Rodrigo Nicolato

Increased serum levels of brain-derived neurotrophic factor in chronic institutionalized patients with schizophrenia.

There is a growing body of evidence implicating the neurotrophin brain-derived neurotrophic factor (BDNF) in the pathogenesis of schizophrenia. As circulating BDNF levels may reflect the BDNF levels in the brain, we assessed serum BDNF in 40 institutionalized schizophrenic patients and 20 healthy controls. Serum BNDF levels were significantly increased in schizophrenic patients when compared to control subjects (p<0.001). Interestingly, serum BDNF correlated positively with the clinical scores at the negative subscale of the positive and negative syndrome scale (PANSS) (r=0.41; p<0.01). Our results confirm the emergent literature on the involvement of BDNF in schizophrenia.

Increased Serum Levels of Inflammatory Markers in Chronic Institutionalized Patients with Schizophrenia

Activation of the cytokine systems may be involved in the neuropathological changes occurring in the central nervous systems of schizophrenic patients. However, associations between the levels of cytokines and the severity of symptoms have not been completely established. Objective: It was the aim of this study to evaluate serum levels of tumor necrosis factor (TNF)-α and their soluble receptors (sTNFR) in schizophrenic patients and healthy controls. Methods: Forty male institutionalized schizophrenic patients (mean age ± SD, 52.3 ± 9.9 years) and 20 asymptomatic matched controls were recruited. The severity of symptoms was assessed using the Brief Psychiatric Rating Scale, the Positive and Negative Syndrome Scale and the Abnormal Involuntary Movement Scale. Serum levels of cytokines were measured by ELISAs. Results: Serum levels of sTNFR1 and sTNFR2 were increased in schizophrenic patients when compared with controls (all p < 0.05), but there was no difference in TNF-α levels. There was no correlation between the length of disease/hospitalization or the severity of symptoms and the serum levels of these molecules. Conclusion: Inflammatory markers are increased in schizophrenia but they do not correlate with symptom severity.

The leukocytes expressing DARPP-32 are reduced in patients with schizophrenia and bipolar disorder

Bipolar disorder (BPD) and schizophrenia (SCZ) are severe disorders representing an enormous social, familiar and individual burden, being SCZ the most disabling psychiatric disorder characterized by psychosis and cognitive impairment. It is well known that SCZ and BPD are associated with abnormalities in dopamine signaling pathway. Recent data in the literature have demonstrated altered expression levels of some proteins involved in the modulation of this pathway in both brain and peripheral tissues. It was shown that protein and mRNA levels of dopamine and cAMP regulated phosphoprotein (DARPP-32) were downregulated in dorsolateral prefrontal cortex (DLPFC) of patients with SCZ or BPD when compared to controls. Due to the difficulty to access brain tissue and the absence of objective laboratory tests for bio-markers, we measured DARPP-32 expression in blood cell sub-populations (CD4+ T lymphocytes, CD56+ NK cells, CD19+ B lymphocytes and CD14+ monocytes) taking advantage of the close relation of nervous and immune systems. Using flow cytometry as the analytical method, our results have shown that the DARPP-32 expression was diminished in CD4+ T lymphocytes, CD19+ B lymphocytes and CD14+ monocytes of BPD patients and was also decreased in CD4+ T lymphocytes and CD56+ NK cells of SCZ patients. These results showed that DARPP-32 expression in immune cells agrees with reports of reduced DARPP-32 protein in the DLPFC of BPD or SCZ patients. Our data suggest that DARPP-32 expression in PBMC could be used as a source of bio-markers to help in the treatment response of neuropsychiatry disorders as a window to the changes in the brain of those patients.

Bipolar disorder prevalence: a systematic review and meta-analysis of the literature

