Phenolics as GABAA Receptor Ligands: An Updated Review.

Natural products can act as potential GABA modulators, avoiding the undesirable effects of traditional pharmacology used for the inhibition of the central nervous system such as benzodiazepines (BZD). Phenolics, especially flavonoids and phlorotannins, have been considered as modulators of the BZD-site of GABAA receptors (GABAARs), with sedative, anxiolytic or anticonvulsant effects. However, the wide chemical structural variability of flavonoids shows their potential action at more than one additional binding site on GABAARs, which may act either negatively, positively, by neutralizing GABAARs, or directly as allosteric agonists. Therefore, the aim of the present review is to compile and discuss an update of the role of phenolics, namely as pharmacological targets involving dysfunctions of the GABA system, analyzing both their different compounds and their mechanism as GABAergic modulators. We focus this review on articles written in English since the year 2010 until the present. Of course, although more research would be necessary to fully establish the type specificity of phenolics and their pharmacological activity, the evidence supports their potential as GABAAR modulators, thereby favoring their inclusion in the development of new therapeutic targets based on natural products. Specifically, the data compiled in this review allows for the directing of future research towards ortho-dihydroxy diterpene galdosol, the flavonoids isoliquiritigenin (chalcone), rhusflavone and agathisflavone (biflavonoids), as well as the phlorotannins, dieckol and triphlorethol A. Clinically, flavonoids are the most interesting phenolics due to their potential as anticonvulsant and anxiolytic drugs, and phlorotannins are also of interest as sedative agents.

Medicinal Plants in the Treatment of Depression. II: Evidence from Clinical Trials.

Depression is a syndrome characterized by deep sadness and the inhibition of psychic functions, sometimes accompanied by neurovegetative disorders, with symptoms of anxiety almost always present. The disease produces alterations in a variety of neural networks and neurotransmission systems, along with a dysfunction of the hypothalamic-pituitary-adrenal axis, which leads to concomitant alterations in the immunological response. Generally, there is a parallel increase in proinflammatory mediators as well as oxidative and nitrosative damage caused by a reduction of antioxidant defenses. In a previous review, we compiled and examined studies of medicinal plants that had been evaluated in preclinical assays, including existing data on 155 species studied and reported as antidepressants or as sources of active principles for treating this condition. This review will thus limit its focus to the 95 clinical trials found in PubMed among the 670 articles on antidepressant-like medicinal plants. To this end, we have reviewed the publications cited in the Cochrane Database of Systematic Reviews, PubMed, and the Science Citation Index from 2000 to 2020. Our review emphasizes those species that have demonstrated the greatest pharmacological potential when studied for their antidepressant properties in humans through clinical trials. Saffron, turmeric, St. John's wort, ginkgo, kava, and golden root are the most relevant plants that have provided important evidence for the treatment of depression in clinical trials.

Salvia miltiorrhiza: una revisión de sus posibilidades terapéuticas / Salvia miltiorrhiza: uma revisão das suas possibilidades terapêuticas / Salvia miltiorrhiza: a review of its therapeutic possibilities

La salvia roja o salvia china, Salvia miltiorrhiza Bunge (Lamiáceas), es una planta perenne originaria de China, conocida como danshen (inglés) o dānshēn (chino). Su raíz, ampliamente utilizada en la medicina oriental, contiene componentes lipofílicos diterpénicos como las tanshinonas, e hidrofílicos, de tipo fenólico, como los ácidos salvianólicos, salviánico A (danshensu), litospérmico y otros. Sus propiedades farmacológicas han sido evaluadas in vivo, in vitro, y en ensayos clínicos, principalmente con extractos, aunque también se ha estudiado el efecto de constituyentes o mezclas concretas de ellos, como el “salvianolato”, que contiene diferentes principios hidrosolubles de la raíz. Uno de los principales problemas en la evaluación del potencial terapéutico de la salvia china es que la mayor parte de estudios clínicos se han realizado con combinaciones de sus preparados o constituyentes con preparados de otros drogas vegetales o incluso fármacos sintéticos. Un elevado número de estudios arrojan resultados prometedores, destacando sus efectos beneficiosos en la enfermedad cardiovascular, infarto de miocardio, angina y aterosclerosis. Además, cabe señalar sus propiedades antiosteoporóticas, antidiabéticas, neuroprotectoras y antitumorales, aunque algunas de ellas solo tienen evidencias preclínicas. Sería deseable incrementar los estudios clínicos con protocolos más acordes con la medicina occidental: el empleo de una única especie botánica, ensayos aleatorizados, doble ciego y controlados con placebo, multicéntricos, y con un mayor número de pacientes. De esta forma, la salvia china podría alcanzar para la fitoterapia europea una consideración similar a la que posee para medicina oriental. (AU)

