Browsing by MeSH term "Anxiety"
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Publication A Mobile Application to Help Self-Manage Pain Severity, Anxiety, and Depressive Symptoms in Patients with Fibromyalgia Syndrome: A Pilot Study.(2022-09-23) Miró, Jordi; Lleixà-Daga, Meritxell; de la Vega, Rocío; Llorens-Vernet, Pere; Jensen, Mark PTreatment for individuals with fibromyalgia syndrome (FMS) is complex and is not always accessible to those who could benefit. The aim of this study was to conduct a preliminary evaluation of a mobile-app-delivered, cognitive behavioral treatment (CBT)-based intervention in helping adults self-manage fibromyalgia symptoms. A total of 100 adults with FMS (M [SD] age = 49.81, [9.99] years; 94% women) were given access to the digital treatment program and downloaded the app. Pain severity, anxiety symptoms, depression symptoms, fatigue, and sleep quality were assessed at pre-treatment, post-treatment, and 3-month follow-up. Fifty-three of the potential participants completed the 47-day treatment. Data showed significant improvements in pain severity (p = 0.007, d = 0.43), anxiety (p = 0.011, d = 0.40) and depressive symptoms (p = 0.001, d = 0.50) from pre-treatment to post-treatment. The effect sizes associated with app use are consistent with improvements seen in previously published clinical trials of CBT for FMS. Improvements were generally maintained, although there was some decrease in the outcomes from post-treatment to the 3-month follow-up. Most participants reported that they were very satisfied with the app. The use of the app was associated with similar levels of improvements found with in-person CBT treatment for FMS. Research to evaluate the effectiveness of the app in a controlled trial is warranted.Publication Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice.(Public Library of Science (PLOS), 2011-09-29) Castilla-Ortega, Estela; Hoyo-Becerra, Carolina; Pedraza, Carmen; Chun, Jerold; Rodríguez De Fonseca, Fernando; Estivill-Torrús, Guillermo; Santín, Luis J; [Castilla-Ortega, E; Pedraza, C; Santín, LJ] Departamento de Psicobiología y Metodología de las CC, Universidad de Málaga, Málaga, Spain. [Hoyo-Becerra, C; Rodríguez de Fonseca, F; Estibill-Torrús, G] Unidad de Investigación, Fundación IMABIS, Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Chun, J] Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, United States of America.BACKGROUND: The lysophosphatidic acid LPA₁ receptor regulates plasticity and neurogenesis in the adult hippocampus. Here, we studied whether absence of the LPA₁ receptor modulated the detrimental effects of chronic stress on hippocampal neurogenesis and spatial memory. METHODOLOGY/PRINCIPAL FINDINGS: Male LPA₁-null (NULL) and wild-type (WT) mice were assigned to control or chronic stress conditions (21 days of restraint, 3 h/day). Immunohistochemistry for bromodeoxyuridine and endogenous markers was performed to examine hippocampal cell proliferation, survival, number and maturation of young neurons, hippocampal structure and apoptosis in the hippocampus. Corticosterone levels were measured in another a separate cohort of mice. Finally, the hole-board test assessed spatial reference and working memory. Under control conditions, NULL mice showed reduced cell proliferation, a defective population of young neurons, reduced hippocampal volume and moderate spatial memory deficits. However, the primary result is that chronic stress impaired hippocampal neurogenesis in NULLs more severely than in WT mice in terms of cell proliferation; apoptosis; the number and maturation of young neurons; and both the volume and neuronal density in the granular zone. Only stressed NULLs presented hypocortisolemia. Moreover, a dramatic deficit in spatial reference memory consolidation was observed in chronically stressed NULL mice, which was in contrast to the minor effect observed in stressed WT mice. CONCLUSIONS/SIGNIFICANCE: These results reveal that the absence of the LPA₁ receptor aggravates the chronic stress-induced impairment to hippocampal neurogenesis and its dependent functions. Thus, modulation of the LPA₁ receptor pathway may be of interest with respect to the treatment of stress-induced hippocampal pathology.Publication Anxiety, depression, health-related quality of life, and mortality among colorectal patients: 5-year follow-up(Springer, 2022-10) Orive, Miren; Anton-Ladislao, Ane; Lázaro, Santiago; Gonzalez, Nerea; Bare, Marisa; Fernandez de Larrea-Baz, Nerea; Redondo, Maximino; Bilbao, Amaia; Sarasqueta, Cristina; Aguirre, Urko; Quintana, José M; REDISSEC-CARESS/CCR group; Consejo Superior de Investigaciones Científicas (España); Conferencia de Rectores de las Universidades Españolas; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Basque Government (España); RETICS-Servicios de Salud Orientados a Enfermedades Crónicas (REDISSEC-ISCIII) (España)Purpose: Health-related quality of life (HRQoL) measurement represents an important outcome in cancer patients. We describe the evolution of HRQoL over a 5-year period in colorectal cancer