Ghrelin receptor antagonist attenuated sickness behavior and activation of HPA-axis induced by immunological challenge in male rats.

AIMS: During illnesses caused by infectious diseases, a suite of brain-mediated responses called sickness syndrome occurs, triggering behavioral and physiological changes. This study investigated whether ghrelin modulates sickness syndrome induced by systemic administration of lipopolysaccharide (LPS). MAIN METHODS: Male Wistar rats were pretreated with vehicle or [D-lys3]-GHRP-6, a ghrelin receptor GHS-R1 antagonist (20 nmol, i.c.v), 30 min before injection of LPS (200 µg/kg, i.p.) or sterile saline. We investigated the behavioral effects in male rats after LPS administration by screening for depressive-like behavior, locomotor activity alterations, and corticosterone release. Changes in body temperature were measured using a biotelemetry probe preimplanted in the peritoneal cavity to evaluate the effect of ghrelin on the thermoregulatory response during immunological challenge. KEY FINDINGS: Pretreatment with [D-lys3]-GHRP-6 blunted most of the assessed parameters related to sickness syndrome, including social withdrawal, anhedonia, depressive-like behavior, and anorexia, reduced the activation of the HPA axis, but did not alter LPS-induced fever. SIGNIFICANCE: Our findings suggest that ghrelin centrally mediates the sickness behavior and activation of HPA, as a ghrelin receptor antagonist attenuates social withdrawal, anhedonia, depressive-like behavior, anorexia, and HPA activation in response to LPS.

Prescription Drug Overdose, Depression, and Other Mental Disorders in the Context of Kidney Disease.

Clinical Background: Mental disorders, especially depression, are associated with several comorbidities in the kidneys. Depression is the psychiatric disorder that mostly affects individuals with chronic kidney disease (CKD) and end-stage kidney disease. Epidemiology: The mainly prescribed drugs involved in overdose cases are opioids, benzodiazepines, and antidepressants. Antidepressants are the main psychiatric drugs that lead to kidney injury, mainly the second-generation ones. However, the prevalence of depression in dialysis patients varies from 22.8 to 39.3%. Therefore, psychiatric patients have 1.5-3 times more hospitalization compared to patients having only CKD. Challenges: Randomized clinical studies should be encouraged. Studies have shown an association between depression and progression of kidney disease. The mechanisms are not completely clear, but changes on neurotransmitter release and endocrine functions appear to be related to it. Additionally, the use of antidepressant and other psychoactive drugs can induce kidney injury. Hyponatremia induced by second-generation antidepressant drugs is an important feature and can be a risk factor for elderly or patients with comorbidities such as cerebral edema, brain damage or coma. Besides this class, drugs used for anxiety and bipolar disorders or sympathomimetic drugs of abuse can trigger acute kidney injury, possibly due to endothelial dysfunction and thromboembolic and ischemic events. Prevention and Treatment: The early detection of renal impairment and the prescription of nephroprotective strategies has been a clinical challenge. Some studies aim to describe the biochemical mechanisms involved and develop clinical management strategies for these patients. This chapter brings attention to this topic, discussing the major mechanisms and clinical features of kidney injury associated with mental illness, and the most relevant clinical strategies.

[Problems and adverse reactions related to opioid analgesics in Colombia]. / Problemas y reacciones adversas relacionadas con analgésicos opioides en Colombia.

INTRODUCTION: The prevalence of pathologies that generate chronic pain is high (10-40%), as is the use of opioids. In Colombia, these drugs rank among the first in terms of prescriptions and the number of deaths related to their consumption is rising (0.71/1,000,000 inhabitants). This study seeks to characterise opioid-related problems (ORP) and the variables associated with their resolution. MATERIALS AND METHODS: It is a study based on secondary information. Incidences were calculated using Ministry of Health data and characteristics related to non-recoverable adverse reactions (ADRs) were determined. RESULTS: Altogether 4,437 problems were identified in 3,063 patients (39.51%, male), adults (45 years old; IQR: 29-62). The most common opioids were tramadol (46.49%, 5 mg; IQR: 5-5) and morphine (19.65%, 3 mg; IQR: 2.6-5). The majority of ORP were ADRs (93.15%) and of these, 32.28% were severe. Women had proportionally more gastrointestinal and neurological disorders, while men had a higher frequency of vascular, psychiatric, urinary and haematological problems (p < 0.05). These reactions did not resolve in 8.39%, and prognosis was associated with oral administration - odds ratio (OR): 9.24; 95% confidence interval (CI 95%): 6.36-13.42; severity (OR: 3.96; CI 95%: 2.71-5.76); age (OR: 1.01; CI 95%: 1.001-1.01); weak opioids (OR: 0.57; CI 95%: 0.4-0.84); and neurological-cardiovascular reactions (OR: 0.36; CI 95%: 0.21-0.61). CONCLUSIONS: Interventions to optimise the prescription of opioids should be encouraged to prevent ADRs with poor prognosis. Studies should be conducted to further investigate the impact of gender and route of administration on the occurrence of ADRs, as well as the severity of skin and gastrointestinal problems, which may be underestimated.

