Brain-Derived Neurotrophic Factor (BDNF) as a Predictor of Treatment Response in Major Depressive Disorder (MDD): A Systematic Review.

Brain-derived neurotrophic factor (BDNF) has been studied as a biomarker of major depressive disorder (MDD). Besides diagnostic biomarkers, clinically useful biomarkers can inform response to treatment. We aimed to review all studies that sought to relate BDNF baseline levels, or BDNF polymorphisms, with response to treatment in MDD. In order to achieve this, we performed a systematic review of studies that explored the relation of BDNF with both pharmacological and non-pharmacological treatment. Finally, we reviewed the evidence that relates peripheral levels of BDNF and BDNF polymorphisms with the development and management of treatment-resistant depression.

BDNF and Cognitive Function in Chilean Schizophrenic Patients.

Despite cognitive symptoms being very important in schizophrenia, not every schizophrenic patient has a significant cognitive deficit. The molecular mechanisms underlying the different degrees of cognitive functioning in schizophrenic patients are not sufficiently understood. We studied the relation between brain-derived neurotrophic factor (BDNF) and cognitive functioning in two groups of schizophrenic patients with different cognitive statuses. According to the Montreal Cognitive Assessment (MoCA) results, the schizophrenic patients were classified into two subgroups: normal cognition (26 or more) and cognitive deficit (25 or less). We measured their plasma BDNF levels using ELISAs. The statistical analyses were performed using Spearman's Rho and Kruskal-Wallis tests. We found a statistically significant positive correlation between the plasma BDNF levels and MoCA score (p = 0.04) in the subgroup of schizophrenic patients with a cognitive deficit (n = 29). However, this correlation was not observed in the patients with normal cognition (n = 11) and was not observed in the total patient group (n = 40). These results support a significant role for BDNF in the cognitive functioning of schizophrenics with some degree of cognitive deficit, but suggest that BDNF may not be crucial in patients with a normal cognitive status. These findings provide information about the molecular basis underlying cognitive deficits in this illness.

Latin American consensus recommendations for the management and treatment of patients with treatment-resistant depression (TRD).

Despite the abundance of literature on treatment-resistant depression (TRD), there is no universally accepted definition of TRD, and available treatment pathways for the management of TRD vary across the Latin American region, highlighting the need for a uniform definition and treatment principles to optimize the management of TRD in Latin America. METHODS: Following a thematic literature review and pre-meeting survey, a Latin America expert panel comprising 14 psychiatrists with clinical experience in managing patients with TRD convened and utilized the RAND/UCLA appropriateness method to develop consensus-based recommendations on the appropriate definition of TRD and principles for its management. RESULTS: The expert panel agreed that 'treatment-resistant depression' (TRD) is defined as 'failure of two drug treatments of adequate doses, for 4-8 weeks duration with adequate adherence, during a major depressive episode'. A stepwise treatment approach should be employed for the management of TRD - treatment strategies can include maximizing dose, switching to a different class, and augmenting or combining treatments. Nonpharmacological treatments, such as electroconvulsive therapy, are also appropriate options for patients with TRD. CONCLUSION: These consensus recommendations on the operational definition of TRD and approved treatments for its management can be adapted to local contexts in the Latin American countries but should not replace clinical judgement. Individual circumstances and benefit-risk balance should be carefully considered while determining the most appropriate treatment option for patients with TRD.

Effects of socioeconomic status in cognition of people with schizophrenia: results from a Latin American collaboration network with 1175 subjects.

BACKGROUND: Cognition heavily relies on social determinants and genetic background. Latin America comprises approximately 8% of the global population and faces unique challenges, many derived from specific demographic and socioeconomic variables, such as violence and inequality. While such factors have been described to influence mental health outcomes, no large-scale studies with Latin American population have been carried out. Therefore, we aim to describe the cognitive performance of a representative sample of Latin American individuals with schizophrenia and its relationship to clinical factors. Additionally, we aim to investigate how socioeconomic status (SES) relates to cognitive performance in patients and controls. METHODS: We included 1175 participants from five Latin American countries (Argentina, Brazil, Chile, Colombia, and Mexico): 864 individuals with schizophrenia and 311 unaffected subjects. All participants were part of projects that included cognitive evaluation with MATRICS Consensus Cognitive Battery and clinical assessments. RESULTS: Patients showed worse cognitive performance than controls across all domains. Age and diagnosis were independent predictors, indicating similar trajectories of cognitive aging for both patients and controls. The SES factors of education, parental education, and income were more related to cognition in patients than in controls. Cognition was also influenced by symptomatology. CONCLUSIONS: Patients did not show evidence of accelerated cognitive aging; however, they were most impacted by a lower SES suggestive of deprived environment than controls. These findings highlight the vulnerability of cognitive capacity in individuals with psychosis in face of demographic and socioeconomic factors in low- and middle-income countries.