A salva vermelha ou salva chinesa, Salvia miltiorrhiza Bunge (Lamiáceas), é uma planta perene originária da China, conhecida como dānshēn (inglês) ou dānshēn (chinês). A sua raiz, amplamente utilizada na medicina oriental, contém componentes diterpénicos lipofílicos, como as tanshinonas, e hidrofílicos, do tipo fenólico, como os ácidos salvianólicos, salviánico A (danshensu), litospérmico e outros. As suas propriedades farmacológicas foram avaliadas in vivo, in vitro e em ensaios clínicos, principalmente com extratos, embora também tenha sido estudado o efeito de constituintes específicos ou misturas deles, como o "salvianolato", que contem diferentes princípios hidrossolúveis da raiz. Um dos principais problemas na avaliação do potencial terapêutico da salva chinesa é que a maioria dos estudos clínicos tem sido realizada com associações de preparações ou constituintes de salva com preparações de outros fármacos vegetais ou mesmo fármacos sintéticos. Um grande número de estudos mostra resultados promissores, destacando os seus efeitos benéficos em doenças cardiovasculares, enfarte do miocárdio, angina e aterosclerose. Além disso, destacam-se também propriedades antiosteoporóticas, antidiabéticas, neuroprotectoras e antitumorais, embora algumas delas tenham apenas evidências pré-clínicas. Seria desejável aumentar os estudos com protocolos mais condizentes com a medicina ocidental: o uso de uma única espécie botânica, ensaios randomizados, duplamente-cegos, controlados por placebo, multicêntricos e com maior número de pacientes. Desse modo, a salva chinesa poderia alcançar na fitoterapia europeia uma reputação semelhante à que tem na medicina oriental. (AU)

Danshen, Salvia miltiorrhiza Bunge (Lamiaceae), is a perennial plant native to China, also known as dānshēn in Chinese. Its root, widely used in oriental medicine, contains lipophilic diterpenic constituents such as tanshinones, and hydrophilic constituents, of phenolic type, such as salvianolic acids, as well as salvianic A (danshensu), lithospermic acids and others. Its pharmacological properties have been evaluated in vivo, in vitro, and in clinical trials, mainly with extracts, although the effect of specific constituents or mixtures of them, such as "salvianolate", containing different watersoluble principles of the root, has also been studied. One of the main problems in evaluating the therapeutic potential of danshen is that most clinical studies were carried out with combinations of its preparations or constituents with preparations of other herbal drugs or even synthetic drugs. A large number of studies display promising results, showing beneficial effects in cardiovascular disease, myocardial infarction, angina and atherosclerosis. In addition, it should be noted anti-osteoporotic, antidiabetic, neuroprotective and antitumor properties, although some of them have only preclinical evidence. It would be desirable to perform additional clinical trials with protocols more aligned with Western medicine: using a single botanical species, randomized, double-blinded, placebo-controlled, multicenter, and with a larger number of patients. In this way, danshen could achieve a similar consideration for European herbal medicine as it has for oriental medicine. (AU)

Medicinal Plants in the Treatment of Depression: Evidence from Preclinical Studies.

Medicinal plants and their extracts are natural remedies with enormous potential for treating various diseases, including depression and anxiety. In the case of depression, hundreds of plants have traditionally been used in folk medicine for generations. Different plant extracts and natural products have been analyzed as potential antidepressant agents with validated models to test for antidepressant-like effects in animals, although other complementary studies have also been employed. Most of these studies focus on the possible mediators implicated in these potential effects, with dopamine, serotonin, and noradrenaline being the principal neurotransmitters implicated, both through interference with receptors and with their metabolism by monoamino oxidases, as well as through neuro-endocrine and neuroprotective effects. There are approximately 650 reports of antidepressant-like medicinal plants in PubMed; 155 of them have been compiled in this review, with a relevant group yielding positive results. Saffron and turmeric are the most relevant species studied in both preclinical and clinical studies; St. John's wort or kava have also been tested extensively. To the best of our knowledge, no review to date has provided a comprehensive understanding of the biomolecular mechanisms of action of these herbs or of whether their potential effects could have real benefits. The purpose of this narrative review is to provide an update regarding medicinal plants from the year 2000 to the present to examine the therapeutic potential of these antidepressant-like plants in order to contribute to the development of new therapeutic methods to alleviate the tremendous burden that depression causes worldwide.