TITLE: Problemas y reacciones adversas relacionadas con analgésicos opioides en Colombia.Introducción. Las patologías que generan dolor crónico tienen alta prevalencia (10-40%), así como el consumo de opioides. En Colombia, estos medicamentos ocupan los primeros lugares de prescripción y existe un incremento en las muertes relacionadas con su consumo (0,71/1.000.000 habitantes). Este estudio busca caracterizar los problemas relacionados con opioides (PRM) y las variables asociadas con su resolución. Materiales y métodos. Es un estudio basado en información secundaria. Se calcularon las incidencias con datos del Ministerio de Salud y se determinaron las características relacionadas con reacciones adversas (RAM) no recuperables. Resultados. Se identificaron 4.437 problemas en 3.063 pacientes (39,51%, hombres), adultos (45 años; RIC: 29-62). Los opioides más comunes fueron tramadol (46,49%, 5 mg; RIC: 5-5) y morfina (19,65%, 3 mg; RIC: 2,6-5). La mayoría de los PRM fueron RAM (93,15%), y de éstas, el 32,28% fueron graves. Las mujeres presentaron proporcionalmente más alteraciones gastrointestinales y neurológicas, mientras que los hombres tuvieron una mayor frecuencia de problemas vasculares, psiquiátricos, urinarios y hematológicos (p menor de 0,05). Estas reacciones no se resolvieron en el 8,39% y el pronóstico se asoció con la administración oral ­odds ratio (OR): 9,24; intervalo de confianza al 95% (IC 95%): 6,36-13,42­, gravedad (OR: 3,96; IC 95%: 2,71-5,76), edad (OR: 1,01; IC 95%: 1,001-1,01), opioides débiles (OR: 0,57; IC 95%: 0,4-0,84) y reacciones neurológicas-cardiovasculares (OR: 0,36; IC 95%: 0,21-0,61). Conclusiones. Se sugiere fomentar intervenciones para optimizar la prescripción de opioides y así prevenir RAM con pobre pronóstico. Deben realizarse estudios que profundicen en el impacto del sexo y la vía de administración sobre la ocurrencia de RAM, así como la gravedad de los problemas cutáneos y gastrointestinales, que podría subestimarse.

Neonatal Rotenone Administration Induces Psychiatric Disorder-Like Behavior and Changes in Mitochondrial Biogenesis and Synaptic Proteins in Adulthood.

Since psychiatric disorders are associated with changes in the development of the nervous system, an energy-dependent mechanism, we investigated whether mitochondrial inhibition during the critical neurodevelopment window in rodents would be able to induce metabolic alterations culminating in psychiatric-like behavior. We treated male Wistar rat puppies (P) with rotenone (Rot), an inhibitor of mitochondrial complex I, from postnatal days 5 to 11 (P5-P11). We demonstrated that at P60 and P120, Rot-treated animals showed hyperlocomotion and deficits in social interaction and aversive contextual memory, features observed in animal models of schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder. During adulthood, Rot-treated rodents also presented modifications in CBP and CREB levels in addition to a decrease in mitochondrial biogenesis and Nrf1 expression. Additionally, NFE2L2-activation was not altered in Rot-treated P60 and P120 animals; an upregulation of pNFE2L2/ NFE2L2 was only observed in P12 cortices. Curiously, ATP/ADP levels did not change in all ages evaluated. Rot administration in newborn rodents also promoted modification in Rest and Mecp2 expression, and in synaptic protein levels, named PSD-95, Synaptotagmin-1, and Synaptophysin in the adult rats. Altogether, our data indicate that behavioral abnormalities and changes in synaptic proteins in adulthood induced by neonatal Rot administration might be a result of adjustments in CREB pathways and alterations in mitochondrial biogenesis and Nrf1 expression, rather than a direct deficiency of energy supply, as previously speculated. Consequently, Rot-induced psychiatric-like behavior would be an outcome of alterations in neuronal paths due to mitochondrial deregulation.

