Cannabidiol as an Adjunctive Treatment for Acute Bipolar Depression: A Pilot Study: Le cannabidiol comme traitement d'appoint de la dépression bipolaire aiguë : une étude pilote.

OBJECTIVE: The treatment of bipolar depression remains challenging due to the limited effective and safe therapeutic options available; thus, developing newer treatments that are effective and well tolerable is an urgent unmet need. The objective of the present trial was to test 150 to 300 mg/day of cannabidiol as an adjunctive treatment for bipolar depression. METHOD: A randomized, double-blind, placebo-controlled pilot study to assess the efficacy of adjunctive cannabidiol in bipolar depression was used. Efficacy parameters were changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 8. Secondary outcomes included response and remission rates, changes in anxiety and psychotic symptoms, and changes in functioning. Patients continued double-blind treatment until week 12 to monitor for adverse effects, laboratory analysis, and manic symptoms. Study registry: NCT03310593. RESULTS: A total of 35 participants were included. MADRS scores significantly decreased from baseline to the endpoint (placebo, -14.56; cannabidiol, -15.38), but there was no significant difference between the groups. Similarly, there were no other significant effects on the secondary outcomes. However, an exploratory analysis showed a significant effect of cannabidiol 300 mg/day in reducing MADRS scores from week 2 to week 8 (placebo, -6.64; cannabidiol, -13.72). There were no significant differences in the development of manic symptoms or any other adverse effects. CONCLUSION: Cannabidiol did not show significantly higher adverse effects than placebo. Despite the negative finding on the primary outcome, an exploratory analysis suggested that cannabidiol should be further studied in bipolar depression in higher doses of at least 300 mg/day and under research designs that could better control for high placebo response.

Ketamine study: Protocol for naturalistic prospective multicenter study on subcutaneous ketamine infusion in depressed patients with active suicidal ideation.

Background: Psychiatric disorders are associated with more than 90% of reported suicide attempts worldwide, but few treatments have demonstrated a direct effect in reducing suicide risk. Ketamine, originally an anesthetic, has been shown anti-suicide effects in clinical trials designed to treat depression. However, changes at the biochemical level were assessed only in protocols of ketamine with very limited sample sizes, particularly when the subcutaneous route was considered. In addition, the inflammatory changes associated with ketamine effects and their correlation with response to treatment, dose-effect, and suicide risk warrant further investigation. Therefore, we aimed to assess whether ketamine results in better control of suicidal ideation and/or behavior in patients with depressive episodes and whether ketamine affects psychopathology and inflammatory biomarkers. Materials and methods: We report here the design of a naturalistic prospective multicenter study protocol of ketamine in depressive episodes carried out at Hospital de Clínicas de Porto Alegre (HCPA) and Hospital Moinhos de Vento (HMV). The study was planned to recruit adult patients with Major depressive disorder (MDD) or Bipolar disorder (BD) types 1 or 2, who are currently in a depressive episode and show symptoms of suicidal ideation and/or behavior according to the Columbia-Suicide Severity Rating Scale (C-SSRS) and have been prescribed ketamine by their assistant psychiatrist. Patients receive ketamine subcutaneously (SC) twice a week for 1 month, but the frequency can be changed or the dose decreased according to the assistant physician's decision. After the last ketamine session, patients are followed-up via telephone once a month for up to 6 months. The data will be analyzed using repeated measures statistics to evaluate the reduction in suicide risk as a primary outcome, as per C-SSRS. Discussion: We discuss the need for studies with longer follow-ups designed to measure a direct impact on suicide risk and that additional information about the safety and tolerability of ketamine in particular subset of patients such as those with depression and ideation suicide. In line, the mechanism behind the immunomodulatory effects of ketamine is still poorly understood. Trial registration: https://clinicaltrials.gov/, identifier NCT05249309.

Differences in coping strategies in adult patients with bipolar disorder and their first-degree relatives in comparison to healthy controls.

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.

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.

Increased cocaine and amphetamine-regulated transcript cord blood levels in the newborns exposed to crack cocaine in utero.

BACKGROUND: Cocaine and amphetamine-regulated transcript (CART) is an endogenous antioxidant present since the embryonic period. CART is activated by high levels of dopamine and might be of interested in understanding the changes in the REDOX system associated with crack/cocaine intake. The goal of this study was to determine whether exposure to crack in utero is associated with increased CART levels. METHODS: In this cross-sectional study with consecutive sampling, we compared the umbilical cord blood (UCB) CART levels (µg/mL) of newborns exposed to crack/cocaine in utero (EN, n = 57) to levels in non-exposed newborns (NEN, n = 99). In addition, we compared serum CART levels between EN and NEN mothers, in the immediate postpartum period. Potential confounders, such as perinatal data (e.g., weight, Apgar, etc.), psychopathology (DSM-IV), and use of drugs other than crack (ASSIST) were assessed. RESULTS: According to general linear model analysis, the adjusted mean CART was significantly higher in EN (0.180, 95% CI 0.088-0.272) than in NEN (0.048, 95% CI 0.020-0.076; p < 0.002; d = 0.68). The difference in CART levels between EN and NEN mothers was not significant (p ≥ 0.05). CONCLUSION: The increase in CART levels in EN UBC suggests a response to crack/cocaine-induced oxidative stress during gestational period, as a potential attempt of neuroprotection. In adult women in puerperium, however, this endogenous antioxidant recruitment does not seem to operate.

Acute stress disorder and defense mechanisms: a study of physical trauma patients admitted to an emergency hospital.

