A primer on the use of machine learning to distil knowledge from data in biological psychiatry.

Applications of machine learning in the biomedical sciences are growing rapidly. This growth has been spurred by diverse cross-institutional and interdisciplinary collaborations, public availability of large datasets, an increase in the accessibility of analytic routines, and the availability of powerful computing resources. With this increased access and exposure to machine learning comes a responsibility for education and a deeper understanding of its bases and bounds, borne equally by data scientists seeking to ply their analytic wares in medical research and by biomedical scientists seeking to harness such methods to glean knowledge from data. This article provides an accessible and critical review of machine learning for a biomedically informed audience, as well as its applications in psychiatry. The review covers definitions and expositions of commonly used machine learning methods, and historical trends of their use in psychiatry. We also provide a set of standards, namely Guidelines for REporting Machine Learning Investigations in Neuropsychiatry (GREMLIN), for designing and reporting studies that use machine learning as a primary data-analysis approach. Lastly, we propose the establishment of the Machine Learning in Psychiatry (MLPsych) Consortium, enumerate its objectives, and identify areas of opportunity for future applications of machine learning in biological psychiatry. This review serves as a cautiously optimistic primer on machine learning for those on the precipice as they prepare to dive into the field, either as methodological practitioners or well-informed consumers.

How evolutionary psychiatry can advance psychopharmacology
.

The prevailing paradigm for psychopharmacology focuses on understanding brain mechanisms as the key to finding new medications and improving clinical outcomes, but frustration with slow progress has inspired many pleas for new approaches. Evolutionary psychiatry brings in an additional basic science that poses new questions about why natural selection left us vulnerable to so many mental disorders, and new insights about how drugs work. The integration of neuroscience with evolutionary psychiatry is synergistic, going beyond reductionism to provide a model like the one used by the rest of medicine. It recognizes negative emotions as symptoms, that are, like pain and cough, useful defenses whose presence should initiate a search for causes. An integrative evolutionary approach explains why agents that block useful aversive responses are usually safe, and how to anticipate when they may cause harm. More generally, an evolutionary framework suggests novel practical strategies for finding and testing new drugs.
.

El paradigma común para la psicofarmacología se centra en entender los mecanismos cerebrales como la clave para encontrar nuevos medicamentos y mejorar los resultados clínicos, pero la frustración con el lento progreso ha inspirado muchos motivos para nuevas aproximaciones. La psiquiatría evolutiva conlleva una ciencia básica adicional que plantea nuevas preguntas sobre el por qué la selección natural nos dejó vulnerables a tantos trastornos mentales y aporta nuevas perspectivas sobre cómo funcionan los fármacos. La integración de las neurociencias con la psiquiatría evolutiva es sinérgica, y va más allá del reduccionismo para proporcionar un modelo como el que utiliza el resto de la medicina. Reconoce las emociones negativas como síntomas, que son, como el dolor y la tos, defensas útiles cuya presencia debe iniciar una búsqueda de causas. Un enfoque evolutivo integrador explica por qué los agentes que bloquean las respuestas aversivas útiles suelen ser seguros y cómo anticipar cuándo pueden causar daño. De manera más general, un marco evolutivo sugiere nuevas estrategias prácticas para encontrar y probar nuevos medicamentos.

Le modèle prévalent de la psychopharmacologie se concentre sur la compréhension des mécanismes du cerveau comme la clé pour découvrir de nouveaux médicaments et améliorer les résultats cliniques, mais la frustration ressentie devant les lents progrès de cette méthode a inspiré de nombreux plaidoyers pour d'autres approches. La psychiatrie évolutionniste apporte une connaissance scientifique fondamentale supplémentaire qui pose de nouvelles questions sur la raison pour laquelle la sélection naturelle nous a laissé si vulnérables à tant de troubles mentaux, et des idées nouvelles sur la façon dont fonctionnent les médicaments. L'intégration de la psychiatrie évolutionniste aux neurosciences est source de synergies, allant bien au-delà du réductionnisme en fournissant un modèle semblable à celui utilisé par le reste de la médecine. Il reconnaît les émotions négatives comme des symptômes, exactement comme le sont la douleur et la toux, défenses habituelles qui doivent initier une recherche des causes. Une approche évolutionniste intégrative explique pourquoi des agents qui bloquent des réactions pertinentes d'aversion sont généralement sans danger, et comment anticiper lorsqu'ils pourraient causer un préjudice. Plus généralement, un modèle évolutionniste propose de nouvelles stratégies pratiques pour trouver et tester de nouveaux médicaments.

Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Fear Extinction Retention: Is It What We Think It Is?

There has been an explosion of research on fear extinction in humans in the past 2 decades. This has not only generated major insights, but also brought a new goal into focus: how to maintain extinction memory over time (i.e., extinction retention). We argue that there are still important conceptual and procedural challenges in human fear extinction research that hamper advancement in the field. We use extinction retention and the extinction retention index to exemplarily illustrate these challenges. Our systematic literature search identified 16 different operationalizations of the extinction retention index. Correlation coefficients among these different operationalizations as well as among measures of fear/anxiety show a wide range of variability in four independent datasets, with similar findings across datasets. Our results suggest that there is an urgent need for standardization in the field. We discuss the conceptual and empirical implications of these results and provide specific recommendations for future work.

Guidelines for the standardized collection of blood-based biomarkers in psychiatry: Steps for laboratory validity - a consensus of the Biomarkers Task Force from the WFSBP.

Recently, there has been a major shift in the field of psychiatry towards the exploration of complex relationships between blood-based biomarkers and the pathophysiology of psychiatric and neuropsychiatric disorders. However, issues with study reproducibility, validity and reliability have hindered progress towards the identification of clinically relevant biomarkers for psychiatry. The achievement of laboratory validity is a crucial first step for the posterior development of clinical validity. There is evidence that the variability observed in blood-based research studies may be minimised with the implementation of standardised pre-analytical methods and uniform clinical protocols (i.e., pre-venipuncture). It has been documented that errors made in the pre-analytical phase account for 46-68.2% of laboratory testing errors. Thus, standardising clinical assessment, ethical procedures and pre-analytical phase of clinical research is essential for the reproducibility, validity and reliability of blood marker assessment, and reducing the risk of invalid test results. Various other areas of research have already moved towards guidelines for the standardised collection of blood-based biomarkers. Here we aim to provide a set of guidelines that we believe would improve biomarker research: (1) pre-venipuncture information and documentation, (2) ethics of participant consent and (3) pre-analytical methods. Ultimately, we hope this will assist study planning and will improve data comparison across studies allowing for the discovery of biomarkers in psychiatry with both laboratorial and clinical validity.

Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

Brain space and time in mental disorders: Paradigm shift in biological psychiatry.

Contemporary psychiatry faces serious challenges because it has failed to incorporate accumulated knowledge from basic neuroscience, neurophilosophy, and brain-mind relation studies. As a consequence, it has limited explanatory power, and effective treatment options are hard to come by. A new conceptual framework for understanding mental health based on underlying neurobiological spatial-temporal mechanisms of mental disorders (already gained by the experimental studies) is beginning to emerge.

Autolesiones en una unidad de hospitalización psiquiátrica infanto-juvenil / Self-injury in a child and adolescent psychiatry inpatient unit

