Serum concentrations of brain-derived neurotrophic factor in patients diagnosed with gender dysphoria undergoing sex reassignment surgery.

INTRODUCTION:: Transsexualism (ICD-10) is a condition characterized by a strong and persistent dissociation with one's assigned gender. Sex reassignment surgery (SRS) and hormone therapy provide a means of allowing transsexual individuals to feel more congruent with their gender and have played a major role in treatment over the past 70 years. Brain-derived neurotrophic factor (BDNF) appears to play a key role in recovery from acute surgical trauma and environmentally mediated vulnerability to psychopathology. We hypothesize that BDNF may be a biomarker of alleviation of gender incongruence suffering. OBJECTIVES:: To measure preoperative and postoperative serum BDNF levels in transsexual individuals as a biomarker of alleviation of stress related to gender incongruence after SRS. METHODS:: Thirty-two male-to-female transsexual people who underwent both surgery and hormonal treatment were selected from our initial sample. BDNF serum levels were assessed before and after SRS with sandwich enzyme linked immunosorbent assay (ELISA). The time elapsed between the pre-SRS and post-SRS blood collections was also measured. RESULTS:: No significant difference was found in pre-SRS or post-SRS BDNF levels or with relation to the time elapsed after SRS when BDNF levels were measured. CONCLUSION:: Alleviation of the suffering related to gender incongruence after SRS cannot be assessed by BDNF alone. Surgical solutions may not provide a quick fix for psychological distress associated with transsexualism and SRS may serve as one step toward, rather than as the conclusion of, construction of a person's gender identity.

Serum concentrations of brain-derived neurotrophic factor in patients diagnosed with gender dysphoria undergoing sex reassignment surgery / Concentração sérica de fator neurotrófico derivado do cérebro em pacientes diagnosticados com disforia de gênero que realizaram cirurgia de redesignação sexual

Abstract Introduction: Transsexualism (ICD-10) is a condition characterized by a strong and persistent dissociation with one's assigned gender. Sex reassignment surgery (SRS) and hormone therapy provide a means of allowing transsexual individuals to feel more congruent with their gender and have played a major role in treatment over the past 70 years. Brain-derived neurotrophic factor (BDNF) appears to play a key role in recovery from acute surgical trauma and environmentally mediated vulnerability to psychopathology. We hypothesize that BDNF may be a biomarker of alleviation of gender incongruence suffering. Objectives: To measure preoperative and postoperative serum BDNF levels in transsexual individuals as a biomarker of alleviation of stress related to gender incongruence after SRS. Methods: Thirty-two male-to-female transsexual people who underwent both surgery and hormonal treatment were selected from our initial sample. BDNF serum levels were assessed before and after SRS with sandwich enzyme linked immunosorbent assay (ELISA). The time elapsed between the pre-SRS and post-SRS blood collections was also measured. Results: No significant difference was found in pre-SRS or post-SRS BDNF levels or with relation to the time elapsed after SRS when BDNF levels were measured. Conclusion: Alleviation of the suffering related to gender incongruence after SRS cannot be assessed by BDNF alone. Surgical solutions may not provide a quick fix for psychological distress associated with transsexualism and SRS may serve as one step toward, rather than as the conclusion of, construction of a person's gender identity.

Resumo Introdução: O transexualismo (CID-10) é uma condição caracterizada por forte e persistente dissociação com o gênero atribuído. A cirurgia de redesignação sexual (CRS) e a terapia hormonal (TH) permitem que indivíduos transexuais se sintam mais congruentes com seu gênero e, por isso, têm desempenhado papel importante nos últimos 70 anos. O fator neurotrófico derivado do cérebro (BDNF) parece desempenhar um papel fundamental na recuperação do trauma cirúrgico agudo e vulnerabilidade ambiental à psicopatologia. Nós hipotetizamos que o BDNF pode ser um biomarcador de alívio do sofrimento de incongruência de gênero pós-CRS. Objetivos: Mensurar os níveis séricos de BDNF no pré e pós-operatório em indivíduos transexuais como biomarcador de alívio de estresse relacionado à incongruência de gênero após a CRS. Métodos: Trinta e duas pessoas transexuais masculino para feminino submetidas a cirurgia e tratamento hormonal foram selecionadas de nossa amostra inicial. O nível sérico de BDNF foi avaliado antes e depois da CRS pela técnica ELISA. O tempo decorrido entre as coletas de sangue pré e pós-CRS foi medido. Resultados: Não houve diferença significativa nos níveis de BDNF pré e pós-CRS ou em relação ao tempo decorrido entre a CRS e a coleta. Conclusão: O alívio do sofrimento relacionado à incongruência de gênero pós-CRS não pode ser avaliado apenas pelo BDNF. Soluções cirúrgicas podem não fornecer uma solução rápida para o sofrimento associado ao transexualismo, e a CRS pode servir como um passo em direção à, em vez de conclusão da, construção da identidade de gênero de uma pessoa.