patients, identifying predictors of change and how they relate to mortality. Methods: Prospective observational cohort study including colorectal cancer (CRC) patients having undergone surgery in nineteen public hospitals who were monitored from their diagnosis, intervention and at 1-, 2-, 3-, and 5-year periods thereafter by gathering HRQoL data using the EuroQol-5D-5L (EQ-5D-5L), European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Multivariable generalized linear mixed models were used. Results: Predictors of Euroqol-5D-5L (EQ-5D-5L) changes were having worse baseline HRQoL; being female; higher Charlson index score (more comorbidities); complications during admission and 1 month after surgery; having a stoma after surgery; and needing or being in receipt of social support at baseline. For EORTC-QLQ-C30, predictors of changes were worse baseline EORTC-QLQ-C30 score; being female; higher Charlson score; complications during admission and 1 month after admission; receiving adjuvant chemotherapy; and having a family history of CRC. Predictors of changes in HADS anxiety were being female and having received adjuvant chemotherapy. Greater depression was associated with greater baseline depression; being female; higher Charlson score; having complications 1 month after intervention; and having a stoma. A deterioration in all HRQoL questionnaires in the previous year was related to death in the following year. Conclusions: These findings should enable preventive follow-up programs to be established for such patients in order to reduce their psychological distress and improve their HRQoL to as great an extent as possible.Publication Anxiety-like behavior and microglial activation in the amygdala after acute neuroinflammation induced by microbial neuraminidase.(2022-07-08) León-Rodríguez, Ana; Fernández-Arjona, María Del Mar; Grondona, Jesús M; Pedraza, Carmen; López-Ávalos, María DShort-term behavioral alterations are associated with infection and aid the recovery from sickness. However, concerns have raised that sustained behavioral disturbances after acute neuroinflammation could relate to neurological diseases in the long run. We aimed to explore medium- and long-term behavioral disturbances after acute neuroinflammation in rats, using a model based on the intracerebroventricular administration of the enzyme neuraminidase (NA), which is part of some pathogenic bacteria and viruses. Neurological and behavioral assessments were performed 2 and 10 weeks after the injection of NA, and neuroinflammation was evaluated by gene expression and histology. No alterations were observed regarding basic neurological functions or locomotor capacity in NA-injected rats. However, they showed a reduction in unsupported rearing, and increased grooming and freezing behaviors, which indicate anxiety-like behavior. A principal component analysis including a larger set of parameters further supported such anxiety-like behavior. The anxiety profile was observed 2 weeks after NA-injection, but not after 10 weeks. Concomitantly, the amygdala presented increased number of microglial cells showing a morphologic bias towards an activated state. A similar but subtler tendency was observed in hypothalamic microglia located in the paraventricular nucleus. Also, in the hypothalamus the pattern recognition receptor toll-like receptor 4 (TLR4) was slightly overexpressed 2 weeks after NA injection. These results demonstrate that NA-induced neuroinflammation provokes anxiety-like behavior in the medium term, which disappears with time. Concurrent microgliosis in the amygdala could explain such behavior. Further experiments should aim to explore subtle but long-lasting alterations observed 10 weeks after NA injection, both in amygdala and hypothalamus, as well as mild behavioral changes.Publication Cancer awareness in older adults: Results from the Spanish Onco-barometer cross-sectional survey(Elsevier, 2023-04) Petrova, Dafina; Pollan-Santamaria, Marina; Garcia-Retamero, Rocio; Rodríguez-Barranco, Miguel; Catena, Andrés; Castillo Portellano, Lucia; Sánchez, Maria-José; Asociación Española Contra el Cáncer; Instituto de Salud Carlos III; Ministerio de Ciencia (España); Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Agencia Estatal de Investigación (España)Background: About half of all cancers are diagnosed in adults older than 65, making them the age group at highest risk of developing this disease. Nurses from different specialties can support individuals and communities in the prevention and early detection of cancer and should be aware of the common knowledge gaps and perceived barriers among older adults. Objectives: The goal of the current research was to investigate personal characteristics, perceived barriers, and beliefs related to cancer awareness in older adults, with a special focus on perceptions about the influence of cancer risk factors, knowledge of cancer symptoms, and anticipated help-seeking. Design: Descriptive cross-sectional study. Participants: Participants were 1213 older adults (≥65 years old) from the representative