Introducción. La creciente prevalencia de conductas suicidas en adolescentes se ha convertido en un problema de salud pública. Existen varios factores asociados con este tipo de conductas: síntomas depresivos y ansiosos, consumo de sustancias, trastornos de conducta, violencia familiar, negligencia, abuso sexual en la infancia, etc. Con frecuencia, el comportamiento suicida se asocia a las autolesiones. Estas pueden definirse como conductas deliberadas destinadas a producir daño físico sin la intención de provocar la muerte. Método. Con la finalidad de estudiar el perfil clínico, las características y su comorbilidad con enfermedades psiquiátricas, hemos realizado un estudio observacional, descriptivo y con carácter prospectivo en los ingresados en la Unidad de Hospitalización Psiquiátrica Infanto Juvenil del Hospital Clínico Universitario de Valladolid durante el año 2016, que hayan presentado autolesiones. Entre las variables estudiadas: edad, sexo, procedencia, diagnóstico, abuso de sustancias, Autoinforme de evaluación funcional de la automutilación (FASM) e Inventario clínico para adolescentes Millon (MACI). Resultados. Durante el año 2016 hubo un total de 110 ingresos, de los cuales 27 (el 24,54%) han presentado autolesiones. En la mayoría de los casos (96,3%) se trata de pacientes de sexo femenino. Presentan alta comorbilidad, con trastorno de la conducta alimentaria (40,74%) y con trastorno por déficit de atención (29,63%). Conclusiones. La detección de estas conductas tiene importancia como señales de otra psicopatología que puede ser menos evidente. Dado que la edad de inicio de las mismas, en nuestro estudio, es los 11,81 años, habrá que prestar especial atención desde Pediatría de Atención Primaria

Introduction. The increasing prevalence of suicidal behavior in adolescents has become a public health problem. There are several factors associated with this type of behavior: depressive and anxious symptoms, substance use, behavioral disorders, family violence, neglect, sexual abuse in childhood... Suicidal behavior is often associated with self-harm. These can be defined as deliberate actions intended to cause physical harm without the intent of causing death. Method. In order to study the clinical profile, characteristics and their comorbidity with other psychiatric diseases, we carried out an observational, descriptive and prospective study in those patients who were admitted to the Child Psychiatric Unit of the Clinico Universitario Hospital of Valladolid during 2016, who have suffered self-harm. Among the variables studied were: age, sex, origin, diagnosis, substance abuse, FASM (self-report of functional evaluation of self-mutilation), and MACI (Millon Adolescents Clinical Inventory). Results. During the year 2016 there was a total of 110 admissions, of which, 27 (24.54%) had been self-injured The majority of cases (96.3%) are female patients. They present a high comorbidity with eating disorders (40.74%) and attention deficit disorder (29.63%). Conclusions. The detection of this behaviour is important as it may indicate the presence of other psychopathology that may be less evident. Given that the average age of onset in our study is 11.81 years old, it would be necessary for Primary Care Paediatrics to pay special attention to this

Toward Neuroproteomics in Biological Psychiatry: A Systems Approach Unravels Okadaic Acid-Induced Alterations in the Neuronal Phosphoproteome.

Neuroproteomics is an evolving field of postgenomic medicine, highlighting the convergence of psychiatry/neurology and proteomics, yet compared with neurogenetics, it has received little attention. This study in rat primary neuronal cultures provides an example of a neuroproteomic approach relevant to the study of psychiatric disease pathophysiology, focusing on Alzheimer's disease. In this context, okadaic acid (OA) is routinely used in experimental designs to investigate phosphorylation-mediated events. It is a potent protein phosphatase (PP) inhibitor, particularly of PP1 and PP2A. Typically, a single protein and its phosphorylation level are monitored upon OA exposure. Although useful, this can be misleading as protein phosphorylation-mediated events involve complex signaling cascades and an array of kinases, phosphatases, and substrates. Bearing in mind the involvement of multiple pathways and cascade cross talk, this study employed a systems approach to analyze OA-induced molecular responses through PP inhibition. We showed that upon OA exposure, the recovery rate of 245 phosphoproteins significantly increased, while that of 75 significantly decreased. The prominent biological processes affected included anatomical structural development, transport, cell differentiation, and signal transduction. The associated phosphointeraction networks identified nodes representing OA-responsive phosphoproteins. Many of these are key players of signaling cascades relevant to a range of pathologies. In summary, the data presented results from a neuroproteomic preclinical study offering an array of phosphoproteins as potential targets for future diagnostic and therapeutic strategies in biological psychiatry. We note, however, the nonspecificity of targeting PPs themselves and emphasize the need for future neuroproteomic approaches toward systems psychiatry.