Evaluation of severe hypoglycemia and common mental disorders in patients receiving insulin analogues for treatment of type 1 diabetes

ABSTRACT This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs.77%, respectively, p = 0.03).

Evaluation of severe hypoglycemia and common mental disorders in patients receiving insulin analogues for treatment of type 1 diabetes.

This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs. 77%, respectively, p = 0.03).

Post-finasteride syndrome

Abstract Finasteride is a 5α-reductase enzyme inhibitor that has been approved for the treatment of male androgenic alopecia since 1997. Over time, it has been considered a safe and well-tolerated drug with rare and reversible side effects. Recently there have been reports of adverse drug-related reactions that persisted for at least three months after discontinuation of this drug, and the term post-finasteride syndrome arose. It includes persistent sexual, neuropsychiatric, and physical symptoms. Studies to date cannot refute or confirm this syndrome as a nosological entity. If it actually exists, it seems to occur in susceptible people, even if exposed to small doses and for short periods, and symptoms may persist for long periods. Based on currently available data, the use of 5α-reductase inhibitors in patients with a history of depression, sexual dysfunction, or infertility should be carefully and individually assessed.

Post-finasteride syndrome.

Finasteride is a 5α-reductase enzyme inhibitor that has been approved for the treatment of male androgenic alopecia since 1997. Over time, it has been considered a safe and well-tolerated drug with rare and reversible side effects. Recently there have been reports of adverse drug-related reactions that persisted for at least three months after discontinuation of this drug, and the term post-finasteride syndrome arose. It includes persistent sexual, neuropsychiatric, and physical symptoms. Studies to date cannot refute or confirm this syndrome as a nosological entity. If it actually exists, it seems to occur in susceptible people, even if exposed to small doses and for short periods, and symptoms may persist for long periods. Based on currently available data, the use of 5α-reductase inhibitors in patients with a history of depression, sexual dysfunction, or infertility should be carefully and individually assessed.

Preventive effects of Topiramate on methylphenidate induced behavioral disorders / Efectos preventivos de topiramato en los trastornos del comportamiento inducidos por metilfenidato

Neuronal cell damage is often caused by prolonged misuse of Methylphenidate (MPH). Topiramate (TPM) carries neuroprotective properties but its assumed mechanism remains unclear. The present study evaluates in vivo role of various doses of TPM and its mechanism against MPH-induced motor activity and related behavior disorder. Thus, we used domoic acid (DOM), bicuculline (BIC), Ketamine (KET), Yohimibine (YOH) and Haloperidole (HAL) as AMPA/kainite, GABAA, NMDA, ɑ2 adrenergic and D2 of dopamine receptor antagonists respectively. Open Field Test (OFT), Elevated Plus Maze (EPM) and Forced Swim Test (FST) were used to study motor activity, anxiety and depression level. TPM (100 and 120 mg/kg) reduced MPH-induced rise and inhibited MPH-induced promotion in motor activity disturbance, anxiety and depression. Pretreatment of animals with KET, HAL, YOH and BIC inhibited TPM- improves anxiety and depression through the interacting with Dopaminergic, GABAA, NMDA and ɑ2-adrenergic receptors.

El daño a las células neuronales a menudo es causado por el uso prolongado de metilfenidato (MPH). El topiramato (TPM) tiene propiedades neuroprotectoras, pero su mecanismo de acción no es claro. El presente estudio evalúa el papel in vivo de varias dosis de TPM y su mecanismo contra la actividad motora inducida por MPH y el trastorno de comportamiento relacionado. Utilizamos ácido domoico (DOM), bicuculina (BIC), ketamina (KET), yohimbina (YOH) y haloperidol (HAL), así como antagonistas AMPA/kainato, GABAA, NMDA, ɑ2-adrenérgico y D2 dopaminérgicos, respectivamente. Se utilizaron las pruebas de campo abierto (OFT), elevación de laberinto (EPM) y natación forzada (FST) para estudiar la actividad motora, la ansiedad y el nivel de depresión. El TPM (100 y 120 mg/kg) redujo el aumento inducido por MPH e inhibió la promoción inducida por MPH en la alteración de la actividad motora, la ansiedad y la depresión. El tratamiento previo de animales con KET, HAL, YOH y BIC inhibió el TPM, mejora la ansiedad y la depresión a través de la interacción con los receptores dopaminérgicos, GABAA, NMDA y ɑ2-adrenérgico.