A facile approach for tuning optical and surface properties of novel biobased Alginate/POTE handleable films via solvent vapor exposure.

Novel biobased films consisting of alginate blends with poly (octanoic acid 2-thiophen-3-yl-ethyl ester) (POTE), a conducting polymer, were prepared by solution casting, and their optical, morphological, thermal, and surface properties were studied. Using UV-visible spectroscopy, atomic force microscopy (AFM), and scanning electron microscopy (SEM), the effects of tetrahydrofuran solvent vapors on the optical properties and surface morphology of biobased films with different POTE contents were studied. Results indicate that morphological rearrangements of POTE take place during the process of solvent exposure. Specifically, the solvent vapor induced the formation of POTE small crystalline domains, which allows envisioning the potential of tuning UV-visible absorbance and wettability behavior of biobased films. Finally, theoretical electronic calculations (specifically frontier molecular orbitals analysis) provided consistent evidence on POTE's preferential orientation and selectivity toward the THF-vapor medium.

BDNF as a Biomarker of Cognition in Schizophrenia/Psychosis: An Updated Review.

Brain Derived Neurotrophic Factor (BDNF) has been linked to cognitive symptoms of schizophrenia, which has been documented in previous reviews by several authors. However, a trend has recently emerged in this field moving from studying schizophrenia as a disease to studying psychosis as a group. This review article focuses on recent BDNF studies in relation to cognition in human subjects during different stages of the psychotic process, including subjects at high risk of developing psychosis, patients at their first episode of psychosis, and patients with chronic schizophrenia. We aim to provide an update of BDNF as a biomarker of cognitive function on human subjects with schizophrenia or earlier stages of psychosis, covering new trends, controversies, current research gaps, and suggest potential future developments in the field. We found that most of current research regarding BDNF and cognitive symptoms in psychosis is done around schizophrenia as a disease. Therefore, it is necessary to expand the study of the relationship between BDNF and cognitive symptoms to psychotic illnesses of different stages and origins.

Beyond the Categorical Distinction Between Borderline Personality Disorder and Bipolar II Disorder Through the Identification of Personality Traits Profiles.

BACKGROUND: The relationship between borderline personality disorder (BPD) and type-II bipolar disorder (BDII) is not clearly understood. Nevertheless, in clinical practice and research, most efforts focus on establishing a categorical distinction between the two. We propose using personality traits as a more informative strategy to describe them. METHODS: Five-Factor Model personality traits were measured in 73 individuals with either BPD or BDII. Latent class cluster analysis was applied to the sample. RESULTS: A three-cluster model resulted the best fit to the data, where all clusters had high neuroticism and low extraversion scores but differed widely on the other traits. The clusters' boundaries did not match the categorical diagnosis. CONCLUSIONS: Our sample showed significant heterogeneity on personality traits, which can have a relevant effect on the outcome of each disorder and that was not captured by the categorical diagnosis. Thus, we advocate for a multivariate approach as a better way to understand the relationship between BPD and BDII.

SERT and BDNF polymorphisms interplay on neuroticism in borderline personality disorder.

OBJECTIVE: Genetic factors underlying different personality traits are not entirely understood, particularly how genes interact to modulate their effect. We studied 76 patients diagnosed with borderline personality disorder (BPD), characterized by extreme levels of personality traits, especially neuroticism (N), in which we genotyped two polymorphisms, the 5HTTLPR of the Serotonin transporter (SERT) gene, and the Val66Met of the Brain-derived neurotrophic factor (BDNF) gene. RESULTS: We found an association with SERT, where S-allele carriers had significantly higher levels of N than L-homozygous. Furthermore, we found that the protective effect of L-homozygosity is only evident on A-allele carriers of the BDNF Val66Met polymorphism. Genetic constitution in SERT and BDNF seems to be important in neuroticism, the most relevant personality trait on BPD.