Nutritional psychiatry: the present state of the evidence.

Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine, N-acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.

Una revisión de los trastornos del sueño en la esquizofrenia / Sleep disorders in schizophrenia: a review

La esquizofrenia se acompaña hasta en un 80% de los pacientes de trastornos del sueño, que son normalmente infradiagnosticados e infratratados debido a su falta de consideración en el manejo de esta enfermedad. Los principales trastornos son el insomnio, el síndrome de piernas inquietas, el síndrome de apnea obstructiva del sueño, la hipersomnia, las parasomnias y los trastornos del ritmo circadiano. Destaca en su importancia el insomnio, ya que puede ser un signo prodrómico de la enfermedad, así como un signo de alarma temprano de una descompensación psicótica incipiente. En pacientes con esquizofrenia se han encontrado alteraciones polisomnográficas en la arquitectura del sueño que se correlacionan tanto con la clínica subjetiva de insomnio como con las manifestaciones clínicas predominantes de la esquizofrenia. Los antipsicóticos pueden alterar la estructura del sueño, pero también tienen un papel importante en el tratamiento de las alteraciones del sueño en la esquizofrenia. Han demostrado una mejoría clínica del insomnio y la corrección polisomnográfica de las alteraciones de la arquitectura del sueño, mejorando la calidad de vida y la capacidad funcional de los pacientes. Sin embargo, pueden también exacerbar otros trastornos comórbidos del sueño, como el síndrome de piernas inquietas o el síndrome de apnea obstructiva del sueño, o provocar hipersomnia u obesidad. Existe evidencia de que los trastornos del sueño en esquizofrenia afectan de forma relevante la calidad de vida y de que influyen en la sintomatología de los pacientes con esquizofrenia, por lo que es muy importante reconocerlos y tratarlos de forma adecuada (AU)

Up to 80% of patients with schizophrenia suffer from sleep disorders, and are usually under-diagnosed and under-treated due to a lack of being taken into account in the management of this illness. The main disorders are insomnia, restless legs syndrome, obstructive sleep apnoea syndrome, hypersomnia, the parasomnias, and circadian rhythm disorders. The importance of insomnia is highlighted, as it can be a prodromic sign of the illness, as well as an early alarm sign of an incipient psychotic decompensation. Polysomnographic changes that correlate with subjective clinical insomnia and with the predominant clinical manifestations of schizophrenia. Antipsychotic drugs can alter the structure of sleep, but they also have an important role in the treatment of sleep alterations in schizophrenia. They have demonstrated a clinical improvement of the insomnia and the polysomnographic correction of the changes in sleep architecture, with an improvement in the quality of life and functional capacity of the patients. However, they can also exacerbate other comorbid sleep disorders such as restless legs syndrome and obstructive sleep apnoea syndrome, or trigger hypersomnia or obesity. There is evidence that sleep disorders in schizophrenia has a significant effect on the quality of life and has an influence on the symptoms of patients with schizophrenia, thus it is very important to recognise them and treat them accordingly (AU)

Disfunción sexual persistente tras el tratamiento con inhibidores selectivos de la recaptación de serotonina: a propósito de un caso tras la retirada de paroxetina / Post-serotonine selective reuptake inhibitors persistent sexual dysfunction after serotonine selective reuptake inhibitors treatment: a case report after stopping paroxetine