[Use and abuse of benzodiazepines in primary healthcare: professional practices in Brazil and Cuba]. / Uso e abuso de benzodiazepínicos na atenção primária à saúde: práticas profissionais no Brasil e em Cuba.

The current study aimed to grasp the healthcare aspects present at the basis of the indiscriminate use of benzodiazepines. Based on a partnership between a Brazilian university and a Cuban university, the study aimed to understand the practices related to the use of these drugs in primary care and the meanings healthcare workers assign to them. The research was part of a multiple case study in the cities of São Paulo and Diadema (Brasil), and Santiago de Cuba (Cuba). The fieldwork data collection strategy was based on individual interviews and focus groups. Data were analyzed thematically and yielded five themes: (i) no man's land: lack of management of benzodiazepine use by primary care workers; (ii) inadequate indications: the benzodiazepine prescribed for unjustifiable situations; (iii) salvation and perdition: the medicine as attenuating the difficulty of acting in mental health by primary care professionals; (iv) limited empowerment to work in mental health; and (v) fragmented care: dissociation of the psychosocial care network. Limited grasp of mental health issues by primary care workers, fragmented care, work overload with what are considered other priorities, deficiencies in the availability of therapeutic resources, and limited investment in specific training contribute to the inadequate use of benzodiazepines. Independently of the health contexts, the challenges are similar for the health systems and can only be confronted if they become a priority for the organizations' management and the health workers as a whole.

O presente estudo buscou compreender aspectos assistenciais presentes na base da utilização indiscriminada de benzodiazepínicos. Com base numa parceria entre uma universidade brasileira e uma cubana, buscou-se o entendimento das práticas relacionadas ao uso desses medicamentos na atenção primária e dos sentidos que profissionais de saúde atribuem a elas. A investigação integrou um estudo de casos múltiplos realizado nos municípios de São Paulo e Diadema (Brasil) e Santiago de Cuba (Cuba). O trabalho de campo adotou como estratégias de coleta de dados entrevistas individuais e grupos focais. Os dados, analisados tematicamente, revelaram cinco temas: (i) terra de ninguém: a ausência de gestão sobre o uso dos benzodiazepínicos pelos profissionais da atenção básica; (ii) indicação inadequada: o benzodiazepínico prescrito psra situações injustificáveis; (iii) salvação e perdição: o medicamento como atenuante da dificuldade de atuação na saúde mental pelos profissionais da atenção primária; (iv) pouco empoderamento dos profissionais da atenção primária para atuação na saúde mental; e (v) cuidado fragmentado: a desarticulação da rede de atenção psicossocial. A pouca apropriação das questões da saúde mental pelos profissionais da atenção primária, a fragmentação do cuidado, a sobrecarga de trabalho com temas considerados prioritários, as deficiências na disponibilidade de recursos terapêuticos e o pouco investimento em formação específica contribuem para o uso não adequado de benzodiazepínicos. Independentemente dos contextos sanitários estudados, os desafios são semelhantes para os sistemas de saúde e só podem ser enfrentados se convertidos em prioridade para a gestão das organizações e para o conjunto dos profissionais.

El presente estudio tuvo como meta comprender aspectos asistenciales existentes en relación con la utilización indiscriminada de benzodiacepinas. A partir de la colaboración entre una universidad brasileña y una cubana, se procuró el entendimiento mutuo de las prácticas relacionadas con el uso de esos medicamentos en la atención primaria, así como el sentido que los profesionales de la salud les atribuyen. La investigación integró un estudio de casos múltiples, realizado en los municipios de Sao Paulo y Diadema (Brasil) y Santiago de Cuba (Cuba). El trabajo de campo adoptó como estrategias de recogida de datos entrevistas individuales y grupos focales. Los datos, analizados temáticamente, revelaron cinco temas que detallamos a continuación. (i) tierra de nadie: la ausencia de gestión sobre el uso de las benzodiacepinas por parte de los profesionales de la atención básica; (ii) indicación inadecuada: las benzodiacepinas para situaciones injustificables; (iii) salvación y perdición: la medicación como atenuación de la dificultad de actuar en la salud mental por los profesionales de la atención primaria; (iv) poco empoderamiento para trabajar en el ámbito de la salud mental y (v) cuidado fragmentado: la desarticulación de la red de atención psicosocial. La escasa asunción de las cuestiones de salud mental por parte de los profesionales de atención primaria, la fragmentación del cuidado, la sobrecarga de trabajo con temas considerados prioritarios, las deficiencias en la disponibilidad de recursos terapéuticos y la poca inversión en formación específica contribuyen al uso no adecuado de benzodiacepinas. Independientemente de los contextos sanitarios estudiados, los desafíos son semejantes en todos los sistemas de salud y sólo pueden enfrentarse si se convierten en prioridad para quienes gestionan instituciones, así como para el conjunto de profesionales.