Comprehensive evaluation and implementation of improvement actions in bovine abattoirs to reduce pathogens exposure.

The slaughter process plays an important role in animal welfare, meat quality, safety and public health through the meat production chain. In this study, we performed a three-stage evaluation: I) comprehensive evaluation, II) implementation of improvement actions and III) verification of the success of the actions implemented in three abattoirs from Argentina during 2016-2018. Risk was estimated using two checklists, quantified on a 1-100 scale and classified as high (1-40), moderate (41-70) and low (71-100). In stages I and III, Salmonella spp., E. coli O157:H7 and non-O157 STEC were detected and isolated in samples from carcasses (n = 252), the environment (n = 252); head meat (n = 21) and viscera washing and chilling water (n = 105). Carcass samples were analyzed for mesophilic aerobic organisms, coliforms and E. coli enumeration. Of 201 water samples taken, 42.0-75.6 % were non-potable quality. After the implementation of improvement actions in stage II (building, processes, systems for water purification and training), the estimation of risk of contamination was reduced from high to moderate in all three abattoirs, the count of indicator microorganisms decreased in two abattoirs, and the presence of pathogens significantly decreased. Salmonella spp. was not isolated from any of the samples collected in two abattoirs. Isolation of E. coli O157:H7 decreased in carcass and was not isolated from viscera washing and chilling water. Isolation of non-O157 STEC decreased in carcass but not in environmental samples. Finally, 75.0-95.0 % of water samples were of potable quality. Although this was only the first step in the process of change and improvement of abattoirs, the assessment of the situation and the proposal of solutions to correct deviations in a joint effort with the health authorities helped to implement a work model for enhancing food safety before meat reaches consumers.

Alteraciones de la cognición social en síndromes de alto riesgo en psicosis / Social cognitive impairment in clinical high risk for psychos

Resumen La esquizofrenia es una enfermedad crónica, severa y que afecta aproximadamente al 1% de la población mundial. Pacientes con esta enfermedad presentan severos déficits en la cognición social (DCS). Estos déficits han sido observados en pacientes de primer episodio y familiares de primer grado. Los DCS determinan el pronóstico a largo plazo en esta enfermedad y son susceptibles de rehabilitación si es que se detectan precozmente. Solo recientemente se han caracterizado los déficits de la cognición social en sujetos de alto riesgo de desarrollar psicosis crónica. Estos sujetos presentan una oportunidad única para modificar la inserción social y modificar el pronóstico, pues no han sido afectados mayormente por la cronicidad de la enfermedad y presentan una sintomatología más leve que en etapas residuales. El presente trabajo pretende realizar una revisión de cómo los DCS están presentes desde etapas prodrómicas de la esquizofrenia y su importancia en la detección precoz de esta enfermedad.

Schizophrenia is a severe chronic disease that affects approximately 1 % of the world's population. Those who suffer this disease have serious deficits in social cognition (DSC), deficits that have been observed in first psychotic episode patients and first-degree relatives. The DSC determine the long-term prognosis in this disease and are susceptible to rehabilitation if they are detected early. Only recent studies have characterized deficits of social cognition in subjects with a high risk of developing chronic psychosis. These subjects present a unique opportunity to modify their social insertion and medical prognosis, as they have not been affected by the chronicity of the disease and present a milder symptomatology than in residual stages. This paper aims to make a review about how the DSC are present in schizophrenia from its prodromal stages and about its importance in the early detection of this disease.

Early psychosis detection program in Chile: A first step for the South American challenge in psychosis research.