Evidencias recientes sugieren que la disfunción sexual que aparece con frecuencia durante el tratamiento con inhibidores selectivos de la recaptación de serotonina (ISRS) o con los inhibidores selectivos de la recaptación de serotonina y noradrenalina (IRSN) persiste en algunos pacientes tras la discontinuación del tratamiento. Se presenta un caso clínico que sugiere probabilidad elevada para realizar esta atribución causal tras la retirada de paroxetina, según los criterios sugeridos por Ben-Sheetrit et al. en el artículo «Post-SSRI sexual dysfunction»: varón joven sin enfermedad física concurrente, sin tratamientos farmacológicos ni uso de tóxicos (salvo consumo muy moderado y ocasional de alcohol) y libre de síntomas afectivos en el momento actual que pudieran explicar mejor la presencia de disfunción sexual. Doce semanas después de la retirada de paroxetina, persiste disminución de la libido y dificultades moderadas en el mantenimiento de la erección. El creciente interés por la evaluación de la disfunción sexual secundaria a antidepresivos, y el compromiso sobre la esfera sexual de nuestros pacientes, facilita la identificación de casos (AU)

Recent evidence suggests that the sexual dysfunction that often appears during treatment with selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and noradrenaline reuptake inhibitors (SNRIs) persists in some patients after stopping the treatment. A clinical case is presented that suggests a high probability having a causal relationship to the withdrawal of paroxetine according to the criteria suggested by Ben-Sheetrit et al. In the article 'Post-SSRI sexual dysfunction': a young male with no concurrent physical illness, with no drug treatments or use of toxic substances (except for very moderate and occasional consumption of alcohol), and free of affective symptoms at the present moment that could better explain the presence of sexual dysfunction. Twelve weeks after withdrawal of paroxetine, there was a persistent decrease in libido and moderate difficulties in maintaining erection. The increasing interest in the evaluation of sexual dysfunction secondary to antidepressants, and the commitment on the sexual sphere of our patients, facilitates the identification of cases (AU)

Síndrome de secreción inadecuada de hormona antidiurética, hiponatremia y antipsicóticos. Revisión de la literatura a propósito de un caso / Syndrome of inappropriate antidiuretic hormone secretion, hyponatraemia and antipsychotics. Review of the evidence and case report

Introducción. La hiponatremia es un efecto secundario asociado al uso de psicofármacos, entre ellos, los antipsicóticos. El síndrome de secreción inadecuada de hormona antidiurética y la polidipsia se han postulado como mecanismos etiopatogénicos subyacentes. Asimismo, se propone que exista una afectación biológica en la esquizofrenia que promueva la hiponatremia. Caso clínico. Presentamos a una paciente de 45 años con diagnóstico de esquizofrenia que comienza con un síndrome de secreción inadecuada de hormona antidiurética probablemente secundario a palmitato de paliperidona. Discusión. A partir de este caso, realizamos una revisión de la literatura disponible y planteamos la interrelación de la hiponatremia, el síndrome de secreción inadecuada de hormona antidiurética, la polidipsia, la propia psicosis y otros mecanismos etiopatogénicos. Conclusiones. La hiponatremia es una complicación importante e impredecible, de la que desconocemos su fisiopatología exacta en pacientes psicóticos. Son necesarios más estudios que esclarezcan su patogenia y determinen la necesidad de seguimiento analítico de pacientes que reciben tratamiento antipsicótico, sobre todo aquellos con diagnóstico de esquizofrenia (AU)

Introduction. Hyponatraemia is an adverse drug reaction to psychotropic medication, among them the antipsychotics. Syndrome of inappropriate antidiuretic hormone secretion and polydipsia have been suggested as aetiopathogenic mechanisms. Moreover, it has been postulated that there is a biological dysfunction in schizophrenia that induces hyponatraemia. Case report. A case is presented on a 45-year old woman with schizophrenia who has an syndrome of inappropriate antidiuretic hormone secretion, which was suspected of being due to paliperidone palmitate. Discussion. A review was made of the available published evidence and proposed the relationship between hyponatraemia, syndrome of inappropriate antidiuretic hormone secretion, polydipsia, the psychosis itself, and other aetiopathogenic mechanisms. Conclusions. Hyponatraemia is an important and unpredictable complication, for which its pathophysiology remains unknown. Further studies are needed to establish its pathogenic mechanisms and to determine the need of analytical monitoring in patients who are on treatment with antipsychotics, especially those with schizophrenia (AU)