Challenges and developments in research of the early stages of bipolar disorder

Recently, attention in the field of bipolar disorder (BD) has focused on prevention, including early detection and intervention, as these strategies have the potential to delay, lessen the severity, or even prevent full-blown episodes of BD. Although knowledge of the neurobiology of BD has advanced substantially in the last two decades, most research was conducted with chronic patients. The objective of this paper is to comprehensively review the literature regarding the early stages of BD, to explore recent discoveries on the neurobiology of these stages, and to discuss implications for research and clinical care. The following databases were searched: PubMed, PsycINFO, Cochrane Library, and SciELO. Articles published in English from inception to December 2015 were retrieved. Several research approaches were used, including examination of offspring studies, retrospective studies, prospective studies of clinical high-risk populations, and exploration of the progression after the first manic episode. Investigations with neuroimaging, cognition assessments, and biomarkers provide promising (although not definitive) evidence of alterations in the neural substrate during the at-risk stage. Research on BD should be expanded to encompass at-risk states and aligned with recent methodological progress in neuroscience.

Inter-relation between brain-derived neurotrophic factor and antioxidant enzymes in bipolar disorder.

OBJECTIVES: Accumulating evidence indicates that oxidative stress and neurotrophins have a bidirectional relationship. In this post hoc, exploratory analysis, we investigated the association between plasma brain-derived neurotrophic factor (BDNF) levels and activities of the antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) in individuals with bipolar disorder (BD) and healthy controls. METHODS: We measured plasma levels of BDNF and activities of GPx and SOD in individuals with BD (n=59) and healthy controls (n=26). Information related to current and past psychiatric/medical history, as well as to metabolic comorbidities, was also reported. RESULTS: There were negative correlations between BDNF, GPx (r=-.449, P≤.001) and GPx/SOD ratio (r=-.503, P<.001), and a positive correlation between BDNF and SOD (r=.254, P=.020). There was a moderating effect of body mass index (BMI) on the association between BDNF and GPx/SOD rate ratio [(RR)=1.002, P=.034]; interactions between impaired glucose metabolism (IGM), GPx (RR=1.016, P=.033), and GPx/SOD ratio (RR=1.026, P=.002) were also observed. These results were significant in models that included age, gender, alcohol, tobacco and medication use. CONCLUSIONS: There was a robust and independent correlation between peripheral BDNF and antioxidant enzyme activities in individuals with BD, which was moderated by metabolic comorbidities. These results reinforce the concept that these systems are associated and further extend knowledge of the putative effect of metabolic comorbidities in the pathophysiological substrates of BD.

Bipolar disorder course, impaired glucose metabolism and antioxidant enzymes activities: A preliminary report.

This study aimed to examine the role of oxidative stress in bipolar disorder (BD) by evaluating the relationship among antioxidant enzymes activities, impaired glucose metabolism (IGM) and illness course. We measured the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPx) in individuals with BD (N = 55) and healthy controls (N = 28). Information related to current and past psychiatric/medical history, as well as prescription of any pharmacological treatments was captured. Impaired glucose metabolism was operationalized as pre-diabetes or type 2 diabetes mellitus. Our results showed that, after adjustment for age, gender, alcohol use, smoking and current medication, both BD (p < 0.001) and IGM (p = 0.019) were associated with increased GPx activity, whereas only BD was associated with decreased SOD activity (p = 0.008). We also observed an interaction between BD and IGM on SOD activity (p = 0.017), whereas the difference between BD and controls was only significant in individuals with IGM (p = 0.009). IGM, GPx and SOD activity were independently associated with variables of illness course. Moreover, IGM moderated the association between SOD activity and number of mood episodes (p < 0.001), as a positive correlation between SOD activity and mood episodes was observed only in participants with IGM. In conclusion, BD and IGM are associated with independent and synergistic effects on markers of oxidative stress. The foregoing observations suggest that the heterogeneity observed in previous studies evaluating antioxidant enzymes in BD may be a function of concurrent IGM; and that imbalances in the oxidative system may subserve the association between BD and IGM, as well as its relationship with illness course.

Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course.

OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course. METHODS: We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. RESULTS: Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM. CONCLUSIONS: BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression.

Impaired glucose metabolism moderates the course of illness in bipolar disorder.

