Cannabinoid receptor gene polymorphisms and cognitive performance in patients with schizophrenia and controls

Objective: To test the hypothesis that genetic variations of cannabinoid receptors contribute to the pathophysiology of cognitive deficits in schizophrenia. Methods: In this genetic association case-control study, cannabinoid receptor polymorphisms CNR1 rs12720071 and CNR2 rs2229579 were tested for association with neurocognitive performance in 69 patients with schizophrenia and 45 healthy controls. Neurocognition was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS). Results: We found a consistent association between CNR1 rs12720071 polymorphism and the cognitive performance of patients in several cognitive domains. Patients with C/C polymorphism presented significantly worse performance in motor speed, verbal fluency, attention/processing speed and reasoning/problem solving. Conclusion: Although limited, our data support the hypothesis that CNR1 variations may be associated with the pathogenesis of cognitive deficits of schizophrenia.

Cannabinoid receptor gene polymorphisms and cognitive performance in patients with schizophrenia and controls.

OBJECTIVE: To test the hypothesis that genetic variations of cannabinoid receptors contribute to the pathophysiology of cognitive deficits in schizophrenia. METHODS: In this genetic association case-control study, cannabinoid receptor polymorphisms CNR1 rs12720071 and CNR2 rs2229579 were tested for association with neurocognitive performance in 69 patients with schizophrenia and 45 healthy controls. Neurocognition was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS). RESULTS: We found a consistent association between CNR1 rs12720071 polymorphism and the cognitive performance of patients in several cognitive domains. Patients with C/C polymorphism presented significantly worse performance in motor speed, verbal fluency, attention/processing speed and reasoning/problem solving. CONCLUSION: Although limited, our data support the hypothesis that CNR1 variations may be associated with the pathogenesis of cognitive deficits of schizophrenia.

Lower circulating levels of angiotensin-converting enzyme (ACE) in patients with schizophrenia.

This study aimed at evaluating changes in the renin-angiotensin system (RAS) in patients with schizophrenia in comparison with controls. Plasma levels of angiotensin-converting enzyme (ACE), ACE2, angiotensin (Ang)-(1-7) and Ang II were assessed in 25 patients with schizophrenia and 20 controls. Patients with schizophrenia presented decreased levels of ACE compared to controls [median (25th-75th percentiles) = 434.79 (341.15-524.02) vs. 508.49 (396.34-608.72); p < 0.05]. No significant differences were found regarding ACE2, Ang-(1-7) and Ang II levels. There were no associations between the measured molecules and clinical parameters. Our results corroborate the hypothesis that the RAS is involved in the pathophysiology of schizophrenia.

Interview-based assessment of cognition is a strong predictor of quality of life in patients with schizophrenia and severe negative symptoms

Objective: To analyze the correlation between quality of life, symptoms, and cognition assessed by the interview-based Schizophrenia Cognition Rating Scale (SCoRS). Methods: Seventy-nine outpatients diagnosed with schizophrenia were evaluated with the Quality of Life Scale – Brazilian version (QLS-BR), the SCoRS, and symptoms scales (Positive and Negative Syndrome Scale [PANSS]). After determining the potential explanatory variables using Spearman’s correlation and Student’s t test results, we ran simple, multivariate, and decision-tree regression analyses to assess the impact of SCoRS and PANSS ratings on mean overall quality of life. Results: Cognitive deficits and negative symptoms were the best predictors of quality of life. A low degree of negative symptoms (PANSS negative < 11) was a strong predictor of better quality of life (QLS ∼ 75), regardless of SCoRS rating. Among participants with more severe negative symptoms, elevated cognitive impairment (interviewer SCoRS ∼ 44) was a predictor of worse quality of life (QLS ∼ 44). Conclusions: Cognitive impairment determined by interview-based assessment seems to be a strong predictor of quality of life in subjects with severe negative symptoms. These results support the usefulness of SCoRS for cognitive assessment that is relevant to the everyday life of patients with schizophrenia.

Interview-based assessment of cognition is a strong predictor of quality of life in patients with schizophrenia and severe negative symptoms.