AIM: Early detection and intervention (EDI) is a main challenge in psychosis research. The Chilean schizophrenia (SZ) national program has universal support and treatment by law for all SZ patients, but this does not yet extend to earlier stages of illness. Therefore, we have piloted an ultra-high risk (UHR) program to demonstrate the utility and feasibility of this public health approach in Chile. METHODS: We introduce "The University of Chile High-risk Intervention Program," which is the first national EDI program for UHR youths. Longitudinal follow-up included clinical and cognitive assessments, and monitoring of physiological sensory and cognitive indices, through electroencephalographic techniques. RESULTS: We recruited 27 UHR youths over 2 years. About 92.6% met criteria for attenuated psychosis syndrome (APS). Mean Scale of Psychosis-Risk Symptoms (SOPS) ratings in the cohort were 6.9 (SD 4.6) for positive, 9.1 (SD 8.3) for negative, 5.4 (SD 5.3) for disorganized and 6.3 (SD 4.1) for general symptoms. About 14.8% met criteria for comorbid anxiety disorders and 44.4% for mood disorders. Most participants received cognitive behavioural therapy (62.9%) and were prescribed low dose antipsychotics (85.2%). The transition rate to psychosis was 22% within 2 years. CONCLUSIONS: We describe our experience in establishing the first EDI program for UHR subjects in Chile. Our cohort is similar in profile and risk to those identified in higher-income countries. We will extend our work to further optimize psychosocial and preventive interventions, to promote its inclusion in the Chilean SZ national program and to establish a South American collaboration network for SZ research.

The delusional dimension of anorexia nervosa: phenomenological, neurobiological and clinical perspectives

Abstract Background Delusional characteristics have been largely ignored in patients suffering from anorexia nervosa (AN). Objectives To review the literature on delusional features in AN from phenomenological, neurobiological, and clinical viewpoints. Methods Data were obtained through searches of Medline, PubMed, SciELO and Cochrane Library. Results Distorted beliefs in AN may range from an overvalued idea to an overt delusion, involving affective, personality and/or psychotic disorders. Studies confirm alterations in monoaminergic systems. It has also been seen a decreased integration of visual/proprioceptive information, and alterations in neural networks involved in body processing. It is known that body image distortion may present "delusional proportions" as a consequence of great concern about body. Concomitantly, "embodied defence hypothesis" has been proposed. Restrictive AN exhibits higher levels of delusionality, and a particular delusional type of AN has been suggested, associated with a worse long-term outcome. Low doses of atypical antipsychotics are recommended combined with cognitive techniques. Discussion Delusional thinking in AN is likely a dynamic and dimensional phenomenon that can vary, both in nature and/or severity, whereas high insight levels, before and after refeeding, result in positive outcomes. Neurobiological research on this topic must be encouraged, since clinical and phenomenological approaches are comparatively more frequently reported.

Shifting the focus toward rare variants in schizophrenia to close the gap from genotype to phenotype.

Schizophrenia (SZ) is a disorder with a high heritability and a complex architecture. Several dozen genetic variants have been identified as risk factors through genome-wide association studies including large population-based samples. However, the bulk of the risk cannot be accounted for by the genes associated to date. Rare mutations have been historically seen as relevant only for some infrequent, Mendelian forms of psychosis. Recent findings, however, show that the subset of patients that present a mutation with major effect is larger than expected. We discuss some of the molecular findings of these studies. SZ is clinically and genetically heterogeneous. To identify the genetic variation underlying the disorder, research should be focused on features that are more likely a product of genetic heterogeneity. Based on the phenotypical correlations with rare variants, cognition emerges as a relevant domain to study. Cognitive disturbances could be useful in selecting cases that have a higher probability of carrying deleterious mutations, as well as on the correct ascertainment of sporadic cases for the identification of de novo variants.

Towards a neurobiological understanding of alexithymia. / Hacia una comprensión neurobiológica de la alexitimia.

Although the specialized literature on the etiology of alexithymia is controversial, neurobiological research has shown relevant advances. The aim of this review is to analyze the available evidence regarding the neurophysiological bases of alexithymia. A comprehensive review of available articles from Medline/PubMed, EBSCO and SciELO was conducted. Previously, alexithymia was linked to a reduced interhemispheric brain connection. From a childhood traumatic perspective, the right prefrontal cortex and the default mode network would experience alterations, first hypermetabolic (dopaminergic and glutamatergic dysregulation) and then hypometabolic-dissociative (serotonergic and opioid dysregulation), resulting in a distorted interoceptive and emotional awareness. Mirror neurons are the essential neurobiological substrate of theory of mind and social cognition, intrinsically linked to alexithymia, involving parietal, temporal, premotor, and cingulate cortices, and inferior frontal gyrus. Other structures involved are the amygdala (facial expression and emotional reactivity), the insula (interoception, emotional integration and empathy) and the cerebellum (limbic cerebellum and somatosensory awareness). Molecular genetics has detected polymorphisms in genes of the serotonin transporter, in the enzyme genes of dopaminergic metabolism and brain-derived neurotrophic factor, while the role of oxytocin is controversial. To sum up, we found several studies demonstrating the overwhelming evidence of a neurobiological basis underlying alexithymia; nevertheless, research is still inconclusive and must include environmental, traumatic, social, and psychological factors that contribute to the origin of the alexithymia.