national Onco-barometer survey conducted in 2020 in Spain. Methods: Questions on the perceived influence of cancer risk factors, knowledge of cancer symptoms, and the Spanish version of the Awareness and Beliefs about Cancer (ABC) questionnaire were administered in computer-assisted telephone interviews. Results: Knowledge of cancer risk factors and symptoms was strongly related to personal characteristics and was limited among males and older individuals. Respondents from lower socio-economic background recognized fewer cancer symptoms. Having personal or family history of cancer had opposite effects on cancer awareness: It was related to more accurate symptom knowledge but also to lower perceptions about the influence of risk factors and more delayed help-seeking. Anticipated help-seeking times were strongly influenced by perceived barriers to help-seeking and beliefs about cancer. Worry about wasting the doctor's time (48% increase, 95% CI [25%-75%]), about what the doctor might find (21% increase [3%-43%]) and not having enough time to go to the doctor (30% increase [5%-60%]) were related to more delayed help-seeking intentions. In contrast, beliefs that reflected higher perceived seriousness of a potential cancer diagnosis were related to shorter anticipated help-seeking times (19% decrease [5%-33%]). Conclusions: These results suggest that older adults could benefit from interventions informing them about how to reduce their cancer risk and addressing emotional barriers and beliefs associated with help-seeking delays. Nurses can contribute to educating this vulnerable group and are in a unique position to address some barriers to help-seeking. Study registration: Not registered.Publication Effectiveness of Physical Activity in Primary Prevention of Anxiety: Systematic Review and Meta-Analysis of Randomized Controlled Trials.(2022-02-05) Moreno-Peral, Patricia; Pino-Postigo, Alberto; Conejo-Cerón, Sonia; Bellón, Darío; Rodríguez-Martín, Beatriz; Martínez-Vizcaíno, Vicente; Bellón, Juan ÁngelThe aim of this study was to evaluate the effectiveness of physical activity in the primary prevention of anxiety. A systematic review of randomized controlled trials (RCTs) was performed. RCTs were searched in seven electronic databases. We included RCTs that assessed either the incidence of anxiety or the reduction of anxiety symptoms which excluded participants with baseline anxiety. Measurements were required to have been made using validated instruments. Objective or subjective (with validated questionnaires) verification of the performance of physical activity was required. Three reviewers carried out the search, selection, data extraction, and risk assessment of Cochrane Collaboration's tool simultaneously and independently, reaching an agreement in their discrepancies by consensus. In addition, a meta-analysis of fixed-effects model was carried out. Three RCTs met inclusion criteria, comprising 350 patients from 3 different countries. A meta-analysis was performed using five comparisons extracted from the selected studies, and the pooled standardized mean difference (SMD) was -0.18 (95% CI: -0.44; 0.07), p = 0.158. The heterogeneity was irrelevant, I2 = 17.7% (p = 0.30). There is no evidence that anxiety can be prevented through physical activity, although the quality of evidence was very low.Publication Effects of Intermittent Alcohol Exposure on Emotion and Cognition: A Potential Role for the Endogenous Cannabinoid System and Neuroinflammation(Frontiers Media, 2017-02-07) Sanchez-Marin, Laura; Pavón, Francisco-Javier; Decara, Juan; Suarez, Juan; Gavito, Ana; Castilla-Ortega, Estela; Rodriguez de Fonseca, Fernando; Serrano, Antonia; Unidad de Gestion Clinica de Salud Mental, Instituto de Investigacion Biomedica de Malaga, Hospital Regional Universitario de Malaga, Universidad de Malaga, Malaga, Spain.Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain. Alcohol-exposed rats exhibited anxiogenic-like responses and impaired recognition memory but no motor alterations. There were brain region-dependent changes in the mRNA levels of the ECS and molecular signals compared with control rats. Thus, overall, alcohol-exposed rats expressed higher mRNA levels of endocannabinoid synthetic enzymes (N-acyl-phosphatidylethanolamine phospholipase D and diacylglycerol lipases) in the medial-prefrontal cortex (mPFC) but lower mRNA levels in the amygdala. Furthermore, we observed lower mRNA levels of receptors CB1 CB2 and peroxisome proliferator-activated receptor-α in the striatum. Regarding neuropeptide signaling, alcohol-exposed rats displayed lower mRNA levels of the neuropeptide Y signaling, particularly NPY receptor-2, in the amygdala and hippocampus and higher mRNA levels of corticotropin-releasing factor in the hippocampus. Additionally, we observed changes of several neuroinflammation-related factors. Whereas, the mRNA levels of toll-like receptor-4, tumor necrosis factor-α, cyclooxygenase-2 and glial fibrillary acidic protein were significantly increased in the mPFC, the mRNA levels of cyclooxygenase-2 and glial