Perinatal factors as risk factors of bipolar disorder onset in young adulthood: a 22-year birth cohort.

BACKGROUND: Bipolar disorder (BD) is a leading cause of disability-adjusted life years in young adults. Complications during prenatal periods have been associated with BD previously. The study aims to examine the association between perinatal factors and BD in order to prevent the risk of developing BD. METHODS: 3,794 subjects from the 1993 Pelotas population-based birth cohort study were included. We assessed 27 initial variables at birth and modelled BD onset at 18 and 22 years. We performed bivariate analysis, using binomial logistic regression models. The variables with p-value smaller than 0.05 were included into a multiple regression with confounding variables. RESULTS: Maternal smoking was associated with a 1.42-fold increased risk of BD at 18 or 22 years old (95% CI: 1.091-1.841), and maternal passive exposure to tobacco with a 1.43-fold increased risk (95% CI: 1.086-1.875). No association was found between other perinatal factors and BD after controlling for confounding factors. CONCLUSION: The results of this cohort corroborate with previous findings in the literature that already indicate the negative outcomes of maternal smoking during pregnancy. They may now be linked to other studies to target these factors for preventing the development of BD.

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.

Differential biomarker signatures in unipolar and bipolar depression: A machine learning approach.

OBJECTIVE: This study used machine learning techniques combined with peripheral biomarker measurements to build signatures to help differentiating (1) patients with bipolar depression from patients with unipolar depression, and (2) patients with bipolar depression or unipolar depression from healthy controls. METHODS: We assessed serum levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-α, interferon-γ, interleukin-17A, brain-derived neurotrophic factor, lipid peroxidation and oxidative protein damage in 54 outpatients with bipolar depression, 54 outpatients with unipolar depression and 54 healthy controls, matched by sex and age. Depressive symptoms were assessed using the Hamilton Depression Rating Scale. Variable selection was performed with recursive feature elimination with a linear support vector machine kernel, and the leave-one-out cross-validation method was used to test and validate our model. RESULTS: Bipolar vs unipolar depression classification achieved an area under the receiver operating characteristics (ROC) curve (AUC) of 0.69, with 0.62 sensitivity and 0.66 specificity using three selected biomarkers (interleukin-4, thiobarbituric acid reactive substances and interleukin-10). For the comparison of bipolar depression vs healthy controls, the model retained five variables (interleukin-6, interleukin-4, thiobarbituric acid reactive substances, carbonyl and interleukin-17A), with an AUC of 0.70, 0.62 sensitivity and 0.7 specificity. Finally, unipolar depression vs healthy controls comparison retained seven variables (interleukin-6, Carbonyl, brain-derived neurotrophic factor, interleukin-10, interleukin-17A, interleukin-4 and tumor necrosis factor-α), with an AUC of 0.74, a sensitivity of 0.68 and 0.70 specificity. CONCLUSION: Our findings show the potential of machine learning models to aid in clinical practice, leading to more objective assessment. Future studies will examine the possibility of combining peripheral blood biomarker data with other biological data to develop more accurate signatures.

Effects of lithium on inflammatory and neurotrophic factors after an immune challenge in a lisdexamfetamine animal model of mania

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.

The prevalence and clinical correlates of cannabis use and cannabis use disorder among patients with bipolar disorder: A systematic review with meta-analysis and meta-regression.

Bipolar disorder (BD) is commonly associated with comorbidities, especially substance use disorders. In light of this, the present review aimed to investigate the prevalence and clinical correlates of cannabis use in BD. Studies evaluating the prevalence of cannabis use among patients with BD and studies reporting a dichotomous sample of patients with cannabis use compared to those without the use were included. Meta-analyses using random-effects models were performed, and sources of heterogeneity were explored using meta-regression. The search resulted in 2918 publications, of which 53 were included. The prevalence of cannabis use was 24% (95%CI:18-29; k = 35; n = 51,756). Cannabis use was significantly associated with being younger, male, and single; having fewer years of education and an earlier onset of affective symptoms; and lifetime psychotic symptoms, suicide attempts, and use of tobacco, alcohol, and other substances. In conclusion, cannabis use present in almost one-quarter of patients with BD and is associated with factors that are highly relevant for both clinical practice and public health.