Infección urinaria por Acinetobacter baumannii e intoxicación por litio. A propósito de un caso / Lithium poisoning and a urinary tract infection due to Acinetobacter baumannii: a case report

El litio es un ion cuyo mecanismo de acción no está claro, pese a que se viene usando desde hace más de 50 años para el tratamiento de los trastornos afectivos. La intoxicación por litio es un cuadro poco frecuente, y en la mayor parte de los casos accidental, que va desde sus formas más leves a cuadros severos en los que se produce una afectación neurológica destacable, dependiendo de las cifras de litemia y del estado clínico inicial del paciente. En este artículo se presenta el caso clínico de un paciente de 63 años diagnosticado de trastorno esquizoafectivo y en tratamiento crónico con carbonato de litio que presenta como motivo de consulta e ingreso una intoxicación por litio con importante repercusión neurológica, a propósito de una infección urinaria por un microorganismo atípico, que cursa con picos febriles y afectación de la función renal (AU)

Even though it has been used in the treatment of bipolar affective disorder for more than 50 years lithium is a chemical element for which exact mechanism of action is still not clearly understood. Lithium poisoning is rare and mostly accidental, and its intensity varies from milder to more severe forms. There is a significant neurological involvement that depends on the total body burden of lithium and the initial clinical status of the patient. A clinical case is presented of a 63 year-old patient diagnosed with schizoaffective disorder and treated with lithium carbonate, who was admitted to hospital due to lithium poisoning with significant neurological repercussions. He also had a urinary infection due to an atypical microorganism with febrile peaks and impaired renal function (AU)

Ácidos grasos omega-3 y depresión: una revisión sistemática / Omega-3 fatty acids and depression: a systematic review

Introducción y objetivos. Los ácidos omega-3 son grasas poliinsaturadas que deben ser aportadas a través de la dieta, encontrándose de forma preformada fundamentalmente en las variedades del pescado azul. Los ácidos omega-3 se hallan en las membranas lipídicas neuronales en gran proporción, aportando estabilidad a las mismas y optimizando la comunicación sináptica. Una dieta pobre en ácidos omega-3, siendo esta una tendencia en los hábitos alimentarios occidentales en los últimos tiempos, podría figurar como un factor de riesgo para la aparición de depresión. Este artículo de revisión trata de valorar la influencia de los ácidos omega-3 en la prevención o el tratamiento de la depresión. Material y métodos. Es presentada una selección de datos de carácter neurobiológico, epidemiológico y clínico, a través de la revisión de las publicaciones más importantes en este sentido, prestando especial atención a los resultados obtenidos en los diferentes metaanálisis de tipo clínico realizados. Conclusiones. Los ácidos omega-3 pueden figurar hoy en día como un agente coadyuvante más para el tratamiento de la depresión, siendo avalada esta recomendación por varios metaanálisis que implican un alto nivel de evidencia, lo que ha motivado que su uso sea contemplado por guías clínicas o recomendaciones de expertos. Algunos metaanálisis encuentran una superioridad del ácido eicosapentaenoico (EPA) frente al ácido docosahexaenoico (DHA) y recomiendan una mayor proporción del primero en los suplementos si se eligen los omega-3 como agentes coadyuvantes en el tratamiento antidepresivo (AU)

Introduction and objectives. Omega-3 acids are polyunsaturated fatty acids that have to be provided in the diet, mostly being present in oily fish. Omega-3 fatty acids are mostly found in neuronal lipid membranes, providing them with stability, as well as optimising synaptic communication. A diet low in omega-3 acids, which is a recent trend in Western eating habits, could be a risk factor for the development of depression. This review attempts to assess the influence of omega-3 fatty in the prevention and treatment of depression. Material and methods. Neurobiological, epidemiological and clinical data of the most important publications on this subject are presented, paying particular attention to the results obtained in the different clinical meta-analyses conducted. Conclusions. Omega-3 fatty acids may currently appear as an adjuvant agent for the treatment of depression, with this recommendation being endorsed by several meta-analyses that involve a high level of evidence, which has led to their use being contemplated in clinical guidelines or recommendations by experts. Some meta-analyses found superiority of eicosapentaenoic acid (EPA) over docosahexaenoic acid (DHA), and recommend a higher proportion of the former if omega-3 fatty acids are chosen as adjuvants agents in antidepressant treatment (AU)

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays.