Do your gut microbes affect your brain dopamine?

Increasing evidence shows changes in gut microbiota composition in association with psychiatric disorders, including anxiety and depression. Moreover, it has been reported that perturbations in gut microbe diversity and richness influence serotonergic, GABAergic, noradrenergic, and dopaminergic neurotransmission. Among these, dopamine is regarded as a main regulator of cognitive functions such as decision making, attention, memory, motivation, and reward. In this work, we will highlight findings that link alterations in intestinal microbiota and dopaminergic neurotransmission, with a particular emphasis on the mesocorticolimbic circuit, which is involved in reward to natural reinforcers, as well as abuse substances. For this, we reviewed evidence from studies carried out on germ-free animals, or in rodents subjected to intestinal dysbiosis using antibiotics, and also through the use of probiotics. All this evidence strongly supports that the microbiota-gut-brain axis is key to the physiopathology of several neuropsychiatric disorders involving those where dopaminergic neurotransmission is compromised. In addition, the gut microbiota appears as a key player when it comes to proposing novel strategies to the treatment of these psychiatric conditions.

Montelukast and Neuropsychiatric Events in Children with Asthma: A Nested Case-Control Study.

OBJECTIVE: To examine the association between montelukast prescription and neuropsychiatric events in children with asthma. STUDY DESIGN: A matched, nested case-control design was used to identify cases and controls from a cohort of children aged 5-18 years with physician-diagnosed asthma from 2004 to 2015, in Ontario, Canada, prescribed an asthma maintenance medication. Cases were children with a hospitalization or emergency department visit for a neuropsychiatric event. Cases were matched to up to 4 controls on birth year, year of asthma diagnosis, and sex. The exposures were dispensed prescriptions for montelukast (yes/no) and number of dispensed montelukast prescriptions in the year before the index date. Conditional logistic regression was used to measure the unadjusted OR and aOR and 95% CIs for montelukast prescription and neuropsychiatric events. Covariates in the adjusted model included sociodemographic factors and measures of asthma severity. RESULTS: In total, 898 cases with a neuropsychiatric event and 3497 matched controls were included. Children who experienced a new-onset neuropsychiatric event had nearly 2 times the odds of having been prescribed montelukast, compared with controls (OR 1.91, 95% CI 1.15-3.18; P = .01). Most cases presented for anxiety (48.6%) and/or sleep disturbance (26.1%). CONCLUSIONS: Children with asthma who experienced a new-onset neuropsychiatric event had nearly twice the odds of having been prescribed montelukast in the year before their event. Clinicians should be aware of the association between montelukast and neuropsychiatric events in children with asthma, to inform prescribing practices and clinical follow-up.

Uso e abuso de benzodiazepínicos na atenção primária à saúde: práticas profissionais no Brasil e em Cuba / Use and abuse of benzodiazepines in primary healthcare: professional practices in Brazil and Cuba / Uso y abuso de benzodiacepinas en la atención primaria de salud: prácticas profesionales en Brasil y Cuba