Effects of lithium on inflammatory and neurotrophic factors after an immune challenge in a lisdexamfetamine animal model of mania.

OBJECTIVE: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. METHODS: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1ß, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. RESULTS: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. CONCLUSION: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.

Differences in coping strategies in adult patients with bipolar disorder and their first-degree relatives in comparison to healthy controls / Diferenças entre as estratégias de coping em pacientes adultos com transtorno bipolar e seus familiares em comparação com controles saudáveis

Abstract Introduction: The objective of this study was to compare patients with bipolar disorder (BD), their first-degree relatives and a group of healthy controls in terms of use of adaptive and maladaptive coping strategies, exploring differences between specific types of strategies and their correlations with clinical variables. Methods: This was a cross-sectional study enrolling 36 euthymic patients with BD, 39 of their first-degree relatives and 44 controls. Coping strategies were assessed using the Brief COPE scale. Results: Significant differences were detected in the use of adaptive and maladaptive strategies by patients, their first-degree relatives and controls. Patients used adaptive strategies less often than the patients' relatives (p<0.001) and controls (p = 0.003). There was no significant difference between first-degree relatives and controls (p=0.707). In contrast, patients (p<0.001) and their relatives (p=0.004) both exhibited higher scores for maladaptive coping than controls. There was no significant difference regarding the use of maladaptive strategies between patients and their relatives (p=0.517). Conclusions: First-degree relatives were at an intermediate level between patients with BD and controls regarding the use of coping skills. This finding supports the development of psychosocial interventions to encourage use of adaptive strategies rather than maladaptive strategies in this population.

Resumo Introdução: O objetivo deste estudo foi comparar os pacientes com transtorno bipolar (TB), seus familiares de primeiro grau e um grupo de controles saudáveis em termos de uso de estratégias adaptativas e não adaptativas, explorando diferenças entre tipos específicos de estratégias e suas correlações com variáveis clínicas. Métodos: Estudo transversal, envolvendo 36 pacientes com TB eutímicos, 39 familiares de primeiro grau e 44 controles. As estratégias de enfrentamento foram avaliadas usando a escala Brief COPE. Resultados: Foram detectadas diferenças significativas no uso de estratégias adaptativas e não adaptativas por pacientes, seus familiares e controles. Os pacientes usaram estratégias adaptativas com menos frequência do que os familiares (p<0,001) e controles (p=0,003). Não houve diferença significativa entre familiares dos pacientes e controles (p=0,707). Por outro lado, os pacientes (p<0,001) e seus familiares (p=0,004) exibiram pontuações mais elevadas para coping não adaptativo em relação aos controles. Não houve diferença significativa quando os pacientes foram comparados com seus familiares (p=0,517). Conclusões: Familiares de primeiro grau estavam em um nível intermediário entre pacientes com TB e controles no que diz respeito ao uso de habilidades de enfrentamento. Esta descoberta apoia o desenvolvimento de intervenções psicossociais para incentivar o uso de estratégias adaptativas em vez de estratégias inadequadas nessa população.

Mental health information online: what we have learned from social media metrics in BuzzFeed's Mental Health Week / Informações de saúde mental on-line: o que aprendemos com as métricas de mídias sociais na Semana de Saúde Mental do BuzzFeed

Abstract Introduction The Internet has seen rapid growth in the number of websites focusing on mental health content. Considering the increased need for access to accurate information about mental health treatment, it is important to understand the promotion of this information online. Objective To analyze BuzzFeed's Mental Health Week (BFMHW) interactions on its own website and in related social media platforms (Facebook, Twitter and YouTube) using metrics of information delivery in mental health topics. Methods We extracted social media metrics from the 20 posts with the highest number of BuzzFeed interactions on the BFMHW website and from 41 videos available on the BFMHW playlist created by the BuzzFeed Video profile on YouTube. We analyzed the format and content used in BuzzFeed's publishing methods as well as the following social media metrics: exposure (presence online, views and time online), influence (likes) and engagement (comments, shares, replies and BuzzFeed interactions). Results Analysis of the variables revealed that audience engagement is associated with the number of medias in which the content is published: views on YouTube and shares on Facebook (0.71, p<0.001), total interactions on Facebook (0.66, p<0.001) and BuzzFeed number of total interactions (0.56, p<0.001). Conclusions Our results suggest that videos on YouTube may be an important information channel, including activity and engagement on other medias such as Facebook. Information may be more effective in reaching the audience if it is delivered in more than one media and includes personal experiences, some humor in content and detailed information about treatment.