fibrillary acidic protein were decreased in the striatum and hippocampus. However, nuclear factor-κβ mRNA levels were lower in the mPFC and striatum and allograft inflammatory factor-1 levels were differentially expressed in the amygdala and hippocampus. In conclusion, rats exposed to adolescent intermittent alcohol displayed anxiety-like behavior and cognitive deficits in adulthood and these alterations were accompanied by brain region-dependent changes in the gene expression of the ECS and other signals associated with neuroinflammation and behavior. An intermittent adolescent alcohol exposure has behavioral and molecular consequences in the adult brain, which might be linked to higher vulnerability to addictive behaviors and psychopathologies.Publication Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition(Public Library of Science (PLOS), 2011-11-30) Cippitelli, Andrea; Astarita, Giuseppe; Duranti, Andrea; Caprioli, Giovanni; Ubaldi, Massimo; Stopponi, Serena; Kallupi, Marsida; Sagratini, Gianni; Rodríguez de Fonseca, Fernando; Piomelli, Daniele; Ciccocioppo, Roberto; [Cippitelli,A; Ubaldi,M; Stopponi,S; Kallupi,M; Ciccocioppo,R] School of Pharmacy,Pharmacology Unit,University of Camerino,Camerino,Italy. [Astarita,G; Piomelli,D] Department of Pharmacology, University of California Irvine, Irvine, California, United States of America. [Duranti,A] Department of Biomolecular Sciences, Medicinal Chemistry and Technology Unit, University of Urbino Carlo Bo, Urbino, Italy. [Caprioli,G; Sagratini,G] School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Camerino,Italy. [Rodríguez de Fonseca,F] Fundación IMABIS, Hospital Carlos Haya de Málaga, Málaga, Spain. [Piomelli,D] Drug Discovery and Development, Italian Institute of Technology, Genova, Italy.Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.Publication Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.(Public Library of Science (PLOS), 2011-11-30) Cippitelli, Andrea; Astarita, Giuseppe; Duranti, Andrea; Caprioli, Giovanni; Ubaldi, Massimo; Stopponi, Serena; Kallupi, Marsida; Sagratini, Gianni; Rodríguez de Fonseca, Fernando; Piomelli, Daniele; Ciccocioppo, Roberto; [Cippitelli,A; Ubaldi,M; Stopponi,S; Kallupi,M; Ciccocioppo,R] School of Pharmacy,Pharmacology Unit,University of Camerino,Camerino,Italy. [Astarita,G; Piomelli,D] Department of Pharmacology, University of California Irvine, Irvine, California, United States of America. [Duranti,A] Department of Biomolecular Sciences, Medicinal Chemistry and Technology Unit, University of Urbino ‘‘Carlo Bo’’, Urbino, Italy. [Caprioli,G; Sagratini,G] School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Camerino,Italy. [Rodríguez de Fonseca,F] Fundación IMABIS, Hospital Carlos Haya de Málaga, Málaga, Spain. [Piomelli,D] Drug Discovery and Development, Italian Institute of Technology, Genova, Italy.Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.Publication Enfermedades mentales comunes en atención primaria: dificultades diagnósticas y terapéuticas, y nuevos retos en predicción y prevención. Informe SESPAS 2020(Elsevier, 2020) Bellón, Juan Ángel; Conejo-Cerón, Sonia; Rodríguez-Bayón, Antonina; Ballesta-Rodríguez, María Isabel; Mendive, Juan Manuel; Moreno-Peral, Patricia; [Bellón,JA] Centro de Salud El Palo, Distrito Sanitario Málaga-Guadalhorce, Servicio Andaluz de Salud, Málaga, España. [Bellón,JA] Departamento de Salud Pública y Psiquiatría, Universidad de Málaga, Málaga, España. [Bellón,JA; Conejo-Cerón,S; Rodríguez-Bayón,A; Ballesta-Rodríguez,MI; Mendive,JM; Moreno-Peral,P] Red de Actividades Preventivas y Promoción de la Salud (redIAPP), Instituto de Salud Carlos III, Madrid, España. [Bellón,JA; Conejo-Cerón,S; Moreno-Peral,P] Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, España. [Rodríguez-Bayón,A] Centro de Salud San José, Distrito Sanitario Jaén Norte, Servicio Andaluz de Salud, Linares (Jaén), España. [Ballesta-Rodríguez,MI] Centro de Salud Federico del Castillo, Distrito Sanitario Jaén, Servicio Andaluz de Salud, Jaén, España. [Mendive,JM] Centro de Atención Primaria La Mina, Institut Català de la Salut, IDIAP Jordi Gol, Barcelona, España.[ES] En atención primaria solo el dolor crónico supera a la depresión y la ansiedad en la pérdida de años de vida ajustados por calidad. Más del 70% de las personas que sufrían enfermedades mentales comunes consultaron por ello a su médico/a de familia. Sin embargo, «la regla de las mitades decrecientes» es una realidad: menos del 50% de las personas consultantes de atención primaria con enfermedades mentales comunes fueron diagnosticadas correctamente, y de ellas, menos del 50% recibieron un tratamiento (farmacológico o psicológico) adecuado, y de estas, menos del 50% fueron adherentes. Los modelos colaborativos de atención a las enfermedades mentales comunes en atención primaria han demostrado su efectividad en ensayos clínicos, pero su implementación en un contexto más general y real es difícil y su efectividad todavía es poco conocida. Se han desarrollado y validado algoritmos de riesgo para predecir el inicio y el pronóstico de las