O presente estudo buscou compreender aspectos assistenciais presentes na base da utilização indiscriminada de benzodiazepínicos. Com base numa parceria entre uma universidade brasileira e uma cubana, buscou-se o entendimento das práticas relacionadas ao uso desses medicamentos na atenção primária e dos sentidos que profissionais de saúde atribuem a elas. A investigação integrou um estudo de casos múltiplos realizado nos municípios de São Paulo e Diadema (Brasil) e Santiago de Cuba (Cuba). O trabalho de campo adotou como estratégias de coleta de dados entrevistas individuais e grupos focais. Os dados, analisados tematicamente, revelaram cinco temas: (i) terra de ninguém: a ausência de gestão sobre o uso dos benzodiazepínicos pelos profissionais da atenção básica; (ii) indicação inadequada: o benzodiazepínico prescrito psra situações injustificáveis; (iii) salvação e perdição: o medicamento como atenuante da dificuldade de atuação na saúde mental pelos profissionais da atenção primária; (iv) pouco empoderamento dos profissionais da atenção primária para atuação na saúde mental; e (v) cuidado fragmentado: a desarticulação da rede de atenção psicossocial. A pouca apropriação das questões da saúde mental pelos profissionais da atenção primária, a fragmentação do cuidado, a sobrecarga de trabalho com temas considerados prioritários, as deficiências na disponibilidade de recursos terapêuticos e o pouco investimento em formação específica contribuem para o uso não adequado de benzodiazepínicos. Independentemente dos contextos sanitários estudados, os desafios são semelhantes para os sistemas de saúde e só podem ser enfrentados se convertidos em prioridade para a gestão das organizações e para o conjunto dos profissionais.

The current study aimed to grasp the healthcare aspects present at the basis of the indiscriminate use of benzodiazepines. Based on a partnership between a Brazilian university and a Cuban university, the study aimed to understand the practices related to the use of these drugs in primary care and the meanings healthcare workers assign to them. The research was part of a multiple case study in the cities of São Paulo and Diadema (Brasil), and Santiago de Cuba (Cuba). The fieldwork data collection strategy was based on individual interviews and focus groups. Data were analyzed thematically and yielded five themes: (i) no man's land: lack of management of benzodiazepine use by primary care workers; (ii) inadequate indications: the benzodiazepine prescribed for unjustifiable situations; (iii) salvation and perdition: the medicine as attenuating the difficulty of acting in mental health by primary care professionals; (iv) limited empowerment to work in mental health; and (v) fragmented care: dissociation of the psychosocial care network. Limited grasp of mental health issues by primary care workers, fragmented care, work overload with what are considered other priorities, deficiencies in the availability of therapeutic resources, and limited investment in specific training contribute to the inadequate use of benzodiazepines. Independently of the health contexts, the challenges are similar for the health systems and can only be confronted if they become a priority for the organizations' management and the health workers as a whole.

El presente estudio tuvo como meta comprender aspectos asistenciales existentes en relación con la utilización indiscriminada de benzodiacepinas. A partir de la colaboración entre una universidad brasileña y una cubana, se procuró el entendimiento mutuo de las prácticas relacionadas con el uso de esos medicamentos en la atención primaria, así como el sentido que los profesionales de la salud les atribuyen. La investigación integró un estudio de casos múltiples, realizado en los municipios de Sao Paulo y Diadema (Brasil) y Santiago de Cuba (Cuba). El trabajo de campo adoptó como estrategias de recogida de datos entrevistas individuales y grupos focales. Los datos, analizados temáticamente, revelaron cinco temas que detallamos a continuación. (i) tierra de nadie: la ausencia de gestión sobre el uso de las benzodiacepinas por parte de los profesionales de la atención básica; (ii) indicación inadecuada: las benzodiacepinas para situaciones injustificables; (iii) salvación y perdición: la medicación como atenuación de la dificultad de actuar en la salud mental por los profesionales de la atención primaria; (iv) poco empoderamiento para trabajar en el ámbito de la salud mental y (v) cuidado fragmentado: la desarticulación de la red de atención psicosocial. La escasa asunción de las cuestiones de salud mental por parte de los profesionales de atención primaria, la fragmentación del cuidado, la sobrecarga de trabajo con temas considerados prioritarios, las deficiencias en la disponibilidad de recursos terapéuticos y la poca inversión en formación específica contribuyen al uso no adecuado de benzodiacepinas. Independientemente de los contextos sanitarios estudiados, los desafíos son semejantes en todos los sistemas de salud y sólo pueden enfrentarse si se convierten en prioridad para quienes gestionan instituciones, así como para el conjunto de profesionales.

Electrophysiological dysfunction induced by anti-ribosomal P protein antibodies injection into the lateral ventricle of the rat brain.