Resumo Introdução O número de sites com foco em conteúdo de saúde mental vem crescendo rapidamente. Considerando a necessidade crescente de acesso a informações precisas sobre tratamento em saúde mental, é importante entender a promoção dessas informações on-line. Objetivo Analisar as interações da Semana de Saúde Mental do BuzzFeed (BuzzFeed's Mental Health Week - BFMHW) em seu próprio site e em plataformas de mídia social relacionadas (Facebook, Twitter e YouTube) usando métricas de entrega de informações em tópicos de saúde mental. Métodos Extraímos métricas de mídias sociais das 20 postagens com o maior número de interações no site da BFMHW e de 41 vídeos disponíveis na playlist da BFMHW criada pelo perfil BuzzFeed Video no YouTube. Analisamos o formato e o conteúdo usados nos métodos de publicação do BuzzFeed, bem como as seguintes métricas de mídias sociais: exposição (presença on-line, visualizações e tempo on-line), influência (curtidas) e engajamento (comentários, compartilhamentos, respostas e interações do BuzzFeed). Resultados A análise das variáveis revelou que o envolvimento do público está associado ao número de mídias em que o conteúdo é publicado: visualizações no YouTube e compartilhamentos no Facebook (0,71, p <0,001), interações totais no Facebook (0,66, p <0,001) e número de interações totais no BuzzFeed (0,56, p <0,001). Conclusões Nossos resultados sugerem que o YouTube pode ser um importante canal de informações, incluindo atividades e envolvimento em outras mídias, como o Facebook. As informações podem alcançar o público de forma mais eficaz se forem exibidas em mais de uma mídia e incluírem experiências pessoais, algum humor no conteúdo e informações detalhadas sobre o tratamento.

Translation and cross-cultural adaptation of the Brazilian Portuguese version of the Emotional Memory Scale / Tradução e adaptação transcultural da versão brasileira da Escala de Memória Emocional

Abstract Background Emotional memory is an important type of memory that is triggered by positive and negative emotions. It is characterized by an enhanced memory for emotional stimuli which is usually coupled with a decrease in memory of neutral preceding events. Emotional memory is strongly associated with amygdala function and therefore could be disrupted in neuropsychiatric disorders. To our knowledge, there is no translated and culturally adapted instrument for the Brazilian Portuguese speaking population to assess emotional memory. Objective To report the translation and cross-cultural adaptation of a Brazilian Portuguese version of the Emotional Memory Scale, originally published by Strange et al. in 2003. Methods The author of the original scale provided 36 lists with 16 words each. Translation was performed by three independent bilingual translators. Healthy subjects assessed how semantically related each word was within the list (0 to 10) and what the emotional valence of each word was (-6 to +6). Lists without negative words were excluded (negative selection), most positive and most unrelated words were excluded (positive and semantic selection, respectively), and lists with low semantic relationship were excluded (semantic assessment). Results Five lists were excluded during negative selection, four words from each list were excluded in positive and semantic selection, and 11 lists were excluded during semantic assessment. Finally, we reached 20 lists of semantically related words; each list had one negative word and 11 neutral words. Conclusion A scale is now available to evaluate emotional memory in the Brazilian population and requires further validation on its psychometrics properties.