Monitoring the effects of therapeutic interventions in depression through self-assessments.

The treatment of major psychiatric disorders is an arduous and thorny path for the patients concerned, characterized by polypharmacy, massive adverse side effects, modest prospects of success, and constantly declining response rates. The more important is the early detection of psychiatric disorders prior to the development of clinically relevant symptoms, so that people can benefit from early interventions. A well-proven approach to monitoring mental health relies on voice analysis. This method has been successfully used with psychiatric patients to 'objectively' document the progress of improvement or the onset of relapse. The studies with psychiatric patients over 2-4 weeks demonstrated that daily voice assessments have a notable therapeutic effect in themselves. Therefore, daily voice assessments appear to be a lowthreshold form of therapeutic means that may be realized through self-assessments. To evaluate performance and reliability of this approach, we have carried out a longitudinal study on 82 university students in 3 different countries with daily assessments over 2 weeks. The sample included 41 males (mean age 24.2±3.83 years) and 41 females (mean age 21.6±2.05 years). Unlike other research in the field, this study was not concerned with the classification of individuals in terms of diagnostic categories. The focus lay on the monitoring aspect and the extent to which the effects of therapeutic interventions or of behavioural changes are visible in the results of self-assessment voice analyses. The test persons showed an over-proportionally good adherence to the daily voice analysis scheme. The accumulated data were of generally high quality: sufficiently high signal levels, a very limited number of movement artifacts, and little to no interfering background noise. The method was sufficiently sensitive to detect: i) habituation effects when test persons became used to the daily procedure; and ii) short-term fluctuations that exceeded prespecified thresholds and reached significance. Results are directly interpretable and provide information about what is going well, what is going less well, and where there is a need for action. The proposed self-assessment approach was found to be well-suited to serve as a health-monitoring tool for subjects with an elevated vulnerability to psychiatric disorders or to stress-induced mental health problems. Daily voice assessments are in fact a low-threshold form of therapeutic means that can be realized through selfassessments, that requires only little effort, can be carried out in the test person's own home, and has the potential to strengthen resilience and to induce positive behavioural changes.

Early Detection of the Risk of Developing Psychiatric Disorders: A Study of 461 Chinese University Students under Chronic Stress.

Chronic stress, a characteristic of modern time, has a significant impact on general health. In the context of psychiatric disorders, insufficient coping behavior under chronic stress has been linked to higher rates of (1) depressive symptoms among subjects of the general population, (2) relapse among patients under treatment for clinical depression, and (3) negative symptoms among subjects with an elevated vulnerability to psychosis. In this normative study we assessed basic coping behavior among 461 Chinese freshman university students along with their consumption behavior and general health in terms of regular exercises, physical health, psychosomatic disturbances, and mental health. The assessments relied on two instruments that have already demonstrated their capability of (1) reliably detecting insufficient coping behavior under chronic stress and (2) reliably quantifying the interrelation between coping behavior and mental health in the Western world. Thus, we aimed to complement existing data and to develop a generally available, socioculturally independent tool that can be used for the early detection of subjects with an elevated risk of mental health problems. Structural analyses yielded essentially the same scales "activity" and "defeatism" as previous studies on 2,500 students from Switzerland, Italy, Spain, the USA, and Argentina. These scales explained 74.3% of the observed variance in coping behavior among the 461 Chinese students. We found highly significant correlations (p < 0.0001) between the "defeatism" scale on the one hand, and the scales "regular use of medicine," "psychosomatic disturbances," and "impaired mental health" on the other. Particularly intriguing was the finding that a neural net classifier could be constructed to identify students with the highest contributions to the interrelation between "coping behavior" and "mental health," yielding a correlation coefficient as high as r = 0.597 for the respective subgroup. Based on the normative data, an online tool for risk assessments was developed with immediate feedback to users. This study provided another piece of evidence regarding the close link between basic coping behavior and mental health, across cultures and ethnicities. In consequence, our approach to quantifying basic coping behavior, along with other risk factors, can be expected to clear the way for an "early" detection of students with an elevated risk of stress-related mental health problems, nota bene prior to the development of clinically relevant symptoms. The socioeconomic impact of the potential prevention of depressive -disorders, and psychiatric disorders in general, may be enormous.