Cytokines produced by both immune and non-immune cells are likely to play roles in the development and/or progression of psychiatric disorders. Indeed, many investigators have compared the blood cytokine levels in psychiatric patients with those of healthy controls or monitored their levels in patients during disease progression to identify biomarkers. Nevertheless, very few studies have confirmed that such cytokines remain stable in healthy individuals through periods of weeks and months. This is an important issue to consider before using blood cytokine levels as biomarkers of disease traits, disease state, or treatment response. Although multiplex assay technology represents an advance in identifying biomarkers because it allows simultaneous examination of large panels of analytes from a small volume of sample, it is necessary to verify whether these assays yield enough sensitivity and reproducibility when applied to the blood from neuropsychiatric patients. Therefore, we compared two multiplex immunoassays, the bead-based Luminex® (Bio-Rad) and the electro-chemiluminescence-based V-plex® (MesoScaleDiscovery), for the detection and quantification of 31 cytokines, chemokines and growth factors in both the sera and plasma of patients with major depressive episodes (MDE) and age- and sex-matched healthy control subjects during a 30-week period. Although both platforms exhibited low coefficients of variability (CV) between the duplicates in the calibration curves, the linearity was better in general for the V-PLEX® platform. However, neither platform was able to detect the absolute values for all of the tested analytes. Among the 16 analytes that were detected by both assays, the intra-assay reproducibility was in general better with the V-PLEX® platform. Although it is not a general rule that the results from sera and plasma will be correlated, consistent results were more frequent with the V-PLEX® platform. Furthermore, the V-PLEX® results were more consistent with the gold standard ELISA simplex assay for IL-6 in both sera and plasma. The intra-individual variability of the measurements, among the sera and plasma for the 4 samples harvested from each healthy individual, was low for Eotaxin, G-CSF, IL-4, IL-7, IL-9, IL-12p40, IL-12p70, IL-15, MIP-1ß, PDGF-BB, TNF, TNF-ß and VEGF, but intermediate or high for IFN-γ, IL-6, IL-8, IL-10, and IP10. Together, these data suggest that extreme caution is needed in translating the results of multiplex cytokine profiling into biomarker discovery in psychiatry.

Clozapina: una revisión / Clozapine: a review

La esquizofrenia es el trastorno psiquiátrico que constituye el paradigma de la enfermedad mental. Su tratamiento continúa siendo un tema controvertido, especialmente cuando hablamos de efectos secundarios, remisión de los síntomas, funcionalidad y calidad de vida del individuo que la sufre. La clozapina, desde su introducción en 1959 y aceptación oficial por la FDA para el tratamiento de la esquizofrenia resistente en 1990, es el medicamento que más controversia ha causado debido a su perfil atípico y a su acción en múltiples receptores que condicionan efectos secundarios que, a pesar de no poner en riesgo la integridad del paciente (p. ej. sialorrea, sedación), sí pueden representar una amenaza para su calidad de vida, o por efectos que pueden por sí mismos poner en riesgo la vida del paciente (p. ej. agranulocitosis, miocarditis); sin embargo, el conocimiento de la molécula, sus indicaciones de uso y la monitorización necesaria son acciones que permiten el uso de la sustancia de una forma segura, que beneficie al paciente y por lo tanto a su familia, principalmente por la acción terapéutica no solo de mejoría en síntomas psicóticos positivos y negativos, sino por su efecto incisivo en el riesgo suicida y la agresividad, mayor que otros antipsicóticos, además de su uso en pacientes que cuentan con patologías concomitantes como enfermedad de Parkinson, discinesia tardía, entre otras (AU)