enfermedades mentales comunes en atención primaria que son útiles para su tratamiento y prevención. Existen evidencias de que las intervenciones psicológicas, psicoeducativas y de ejercicio físico son efectivas en prevención primaria, incluso en atención primaria, aunque su efecto es pequeño o moderado. Estas intervenciones tienen un gran potencial para ser escalables en las escuelas, el ámbito laboral y la atención primaria; además, cuando se administran mediante tecnologías de la información y la comunicación (p. ej., App), en programas autoguiados o mínimamente guiados, han demostrado su efectividad para el tratamiento y la prevención de las enfermedades mentales comunes. También son muy accesibles y de bajo coste, y contribuyen a la implementación masiva de estas intervenciones en diferentes contextos. [EN] In primary health care only chronic pain surpass depression and anxiety in loss of quality-adjusted life years. More than 70% of people suffering from common mental disorders consulted their GPs for this reason. However, 'the declining halves rule' is a reality: less than 50% of primary care attendees with common mental disorders were correctly diagnosed, of these less than 50% received adequate treatment (pharmacological or psychological) and of these less than 50% patients were adherent. Collaborative models of common mental disorders care in primary health care have demonstrated their effectiveness through clinical trials; however, its implementation in a more general and real context is difficult and its effectiveness remains unclear. Risk algorithms have been developed and validated in primary health care to predict the onset and prognosis of common mental disorders; which are useful for their treatment and prevention. There is evidence that psychological and psychoeducational interventions (and possibly those of physical exercise) are effective for the primary prevention of common mental disorders, even in primary health care; although their effects are small or moderate. These interventions have a high potential to be scalable in schools, workplace and primary health care; in addition, when they are administered through information and communication technologies (e.g. by App), in self-guided or minimally guided programs, they have demonstrated their effectiveness for the treatment and prevention of common mental disorders. They are also very accessible, have low cost and contribute to the massive implementation of these interventions in different settings.Publication Evidence of Higher Oxidative Status in Depression and Anxiety(Hindawi, 2014) Grases, G.; Colom, M. A.; Fernández, Rafael Alonso; Costa-Bauza, Antonia; Grases, FWe use a simple method for evaluating antioxidative status, by measuring the redox potential of urine, and correlate the findings with measures of anxiety and depression. We include 63 individuals (28 males and 35 females aged between 20 and 65 years). The validated anxiety State-Trait Anxiety Inventory questionnaire and the validated BDI (Beck Depression Inventory) questionnaire were used to evaluate anxiety and depression. Antioxidative status was determined by measuring the redox potential of urine collected in standard conditions. Correlation of the antioxidant capacity of urines evaluated using the ferric ion/specific dye method or through redox potential using the platinum electrode demonstrated the suitability of this last procedure. We found that normal anxiety state values corresponded to low urine redox potentials, whereas higher anxiety states were associated with high urinary redox potential. We also found that individuals with normal BDI values had significantly lower urine redox potentials than individuals with higher BDI values.Publication Exposure to a Highly Caloric Palatable Diet During Pregestational and Gestational Periods Affects Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Adiposity and Anxiety-Like Behaviors in Male Rat Offspring.(Frontiers Media, 2016-01-06) Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemí; Alén, Francisco; Antón, María; Decara, Juan; Ouro, Daniel; Orio, Laura; Suarez, Juan; Lutz, Beat; Rodríguez de Fonseca, Fernando; Gómez de Heras, Raquel; [Ramírez-López,MT; Vázquez,M; Blanco,RN; Alén,F; Antón,M; Ouro,L; Rodríguez de Fonseca,F; Gómez de Heras,R] Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Madrid, Spain. [Vázquez,M; Degara,J; Suarez,J; Rodríguez de Fonseca,F] Unidad de Gestión Clínica de Salud Mental, Instituto IBIMA, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Bindila,L; Lomazzo,E; Hofmann,C; Lutz,B] Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.Exposure to unbalanced diets during pre-gestational and gestational periods may result in long-term alterations in metabolism and behavior. The contribution of the endocannabinoid system to these long-term adaptive responses is unknown. In the present study, we investigated the impact of female rat exposure to a hypercaloric-hypoproteic palatable diet during pre-gestational, gestational and lactational periods on the development of male offspring. In addition, the