Depresión e inflamación: potencial terapéutico de curcumina / Depressão e inflamação: potencial terapêutico da curcumina / Depression and inflammation: therapeutic po-tential of curcumin

La depresión es un síndrome caracterizado por una tristeza profunda y por la inhibición de las funciones psíquicas, a veces acompañado de trastornos neurovegetativos. Hay pérdida de interés, anhedonia, apatía, cambios en el sueño y el apetito, tristeza y posible ideación suicida. Se trata de un trastorno multifactorial, con disfunciones en redes neuronales y sistemas de neurotransmisión, afectando principalmente a las monoaminas. También son relevantes otros factores como el desajuste en la funcionalidad del eje hipotálamo-hipófiso-suprarrenal y el aumento de diferentes mediadores proinflamatorios. Los daños oxidativo y nitrosativo causados por la disminución de las defensas antioxidantes están también implicados. Existen múltiples estudios sobre plantas medicinales utilizadas en patologías del sistema nervioso central, y especialmente en depresión. Entre ellas destaca el potencial farmacológico de la cúrcuma que ha mostrado su efecto antiinflamatorio y antidepresivo en diferentes ensayos clínicos, tanto en animal de experimentación como en humanos. En consecuencia, esta revisión se centra en los principales estudios realizados con esta especie y especialmente con su principio de mayor potencial terapéutico, la curcumina

A depressão é uma síndrome caracterizada por profunda tristeza e inibição das funções psíquicas, às vezes acompanhada de distúrbios neurovegetativos. Há perda de interesse, anedonia, apatia, alterações no sono e apetite, tristeza e possível ideação suicida. A depressão é uma doença multifactorial com disfunções em redes neuronais e sistemas de neurotransmissão, afectando principalmente as monoaminas, embora outros aspectos, como disfunções do eixo hipotálamo-hipófise-adrenal e o aumento de diferentes mediadores pró-inflamatórios também sejam relevantes. Estão também implicados nesta patología os danos oxidativos e nitrosativos causados pela diminuição das defesas antioxidantes. Há vários estudos sobre plantas medicinais utilizadas em patologias do sistema nervoso central, e especialmente na depressão. Destaca-se a raíz de cúrcuma como a de maior potencial farmacológico, estudada e reconhecida como anti-inflamatória e como antidepressiva em diferentes en-saios pré-clínicos e clínicos, tanto em animais como em seres humanos. Consequentemente, esta revisão centra-se nos principais estudos realizados com esta espécie e, especialmente, com o seu principio activo de maior potencial terapêutico, a curcumina

Depression is a syndrome characterized by deep sadness and inhibition of psychic functions, sometimes accompanied by neurovegetative disorders. There is loss of interest, anhedonia, apathy, changes in sleep and appetite, sadness and possible suicidal ideation. Depression is a multifactorial disorder, with dysfunctions in neural networks and neurotransmission systems, mainly affecting monoamines, although other facets are relevant, such as the dysfunction of the hypothalamic-pituitary-adrenal axis and different pro-inflammatory mediators. Oxidative and nitrosative damage caused by decreased antioxidant defenses is also implicated. There are multiple studies on medicinal plants used in pathologies of the central nervous system, There are multiple studies on medicinal plants used in pathologies of the cen-tral nervous system, and especially in depression. Of these, turmeric stands out as having the greatest pharmacological potential, since it has been studied and recognized as an anti-inflammatory and antidepressant in different works, both in experimental animals and in humans, through clinical trials. Consequently, this review focuses on the main studies conducted with this species and especially with its most relevant principle, curcumin

Assessing Chronic Stress, Coping Skills, and Mood Disorders through Speech Analysis: A Self-Assessment 'Voice App' for Laptops, Tablets, and Smartphones.

