within a tweet as either scientific or nonscientific. Finally, the number of retweets generated as well as the dissemination and sentiment score obtained by the antiobesity drugs analyzed were also measured. RESULTS We analyzed a total of 2045 tweets, 945 of which were excluded according to the criteria of the study. Finally, 320 out of the 1,100 remaining tweets were also excluded because their content, although related to drugs for obesity treatment, did not address the efficacy, side effects, or adherence to medication. Liraglutide and semaglutide accumulated the majority of tweets (682/780, 87.4%). Notably, the content that generated the highest frequency of tweets was related to treatment efficacy, with liraglutide-, semaglutide-, and lorcaserin-related tweets accumulating the highest proportion of positive consideration. We found the highest percentages of tweets with scientific links in those posts related to liraglutide and semaglutide. Semaglutide-related tweets obtained the highest probability of likes and were the most disseminated within the Twitter community. CONCLUSIONS This analysis of posted tweets related to antiobesity drugs shows that the interest, beliefs, and experiences regarding these pharmacological treatments are heterogeneous. The efficacy of the treatment accounts for the majority of interest among Twitter users.
-
9.
MicroRNAs as Critical Biomarkers of Major Depressive Disorder: A Comprehensive Perspective.
Ortega, MA, Alvarez-Mon, MA, García-Montero, C, Fraile-Martinez, O, Lahera, G, Monserrat, J, Muñoz-Merida, L, Mora, F, Rodríguez-Jiménez, R, Fernandez-Rojo, S, et al
Biomedicines. 2021;(11)
Abstract
Major Depressive Disorder (MDD) represents a major global health concern, a body-mind malady of rising prevalence worldwide nowadays. The complex network of mechanisms involved in MDD pathophysiology is subjected to epigenetic changes modulated by microRNAs (miRNAs). Serum free or vesicles loaded miRNAs have starred numerous publications, denoting a key role in cell-cell communication, systematically and in brain structure and neuronal morphogenesis, activity and plasticity. Upregulated or downregulated expression of these signaling molecules may imply the impairment of genes implicated in pathways of MDD etiopathogenesis (neuroinflammation, brain-derived neurotrophic factor (BDNF), neurotransmitters, hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, circadian rhythms...). In addition, these miRNAs could serve as potential biomarkers with diagnostic, prognostic and predictive value, allowing to classify severity of the disease or to make decisions in clinical management. They have been considered as promising therapy targets as well and may interfere with available antidepressant treatments. As epigenetic malleable regulators, we also conclude emphasizing lifestyle interventions with physical activity, mindfulness and diet, opening the door to new clinical management considerations.