BACKGROUND: The longitudinal course of bipolar disorder (BD) is highly heterogeneous, and is moderated by the presence of general medical comorbidities. This study aimed to investigate the moderating effects of impaired glucose metabolism (IGM) on variables of illness course and severity in a BD population. METHODS: Fifty-five patients with BD were evaluated. All subjects were evaluated with respect to current and past psychiatric and medical disorders, as well as lifetime use of any medication. Body mass index (BMI) and metabolic parameters were obtained. IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. RESULTS: Thirty (54.5%) individuals had IGM. After adjustment for age, gender, ethnicity, alcohol use, smoking, BMI and past and current exposure to psychotropic medications, individuals with IGM, when compared to euglycemic participants, had an earlier age of onset (RR: 0.835, p=0.024), longer illness duration (RR: 1.754, p=0.007), a higher number of previous manic/hypomanic episodes (RR: 1.483, p=0.002) and a higher ratio of manic/hypomanic to depressive episodes (RR: 1.753, p=0.028). Moreover, we observed a moderating effect of IGM on the association between number of mood episodes and other variables of illness course, with the correlation between lifetime mood episodes and frequency of episodes being significantly greater in the IGM subgroup (RR: 1.027, p=0.029). All associations observed herein remained significant after adjusting for relevant confounding factors (e.g. age, alcohol and tobacco use, exposure to psychotropic agents, BMI). LIMITATIONS: Cross-sectional design, small sample size. CONCLUSIONS: Comorbid IGM may be a key moderator of illness progression in BD.

Functioning in early and late stages of schizophrenia / Funcionalidade nos estágios inicial e final da esquizofrenia

INTRODUCTION: Schizophrenia is frequently associated with a debilitating course and prominent impairment in social and occupational functioning. Although the criteria for classification into stages have not been defined in the literature, illness duration and functioning seem to be good candidates. OBJECTIVE: To compare functioning of patients with schizophrenia at different stages of the disease (early vs. late) and healthy sex- and age-matched controls. METHODS: This double-blinded, case-controlled study included 79 individuals: 23 patients with schizophrenia diagnosed up to 5 years earlier; 19 patients with schizophrenia diagnosed at least 20 years earlier; and healthy matched controls. Diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis I Disorder. Functioning was assessed using the Functioning Assessment Short Test (FAST). RESULTS: Patients in the early stage had significantly higher scores than healthy controls in total FAST and in autonomy, occupational functioning, cognitive functioning and interpersonal relationships. Individuals in the late stage had significantly poorer functioning than controls in all domains. The comparison of functioning between the two groups of patients revealed no significant differences, except in occupational functioning, in which late stage patients had a poorer performance. CONCLUSION: Functioning impairment in schizophrenia tends to remain stable despite illness duration. Therefore, functioning should be effectively assessed at an early stage, as illness duration alone may not be the most reliable criterion to stage patients with schizophrenia (AU)

INTRODUÇÃO: A esquizofrenia está frequentemente associada a um curso debilitante e a um importante comprometimento no funcionamento social e ocupacional. Embora os critérios para classificação em diferentes estágios ainda não tenham sido definidos, a duração da doença e a funcionalidade têm sido apontadas como bons candidatos. OBJETIVO: Comparar a funcionalidade de indivíduos com esquizofrenia no estágio inicial e final com controles saudáveis correspondentes em idade e sexo. MÉTODOS: Neste estudo caso-controle, duplo-cego, foram incluídos 79 pacientes: 23 com diagnóstico de esquizofrenia feito até 5 anos atrás (estágio inicial); 19 diagnosticados há pelo menos 20 anos (estágio final); e controles saudáveis pareados. O diagnóstico foi estabelecido pela Entrevista Clínica Estruturada para Transtornos do Eixo I do Manual Diagnóstico e Estatístico de Transtornos Mentais, 4ª edição (DSM-IV). A funcionalidade foi avaliada através da escala Teste Breve de Avaliação Funcional (FAST). RESULTADOS: Os pacientes em estágio inicial tiveram escores significativamente maiores do que controles saudáveis na escala FAST (escore total e domínios autonomia, funcionamento ocupacional, funcionamento cognitivo e relações interpessoais). Os indivíduos em estágio final apresentaram funcionalidade pior que os controles em todos os domínios. A comparação entre os dois grupos não mostrou diferenças, exceto no funcionamento ocupacional, em que os pacientes em estágio final apresentaram um desempenho pior. CONCLUSÃO: O prejuízo da funcionalidade na esquizofrenia tende a permanecer estável ao longo da doença. Portanto, a funcionalidade deve ser avaliada nos estágios iniciais da doença, já que a duração da doença por si só pode não ser o critério mais confiável para definir o estágio de pacientes com esquizofrenia (AU)

Similarities in serum oxidative stress markers and inflammatory cytokines in patients with overt schizophrenia at early and late stages of chronicity.