BACKGROUND: Computerized speech analysis (CSA) is a powerful method that allows one to assess stress-induced mood disturbances and affective disorders through repeated measurements of speaking behavior and voice sound characteristics. Over the past decades CSA has been successfully used in the clinical context to monitor the transition from 'affectively disturbed' to 'normal' among psychiatric patients under treatment. This project, by contrast, aimed to extend the CSA method in such a way that the transition from 'normal' to 'affected' can be detected among subjects of the general population through 10-20 self-assessments. METHODS: Central to the project was a normative speech study of 5 major languages (English, French, German, Italian, and Spanish). Each language comprised 120 subjects stratified according to gender, age, and education with repeated assessments at 14-day intervals (total n = 697). In a first step, we developed a multivariate model to assess affective state and stress-induced bodily reactions through speaking behavior and voice sound characteristics. Secondly, we determined language-, gender-, and age-specific thresholds that draw a line between 'natural fluctuations' and 'significant changes'. Thirdly, we implemented the model along with the underlying methods and normative data in a self-assessment 'voice app' for laptops, tablets, and smartphones. Finally, a longitudinal self-assessment study of 36 subjects was carried out over 14 days to test the performance of the CSA method in home environments. RESULTS: The data showed that speaking behavior and voice sound characteristics can be quantified in a reproducible and language-independent way. Gender and age explained 15-35% of the observed variance, whereas the educational level had a relatively small effect in the range of 1-3%. The self-assessment 'voice app' was realized in modular form so that additional languages can simply be 'plugged in' once the respective normative data become available. Results of the longitudinal self-assessment study in home environments demonstrated that CSA methods work well under most circumstances. CONCLUSIONS: We have successfully developed and tested a self-assessment CSA method that can monitor transitions from 'normal' to 'affected' in subjects of the general population in the broader context of mood disorders. Our easy-to-use 'voice app' evaluates sequences of 10-20 repeated assessments and watches for affect- and stress-induced deviations from baseline that exceed language-, gender-, and age-specific thresholds. Specifically, the 'voice app' provides users with stress-related 'biofeedback' and can help to identify that 10-15% subgroup of the general population that exhibits insufficient coping skills under chronic stress and may benefit from early detection and intervention prior to developing clinically relevant symptoms.

An Internet-based program for depression using activity and physiological sensors: efficacy, expectations, satisfaction, and ease of use.

PURPOSE: Computerized cognitive behavioral therapy (CCBT) has been shown to be efficacious. Moreover, CCBT can be enhanced by using physiological and activity sensors, but there is no evidence about the acceptability of all these tools. The objective of this study is to examine the efficacy, expectations, satisfaction, and ease of use of an Internet-based CCBT program for preventing depression, with and without sensors (electroencephalography, electrocardiograhpy ECG, and actigraphy), in a high-risk population (unemployed men). PATIENTS AND METHODS: Sixty participants at risk of depression (unemployed men) were randomly assigned to three experimental conditions: 1) intervention program (N=22), 2) intervention program plus sensors (N=19), and 3) control group (N=19). Participants completed depression, anxiety, positive and negative affect, and perceived stress measures. Furthermore, they also completed the measures for expectation, satisfaction, and the ease of use of the program. RESULTS: Results showed that the two intervention groups improved significantly more than the control group on the clinical variables, and the improvements were greater in the group that used sensors than in the group that did not use them. Furthermore, participants in both intervention groups scored high on expectations and satisfaction with the CCBT program (with and without sensors). The mean score for usability was 88 out of 100 (standard deviation =12.32). No significant differences were found between groups on any of these variables. CONCLUSION: This is the first study to analyze the efficacy, expectations, satisfaction, and ease of use of an Internet-based program using physiological and activity sensors. These results suggest that an Internet program for depression with or without physiological and activity sensors is effective, satisfactory, and easy to use.

Quantifying insufficient coping behavior under chronic stress: a cross-cultural study of 1,303 students from Italy, Spain and Argentina.

The question of how to quantify insufficient coping behavior under chronic stress is of major clinical relevance. In fact, chronic stress increasingly dominates modern work conditions and can affect nearly every system of the human body, as suggested by physical, cognitive, affective and behavioral symptoms. Since freshmen students experience constantly high levels of stress due to tight schedules and frequent examinations, we carried out a 3-center study of 1,303 students from Italy, Spain and Argentina in order to develop socioculturally independent means for quantifying coping behavior. The data analysis relied on 2 self-report questionnaires: the Coping Strategies Inventory (COPE) for the assessment of coping behavior and the Zurich Health Questionnaire which assesses consumption behavior and general health dimensions. A neural network approach was used to determine the structural properties inherent in the COPE instrument. Our analyses revealed 2 highly stable, socioculturally independent scales that reflected basic coping behavior in terms of the personality traits activity-passivity and defeatism-resilience. This replicated previous results based on Swiss and US-American data. The percentage of students exhibiting insufficient coping behavior was very similar across the study sites (11.5-18.0%). Given their stability and validity, the newly developed scales enable the quantification of basic coping behavior in a cost-efficient and reliable way, thus clearing the way for the early detection of subjects with insufficient coping skills under chronic stress who may be at risk of physical or mental health problems.