Objective Anti-ribosomal P antibodies (anti-P) are strongly associated with neuropsychiatric lupus. This study was designed to determine whether these antibodies are capable of causing electro-oscillogram (EOSG) and behavior alterations in rats. Methods IgG fraction anti-P positive and affinity-purified anti-P antibodies were injected intraventricularly in rats. Sequential cortical and subcortical EOSGs were analyzed during 30 days. IgG anti-Ro/SS-A and normal IgG were used as controls. Results All 13 animals injected with IgG anti-P demonstrated a high prevalence of polyspikes, diffusely distributed in hippocampal fields and cerebral cortex. These abnormalities persisted approximately a month. Remarkably, an identical electrical disturbance was observed with the inoculation of affinity-purified anti-P antibodies. The EOSG alterations were associated with behavioral disorders with varying degrees of severity in every animal injected with anti-P. In contrast, no changes in EOSG or behavioral disturbances were observed in the control group. Conclusion Our study indicates that anti-P antibodies can directly induce electrophysiological dysfunction in central nervous system particularly in hippocampus and cortex associated with behavior disturbances.

A Protocol for Generation of a Corticosterone Model of Psychiatric Disorders.

Some patients with psychiatric disorders show hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. This may be due to an impaired feedback inhibition and can be seen through increased levels of circulating cortisol. Here a protocol is described to mimic this situation by subcutaneous implantation of corticosterone pellets in mice. We also present characterization of the model by looking at effects on neuronal proliferation in hippocampus, one of the main tissues known to be affected by HPA axis hyper-activation. Such tissues could be used in analyses by proteomic platforms.

Exposure to pesticides and mental disorders in a rural population of Southern Brazil.

INTRODUCTION: Exposure to pesticides has been associated with mental disorders, especially in occupationally exposed populations, such as farmers. This effect has been attributed to the neurotoxic and endocrine-disrupting activity of pesticides, as suggested by experimental studies. OBJECTIVE: To determine the prevalence of common mental disorders and self-reported depression, and analyze their association with the exposure to pesticides in a rural population resident in the municipality of Dom Feliciano, Rio Grande do Sul, where tobacco farming is the main economic activity. METHODOLOGY: A cross-sectional study evaluating the prevalence of common mental disorders and self-reported depression in a sample of 869 adult individuals resident in Dom Feliciano, between October 2011 and March 2012 was performed. The evaluation of common mental disorders was performed using the Self-Reporting Questionnaire (SRQ-20), setting a cutoff point of 8 for both genders. A standardized questionnaire was used to obtain information on self-reported depression upon prior diagnosis by a health professional, and self-reported exposure to pesticide. In order to evaluate the association between exposure to pesticides and mental disorders, a non-conditional multivariate logistic regression analysis was performed. RESULTS: The prevalence of common mental disorders and self-reported depression in the sample population were 23% and 21%, respectively. Among individuals who reported depression, an increase of 73% was observed in the odds of pesticide exposure at an age equal to or less than 15 years. There was a positive association between self-reported pesticide poisoning and common mental disorders (OR=2.63; 95% CI, 1.62-4.25) as well as self-reported depression (OR=2.62; 95% CI, 1.63-4.21). Individuals who reported depression had a greater odds of exposure to pyrethroids (OR=1.80; 95% CI, 1.01-3.21) and aliphatic alcohol (OR=1.99; 95% CI, 1.04-3.83). An SRQ-20≥8 was associated with an approximately seven times higher odds of exposure to aliphatic alcohol (95% CI, 1.73-27.53). Self-reported depression positively correlated with a greater period of exposure to dinitroaniline (OR=2.20; 95% CI, 1.03-4.70) and sulphonylurea (OR=4.95; 95% CI, 1.06-23.04). CONCLUSION: The results suggest that exposure to pesticides could be related mental disorders. However, other common risk factors in tobacco farming, the main local economic activity, cannot be excluded.

Toxoplasma gondii exposure in patients suffering from mental and behavioral disorders due to psychoactive substance use.