hypothalamic and hippocampal endocannabinoid contents at birth and the behavioral performance in adulthood were investigated. Exposure to a palatable diet resulted in low weight offspring who exhibited low hypothalamic contents of arachidonic acid and the two major endocannabinoids (anandamide and 2-arachidonoylglycerol) at birth. Palmitoylethanolamide, but not oleoylethanolamide, also decreased. Additionally, pups from palatable diet-fed dams displayed lower levels of anandamide and palmitoylethanolamide in the hippocampus. The low-weight male offspring, born from palatable diet exposed mothers, gained less weight during lactation and although they recovered weight during the post-weaning period, they developed abdominal adiposity in adulthood. These animals exhibited anxiety-like behavior in the elevated plus-maze and open field test and a low preference for a chocolate diet in a food preference test, indicating that maternal exposure to a hypercaloric diet induces long-term behavioral alterations in male offspring. These results suggest that maternal diet alterations in the function of the endogenous cannabinoid system can mediate the observed phenotype of the offspring, since both hypothalamic and hippocampal endocannabinoids regulate feeding, metabolic adaptions to caloric diets, learning, memory, and emotions.Publication How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort(BioMed Central (BMC), 2021-05) Suarez-García, Ines; Alejos, Belén; Pérez-Elías, Maria-Jesús; Iribarren, Jose-Antonio; Hernando, Asunción; Ramírez, Margarita; Tasias, María; Pascual-Carrasco, Mario; Jarrin-Vera, Inmaculada; Hernando Sebastian, Victoria; CoRIS Cohort; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Red de Investigación Cooperativa en Investigación en Sida (España)Background: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women.Publication Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia(Frontiers Media, 2015-01-05) Galeano, Pablo; Blanco, Eduardo; Logica Tornatore, Tamara M A; Romero, Juan I; Holubiec, Mariana I; Rodríguez de Fonseca, Fernando; Capani, Francisco; [Galeano,P; Blanco,E; LogicaTornatore,TMA; Romero,JI; Holubiec,MI; Capani,F] Facultad de Medicina, Instituto de Investigaciones Cardiológicas Prof. Dr. Alberto C. Taquini (ININCA), Universidad de Buenos Aires (CONICET), Buenos Aires, Argentina. [Galeano,P] Instituto de Investigaciones Bioquímicas de Buenos Aires (CONICET), Fundación Instituto Leloir, Buenos Aires, Argentina. [Blanco,E; Rodríguez de Fonseca,F] Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga - Hospital Regional Universitario de Málaga (UGC Salud Mental), Málaga, Spain. [Blanco,E] Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga, Málaga, Spain.Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia.Publication Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia.(Frontiers Media, 2015-01-05) Galeano, Pablo; Blanco, Eduardo; Logica Tornatore, Tamara M A; Romero, Juan I; Holubiec, Mariana I; Rodríguez de Fonseca, Fernando; Capani, Francisco; [Galeano,P; Blanco,E; LogicaTornatore,TMA; Romero,JI; Holubiec,MI; Capani,F] Facultad de Medicina, Instituto de Investigaciones Cardiológicas “Prof. Dr. Alberto C. Taquini” (ININCA), Universidad de Buenos Aires (CONICET), Buenos Aires, Argentina. [Galeano,P] Instituto de Investigaciones Bioquímicas de Buenos Aires (CONICET), Fundación Instituto Leloir, Buenos Aires, Argentina. [Blanco,E; Rodríguez de Fonseca,F] Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga - Hospital Regional Universitario de Málaga (UGC Salud Mental), Málaga, Spain. [Blanco,E] Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga, Málaga, Spain.Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia.Publication maLPA1-null mice as an endophenotype of anxious depression(Nature Publishing Group, 2017-04-04) Moreno-Fernández, R D; Pérez-Martín, M; Castilla-Ortega, E; Rosell Del Valle, C; García-Fernández, M I; Chun, J; Estivill-Torrús, G; Rodríguez de Fonseca, F; Santín, L J; Pedraza, C; [Moreno-Fernández ,RD; Rosell del Valle,C; Santín,LJ; Pedraza,C] Departamento de Psicobiología y Metodología de las CC, Facultad de Psicología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Pérez-Martín,M] Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Castilla-Ortega,E; Rodríguez de Fonseca,F] Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain. [García-Fernández,MI] Departamento de Fisiología y Medicina Deportiva, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Chun,J] Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. [Estivill-Torrús,G] Unidad de Gestión Clínica de Neurociencias, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitarios de Málaga, Málaga, Spain.Anxious depression is a prevalent disease with devastating consequences and a poor prognosis. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts as an intracellular signalling molecule. The loss of this receptor induces anxiety and several behavioural and neurobiological changes that have been strongly associated with depression. In this study, we sought to investigate the involvement of the LPA1 receptor in mood. We first examined hedonic and despair-like behaviours in wild-type and maLPA1 receptor null mice. Owing to the behavioural response exhibited by the maLPA1-null mice, the panic-like reaction was assessed. In addition, c-Fos expression was evaluated as a measure of the functional activity, followed by interregional correlation matrices to establish the brain map of functional activation. maLPA1-null mice exhibited anhedonia, agitation and increased stress reactivity, behaviours that are strongly associated with the psychopathological endophenotype of depression with anxiety features. Furthermore, the functional brain maps differed between the genotypes. The maLPA1-null mice showed increased limbic-system activation, similar to that observed in depressive patients. Antidepressant treatment induced behavioural improvements and functional brain normalisation. Finally, based on validity criteria, maLPA1-null mice are proposed as an animal model of anxious depression. Here, for we believe the first time, we have identified a possible relationship between the LPA1 receptor and anxious depression, shedding light on the unknown neurobiological basis of this subtype of depression and providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, especially for the anxious subtype of depression.Publication Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Overweight and Increased Adiposity at Adulthood in Male Rat Offspring.(Frontiers Media, 2016-11-01) Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosarío Noemí; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Ouro, Daniel; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Rodríguez de Fonseca, Fernando; [Ramírez-López,MT; Vázquez,M; Blanco,RN; Alén,F; Antón,M; Ouro,D; Orio,L; Gómez de las Heras,R; Rodriguez de Fonseca,F] Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Madrid, Spain. [Vázquez,M; Decara,J; Arco,R; Suárez,J; Rodríguez de Fonseca,F] Instituto de Investigación Biomédica de Málaga (IBIMA), Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Bindila,L; Lomazzo,E; Hormann,C; Lutz,B] Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult male offspring. We found that calorie-restricted dams tended to have a reduced litter size, although the offspring showed normal weight at birth. Pups from calorie-restricted dams also exhibited a strong decrease in the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), arachidonic acid (AA) and palmitoylethanolamide (PEA) in the hypothalamus at birth. Additionally, pups from diet-restricted dams displayed reduced levels of AEA in the hippocampus without significant differences in the olfactory bulb. Moreover, offspring exhibited increased weight gain, body weight and adiposity in adulthood as well as increased anxiety-related responses. We propose that endocannabinoid signaling is altered by a maternal caloric restriction implemented during the preconceptional and pregnancy periods, which might lead to modifications of the hypothalamic and hippocampal circuits, potentially contributing to the long-term effects found in the adult offspring.Publication Oleoyl lysophosphatidic acid: a new mediator of emotional behavior in rats.(Public Library of Science (PLOS), 2014-01-07) Castilla-Ortega, Estela; Escuredo, Leticia; Bilbao, Ainhoa; Pedraza, Carmen; Orio, Laura; Estivill-Torrús, Guillermo; Santín, Luis J; Rodríguez de Fonseca, Fernando; Pavón, Francisco Javier; [Castilla-Ortega,E; Bilbao,A; Orio,L; Rodríguez de Fonseca,F; Pavón,FJ] Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Castilla-Ortega,E; Pedraza,C; Santín, LJ] Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Universidad de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Escuredo,L; Orio,L; Rodríguez de Fonseca,F] Departamento de Psicobiología, Universidad Complutense de Madrid, Madrid, Spain. [Estivill-Torrús,G] Unidad de Gestión Clínica de Neurociencias, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.The role of lysophosphatidic acid (LPA) in the control of emotional behavior remains to be determined. We analyzed the effects of the central administration of 1-oleoyl-LPA (LPA 18∶1) in rats tested for food consumption and anxiety-like and depression-like behaviors. For this purpose, the elevated plus-maze, open field, Y maze, forced swimming and food intake tests were performed. In addition, c-Fos expression in the dorsal periaqueductal gray matter (DPAG) was also determined. The results revealed that the administration of LPA 18∶1 reduced the time in the open arms of the elevated plus-maze and induced hypolocomotion in the open field, suggesting an anxiogenic-like phenotype. Interestingly, these effects were present following LPA 18∶1 infusion under conditions of novelty but not under habituation conditions. In the forced swimming test, the administration of LPA 18∶1 dose-dependently increased depression-like behavior, as evaluated according to immobility time. LPA treatment induced no effects on feeding. However, the immunohistochemical analysis revealed that LPA 18∶1 increased c-Fos expression in the DPAG. The abundant expression of the LPA1 receptor, one of the main targets for LPA 18∶1, was detected in this brain area, which participates in the control of emotional behavior, using immunocytochemistry. These findings indicate that LPA is a relevant transmitter potentially involved in normal and pathological emotional responses, including anxiety and depression.Publication Prevalence of Anxiety and Depression Symptoms and Their Relationship with Nutritional Status and Mortality in Patients with Colorectal Cancer.