Schizophrenia (SZ) is a debilitating neurodevelopmental disorder that strikes at a critical period of a young person's life. Its pathophysiology could be the result of deregulation of synaptic plasticity, with downstream alterations of inflammatory immune processes regulate by cytokines, impaired antioxidant defense and increased lipid peroxidation. The aim of this study was to examine serum oxidative stress markers and inflammatory cytokines in early and late phases of chronic SZ. Twenty-two patients at early stage (within first 10 years of a psychotic episode), 39 at late stage (minimum 10 years after diagnosis of SZ) and their respective matched controls were included. Each subject had 5 ml blood samples collected by venipuncture to examined thiobarbituric acid-reactive substances (TBARS), total reactive antioxidant potential (TRAP), protein carbonyl content (PCC), Interleukins 6 and 10 (IL-6, IL-10) and tumor necrosis factor alpha (TNF-alpha). TBARS, IL-6 and PCC levels were significantly higher in patients with SZ at early and late stages than in controls. There were no differences for TRAP and TNF-alpha levels in patients with SZ at early and late stages than in controls. IL-10 levels were decreased in patients at late stage and a decrease trend in early stage was found. Results provided evidence consistent with comparable biological markers across chronic SZ. The concept of biochemical staging proposed by others for bipolar disorder is not seen in this cohort of patients with SZ, at least for cytokines and oxidative stress markers. Our findings reinforce the need of assessment of individuals in ultra high risk to develop psychosis and first-episode population.

Stereotactic radiosurgery of intracranial tumors: a comparison of intensity-modulated radiosurgery and dynamic conformational arc.

PURPOSE: Intensity-modulated radiosurgery (IMRT) and dynamic conformational arc (DCA) are two techniques for linac-stereotactic radiosurgery using the micro-multileaf collimator. The objective of this study is to examine advantages and disadvantages of these techniques in the treatment of treatment of intracranial tumors. MATERIALS AND METHODS: SRS treatment plans were developed for 21 patients with vestibular schwannoma, glomus jugulare, pituitary adenoma and cavernous sinus meningioma. For all patients, we developed an IMRT and a DCA plan using BrainLab Iplan 4.1. Plans were evaluated using the target coverage conformity index (CI), homogeneity index (HI), Gradient Index (GI) and doses in critical structures (optic pathways and brainstem). RESULTS: In the overall comparison of both techniques, HI and CI was better in the IMRT group, showing a statistically significant difference. The GI was similar in two groups. Comparison of the mean dose in critical structures of the techniques revealed no statistically significant differences. The DCA plan was acceptable in 9 patients and IMRT in 15 patients. IMRT was preferred in 14 out of 15 patients due to better CI and lower dose in critical structures with adequate target coverage. CONCLUSIONS: IMRT is the preferred stereotactic radiosurgery technique for most intracranial benign tumors close to critical structures.

Bilateral malignant metastases to the internal auditory canal: radiosurgical management.

Malignant melanomas constitute 1-8% of all malignant tumors and are the third most common tumor to metastasize to the central nervous system. However, metastases to the cerebellopontine angle (CPA) are rare, accounting for only 0.2 to 0.7% of the lesions identified in this location Case Report. A 62-year-old white man with a history of melanoma of the back, who had had all lesions completely excised, was reportedly tumor-free for 6 years. The patient presented bilateral metastatic CPA melanoma. Left side tumor was treated with surgery with partial resection (lost hearing) and radisorugery. Right side lesion was treated with radiosurgery and hearing preserved for 8 months, tumor controlled for 12 months, until death due to leptomeningeal carcinomatosis after 13 months of radiosurgey. The patient underwent intensity-modulated stereotactic radiosurgery using BrainLab Iplan 4.1 for both IAC lesions, the dose was 18Gy prescribed to the 80% isodose line delivered by 11 fields. The patient presented no post-radiosurgery neurological complications. Conclusion: In patients with lesions in the CPA, a diagnosis of melanoma should be included, particularly in cases with rapid progression of symptoms. Therefore, radiosurgery is a viable treatment option since the hearing can be preserved and tumor control achieved.

Reassessing tumor markers in local recurrences of breast cancer: a new insight.

BACKGROUND: It is believed that a local recurrence of a primitive breast cancer has the same prognostic factor profile as its primary breast cancer tumor. MATERIAL/METHODS: We compared the immunohistochemical expressions of the tumor suppressor protein p53, estrogen receptor (ER), c-erbB2, and E-cadherin in 57 primary invasive breast cancers and in their respective LRs. The McNemar test and the kappa index were used for statistical analysis. RESULTS: In 30 patients (52.6%) the expression of at least one of these markers was different between the primary and locally recurrent tumors. No significant difference was observed between variations in the positive and negative expressions in the primary tumor and local recurrence in cerbB2 (kappa = 0.86), E-cadherin (kappa = 0.55), and p53 (kappa = 0.7). However, the ER presented a low kappa index (kappa = 0.26, p > 0.05). CONCLUSIONS: ER expression should be reviewed in local recurrent breast cancer. This relevant change in ER expression is likely to change the current clinical practice in breast cancer evaluation and treatment.