OBJECTIVE: To analyze the correlation between quality of life, symptoms, and cognition assessed by the interview-based Schizophrenia Cognition Rating Scale (SCoRS). METHODS: Seventy-nine outpatients diagnosed with schizophrenia were evaluated with the Quality of Life Scale - Brazilian version (QLS-BR), the SCoRS, and symptoms scales (Positive and Negative Syndrome Scale [PANSS]). After determining the potential explanatory variables using Spearman's correlation and Student's t test results, we ran simple, multivariate, and decision-tree regression analyses to assess the impact of SCoRS and PANSS ratings on mean overall quality of life. RESULTS: Cognitive deficits and negative symptoms were the best predictors of quality of life. A low degree of negative symptoms (PANSS negative < 11) was a strong predictor of better quality of life (QLS ∼ 75), regardless of SCoRS rating. Among participants with more severe negative symptoms, elevated cognitive impairment (interviewer SCoRS ∼ 44) was a predictor of worse quality of life (QLS ∼ 44). CONCLUSIONS: Cognitive impairment determined by interview-based assessment seems to be a strong predictor of quality of life in subjects with severe negative symptoms. These results support the usefulness of SCoRS for cognitive assessment that is relevant to the everyday life of patients with schizophrenia.

Functional capacity: a new framework for the assessment of everyday functioning in schizophrenia.

Historically, measures of everyday functioning have focused exclusively on real-world performance. Despite the unquestionable value of "real-world functioning", it has become clear that instruments for its assessment might not be as accurate as desirable. Functional capacity is a domain of everyday functioning that can be assessed through performance-based measures. In the last decade, functional capacity has become a cornerstone for the assessment of everyday functioning, since, alongside measures of real-world functioning, it provides a much more comprehensive picture of functional outcomes than any measurement alone. Functional capacity is more stable and less vulnerable to influence from environmental factors than other domains, and its correlation with cognitive functions has encouraged the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project to suggest that a performance-based measure of functional capacity be included as a co-primary assessment of cognition in clinical trials. Functional capacity assessment instruments may be also useful in the evaluation of remission in schizophrenia. Validation of these instruments in different countries is desirable, and should always include cross-cultural adaptation; within large countries, adjustment for regional variations should be considered.

Functional capacity: a new framework for the assessment of everyday functioning in schizophrenia

Historically, measures of everyday functioning have focused exclusively on real-world performance. Despite the unquestionable value of “real-world functioning”, it has become clear that instruments for its assessment might not be as accurate as desirable. Functional capacity is a domain of everyday functioning that can be assessed through performance-based measures. In the last decade, functional capacity has become a cornerstone for the assessment of everyday functioning, since, alongside measures of real-world functioning, it provides a much more comprehensive picture of functional outcomes than any measurement alone. Functional capacity is more stable and less vulnerable to influence from environmental factors than other domains, and its correlation with cognitive functions has encouraged the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project to suggest that a performance-based measure of functional capacity be included as a co-primary assessment of cognition in clinical trials. Functional capacity assessment instruments may be also useful in the evaluation of remission in schizophrenia. Validation of these instruments in different countries is desirable, and should always include cross-cultural adaptation; within large countries, adjustment for regional variations should be considered.

UCSD Performance-Based Skills Assessment (UPSA): validation of a Brazilian version in patients with schizophrenia.

The UCSD Performance-based Skills Assessment (UPSA) is a measure of Functional Capacity and assesses skills involved in community tasks. It has good psychometrics properties, and is currently recommended as a co-primary assessment of cognition in the MATRICS Project. To our knowledge so far, there are no studies in western developing countries concerning Functional Capacity in Schizophrenia. The aims of this study were to translate, culturally adapt and validate the UPSA to assess Functional Capacity in community-dwelling patients with Schizophrenia living in Brazil. Eighty-two subjects (52 patients, 30 controls) were evaluated using: the Brazilian version of the UPSA (UPSA-1-BR), PANSS, Personal and Social Performance (PSP) and Global Assessment of Functioning (GAF). In the reliability test, UPSA-1-BR showed good Internal Consistency (Cronbach's alpha of 0.88) and strong correlation between test and retest (4-month gap; r = 0.91; p < 0.01). Spearman's rho values showed a moderate correlation between UPSA-1-BR and both PSP (0.50; p < 0.01) and GAF (0.46; p < 0.01) scores. UPSA-1-BR is capable of differentiating people with and without Schizophrenia. Patients scored lower than controls (58.9 versus 79.1), with an AUC of 0.79 (95%IC: 0.69-0.89). Sensitivity and specificity values of 0.71 and 0.70, respectively, were found in the cut-off point of 73.5, for separation of patients and controls, with predictive values of 80% (positive) and 58% (negative). UPSA-B-BR was also evaluated. UPSA-1-BR and its brief version presented adequate psychometric properties and proved to be valid and reliable instruments in the assessment of Functional Capacity in subjects with Schizophrenia.