Schizophrenia is a psychiatric disorder that is the paradigm of mental illness. Its treatment remains a controversial issue, especially as regards side effects, remission of symptoms, function, and the quality of life of the individual who suffers from it. Clozapine, since its introduction in 1959, and its formal acceptance by the FDA for treatment resistant schizophrenia in 1990, is the drug that has led to most controversy, due to its atypical profile action at multiple receptors. These actions determine the side effects (e.g., hyper-salivation, sedation), and although not placing the integrity of the patient at risk, can be a threat to their quality of life. There are other side effects that can, in themselves, endanger the patient's life (e.g., agranulocytosis, myocarditis). However, the knowledge of the molecule, its indications for use, as well as mandatory monitoring, are actions that allow the safe use of the substance that can benefit the patients, and therefore their families. This is mainly due to the therapeutic action not only improving the positive and negative psychotic symptoms, but also its significant effect on suicidality and aggressiveness, which is greater than other antipsychotics. It can also be used in patients with concomitant diseases, such as Parkinson's disease, and tardive dyskinesia (AU)

La carga familiar de los cuidadores de personas jóvenes y adultas diagnosticadas de discapacidad intelectual y trastorno mental: una revisión sistemática / The family burden of caregivers of young and adult people diagnosed with intellectual disability and mental disorders: a systematic review

El presente artículo recoge y analiza la información publicada sobre la carga familiar en cuidadores de personas jóvenes y adultas diagnosticadas de discapacidad intelectual y trastorno mental asociado. El objetivo del presente trabajo es recopilar y promover la investigación sobre dicha temática. Se han seleccionado los estudios existentes en referencia a los factores que contribuyen a una mayor carga familiar, como son las variables clínicas y diagnósticas, los factores psicológicos y sociales, así como los factores facilitadores encaminados a reducir la carga familiar. La búsqueda bibliográfica se realizó en las bases de datos MEDLINE, PsycINFO, Social Services Abstracts y PSICODOC con los siguientes términos: discapacidad intelectual, trastorno mental, carga familiar y adultos. Se encontró un total de 99 estudios, de los cuales se seleccionaron 8 para su revisión. Los resultados evidencian que la carga familiar es más prevalente cuando se asocia con la comorbilidad entre discapacidad intelectual y trastorno psiquiátrico. Además, el impacto familiar tiene como consecuencia repercusiones emocionales, psicológicas, sociales y de salud en los cuidadores. Los estudios analizados enfatizan la necesidad de futuros estudios para ampliar la investigación tanto a nivel clínico y diagnóstico, para priorizar una detección precoz y un tratamiento adecuado, como a nivel psicosocial, con el fin de identificar las necesidades y el apoyo necesario para reducir la carga familiar global percibida por los cuidadores (AU)

This paper collects and analyses the published information on the family burden of caregivers of young and adult people with intellectual disability and mental disorders. The aim of this study is to compile and promote research into this subject. A selection has been made of existing studies that refer to the factors that contribute to a greater family burden, such as clinical and diagnostic variables, psychological and social factors, as well as those factors that tend to reduce the family burden. A bibliographic research has been carried out in the databases MEDLINE, PsycINFO, Social Services Abstracts and PSICODOC bases using the following terms: intellectual disability, mental disorder, family burden, and adult. A total of 99 studies were found, 8 of which were selected for review. The results demonstrate that the family burden is more prevalent when it is associated with comorbidity between intellectual disability and psychiatric disorder. Moreover the family burden has emotional, psychological, social, and health repercussions on the caregivers. The analysed studies emphasise the need of further research in order to broaden the investigation at a clinical and diagnostic level, so that early detection and appropriate treatment are prioritised. This should also be at a psychosocial level, which would help to identify the needs and the support aimed at reducing the overall family burden perceived by the caregivers (AU)