Si bien la literatura especializada sobre la etiología de la alexitimia es controvertida, la investigación neurobiológica sobre el fenómeno ha demostrado importantes avances. El objetivo de esta revisión es analizar la evidencia disponible en relación a las bases neurofisiológicas de la alexitimia. Se realizó una revisión exhaustiva de artículos disponibles en MEDLINE/PubMed, EBSCO y SciELO. Inicialmente, se vinculó a la alexitimia con una conexión cerebral interhemisférica reducida. Desde la perspectiva traumática infantil, la corteza prefrontal derecha y la red neuronal por defecto experimentarían alteraciones, primero hipermetabólicas (desregulación dopaminérgica y glutamatérgica) y luego hipometabólicas-disociativas (desregulación serotoninérgica y opioide), resultando en una consciencia interoceptiva y emocional distorsionada. Las neuronas espejo son el sustrato neurobiológico fundamental de la teoría de la mente y la cognición social, intrínsecamente vinculadas con la alexitimia, involucrando cortezas como la parietal, la temporal, la premotora, la cingulada y el giro frontal inferior. Otras estructuras involucradas son amígdala (expresión facial y reactividad emocional), ínsula (interocepción, integración emocional y empatía) y cerebelo (cerebelo límbico y consciencia somatosensorial). La genética molecular ha detectado polimorfismos en el gen del transportador de serotonina, en los genes de las enzimas del metabolismo dopaminérgico y del factor neurotrófico derivado del cerebro, mientras que el rol de la oxitocina es controvertido. En conclusión, numerosos estudios demuestran contundentemente la existencia de una neurobiología subyacente a la alexitimia. Sin embargo, la investigación es aún poco concluyente y debe considerar los factores ambientales, traumáticos, sociales y psicológicos que contribuyen al origen del fenómeno.

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD.

From Molecules to the Clinic: Linking Schizophrenia and Metabolic Syndrome through Sphingolipids Metabolism.

Metabolic syndrome (MS) is a prevalent and severe comorbidity observed in schizophrenia (SZ). The exact nature of this association is controversial and very often accredited to the effects of psychotropic medications and disease-induced life-style modifications, such as inactive lifestyle, poor dietary choices, and smoking. However, drug therapy and disease-induced lifestyle factors are likely not the only factors contributing to the observed converging nature of these conditions, since an increased prevalence of MS is also observed in first episode and drug-naïve psychosis populations. MS and SZ share common intrinsic susceptibility factors and etiopathogenic mechanisms, which may change the way we approach clinical management of SZ patients. Among the most relevant common pathogenic pathways of SZ and MS are alterations in the sphingolipids (SLs) metabolism and SLs homeostasis. SLs have important structural functions as they participate in the formation of membrane "lipid rafts." SLs also play physiological roles in cell differentiation, proliferation, and inflammatory processes, which might be part of MS/SZ common pathophysiological processes. In this article we review a plausible mechanism to explain the link between MS and SZ through a disruption in SL homeostasis. Additionally, we provide insights on how this hypothesis can lead to the developing of new diagnostic/therapeutic technologies for SZ patients.