BACKGROUND: Toxoplasma gondii infection has been associated with psychiatric diseases. However, there is no information about the link between this infection and patients with mental and behavioral disorders due to psychoactive substance use. METHODS: We performed a case-control study with 149 psychiatric patients suffering from mental and behavioral disorders due to psychoactive substance use and 149 age- and gender-matched control subjects of the general population. We searched for anti-T. gondii IgG and IgM antibodies in the sera of participants by means of commercially available enzyme-linked immunoassays. Seroprevalence association with socio-demographic, clinical and behavioral characteristics in psychiatric patients was also investigated. RESULTS: Anti-T. gondii IgG antibodies were present in 15 (10.1%) of 149 cases and in 14 (9.4%) of 149 controls (P=1.0). Anti-T. gondii IgM antibodies were found in 11 (7.4%) of the 149 cases and in 16 (10.7%) of the 149 controls (P=0.31). No association of T. gondii exposure with socio-demographic characteristics of patients was found. Multivariate analysis of clinical and behavioral characteristics of cases showed that T. gondii seropositivity was positively associated with consumption of opossum meat (OR=10.78; 95% CI: 2.16-53.81; P=0.003) and soil flooring at home (OR=11.15; 95% CI: 1.58-78.92; P=0.01), and negatively associated with suicidal ideation (OR=0.17; 95% CI: 0.05-0.64; P=0.008). CONCLUSIONS: Mental and behavioral disorders due to psychoactive substance use do not appear to represent an increased risk for T. gondii exposure. This is the first report of a positive association of T. gondii exposure with consumption of opossum meat. Further studies to elucidate the role of T. gondii infection in suicidal ideation and behavior are needed to develop optimal strategies for the prevention of infection with T. gondii.

Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long-Standing Model.

The administration of reserpine to rodents was one of the first models used to investigate the pathophysiology and screening for potential treatments of Parkinson's disease (PD). The reserpine model was critical to the understanding of the role of monoamine system in the regulation of motor and affective disorders, as well as the efficacy of current PD treatments, such as L-DOPA and dopamine agonists. Nevertheless, with the introduction of toxin-induced and genetic models of PD, reserpine became underused. The main rationale to this drawback was the supposed absence of reserpine construct validity with PD. Here, we highlight classical and recent experimental findings that support the face, pharmacological, and construct validity of reserpine PD model and reason against the current rationale for its underuse. We also aim to shed a new perspective upon the model by discussing the main challenges and potentials for the reserpine model of PD.

ICD-10 mental and behavioural disorders due to use of crack and powder cocaine as treated at a public psychiatric emergency service: an analysis of visit predictors.

The present study investigated the predictors of an increased number of visits from individuals with some of the diagnoses noted in chapter F14 of ICD-10, from calls to the emergency psychiatric unit of a general hospital in São Paulo state, Brazil, in the period 2011-2012. Poisson regression models were carried out for the outcome variable, accounting for number of subsequent visits to the psychiatric emergency unit. For the analysis of this outcome we took into account the exposure time of each individual in the study. Our findings point to a population at risk for frequent psychiatric emergency service visits: individuals over 25 years. This population should be targeted for interventions on entry into public healthcare due to increased psychiatric morbidity and greater clinical morbidity already confirmed by previous studies. We discussed the need of these individuals for special attention during the clinical or psychiatric emergency consultation which, unfortunately, may be the access point for the public health system. None of the other variables were related to the outcome of interest, such as those related to the level of individual entry into the care network before and after treatment, and other variables related to medical acts during the visit.

Occupational exposure to pesticides, nicotine and minor psychiatric disorders among tobacco farmers in southern Brazil.

INTRODUCTION: Exposure to pesticides has been associated with psychiatric problems among farm workers, although there is still controversy as to chemical types, intensity and forms of exposure that represent risk factors for neuropsychological problems. Furthermore, tobacco workers are exposed to dermal absorption of nicotine, although its effect on mental health has not yet been studied. OBJECTIVES: To identify the prevalence of minor psychiatric disorders (MPD) among tobacco farmers and associated factors, paying special attention to pesticide and nicotine exposure. METHODS: This is a cross-sectional study with a representative sample of tobacco growers, characterizing economic indicators of the farms, socio-demographic factors, lifestyle habits and occupational exposures. Multivariate analysis was performed using a hierarchical Poisson regression model. RESULTS: A total of 2400 tobacco farmers were assessed and MPD prevalence was 12%. MPD was higher among women (PR 1.4), workers aged 40 or over, tenants/employees (PR 1.8) and those who reported having difficulty in paying debts (PR 2.0). Low socioeconomic status was inversely associated with MPD prevalence. Tasks involving dermal exposure to pesticides showed risk varying between 35% and 71%, whereas tobacco growers on farms using organophosphates had 50% more risk of MPD than those not exposed to this kind of pesticide. The number of pesticide poisoning and green tobacco sickness episodes showed linear association with MPD. CONCLUSIONS: The study reinforces the evidence of the association between pesticide poisoning and mental health disorders. It also points to increased risk of MPD from low socioeconomic status, dermal pesticide exposure as well as from exposure to organophosphates. Furthermore, the study reveals intense nicotine exposure as a risk for tobacco farmers' mental health.