Affective state and voice: cross-cultural assessment of speaking behavior and voice sound characteristics--a normative multicenter study of 577 + 36 healthy subjects.

BACKGROUND: Human speech is greatly influenced by the speakers' affective state, such as sadness, happiness, grief, guilt, fear, anger, aggression, faintheartedness, shame, sexual arousal, love, amongst others. Attentive listeners discover a lot about the affective state of their dialog partners with no great effort, and without having to talk about it explicitly during a conversation or on the phone. On the other hand, speech dysfunctions, such as slow, delayed or monotonous speech, are prominent features of affective disorders. METHODS: This project was comprised of four studies with healthy volunteers from Bristol (English: n = 117), Lausanne (French: n = 128), Zurich (German: n = 208), and Valencia (Spanish: n = 124). All samples were stratified according to gender, age, and education. The specific study design with different types of spoken text along with repeated assessments at 14-day intervals allowed us to estimate the 'natural' variation of speech parameters over time, and to analyze the sensitivity of speech parameters with respect to form and content of spoken text. Additionally, our project included a longitudinal self-assessment study with university students from Zurich (n = 18) and unemployed adults from Valencia (n = 18) in order to test the feasibility of the speech analysis method in home environments. RESULTS: The normative data showed that speaking behavior and voice sound characteristics can be quantified in a reproducible and language-independent way. The high resolution of the method was verified by a computerized assignment of speech parameter patterns to languages at a success rate of 90%, while the correct assignment to texts was 70%. In the longitudinal self-assessment study we calculated individual 'baselines' for each test person along with deviations thereof. The significance of such deviations was assessed through the normative reference data. CONCLUSIONS: Our data provided gender-, age-, and language-specific thresholds that allow one to reliably distinguish between 'natural fluctuations' and 'significant changes'. The longitudinal self-assessment study with repeated assessments at 1-day intervals over 14 days demonstrated the feasibility and efficiency of the speech analysis method in home environments, thus clearing the way to a broader range of applications in psychiatry.

Relationship between eating styles and temperament in an Anorexia Nervosa, Healthy Control, and Morbid Obesity female sample.

OBJECTIVES: Eating styles have been studied in both Obesity (OB) and Eating Disorders (ED), but they have not been examined in these two weight conditions together. The present study explores differences in eating styles in an Anorexia Nervosa (AN) and OB sample, compared to Healthy Controls (HC), and it analyses their relationship with Body Mass Index (BMI) and personality traits. METHOD: The total sample consisted of 291 female participants (66 AN, 79 OB and 146 HC). EVALUATION: Assessment measures included the Dutch Eating Behaviour Questionnaire-DEBQ- and the Temperament and Character Inventory-Revised-TCI-R-. RESULTS: The MANCOVA test showed significant differences among the three groups for all eating styles, with emotional eating being more typical in the OB group and restrained eating more typical in the AN group. Partial correlation analyses showed relationships between emotional and external eating and BMI, as well as relationships with different temperament and character traits. The stepwise discriminant function analysis showed that the DEBQ correctly classified 65.6% of the sample into the three weight categories; when combined with the TCI-R, correct classification increased to 72.6%. CONCLUSIONS: Weight conditions showed different eating behaviour patterns. Temperament and character traits were related to eating behaviours. DEBQ and TCI-R were able to discriminate between groups. Differences in eating styles in the weight groups can have implications for understanding the development and maintenance of OB and ED.

Modulation of the Endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans.

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = -.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = -.17) or AEA (r = -.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches.

Smiling is fun: a Coping with Stress and Emotion Regulation Program.