Reductions in glycemic and lipid profiles in hypertensive patients undergoing the Brazilian Dietary Approach to Break Hypertension: a randomized clinical trial.

Hypertensive patients often have an unfavorable lipid and glucose profile. The main goal of dietary treatment for these patients is to achieve adequate control of blood pressure and reducing cardiovascular morbidity and mortality. The aim of this study was to evaluate whether the Brazilian Dietary Approach to Break Hypertension (BRADA) based on Dietary Approaches to Stop Hypertension but with both low sodium and glycemic index foods could reduce lipid and glycemic profiles in hypertensive patients who were seeing primary health care providers in a low-income region of Brazil. A randomized study of 206 individuals were followed up for the duration of 6 months. The experimental group received orientation and planned monthly menus from the BRADA diet. In the control group, counseling was based on standard care and mainly focused on salt intake reduction. Differences in all biochemical parameters were compared at the baseline and at the 6-month follow-up period. The mean age was 60.1 (±12.9) years old, and 156 subjects (119 females) completed the study. An intention-to-treat analysis showed that both groups reduced fasting plasma glucose, glycated hemoglobin, total cholesterol, and low-density lipoprotein cholesterol concentrations; however, statistically significant between-group differences were found for these parameters. The mean difference in fasting glucose was -7.0 (P < .01), -0.2 for HbA1c (P < .01), -28.6 for TC (P < .01), and -23.8 for LDL-c (P < .01) for the experimental group compared with the control group. This study showed the efficacy of the BRADA diet to treat hypertension on biochemical parameters tested in a primary health care service setting.

Cognitive performance and peripheral endocannabinoid system receptor expression in schizophrenia.

Schizophrenia is a chronic psychiatric syndrome characterized by generalized cognitive deficits that are associated with functional impairment. The endocannabinoid system (ECS) modulates neurotransmission and neuronal plasticity and is important for cognitive functioning. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of schizophrenia and that alteration of the ECS on peripheral lymphocytes could reflect central changes. The objective of this study was to compare levels of peripheral endocannabinoid receptor expression in patients with schizophrenia and healthy subjects and find evidence of association between peripheral expression of those receptors and cognitive performance. Patients with stabilized schizophrenia (N=53) and controls (N=22) underwent clinical and cognitive evaluation, and assessment of cannabinoid receptor expression on the surface of peripheral immune cells (lymphocytes, natural killer cells and monocytes) by flow cytometry. Patients with schizophrenia had lower levels of cannabinoid receptor expression on total T lymphocytes, but after controlling for possible confounders this difference did not remain significant. In patients, increased cannabinoid receptor expression on lymphocytes and monocytes was significantly correlated with worst cognitive performance. These data provide additional evidence of the involvement of the ECS in the pathophysiology of cognitive deficits in schizophrenia.

The endocannabinoid system and its role in schizophrenia: a systematic review of the literature / O sistema endocanabinoide e seu papel na esquizofrenia: uma revisão sistemática da literatura

OBJECTIVE: Schizophrenia is a psychiatric disorder whose mechanisms have remained only partially elucidated. The current proposals regarding its biological basis, such as the dopaminergic hypothesis, do not fully explain the diversity of its symptoms, indicating that other processes may be involved. This paper aims to review evidence supporting the involvement of the endocannabinoid system (ECS), a neurotransmitter group that is the target of Cannabis sativa compounds, in this disorder. METHODS: A systematic review of original papers, published in English, indexed in PubMed up to April, 2012. RESULTS: Most studies employed genetics and histological, neuroimaging or neurochemical methods - either in vivo or post-mortem - to investigate whether components of the ECS are compromised in patients. Overall, the data show changes in cannabinoid receptors in certain brain regions as well as altered levels in endocannabinoid levels in cerebrospinal fluid and/or blood. CONCLUSIONS: Although a dysfunction of the ECS has been described, results are not entirely consistent across studies. Further data are warrant to better define a role of this system in schizophrenia.