Resumo Introdução Memória emocional é um tipo importante de memória que é acionado por emoções positivas e negativas. Ela é caracterizada por um aumento de memória para estímulos emocionais que normalmente está associado a um prejuízo de memória para eventos neutros que os precedem. Memória emocional é fortemente relacionada à função da amígdala e, portanto, pode estar alterada em transtornos neuropsiquiátricos. Pelo nosso conhecimento, não existe instrumento traduzido e adaptado culturalmente para a população falante de português brasileiro para avaliar memória emocional. Objetivo Descrever a tradução e adaptação transcultural para o português brasileiro da Escala de Memória Emocional, originalmente publicada por Strange et al. em 2003. Métodos O autor da escala original forneceu 36 listas com 16 palavras cada. A tradução foi feita por três tradutores bilíngues e independentes. Sujeitos saudáveis foram selecionados para avaliar o quanto cada palavra era semanticamente relacionada dentro da lista (0 a 10) e qual era a valência emocional de cada palavra (-6 a +6). Listas sem palavras negativas foram excluídas (seleção negativa), palavras mais positivas e menos relacionadas de cada lista foram excluídas (seleções positiva e semântica, respectivamente) e listas com relação semântica fraca foram excluídas (avaliação semântica). Resultados Cinco listas foram excluídas durante a seleção negativa, quatro palavras de cada lista foram excluídas nas seleções positiva e semântica, e 11 listas foram excluídas na avaliação semântica. Por fim, chegamos em 20 listas de palavras semanticamente relacionadas; cada lista com uma palavra negativa e 11 palavras neutras. Conclusão Uma escala está disponível para avaliar memória emocional na população brasileira e requer posterior validação de suas propriedades psicométricas.

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.

Telomere Length, Oxidative Stress, Inflammation and BDNF Levels in Siblings of Patients with Bipolar Disorder: Implications for Accelerated Cellular Aging.

Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls. Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed. Serum levels of brain-derived neurotrophic factor, interleukin-6, interleukin-10, tumor necrosis factor-α, C-C motif chemokine 11, C-C motif chemokine 24, and 3-nitrotyrosine were measured, as were the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Results: Telomere length was different between the 3 groups (P = .041) with both patients and siblings showing a shorter T/S ratio compared with healthy controls. Patients showed increased levels of interleukin-6 (P = .005) and interleukin-10 (P = .002) compared with controls as well as increased levels of interleukin-6 (p = 0.014) and CCL24 (P = .016) compared with their siblings. C-C motif chemokine 11 levels were increased in siblings compared with controls (P = .015), and a similar tendency was found in patients compared with controls (P = .045). Glutathione peroxidase activity was decreased in patients compared with controls (P = .006) and siblings (P = .025). No differences were found for the other markers. Conclusions: The present results suggest that unaffected siblings may present accelerated aging features. These neurobiological findings may be considered as endophenotypic traits. Further prospective studies are warranted.

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.

Peripheral adenosine levels in euthymic patients with bipolar disorder.

Recent evidence points to the involvement of the purinergic signaling in the pathophysiology of bipolar disorder. The aim of this study was to assess the serum levels of adenosine and to evaluate its relation to functioning in 24 euthymic patients with bipolar disorder type I and in 25 matched healthy controls. Subjects were evaluated using the functioning assessment short test. Serum purine levels were measured by high pressure liquid chromatography. Our results show a decrease in serum adenosine levels in bipolar disorder patients compared with controls (t= -4.8, df= 43.96, p<0.001). Moreover, a significant negative correlation was found between patient adenosine levels and depression scale scores (r= -0.642, p= 0.001). Higher functional impairment was linked to lower levels of adenosine in patients (rho= -0.551, p= 0.008). Taken together, our results provide evidence for a purinergic imbalance in bipolar disorder, specifically an adenosinergic dysfunction. Our results also indicate a relation between adenosine levels and the functional impairment caused by the disorder, which could demonstrate a potential relation of adenosine levels in worsening of symptoms.

Socioeconomic Disadvantage Moderates the Association between Peripheral Biomarkers and Childhood Psychopathology.

