Major depressive disorder (MDD) is a highly prevalent disorder, which has been associated with an abnormal response of the hypothalamus-pituitary-adrenal (HPA) axis. Reports have argued that an abnormal HPA axis response can be due to an altered P-Glycoprotein (P-GP) function. This argument suggests that genetic polymorphisms in ABCB1 may have an effect on the HPA axis activity; however, it is still not clear if this influences the risk of MDD. Our study aims to evaluate the effect of ABCB1 C1236T, G2677TA and C3435T genetic polymorphisms on MDD risk in a subset of Portuguese patients. DNA samples from 80 MDD patients and 160 control subjects were genotyped using TaqMan SNP Genotyping assays. A significant protection for MDD males carrying the T allele was observed (C1236T: odds ratio (OR)=0.360, 95% confidence interval [CI]: [0.140-0.950], p=0.022; C3435T: OR=0.306, 95% CI: [0.096-0.980], p=0.042; and G2677TA: OR=0.300, 95% CI: [0.100-0.870], p=0.013). Male Portuguese individuals carrying the 1236T/2677T/3435T haplotype had nearly 70% less risk of developing MDD (OR=0.313, 95% CI: [0.118-0.832], p=0.016, FDR p=0.032). No significant differences were observed regarding the overall subjects. Our results suggest that genetic variability of the ABCB1 is associated with MDD development in male Portuguese patients. To the best of our knowledge, this is the first report in Caucasian samples to analyze the effect of these ABCB1 genetic polymorphisms on MDD risk.

a b s t r a c tBackground: Hippocampal neurogenesis has been suggested as a downstream event of antidepressants (AD) mechanism of action and might explain the lag time between AD administration and the ther-apeutic effect. Despite the widespread use of AD in the context of Major Depressive Disorder (MDD) there are no reliable biomarkers of treatment response phenotypes, and a significant proportion of patients display Treatment Resistant Depression (TRD). Fas/FasL system is one of the best-known death-receptor mediated cell signaling systems and is recognized to regulate cell proliferation and tumor cell growth. Recently this pathway has been described to be involved in neurogenesis and neuroplasticity. Methods: Since FAS -670A4G and FASL -844T4C functional polymorphisms never been evaluated in the context of depression and antidepressant therapy, we genotyped FAS -670A 4G and FASL -844T4C in a subset of 80 MDD patients to evaluate their role in antidepressant treatment response phenotypes. Results: We found that the presence of FAS -670G allele was associated with antidepressant bad prog-nosis (relapse or TRD: OR ¼6.200; 95% CI: [1. .499]; p¼0.001), and we observed that patients carrying this allele have a higher risk to develop TRD (OR ¼10.895; 95% CI: [1.362-87.135]; p¼0.008). Moreover, multivariate analysis adjusted to potentials confounders showed that patients carrying G allele have higher risk of early relapse (HR ¼3.827; 95% CI: [1.072-13.659]; p¼0.039). FAS mRNA levels were down-regulated among G carriers, whose genotypes were more common in TRD patients. No association was found between FASL-844T 4C genetic polymorphism and any treatment phenotypes. Limitations: Small sample size. Patients used antidepressants with different mechanisms of action. Conclusion: To the best of our knowledge this is the first study to evaluate the role of FAS functional polymorphism in the outcome of antidepressant therapy. This preliminary report associates FAS -670A4G genetic polymorphism with Treatment Resistant Depression and with time to relapse. The current results may possibly be given to the recent recognized role of Fas in neurogenesis and/or neu-roplasticity.

The IL6-174G > C polymorphism influences antidepressant treatment outcome in this sub-set of MDD patients, providing a putative mechanistic link for the dysregulated IL-6 levels described in the literature in patients with TRD.

Recent studies suggest that immune activation and cytokines, such as IL-18, are involved in depression. IL-18 is expressed in brain and is increased in patients with moderate to severe depression. In this study we aim to evaluate the role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes, specifically relapse and treatment resistant depression (TRD). We genotyped the referred polymorphisms in a subset of 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months. Patients carrying IL18-607 CA or AA genotypes were significantly more prone to relapse after AD treatment and present a significantly lower time to relapse than patients carrying CC genotype. Similarly, patients carrying IL18-137 GC or CC genotypes have a significantly higher risk of relapse and display relapse significantly earlier than the ones carrying GG genotype. Due to the low number of IL18-607 CC and IL18-137 GG in the relapse subgroup (n=3 and n=5, respectively), results were validated by bootstrapping analysis, and remained significant. No association was found between the evaluated genetic polymorphisms and TRD. IL18 peripheral mRNA levels were upregulated in IL18-607 CA or AA carriers. This preliminary report indicates that IL18-607C>A and IL18-137G>C genetic polymorphisms seem to influence depression relapse after antidepressant treatment in our subset of depressed patients, and may possibly contribute to the disregulated IL-18 levels found in patients with depression.