OBJETIVO: A esquizofrenia é um transtorno psiquiátrico cujos mecanismos permanecem apenas parcialmente elucidados. As atuais propostas relativas à base biológica, tais como a hipótese dopaminérgica, não explicam por completo a diversidade de seus sintomas, o que indica que outros processos podem estar envolvidos. Este artigo tem como objetivo revisar indícios que sustentem o envolvimento do sistema endocanabinoide (SECB), um grupo de neurotransmissoresalvo dos compostos da Cannabis sativa, nesse transtorno. MÉTODOS: Revisão sistemática dos artigos originais, publicados em inglês e indexados no PubMed até abril de 2012. RESULTADOS: A maioria dos estudos empregou métodos neuroquímicos ou de neuroimagem genéticos e histológicos - tanto in vivo quanto post-mortem - para investigar se os componentes do SECB estão comprometidos nos pacientes. De modo geral, os dados mostram mudanças nos receptores canabinoides em determinadas regiões cerebrais, bem como a alteração dos níveis de endocanabinoides no líquido cefalorraquidiano e/ou no sangue. CONCLUSÕES: Ainda que a disfunção do SECB tenha sido descrita, os resultados dos estudos não são totalmente consistentes. São necessários mais dados para definir melhor o papel desse sistema na esquizofrenia.

The endocannabinoid system and its role in schizophrenia: a systematic review of the literature.

OBJECTIVE: Schizophrenia is a psychiatric disorder whose mechanisms have remained only partially elucidated. The current proposals regarding its biological basis, such as the dopaminergic hypothesis, do not fully explain the diversity of its symptoms, indicating that other processes may be involved. This paper aims to review evidence supporting the involvement of the endocannabinoid system (ECS), a neurotransmitter group that is the target of Cannabis sativa compounds, in this disorder. METHODS: A systematic review of original papers, published in English, indexed in PubMed up to April, 2012. RESULTS: Most studies employed genetics and histological, neuroimaging or neurochemical methods - either in vivo or post-mortem - to investigate whether components of the ECS are compromised in patients. Overall, the data show changes in cannabinoid receptors in certain brain regions as well as altered levels in endocannabinoid levels in cerebrospinal fluid and/or blood. CONCLUSIONS: Although a dysfunction of the ECS has been described, results are not entirely consistent across studies. Further data are warrant to better define a role of this system in schizophrenia.

Neuro-transmitters in the central nervous system & their implication in learning and memory processes.

This review article gives an overview of a number of central neuro-transmitters, which are essential for integrating many functions in the central nervous system (CNS), such as learning, memory, sleep cycle, body movement, hormone regulation and many others. Neurons use neuro-transmitters to communicate, and a great variety of molecules are known to fit the criteria to be classified as such. A process shared by all neuro-transmitters is their release by excocytosis, and we give an outline of the molecular events and protein complexes involved in this mechanism. Synthesis, transport, inactivation, and cellular signaling can be very diverse when different neuro-transmitters are compared, and these processes are described separately for each neuro-transmitter system. Here we focus on the most well known neuro-transmitters: acetyl-choline, catechol-amines (dopamine and nor-adrenalin), indole-amine (serotonin), glutamate, and gamma-amino-butyric acid (GABA). Glutamate is the major excitatory neuro-transmitter in the brain and its actions are counter-balanced by GABA, which is the major inhibitory substance in the CNS. A balance of neuronal transmission between these two neuro-transmitters is essential to normal brain function. Acetyl-choline, serotonin and catechol-amines have a more modulatory function in the brain, being involved in many neuronal circuits. Apart from summarizing the current knowledge about the synthesis, release and receptor signaling of these transmitters, some disease states due to alteration of their normal neuro-transmission are also described.