OBJECTIVE Bipolar disorder (BD) is common in clinical psychiatric practice, and several studies have estimated its prevalence to range from 0.5 to 5% in community-based samples. However, no systematic review and meta-analysis of the prevalence of BD type 1 and type 2 has been published in the literature. We carried out a systematic review and meta-analysis of the lifetime and 1-year prevalence of BD type 1 and type 2 and assessed whether the prevalence of BD changed according to the diagnostic criteria adopted (DSM-III, DSM-III-R vs. DSM-IV). METHODS We searched MEDLINE, Scopus, Web of Science, PsycINFO, and the reference lists of identified studies. The analyses included 25 population- or community-based studies and 276,221 participants. RESULTS The pooled lifetime prevalence of BD type 1 was 1.06% (95% confidence interval [95%CI] 0.81-1.31) and that of BD type 2 was 1.57% (95%CI 1.15-1.99). The pooled 1-year prevalence was 0.71% (95%CI 0.56-0.86) for BD type 1 and 0.50% (95%CI 0.35-0.64) for BD type 2. Subgroup analysis showed a significantly higher lifetime prevalence of BD type 1 according to the DSM-IV criteria compared to the DSM-III and DSM-IIIR criteria (p < 0.001). CONCLUSION This meta-analysis confirms that estimates of BD type 1 and type 2 prevalence are low in the general population. The increase in prevalence from DSM-III and DSM-III-R to DSM-IV may reflect different factors, such as minor changes in diagnostic operationalization, use of different assessment instruments, or even a genuine increase in the prevalence of BD.

Expression of neuronal calcium sensor-1 (NCS-1) is decreased in leukocytes of schizophrenia and bipolar disorder patients

Schizophrenia (SCZ) and bipolar disorder (BPD) are severe illnesses representing an enormous social, familiar and individual burden that affect 1% of the population world-wide. Several evidences indicate abnormalities of the dopamine system in both SCZ and BPD. Neuronal calcium sensor-1 (NCS-1) is a protein that has many functions in neurotransmission such as inhibition of dopamine D(2) receptor desensitization, regulation of ionic channels and enhancement of exocytosis of neurotransmitters. In addition, NCS-1 protein expression and mRNA levels were found increased in pre-frontal cortex (PFC) of SCZ and BPD patients. NCS-1 expression in neural and neuroendocrine cells is well documented and, recently, it was shown that NCS-1 is also expressed in mast cells and neutrophils. NCS-1 has important functions in mast cells since it stimulates Fc epsilon RI-triggered exocytosis and the release of arachidonic acid metabolites. Then, due to the known close relation between the nervous and immune systems, we sought to investigate the NCS-1 expression in lymphocytes and monocytes (CD4+ T lymphocytes, CD56+ NK cells, CD19+ B lymphocytes and CD14+ monocytes) of SCZ and BPD patients. Using flow cytometry, our results have shown that NCS-1 expression was diminished in CD4+T lymphocytes, CD19+ B lymphocytes and CD14+ monocytes of BPD patients and also decreased in CD4+ T lymphocytes and CD56+ NK cells of SCZ patients. Results suggest that immune cells might be a cellular model for studies with SCZ and BPD patients considering NCS-1 functions. Efforts need to be done to investigate the motive of the decreased percentage of immune cells expressing NCS-1 in patients with SCZ and BPD.

Clinical Applicability and Cutoff Values for an Unstructured Neuropsychological Assessment Protocol for Older Adults with Low Formal Education

Background and Objectives The neuropsychological exam plays a central role in the assessment of elderly patients with cognitive complaints. It is particularly relevant to differentiate patients with mild dementia from those subjects with mild cognitive impairment. Formal education is a critical factor in neuropsychological performance; however, there are few studies that evaluated the psychometric properties, especially criterion related validity, neuropsychological tests for patients with low formal education. The present study aims to investigate the validity of an unstructured neuropsychological assessment protocol for this population and develop cutoff values for clinical use. Methods and Results A protocol composed by the Rey-Auditory Verbal Learning Test, Frontal Assessment Battery, Category and Letter Fluency, Stick Design Test, Clock Drawing Test, Digit Span, Token Test and TN-LIN was administered to 274 older adults (96 normal aging, 85 mild cognitive impairment and 93 mild Alzheimer`s disease) with predominantly low formal education. Factor analysis showed a four factor structure related to Executive Functions, Language/Semantic Memory, Episodic Memory and Visuospatial Abilities, accounting for 65% of explained variance. Most of the tests showed a good sensitivity and specificity to differentiate the diagnostic groups. The neuropsychological protocol showed a significant ecological validity as 3 of the cognitive factors explained 31% of the variance on Instrumental Activities of Daily Living. Conclusion The study presents evidence of the construct, criteria and ecological validity for this protocol. The neuropsychological tests and the proposed cutoff values might be used for the clinical assessment of older adults with low formal education.

