Early growth response 1 (EGR1) is downregulated in peripheral blood from patients with major psychiatric disorders.

OBJECTIVES: To evaluate relative expression of genes with the potential to translate environmental stimuli into long-term alterations in the brain - namely Early Growth Response (EGR)1, EGR3, and Cryptochrome Circadian Regulator 2 (CRY2) - in peripheral blood from patients with Bipolar Disorder (BD), Schizophrenia (SZ), Major Depressive Disorder (MDD) and healthy controls (HC). METHODS: Thirty individuals ranging from 18 to 60 years were recruited for each group (BD, SZ, MDD or HC) from a Brazilian public hospital. Therefore, individuals' peripheral blood was collected and EGR1, EGR3 and CRY2 gene expression analyzed by PCR Real Time. RESULTS: EGR1 mRNA levels are significantly lower in psychiatric patients when compared to HC, but there is no difference for EGR3 and CRY2. Exploring the findings for each diagnosis, there is a significant difference between each diagnosis group only for EGR1, which was lower in BD, MDD and SZ as compared to HC. No significant correlations were found between gene expression and clinical features. CONCLUSIONS: EGR1 is downregulated in psychiatric patients, regardless of the diagnosis and may be a potential common target in major psychiatric disorders. EGR1, as a transcription factor, modulates many other genes and participates in crucial neuronal and synaptic processes, such as plasticity, neurotransmitters metabolism, vesicular transport and signaling pathways. The study of EGR1 and its upstream regulators in psychiatry might lead to potential new therapeutic targets.

Earlier age of onset is associated with a pro-inflammatory state in major depressive disorder.

Major depressive disorder (MDD) is a common condition that affects the general population over a wide range of ages, regardless of gender and social background. Early-onset of MDD in adulthood, between ages of 18 and 30 years, is associated with worse outcomes and increased years of disability. Stress load and physical health have been associated with age of onset in MDD. We aim to investigate whether early onset MDD might be associated with changes in systemic inflammatory markers. We examined levels of following cytokines: IL-1ß, IL-6, IL-10 and TNFα in 234 patients with MDD. Higher serum levels of TNFα and IL-1ß are associated with the early onset of the disorder in patients with MDD. IL-6 levels were also higher in the early onset group and IL-10 levels were higher in the late onset group, but with no significant difference. Changes in the anti-inflammatory/pro-inflammatory balance have been described in mood disorders and may be implicated in its severity and pattern of progression. Our findings reinforce that higher serum levels of IL-1ß and TNFα may be associated with the earlier onset subgroup of MDD patients. Future research that target inflammatory markers of immune modulation may be, key in the search for novel preventative therapeutics.

Sydney Melancholia Prototype Index (SMPI): translation and cross-cultural adaptation to Brazilian Portuguese.

INTRODUCTION: Depression is possibly not a single syndrome but rather comprises several subtypes. DSM-5 proposes a melancholia specifier with phenotypic characteristics that could be associated with clinical progression, biological markers or therapeutic response. The Sydney Melancholia Prototype Index (SMPI) is a prototypic scale aimed to improve the diagnosis of melancholia. So far, there is only an English version of the instrument available. The aim of this study is to describe the translation and adaptation of the English version of the SMPI into Brazilian Portuguese. METHODS: Translation and cross-cultural adaptation of the self-report (SMPI-SR) and clinician-rated (SMPI-CR) versions into Brazilian Portuguese were done following recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). This guideline includes the following steps: preparation, forward translation, reconciliation, back translation, back translation review, harmonization, cognitive debriefing, debriefing results review, proofreading and final report. RESULTS: The Brazilian Portuguese versions of the SMPI were well-accepted by respondents. Changes in about two-thirds of the items were considered necessary to obtain the final Brazilian Portuguese version of the SMPI. CONCLUSIONS: Both versions of the SMPI are now available in Brazilian Portuguese. The instrument could become an important option to enhance studies on melancholia in Portuguese-speaking samples.