Emotional disorders (Anxiety disorders and Mood disorders) are one of the most common health problems worldwide, and their economic costs are very high. People suffering from emotional disorders often use maladaptive emotion regulation strategies and have low coping behaviour that contributes to the presence of clinical symptoms. For this reason, it is important to develop strategies to monitor coping and promote emotion regulation in people exposed to high levels of stress. Information and Communication Technologies (ICT) can help us in this task. Recent systematic reviews of literature on evidence-based CBT treatments delivered via the Internet show that these approaches are effective. We have developed an intervention program ICT based: Coping with Stress and Emotion Regulation Program (Smiling is Fun), a self-applied program via the Internet. Smiling is Fun follows a transdiagnostic perspective, and it is based on CBT techniques. However, it also includes other psychological strategies to improve positive mood. The aim of the present work is to describe Smiling is Fun and the study designed to test its efficacy.

Online predictive tools for intervention in mental illness: the OPTIMI project.

Mental health care represents over a third of the cost of health care to all EU nations and in US is estimated to be around the 2'5% of the gross national product. It additionally results in further costs to the economy in lost productivity. Depression and Stress related disorders are the most common mental illnesses and the prevention of depression and suicide is one of the 5 central focus points in the European Pact for Mental Health and Well Being. While other mental illnesses may benefit in the long term, Depression and Stress will be the focal point mental illnesses mentioned in OPTIMI. Currently the main treatments for mental illness are pharmacological and evidence based Cognitive Behavioral Therapy (CBT). CBT comprises a set of therapist and patient processes whose format allows for the whole treatment process to be computerized and personalized, Computerised CBT (CCBT). OPTIMI will try to improve the state of the art by monitoring stress and poor coping behavior in high risk population, and by developing tools to perform prediction through early identification of the onset of depression. The main goal of OPTIMI is to improve CCBT programs in order to enhance both efficacy and therapeutic effectiveness. The presentation will outline the main goals the project is aiming and its clinical rationale.

Contributions of functional magnetic resonance in the field of psychological treatments with virtual reality.

Many studies have been developed using brain imaging methods to investigate psychological disorders. On the other hand, there are many studies that make use of virtual reality (VR) to simulate a real condition during psychological treatments. In this research, we plan to analyze brain activity during the exposure to a virtual environment related to phobias. Our first goal is to study the possibility of activating brain areas related to phobias, specifically phobias to small animals (spiders and cockroaches), using virtual reality as stimulus, while the patient is inside a functional magnetic resonance imaging (fMRI) machine. The second goal of the research is to analyze if there are differences in the activated areas after patients have followed a psychological treatment for this specific phobia. That is why two different sessions with fMRI will be performed, before and after an intensive treatment for the phobia. In the fMRI room, participants will wear special glasses to visualize the VR environments in which they have to navigate (using also a joystick adapted to fMRI). They will have to perform some tasks while being exposed to the phobic stimuli. The VR environment used in the fMRI sessions has three different conditions: first, a clean room without spiders or cockroaches; second, the same room, but dirty and disordered (giving the sensation of having small animals, although actually there are none); third, the same dirty room but having spiders and cockroaches. It is our hypothesis that the patients will get anxious in the situation in which it is possible that the animal appears and the patterns of brain activation will be different in this condition.

Effects of housing and nicotine on shuttle-box avoidance in male NMRI mice.

The present study aimed to evaluate whether housing condition could interact with nicotine administration in influencing the acquisition of a two-way active avoidance task. Male NMRI mice were either group- or individually housed for 30 days and, after this period, evaluated both in the actimeter and, 24h later, in the elevated plus-maze. On the basis of the percentage of time spent in the open arms of the plus-maze, both group- and individually housed mice were sub-classified into three groups with high, moderate or low anxiety baseline levels. Effects of nicotine on the acquisition of the two-way active avoidance task was assessed in each of these groups of mice using an automated shuttle-box. Mice were treated with nicotine (0.35 mg/kg) or vehicle before each daily training session in the shuttle-box (30 trials) over 5 days. The results showed that motor activity counts were significantly higher in individually housed mice than in group-housed counterparts. The factor "anxiety" in the active avoidance test did not reach statistical significance but the factor "housing" did. The number of avoidances was higher in individually housed than in group-housed mice. Separate analyses performed for individually and group-housed animals indicated that group-housed nicotine-treated mice displayed fewer number of avoidances than saline-treated counterparts. It was concluded that housing condition may be a useful variable in evaluating the effects of nicotine on learning tasks. Indeed, the two-way active avoidance task seems to be sensitive to housing condition.