(2022-10-19) Soria-Utrilla, Virginia; Sánchez-Torralvo, Francisco José; González-Poveda, Iván; Mera-Velasco, Santiago; Porras, Nuria; Toval-Mata, José Antonio; García-Olivares, María; Ruiz-López, Manuel; Gonzalo-Marín, Montserrat; Carrasco-Campos, Joaquín; Tapia, María José; Santoyo-Santoyo, Julio; Olveira, GabrielAnxiety and depression are common in patients with cancer. The aim of this study is to determine the prevalence of anxiety and depression symptoms in colorectal cancer (CRC) patients awaiting elective surgery and whether there is an association with their preoperative nutritional status and postoperative mortality. A prospective study was conducted on 215 patients with CRC proposed for surgery. Data about nutritional status were collected using the Global Leadership Initiative on Malnutrition (GLIM) criteria, while anxiety and depression symptoms data were collected using Hospital Anxiety and Depression Scale (HADS). HADS detected possible anxiety in 41.9% of patients, probable anxiety in 25.6%, possible depression in 21.9%, and probable depression in 7.9%. GLIM criteria found 116 (53.9%) patients with malnutrition. The HADS score for depression subscale was significantly higher in malnourished patients than in well-nourished (5.61 ± 3.65 vs. 3.95 ± 2.68; p = 0.001). After controlling for potential confounders, malnourished patients were 10.19 times more likely to present probable depression (95% CI 1.13-92.24; p = 0.039). Mortality was 1.9%, 4,2%, and 5.6% during admission and after 6 and 12 months, respectively. Compared to patients without depressive symptomatology, in patients with probable depression, mortality risk was 14.67 times greater (95% CI 1.54-140.21; p = 0.02) during admission and 6.62 times greater (95% CI 1.34-32.61; p = 0.02) after 6 months. The presence of anxiety and depression symptoms in CRC patients awaiting elective surgery is high. There is an association between depression symptoms, preoperative nutritional status, and postoperative mortality.Publication Prevention of depression through nutritional strategies in high-risk persons: rationale and design of the MooDFOOD prevention trial(BioMed Central (BMC), 2016-06-08) Roca, Miquel; Kohls, Elisabeth; Gili, Margalida; Watkins, Ed; Owens, Matthew; Hegerl, Ulrich; van Grootheest, Gerard; Bot, Mariska; Cabout, Mieke; Brouwer, Ingeborg A; Visser, Marjolein; Penninx, Brenda W; MooDFOOD Prevention TrialBackground: Obesity and depression are two prevalent conditions that are costly to individuals and society. The bidirectional association of obesity with depression, in which unhealthy dietary patterns may play an important role, has been well established. Few experimental studies have been conducted to investigate whether supplementing specific nutrients or improving diet and food-related behaviors can prevent depression in overweight persons. Method/Design: The MooDFOOD prevention trial examines the feasibility and effectiveness of two different nutritional strategies [multi-nutrient supplementation and food-related behavioral change therapy (FBC)] to prevent depression in individuals who are overweight and have elevated depressive symptoms but who are not currently or in the last 6 months meeting criteria for an episode of major depressive disorder (MDD). The randomized controlled prevention trial has a two-by-two factorial design: participants are randomized to daily multi-nutrient supplement (omega-3 fatty acids, calcium, selenium, B-11 vitamin and D-3 vitamin) versus placebo, and/or FBC therapy sessions versus usual care. Interventions last 12 months. In total 1000 participants aged 18-75 years with body mass index between 25-40 kg/m(2) and with a Patient Health Questionnaire-9 score >= 5 will be recruited at four study sites in four European countries. Baseline and follow-up assessments take place at 0, 3, 6, and 12 months. Primary endpoint is the onset of an episode of MDD, assessed according to DSM-IV based criteria using the MINI 5. 0 interview. Depressive symptoms, anxiety, food and eating behavior, physical activity and health related quality of life are secondary outcomes. During the intervention, compliance, adverse events and potentially mediating variables are carefully monitored. Discussion: The trial aims to provide a better understanding of the causal role of specific nutrients, overall diet, and food-related behavior change with respect to the incidence of MDD episodes. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective nutritional public health strategies for the prevention of clinical depression.