Increase in dopaminergic, but not serotoninergic, receptors in T-cells as a marker for schizophrenia severity

Schizophrenia is characterized by a slow deteriorating mental illness. Although the pathophysiology mechanisms are not fully understood, different studies have suggested a role for the immune system in the pathogenesis of schizophrenia. To date, an altered expression or signaling of neurotransmitters receptors is observed in immune cells during psychiatric disorders. In the present study, we investigated the expression of different serotonin and dopamine receptors in T-cells of schizophrenic and control patients. We used flow cytometry to determine the pattern of expression of dopamine (D2 and D4) and serotonine receptors (SR1A, SR1C, SR2A, SR2B), as well as serotonin transporter (ST), in T-cell subsets (CD4 and CD8). Expression of serotonin receptors and ST in T-cells of schizophrenic patients were not different from controls. However, the percentages of CD4+D4+ and CD8+D4+ were increased in schizophrenic patients as compared to controls. In addition, increased percentages of CD8+D2+ cells were also observed in schizophrenic patients, albeit this population revealed lower CD4+D2+ cells in comparison to controls. Interestingly, a relationship between clinical symptoms and immunological parameters was also observed. We showed that the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were positively related to CD8+D2+ cells, though AIMS was inversely related to CD4+D4+ cells. In conclusion, the alteration in the pattern of cell population and molecules expressed by them might serve as a promising biomarker for diagnosis of schizophrenia.

Sintomas depressivos no câncer de mama: Inventário de Depressão de Beck - Short Form

OBJECTIVES: To verify the prevalence of depressive symptoms in women with breast cancer and identify risk factors associated to its occurrence. METHODS: It was a transversal study where 71 women with breast cancer were interviewed. Two instruments were applied, being one questionnaire used to verify sociodemographic and clinical data, and the Beck Depression Inventory - Short Form to evaluate depressive symptoms. Descriptive methods and chi-square test were utilized to analyze data, evaluating association between depressive symptoms, sociodemographic and clinical data. Significance level was considered of 5%. RESULTS: Depressive symptoms prevalence was 29,6%. Factors associated to the presence of this kind of symptoms were: chemotherapic treatment (p = 0,021), pain presence (p = 0,018), upper limb movement limitation (p = 0,010) and bad health perception (p = 0,018). CONCLUSION: Depressive symptoms were frequent in association with breast cancer, and this suggests that women mental status with this kind of cancer must be investigated and treated when necessary, lowing the impact of depressive symptoms in womens life.

Fidedignidade e validade de construto do Teste de Aprendizagem Auditivo-Verbal de Rey em idosos brasileiros

Background: The Rey Auditory-Verbal Learning Test (RAVLT) is widely used for the assessment of episodic memory. However, there are few studies in Brazil assessing its psychometric properties. Objectives: To search for evidence of reliability and construct validity of the RAVLT, and to assess the influence of age, schooling, gender, and depressive symptoms on test performance. Methods: One hundred twenty-six healthy older adults (aged 60 and over) performed the RAVLT, Mini-Mental State Exam (MMSE), Clock Drawing Test (CDT) and the Geriatric Depression Scale. Reliability was assessed by analysis of internal consistency, and construct validity by factor analysis and correlations with the MMSE and CDT. The influence of age, schooling and depressive symptoms was estimated by conducting linear regression analysis, and the role of gender by comparing the performance of males and females. Results: The RAVLT showed a high internal consistency, weak correlations with the MMSE and CDT, and a bifactorial structure, which is related to the processes of learning and episodic memory retrieval. Only age and gender affected test performance. Discussion: Our results provide evidence of reliability and construct validity in the tested RAVLT version, attesting its potential for clinical and research purposes for the Brazilian elderly population.

Lithium and topiramate association in the treatment of comorbid pathological gambling and bipolar disorder

Rodrigo Nicolato , Marco Aurelio Romano-Silva, Humberto Correa, Department of Psychiatry, Federal University of Minas Gerais, João Vinı́cius Salgado, Department of Neuroscience, Fumec University, Belo Horizonte, and Antonio Lucio Teixeira, Department of Internal Medicine, Federal University of Minas Gerais, Brazil : Pathological gambling (PG) is traditionally classified as an impulsive control disorder (ICD). Recently it has been proposed that PG may be related to bipolar disorder (BD) because both conditions share clinical features and respond to mood-stabilizing drugs [1,2]. Furthermore PG may be present in a significant number of patients with BD [2]. Herein we describe a refractory patient with comorbid PG and BD in whom clinical control was achieved only with the association of lithium and topiramate. A 57-year-old woman presented to the Department of Psychiatry, Federal University of Minas Gerais, Brazil, with the complaint of gambling behaviour over the last 5 years. During this period she ran up a debt of