Abstract Objectives Evidence suggests that ketamine’s influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD). Methods Participants (n = 53) are from a randomized, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards. Results There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms. Conclusion There was no significant treatment impact on BDNF serum levels – neither with ketamine nor esketamine – despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion. This clinical trial is registered on the Japan Primary Registries Network: UMIN000032355. ketamines s brainderived brain derived (BDNF action treatmentresistant resistant . (TRD) 53 randomized doubleblind double blind singledose single dose 0.5mg/kg, 05mgkg mgkg 0 5mg kg mg (0.5mg/kg 27 0.25mg/kg, 025mgkg 25mg (0.25mg/kg 26 2 MontgomeryÅsberg Montgomery Åsberg MADRS. MADRS (MADRS) infusion afterwards postinfusion post points effect symptoms Network UMIN000032355 UMIN (TRD 5 0.5mg/kg 0.25mg/kg (MADRS UMIN00003235 UMIN0000323 UMIN000032 UMIN00003 UMIN0000 UMIN000 UMIN00 UMIN0

Abstract Introduction Anhedonia is defined as the reduced ability to feel pleasure and is a core symptom of various psychiatric disorders such as depression and schizophrenia. The Snaith-Hamilton Pleasure Scale (SHAPS) was developed to assess the presence of anhedonia. The objective of this study was to assess the psychometric properties of the Brazilian Portuguese version of the SHAPS. Methods In this study, the SHAPS (14 items) was translated into Brazilian Portuguese and validated using data obtained from 228 subjects within a clinical sample. Psychometric properties were assessed using item response theory (logistic models) and classical test theory (Cronbach’s alpha). We checked for external validity using a non-parametric correlation with an independent scale: Hospital Anxiety and Depression Scale – Depression subscale (HAD-D). Results The SHAPS presented good internal consistency, with a Cronbach’s α coefficient of 0.759 and adequacy to an IRT 1 parameter logistic (Rasch) model. The SHAPS presented significant correlation with the external measure HAD-D, with Spearman’s ρ = 0.249 (S = 1368914; p < 0.001). Conclusion These results suggest that the Brazilian Portuguese version of the SHAPS is a reliable and valid instrument to assess hedonic tone.

Abstract Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects on psychogenic symptoms induced by ketamine in healthy subjects. Methods: Healthy subjects (N = 38) were assigned to distinct groups that received SNP in different doses (0.15, 0.25, and 0.5 mcg/kg/min). First, participants received an infusion of SNP or placebo over 75 minutes. After 10 minutes, they were injected for 1 minute with a bolus of 0.26 mg/kg of ketamine and a maintenance dose was started 5 minutes later, with 0.25 mg/kg/h of ketamine for 50 minutes. Results: Ketamine-induced psychopathological alterations induced were reduced by SNP, as assessed with the Brief Psychological Rating Scale. Scores in the objective subscale of the Clinician-Administered Dissociative States Scale were also lower in SNP sessions compared to placebo. SNP had protective effects against deterioration in facial emotion and identity recognition tasks induced by ketamine. Discussion: Our findings support the view that SNP has preventative properties against psychotic manifestations.

OBJETIVO: Avaliar a combinação de dois fatores: clinical dementia rating sum of boxes scores (CDR-SB) e volume hipocampal (VH) como preditores de conversão de ditúrbio cognitivo leve (DCL) em demência. MÉTODO: Vinte e oito indivíduos (9 normais e 19 com DCL) foram classificados de acordo com a soma dos escores CDR-SB em 3 grupos. RESULTADOS: O volume do hipocampo foi significativamente menor no grupo de alto risco e naqueles que desenvolveram demência depois de dois anos. A taxa de conversão foi crescente entre os três grupos. CONCLUSÃO: Propusemos uma medição adicional do volume do hipocampo que pode ser útil no prognóstico. No entanto, notou-se que a CDR-SB é um método tão eficiente quanto neuroimagem para prever demência com a vantagem de ser um processo de baixo custo e de fácil implementação, mais consistente com a política pública.

OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.

OBJETIVO: Relatar estudos de neuroimagens estruturais e funcionais explorando o papel potencial do córtex orbitofrontal (COF) na fisiopatologia dos transtornos psiquiátricos (TP) mais prevalentes. MÉTODO: Foi realizada uma revisão não sistemática da literatura no MEDLINE, usando como parâmetros os seguintes termos: "córtex orbitofrontal", "esquizofrenia", "transtorno bipolar", "depressão maior", "transtornos ansiosos", "transtornos de personalidade" e "dependência a drogas". A pesquisa eletrônica foi feita até julho de 2011. DISCUSSÃO: Foram relatadas anormalidades estruturais e funcionais do COF em muitos TP, particularmente esquizofrenia, transtornos afetivos, transtornos ansiosos, transtornos de personalidade e dependência a drogas. Estudos de aquisição de imagens estruturais por ressonância magnética relataram a redução do volume do COF em pacientes portadores de esquizofrenia, transtornos afetivos, TEPT, transtorno do pânico, transtornos de personalidade do grupo B e dependência a drogas. Além disso, estudos de aquisição de imagens funcionais por ressonância magnética empregando paradigmas cognitivos demonstraram alterações na atividade do COF em todos os TP anteriormente relacionados. CONCLUSÃO: Estudos de neuroimagens observaram um envolvimento importante do COF em vários TP. Entretanto, estudos futuros são claramente necessários para caracterizar o papel específico do COF em cada TP, assim como para a compreensão de seu papel tanto no comportamento normal como no patológico, na regulação do humor e no funcionamento cognitivo.