Sydney Melancholia Prototype Index (SMPI): translation and cross-cultural adaptation to Brazilian Portuguese

Abstract Introduction Depression is possibly not a single syndrome but rather comprises several subtypes. DSM-5 proposes a melancholia specifier with phenotypic characteristics that could be associated with clinical progression, biological markers or therapeutic response. The Sydney Melancholia Prototype Index (SMPI) is a prototypic scale aimed to improve the diagnosis of melancholia. So far, there is only an English version of the instrument available. The aim of this study is to describe the translation and adaptation of the English version of the SMPI into Brazilian Portuguese. Methods Translation and cross-cultural adaptation of the self-report (SMPI-SR) and clinician-rated (SMPI-CR) versions into Brazilian Portuguese were done following recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). This guideline includes the following steps: preparation, forward translation, reconciliation, back translation, back translation review, harmonization, cognitive debriefing, debriefing results review, proofreading and final report. Results The Brazilian Portuguese versions of the SMPI were well-accepted by respondents. Changes in about two-thirds of the items were considered necessary to obtain the final Brazilian Portuguese version of the SMPI. Conclusions Both versions of the SMPI are now available in Brazilian Portuguese. The instrument could become an important option to enhance studies on melancholia in Portuguese-speaking samples.

BDNF prevents central oxidative damage in a chronic unpredictable mild stress model: The possible role of PRDX-1 in anhedonic behavior.

Prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis and sustained increase of glucocorticoids have been evidenced in major depression and are related to changes involving neurotrophins and markers of oxidative stress in response to inflammation. This study aimed to evaluate central measures of brain-derived neurotrophic factor (BDNF), oxidative damage and total antioxidant capacity in rats submitted to chronic unpredictable mild stress (CUMS), as well as to investigate the relationship between BDNF levels and differentially processes. For this purpose, male Wistar rats were submitted to CUMS for six weeks. Based on a sucrose preference test (SPT), the animals were divided into anhedonic or non-anhedonic clusters. Afterwards, forced swim test (FST) and open field test (OFT) were performed, and the animals were euthanized. Brain tissue was collected, followed by quantification of oxidative damage, total antioxidant capacity and BDNF levels. Anhedonic behavior was evidenced in stress-susceptible animals through decreased sucrose preference. No differences were found in FST or OFT results. We observed increased BDNF levels in the hippocampus (HPC) of animals exposed to the CUMS protocol, accompanied by decreased total antioxidant capacity, despite the absence of oxidative damage to lipids and proteins. Moreover, we used a bioinformatics approach to identify proteins involved in oxidative stress and inflammation pathways, which were differentially expressed in anhedonic animals from other studies with similar experimental protocol. expressed proteins (DEP) involved in oxidative stress and inflammatory biological Anhedonic behavior was associated with peroxiredoxin-1 (PRDX-1) up-regulation and down-regulation of proteins involved with apoptotic and inflammation signaling (RELA, ASK-1 and TAK-1) in the HPC. Taken together, these data suggest that BDNF and PRDX-1 might be involved in initial stress response, playing a compensatory role by preventing oxidative damage to lipids and proteins through the modulation of antioxidant defense after CUMS in anhedonic animals.

Application of multi-block analysis and mixture design with process variable for development of chocolate cake containing yacon (Smallanthus sonchifolius) and maca (Lepidium meyenii).

BACKGROUND: In this study, a chocolate cake formulation was developed with partial substitution of wheat flour by yacon and maca flour. A simplex-centroid design was applied to determine the proportions of the three flours, and the amount of water was included as a process variable at three distinct levels. According to the overall acceptability of the cakes, the tasters were separated into two groups using k-means. RESULTS: After segmentation, regression models were constructed for overall acceptability of each group; R2adjusted values of 92.5% for group 1 and 98.9% for group 2 were obtained. Using the sequential simplex method an optimized formulation was determined for group 1 (0.49 kgwheat kg-1total flour , 0.37 kgyacon kg-1total flour , 0.14 kgmaca kg-1total flour and 140.0 mL of water) and another for group 2 (0.35 kgwheat kg-1total flour , 0.65 kgyacon kg-1total flour and 120.0 mL of water). In addition to these formulations, a third formulation was proposed with a greater maca proportion (0.32 kgmaca kg-1total flour ), which does not significantly alter the overall acceptability of both groups. The three optimized formulations and two control formulations were evaluated through free-choice profiling. The data were evaluated using the multi-block method common components and specific weights analysis (CCSWA). CONCLUSION: It was observed that a greater proportion of maca intensified brownness and burnt aroma and taste, whereas a larger proportion of yacon produced a better appearance, softness, sweetness and chocolate flavor. © 2017 Society of Chemical Industry.