Epilepsia refratária: a experiência do Núcleo Avançado de Tratamento das Epilepsias do Hospital Felício Rocho (NATE) no período de março de 2003 a dezembro de 2006 / Refractory epilepsy: the experience of the NATE

INTRODUÇÃO: A epilepsia é um problema de saúde pública. Afeta mais de cinqüenta milhões de pessoas em todo mundo e mais de vinte milhões deles continuam apresentando crises que não controlam satisfatoriamente com o uso de medicamentos. As epilepsias refratárias correspondem a cerca de 20 por cento dos pacientes epilépticos e boa parte desses apresentam crises parciais complexas passíveis de tratamento cirúrgico. A indicação cirúrgica criteriosa tem se mostrado eficiente para o controle das crises. OBJETIVO: Apresentar dados epidemiológicos e cirúrgicos dos pacientes submetidos ao tratamento cirúrgico no NATE. METODOLOGIA: Estudo retrospectivo com análise de prontuários e classificação do controle de crises de 46 pacientes considerando a Escala de Engel. RESULTADOS: Predomina o sexo masculino, solteiros, sem história familiar para epilepsia. Pacientes procedentes do Estado de Minas Gerais e outros estados da união. Início das crises na infância para 58,8 por cento dos pacientes sendo o tipo de crise mais freqüente a crise parcial complexa. O déficit de memória foi a queixa cognitiva mais comum. CONCLUSÃO: O controle de crise foi compatível com Engel Ia (sem crise) para 67 por cento dos pacientes. O tratamento cirúrgico revelou-se eficiente para o controle das crises dos pacientes portadores de epilepsia refratária ao tratamento medicamentoso.

INTRODUCTION: Epilepsy is a health public problem. Afflicts more than 50 million people worldwide, and more than 20 million of those affected do not have satisfactory seizures control with medicine. The refractory epilepsy represents 20 percent of all epileptic patients and most of them present partial seizures which can be treated by surgical treatment. The careful surgical recommendation can be efficient to seizure control. PURPOSE: The aim of this study was to present epidemiological and surgical data about patients submitted to surgical treatment in NATE - Advanced Center of Epilepsy Treatment. METHOD: We used a retrospective assessment method and control seizure classification from Engel Scale for 46 epileptic patients submitted to surgical treatment. RESULTS: Our results showed predominant male patients, single, without family history for epilepsy. The patients were from cities of Minas Gerais State and from another States in Brazil. The first seizure occurred in the childhood for 58,8 percent of patients and the more frequent seizure type was complex partial seizure. The predominant cognitive complaint was about memory. CONCLUSION: The surgical treatment for seizure control was good for 67 percent of patients that display Engel Ia classification (without seizures) and has a high likelihood for success in medically intractable temporal lobe epilepsy.

Effects of acute and chronic treatment with Hypericum perforatum L. (LI 160) on different anxiety-related responses in rats.

The study investigates the effects of acute and chronic oral treatment with Hypericum perforatum L. (HP LI 160, 62.5-500 mg/kg) in rats submitted to different anxiety models: the elevated T-maze (for inhibitory avoidance and escape measurements), the light/dark transition, and the cat odor test. These models were selected for their presumed capacity of evidencing specific subtypes of anxiety disorders as recognized in clinical practice. The results showed that acute HP (125 mg/kg) impaired elevated T-maze inhibitory avoidance, an anxiolytic effect, without altering escape performance. Chronic HP (250 mg/kg) enhanced avoidance latencies only in animals that were preexposed to the open arms of the maze. Preexposure shortens escape latency, improving it as an escape index. Differently from the reference drug imipramine (IMP, 15 mg/kg), chronic HP did not impair escape from the open arms of the maze. On the other hand, similarly to IMP, the extract increased the number of transitions between the two compartments in the light/dark transition model. Treatment regimens with HP and IMP did not alter behavioral responses of rats to a cloth impregnated with cat odor. These observations suggest that HP LI 160 exerts anxiolytic-like effects in a specific subset of defensive behaviors, particularly those related to generalized anxiety.