Antipsicóticos y suicidio / Antipsychotics and suicide

La relación entre antipsicóticos y suicidio es controversial debido a las diferencias expuestas en la literatura acerca de su acción específica. Uno de los puntos de discusión ha sido el aumento de la sintomatología depresiva y el impacto de algunos efectos secundarios sobre la suicidalidad, principalmente acinesia, acatisia y disquinesia tardía. Otro elemento controvertido es el efecto paradójico producto de la aminoración de los síntomas positivos al incrementar paralelamente la instrospección. Se revisará críticamente la principal evidencia disponible en torno al uso de antipsicóticos en relación al suicidio en el contexto de trastornos psicóticos y afectivos. No existe evidencia directa que avale una disminución en las tasas de suicidio con el uso de antipsicóticos de primera generación en trastornos psicóticos, probablemente por fallas metodológicas y por la multifactorialidad del fenómeno. En relación a los de segunda generación, podrían participar como protectores frente al riesgo suicida. En los trastornos esquizofrénicos se ha considerado a la clozapina como un fármaco antisuicida, debido a una acción antidepresiva directa y un efecto indirecto mediado por un mejoramiento en las funciones cognitivas. El mayor uso de antipsicóticos en los trastornos afectivos se observa en el espectro bipolar, sin reportarse mayor efectividad en el manejo del suicidio al compararse con estabilizadores del ánimo. Es crucial identificar el mecanismo de acción específico de los antipsicóticos para evaluar su real efecto sobre la suicidalidad.

The opinions about the relationship between antipsychotics and suicide are controversial due to differences on reported evidence about their specific action. One ofthe most discussed topics is the increase of depressive symptomatology and the impact of some secondary effects on suicidality, mainly akinesia, akathisia and tardive diskynesia. Another polemical topic is the paradoxical effect due to the decrease ofpositive symptoms when increasing insight. We performed a critical review of the available literature concerning to the use of antipsychotics in relation to suicide in the context of psychotic and affective disorders. When appraising psychotic disorders, there was no direct evidence to support a reduction in suicide rates when using first-generation antipsychotics, probably due to methodological issues and multifactoriality ofthe phenomenon. Nevertheless, second-generation antipsychotics could be protective against suicide risk, specifically clozapine, which is considered as an antisuicidal drug on schizophrenic disorders due to a direct antidepressant action and an indirect effect mediated by an improvement in cognitive functions. On the other hand, when appraising affective disorders, bipolar spectrum has demonstrated the greatest use of antipsychotics drugs, showing effectiveness in the management ofsuicide not greater than mood stabilizers. It becomes essential to identify the specific mechanism of action of antipsychotic drugs to assess their real effect on suicidality.

Psicofarmacología del suicidio II parte: Estabilizadores del ánimo y suicidio / Mood stabilizers and suicide: Part II

Lithium and anticonvulsants have been widely used as mood stabilizers (MS) in bipolar affective disorder (BAD), showing a reduction of suicide risk, even more, the anti-suicidal effect of lithium would be independent of its stabilizer property. The action mechanisms of the drug are not completely known and clinical research is hampered due to the heterogeneity of the studied samples, however, some mechanisms related to neurotransmitters metabolism and neurotrophic and neuroprotective factors have been proposed in order to explain its effect. Despite the current decline in the use of lithium as a MS it remains as the anti-suicidal drug of choice in bipolar patients.

El litio y los anticonvulsivantes han sido ampliamente empleados como estabilizadores del ánimo (EA) en el trastorno afectivo bipolar (TAB), demostrando además una reducción del riesgo de suicidio. En el caso particular del litio, dicho efecto sería independiente de su acción estabilizadora. Si bien los mecanismos de acción de la droga no son completamente conocidos y la investigación clínica se ve dificultada debido a la heterogeneidad de las muestras estudiadas, se han propuesto distintas vías que explicarían su efecto, relacionadas con el metabolismo de los neurotransmisores y con factores neurotróficos y neuroprotectores. Pese a la disminución actual en el uso del litio como EA, continúa siendo el fármaco antisuicida de elección en pacientes bipolares.

Ethnopsychopharmacology and pharmacogenomics.

Significant differences in response to psychotropic drugs are observed in various ethnic and cultural groups. Ethnopsychiatry is the study of how culture and genetic differences in human groups determine and influence the response to psychotropic agents. Meanwhile, pharmacogenomics studies the influence of genetic variations in the response of patients to different drugs. Pharmacogenetic tests are used to predict drug response and the potential for adverse effects. There are important genetic variations that influence the metabolism and action of psychotropic drugs in different ethnic groups. As examples, the frequencies of CYP2D6 polymorphisms and of the long and short alleles of the promoter region of the serotonin transporter are analyzed. Studies found significant differences in the frequency of polymorphisms of both genes in different countries and ethnic groups. On the basis of this review, the importance of considering ethnic and cultural factors in the prescription of drugs and in the need of further pharmacogenetic studies in different countries and geographical regions is reaffirmed.