OBJECTIVE: To report structural and functional neuroimaging studies exploring the potential role of the orbitofrontal cortex (OFC) in the pathophysiology of the most prevalent psychiatric disorders (PD). METHOD: A non-systematic literature review was conducted by means of MEDLINE using the following terms as parameters: "orbitofrontal cortex", "schizophrenia", "bipolar disorder", "major depression", "anxiety disorders", "personality disorders" and "drug addiction". The electronic search was done up to July 2011. DISCUSSION: Structural and functional OFC abnormalities have been reported in many PD, namely schizophrenia, mood disorders, anxiety disorders, personality disorders and drug addiction. Structural magnetic resonance imaging studies have reported reduced OFC volume in patients with schizophrenia, mood disorders, PTSD, panic disorder, cluster B personality disorders and drug addiction. Furthermore, functional magnetic resonance imaging studies using cognitive paradigms have shown impaired OFC activity in all PD listed above. CONCLUSION: Neuroimaging studies have observed an important OFC involvement in a number of PD. However, future studies are clearly needed to characterize the specific role of OFC on each PD as well as understanding its role in both normal and pathological behavior, mood regulation and cognitive functioning.

A maconha é a droga ilícita mais utilizada. Apesar disto, apenas um pequeno número de estudos investigaram as conseqüências neurotóxicas de longo prazo do uso de cannabis. As técnicas de neuroimagem se constituem em poderosos instrumentos para investigar alterações neuroanatômicas e neurofuncionais e suas correlações clínicas e neuropsicológicas. Uma revisão computadorizada da literatura foi conduzida nos indexadores MEDLINE e PsycLIT entre 1966 e novembro de 2004 com os termos 'cannabis', 'marijuana', 'neuroimaging', 'magnetic resonance', 'computed tomography', 'positron emission tomography', 'single photon emission computed tomography", 'SPET', 'MRI' e 'CT'. Estudos de neuroimagem estrutural apresentam resultados conflitantes, com a maioria dos estudos não relatando atrofia cerebral ou alterações volumétricas regionais. Contudo, há uma pequena evidência de que usuários de longo prazo que iniciaram um uso regular no início da adolescência apresentam atrofia cerebral assim como redução na substância cinzenta. Estudos de neuroimagem funcional relatam aumento na atividade neural em regiões que podem estar relacionadas com intoxicação por cannabis e alteração do humor (lobos frontais mesial e orbital) e redução na atividade de regiões relacionadas com funções cognitivas prejudicadas durante a intoxicação aguda. A questão crucial se efeitos neurotóxicos residuais ocorrem após o uso prolongado e regular de maconha permanece obscura, não existindo até então estudo endereçando esta questão diretamente. Estudos de neuroimagem com melhores desenhos, combinados com avaliação cognitiva, podem ser elucidativos neste aspecto.

Cannabis is the most widely used illicit drug. Despite this, only a small number of studies have investigated the long-term neurotoxic consequences of cannabis use. Structural and functional neuroimaging techniques are powerful research tools to investigate possible cannabis-induced pathophysiological changes. A computer literature review was conducted in the MEDLINE and PsycLIT databases between 1966 and November of 2004 with the search terms 'cannabis', 'marijuana', 'neuroimaging', 'magnetic resonance', 'computed tomography', 'positron emission tomography', 'single photon emission computed tomography", 'SPET', 'MRI' and 'CT'. Structural neuroimaging studies have yielded conflicting results. Most studies report no evidence of cerebral atrophy or regional changes in tissue volumes, and one study suggested that long-term users who started regular use on early adolescence have cerebral atrophy as well as reduction in gray matter. However, several methodological shortcomings limit the interpretation of these results.Functional neuroimaging studies have reported increases in neural activity in regions that may be related with cannabis intoxication or mood-change effects (orbital and mesial frontal lobes, insula, and anterior cingulate) and decreases in activity of regions related with cognitive functions impaired during acute intoxication.The important question whether residual neurotoxic effects occur after prolonged and regular use of cannabis remains unclear, with no study addressing this question directly. Better designed neuroimaging studies, combined with cognitive evaluation, may be elucidative on this issue.