BACKGROUND: Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF. METHODS AND FINDINGS: Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-demographic characteristics and mental health problems using the Child Behaviour Checklist (CBCL) DSM-oriented scales. SED was evaluated using a cumulative risk model. Generalized linear models were used to assess associations between SED, biomarkers levels and psychopathology. SED was significantly associated with serum levels of IL6 (RR = 1.026, 95% CI 1.004; 1.049, p = 0.020) and TBARS (RR = 1.077, 95% CI 1.028; 1.127, p = 0.002). The association between SED and BDNF was not statistically significant (RR = 1.031, 95% CI 0.997; 1.066, p = 0.077). SED was also significantly associated with all CBCL DSM-oriented scales (all p < 0.05), whereas serum biomarkers (i.e. IL6, TBARS, BDNF) were associated with specific subscales. Moreover, the associations between serum biomarkers and domains of psychopathology were moderated by SED, with stronger correlations between mental health problems, IL6, TBARS, and BDNF being observed in children with high SED. CONCLUSIONS: In children, SED is highly associated with mental health problems. Our findings suggest that this association may be moderated via effects on multiple interacting neurobiological systems.

The FKBP5 polymorphism rs1360780 is associated with lower weight loss after bariatric surgery: 26 months of follow-up.

BACKGROUND: Bariatric surgery is the most effective treatment choice for severe obesity. Recent literature indicates that FK506-binding protein 51 (FKBP51) could play a role in energy homeostasis, influencing adipogenesis and weight. OBJECTIVE: To evaluate if the presence of the T allele of the FKBP5 SNP rs1360780, associated with increased FKBP51 expression, could influence weight loss after bariatric surgery. SETTING: Hospital de Clínicas de Porto Alegre, Brazil. METHODS: Forty-two patients awaiting bariatric surgery were included, and the presence of the FKBP5 rs1360780 polymorphism was evaluated. During the postoperative period, a 26-month follow-up of weight loss was performed (n = 42, 36, 35, 35, and 30, from the first to fifth postoperative evaluation, respectively; loss to follow-up: 28.6%). RESULTS: Carriers of the T allele presented significantly lower weight loss compared with patients with the C/C genotype after the 12th to 14th month follow-up period. Differences in weight loss between genotypes ranged from 14.2% to 19.9% of excess weight loss (P = .045 and .004, respectively) and from 7.6% to 9.0% of total weight loss (P = .002 for both comparisons). Furthermore, carriers of the T allele also presented an earlier cessation of weight loss after surgery. CONCLUSION: The presence of the T allele of the FKBP5 SNP rs1360780 was associated with weight loss after bariatric surgery. Bariatric surgery can interact with genes involved in metabolic regulation, leading to different weight loss outcomes.

Reduced Neurite Density in Neuronal Cell Cultures Exposed to Serum of Patients with Bipolar Disorder.

BACKGROUND: Increased inflammatory markers and oxidative stress have been reported in serum among patients with bipolar disorder (BD). The aim of this study is to assess whether biochemical changes in the serum of patients induces neurotoxicity in neuronal cell cultures. METHODS: We challenged the retinoic acid-differentiated human neuroblastoma SH-SY5Y cells with the serum of BD patients at early and late stages of illness and assessed neurite density and cell viability as neurotoxic endpoints. RESULTS: Decreased neurite density was found in neurons treated with the serum of patients, mostly patients at late stages of illness. Also, neurons challenged with the serum of late-stage patients showed a significant decrease in cell viability. CONCLUSIONS: Our findings showed that the serum of patients with bipolar disorder induced a decrease in neurite density and cell viability in neuronal cultures.

Rumination as a Marker of Psychological Improvement in Transsexual Women Postoperative.

Purpose: This study aimed to analyze rumination levels of transsexual women before and after gender affirmation surgery (GAS). Rumination scores may represent a broader measure of GAS success and an alternative to patient-reported satisfaction, quality of life, well-being, or the presence of "caseness" for anxiety or depression as previously established in the literature. Methods: Thirty-nine transsexual women were recruited. The participants completed the rumination scale of the Response Styles Questionnaire (RSQ) and were divided into three subsets according to the treatment time. Results: The rumination scores were lower in the transsexual women who had undergone surgical procedures on primary sexual characteristics and gradually decreased with each additional procedure completed with respect to secondary sexual characteristics. Conclusion: Rumination appears to comprise an important marker of improvement in post-GAS transsexual women.

Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Studies investigating inflammatory markers in post-traumatic stress disorder (PTSD) have yielded mixed results. The aim of our study was to compare concentrations of inflammatory markers in patients with PTSD compared with healthy controls. METHODS: We did a meta-analysis and meta-regression of studies comparing inflammatory markers between patients with PTSD and healthy controls by searching PubMed, Embase, Scopus, Web of Science, and PsycINFO for articles published between Jan 1, 1960, and April 7, 2015. From eligible studies (ie, cross-sectional studies or baseline data from longitudinal studies of peripheral blood cytokine concentrations that compared adults with PTSD with healthy controls), we extracted outcomes of interest, such as mean and SD of peripheral blood cytokines, the time of day blood was collected, whether the study allowed patients with comorbid major depressive disorder in the PTSD group, whether patients were medication free, and severity of PTSD symptoms. We undertook meta-analyses whenever values of inflammatory markers were available in two or more studies. A random-effects model with restricted maximum-likelihood estimator was used to synthesise the effect size (assessed by standardised mean difference [SMD]) across studies. FINDINGS: 8057 abstracts were identified and 20 studies were included. Interleukin 6 (SMD 0.88; p=0.0003), interleukin 1ß (SMD 1.42; p=0.045), and interferon γ (SMD 0.49; p=0.002) levels were higher in the PTSD group than in healthy controls. Subgroup meta-analysis of patients who were not given medication showed higher tumour necrosis factor α (TNFα; SMD 0.69, 95% CI 0.35-1.02; p<0.0001) in the PTSD group than the control group in addition to the aforementioned cytokines. TNFα (SMD 1.32, 0.13-2.50; p=0.003), interleukin 1ß (SMD 2.35, 0.01-4.68; p=0.048), and interleukin 6 (SMD 1.75, 0.97-2.53; p<0.0001) levels remained increased in the PTSD group in a subgroup meta-analysis of studies that excluded comorbid major depressive disorder. Illness duration was positively associated with interleukin 1ß levels (b=0.33, p<0.0001) and severity with interleukin 6 (b=0.02, p=0.042). A model composed of several variables-presence of comorbid major depressive disorder, use of psychotropic medications, assay used, and time of day blood was collected-explained the large amount of heterogeneity between interleukin 1ß, interleukin 6, and C-reactive protein studies. Egger's linear regression test revealed a potential publication bias for interleukin 1ß. Additionally, for most inflammatory markers, study heterogeneity was reported to be high (I(2)>75%). INTERPRETATION: PTSD is associated with increased interleukin 6, interleukin 1ß, TNFα, and interferon γ levels. This information might be useful for consideration of chronic low-grade inflammation as a potential target or biomarker in PTSD treatment. Use of psychotropic medication and presence of comorbid major depressive disorder were important moderators that might explain the inconsistency between results of previous studies. Our search strategy used a range of databases and we made exhaustive effort to acquire data by contacting the authors. Notably, high levels of between-study heterogeneity were recorded for most cytokine variables measured in our analysis. However, meta-regression analysis could explain a large amount of this heterogeneity. FUNDING: None.

Rumination in bipolar disorder: a systematic review

Objective:To conduct a systematic review of the literature about the symptom of rumination in bipolar disorder (BD).Methods:We searched the MEDLINE (PubMed), ISI Web of Knowledge, PsycINFO, and SciELO databases using the descriptors “rumination” and “bipolar disorder” and no time limits. This strategy yielded 105 references, of which 74 were selected. Inclusion criteria were studies involving patients with BD and the use of at least one validated scale for the assessment of rumination. Review articles were excluded. Seventeen articles were ultimately analyzed and included in the review.Results:Rumination is present in all BD phases, is a stable interepisodic symptom, is associated with symptoms of depression, anxiety, and hypomania, and may occur in response to both positive and negative affect. There is no research on rumination and neurobiological findings in patients with BD.Conclusions:Rumination seems to be independent of mood state, but shows close relationship with it. It is possible that rumination has a negative impact on cognitive and executive functions, particularly inhibitory control. Finally, rumination is an important symptom in both phases of BD, and, therefore, may be a useful target for further exploration as a dimensional domain and a transdiagnostic phenomenon in Research Domain Criteria (RDoC) projects.