Background:Several reports indicate that Bipolar Disorder (BD) is frequently underdiagnosedleading to overuse of antidepressants and underuse of mood stabilizers.Aims and methods:The aim is to review literature concerning this subject published since 2000.Results:BD seems to be frequently underdiagnosed. Several studies, as EPIDEP and NEMESIS, reveal insufficiencies on the diagnosis of this disorder, suggesting that clinicians miss this diagnosis about half of the times, and that about three quarters of these patients are not receiving appropriate treatment, respectively.BD is often misdiagnosed as Major Depression Disorder (MDD), with approximately 40% of BD patients being initially diagnosed as MDD. On the other hand, a large fraction of patients initially diagnosed as MDD will change diagnosis to BD during follow-up, with some authors presenting values as high as 67%. Studies comparing the depressive features of MDD and BD point to some strong clinical indicators of bipolarity in patients presenting with depression, such as family history, seasonal pattern, postpartum onset, psychotic symptoms, younger age, suicidal behaviours, among others.To a lesser extent, BD can also be misdiagnosed as: substance abuse, borderline personality, obsessive-compulsive disorder, among others.It is also important to consider that a large fraction of patients with BD diagnosis will change diagnosis during the follow-up period.Conclusion:BD patients with the diagnosis may represent only a fraction of the subjects with this disorder, and the true epidemiological extent of this problem needs further investigation.

Introduction: Recent studies suggested that immune activation and cytokines might be involved in depression. The proinflammatory cytokine interleukin-18 (IL-18) is less reported in depression but is still relevant since it is expressed in the brain and serum levels of IL-18 have been found to be increased in patients with moderate to severe depression. Therefore, it seems reasonable that IL-18 promoter SNPs may have an effect in antidepressant response phenotypes. Objectives: We aim to evaluate the role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes, specifically remission, relapse and treatment resistant depression (TRD). Methods: We genotyped the referred polymorphisms in a subset of 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months. Results: We found that patients carrying IL18-607 CA or AA genotypes are more prone to relapse after AD treatment (OR=4.145; 95%CI: [1.038-16.555]; p=0.043) and present a lower time to relapse than patients carrying CC genotype (69 vs 115 weeks, p=0.019, Log-rank test). We also observed that patients carrying IL18-137 GC or CC genotypes have a higher risk of relapse (OR=3.988; 95%CI: [1.176-13.516]; p=0.022) and display relapse earlier than the ones carrying GG genotype (64 vs 112 weeks, p=0.006, Log-rank test). No association was found between the evaluated genetic polymorphisms and remission or TRD. Conclusions: The IL18-607A>C and IL18-137G>C polymorphisms seems to influence relapse after antidepressant treatment in our subset of depressed patients. These polymorphisms may possibly contribute to the elevated IL-18 levels found in patients with moderate to severe depression.

The term stigma comes from Greek, being related to the identification of people through a physical mark, which can generate marginalization. The literature points out four types of stigmas: public, institutional, self-esteem, and courtesy. People with Autistic Spectrum Disorders are stigmatized in various cultures and societies. This study describes the view on stigma regarding Autistic Spectrum Disorder among undergraduate medical and nursing students. This is a cross-sectional study of a qualitative approach, whose data were collected through two focus groups, one with medical and another with nursing students, from a public university in Alagoas, Brazil. A script with eight questions for discussion in the focus groups was used. The speeches were recorded, transcribed, and analyzed with the IRAMUTEQ software, based on content analysis. The Descending Hierarchical Classification showed five categories related to the disorder, which were: 1 - Approach to the person with the disorder; 2 - Experience of Stigma; 3 - Segregation of People with Disorders; 4 - Care of the Person with the Disorder and Class; 5 - Challenges faced by the people affected.

Resumo O termo estigma é oriundo do grego, relacionado a identificação de pessoas através de marcação física. A literatura aponta quatro tipos de estigmas: púbico, institucional, autoestima e de cortesia. Pessoas com Transtornos do Espectro Autista são estigmatizadas em diversas culturas e sociedades. Este estudo descreve a visão sobre estigma em relação ao Transtorno do Espectro Autista entre estudantes dos cursos medicina e enfermagem. Estudo transversal, qualitativo, dados coletados por meio de dois grupos focais, um com estudantes de medicina, outro com enfermagem, de uma universidade pública, em Alagoas. Foi utilizado um roteiro com oito perguntas para discussão nos grupos focais. As falas foram gravadas, transcritas e analisadas no software IRAMUTEQ, embasada na análise de conteúdo. A Classificação Hierárquica Descendente apresentou cinco categorias relacionadas ao Transtorno, que foram: 1 - Abordagem da pessoa com o Transtorno; 2 - Vivência de Estigma; 3 - Segregação de Pessoas com Transtorno; 4 - Cuidado com a Pessoa com o Transtorno; e a Classe 5 - Desafios enfrentados pelas pessoas acometidas