INTRODUCTION: Acute stress disorder (ASD) encompasses a set of symptoms that can arise in individuals after exposure to a traumatic event. This study assessed the defense mechanisms used by victims of physical trauma who developed ASD. METHOD: This was a controlled cross-sectional study of 146 patients who suffered physical trauma and required hospitalization. A structured questionnaire was used to evaluate ASD symptoms based on DSM-5 diagnostic criteria, in addition to the Defense Style Questionnaire (DSQ). RESULTS: Ten participants (6.85%) received a positive diagnosis of ASD, and 136, (93.15%) a negative diagnosis. The majority of the sample consisted of men with median age ranging from 33.50 to 35.50. The most prevalent defense mechanisms among the 10 patients with ASD were cancellation and devaluation, which belong to the neurotic and immature factors, respectively. Positive associations between the presence of symptoms from criterion B of the DSM-5 and defense mechanisms from the DSQ were found. These included the mechanisms of undoing, projection, passive aggression, acting out, autistic fantasy, displacement, and somatization. CONCLUSION: Patients with ASD employed different defense mechanisms such as undoing and devaluation when compared to patients not diagnosed with ASD. These results mark the importance of early detection of ASD symptoms at a preventative level, thereby creating new possibilities for avoiding exacerbations related to the trauma, which represents an important advance in terms of public health.

Acute stress disorder and defense mechanisms: a study of physical trauma patients admitted to an emergency hospital / Transtorno de estresse agudo e mecanismos de defesa: pesquisa com pacientes que sofreram trauma físico atendidos em um hospital de emergência

Abstract Introduction: Acute stress disorder (ASD) encompasses a set of symptoms that can arise in individuals after exposure to a traumatic event. This study assessed the defense mechanisms used by victims of physical trauma who developed ASD. Method: This was a controlled cross-sectional study of 146 patients who suffered physical trauma and required hospitalization. A structured questionnaire was used to evaluate ASD symptoms based on DSM-5 diagnostic criteria, in addition to the Defense Style Questionnaire (DSQ). Results: Ten participants (6.85%) received a positive diagnosis of ASD, and 136, (93.15%) a negative diagnosis. The majority of the sample consisted of men with median age ranging from 33.50 to 35.50. The most prevalent defense mechanisms among the 10 patients with ASD were cancellation and devaluation, which belong to the neurotic and immature factors, respectively. Positive associations between the presence of symptoms from criterion B of the DSM-5 and defense mechanisms from the DSQ were found. These included the mechanisms of undoing, projection, passive aggression, acting out, autistic fantasy, displacement, and somatization. Conclusion: Patients with ASD employed different defense mechanisms such as undoing and devaluation when compared to patients not diagnosed with ASD. These results mark the importance of early detection of ASD symptoms at a preventative level, thereby creating new possibilities for avoiding exacerbations related to the trauma, which represents an important advance in terms of public health.

Resumo Introdução: O transtorno de estresse agudo (TEA) reúne um conjunto de sintomas que pode surgir nos indivíduos após exposição a um evento traumático. Este estudo verificou a relação entre o estilo defensivo e o desenvolvimento de TEA e seus sintomas em uma amostra de pacientes que sofreram trauma físico. Métodos: Este estudo transversal controlado envolveu 146 pacientes que sofreram trauma físico e necessitaram hospitalização. Um questionário estruturado foi utilizado para avaliar sintomas de TEA, baseado nos critérios diagnósticos do DSM-5, além do Questionário de Estilo Defensivo (Defense Style Questionnaire - DSQ). Resultados: Dez (6,85%) pacientes tiveram diagnóstico positivo para TEA, e 136 (93,15%), diagnóstico negativo. A maioria da amostra foi composta por homens com idade mediana variando de 33,50 a 35,50. Nos 10 pacientes positivos para TEA, destacou-se a maior utilização de mecanismos de defesa de anulação e desvalorização, pertencentes ao fator neurótico e ao fator imaturo, respectivamente. Foram observadas associações positivas entre presença de sintomas de TEA do critério B do DSM-5 e os mecanismos de defesa do DSQ, sobretudo nos mecanismos de anulação, projeção, agressão passiva, acting out, fantasia autística, deslocamento e somatização. Conclusão: Pacientes com TEA utilizaram mais mecanismos de defesa do tipo anulação e desvalorização quando comparados aos pacientes sem diagnóstico de TEA. Ressalta-se a importância da detecção precoce de sintomas de TEA a fim de evitar outros agravos relacionados ao trauma, o que representa uma importante evolução em termos de saúde pública.

Childhood trauma and suicide attempt: A meta-analysis of longitudinal studies from the last decade.

Childhood trauma (CT) is a modifiable risk factor for lifetime suicide attempts (SA). However, the extent to which each type of CT increases SA risk is unclear. This study aimed to conduct a meta-analysis of longitudinal studies published in the last 10 years about the relationship between CT and lifetime SA risk. The PUBMED, PsycINFO, ISI, and EMBASE databases were searched for cohort studies that reported AS during follow-up and included an assessment of CT. A meta-analysis was conducted to identify potential effects of each type of CT on SA. Seven unique studies were included for review. Sexual (n=6, OR=3.73, 95%CI 2.94-4.75, p<0.001), physical (n=6, OR=4.11, 95%CI 2.30-7.33, p<0.001), and emotional abuse (n=3, OR=3.98, 95%CI 2.89-5.64, p<0.001), as well as physical neglect (n=2, OR=3.42, 95%CI 2.09-5.59, p<0.001), were associated with SA. Emotional neglect and a broken home were not significantly associated with further SA. The modes of CT that most contribute to SA in later life are physical, emotional, and sexual abuse and physical neglect, in descending order.

Differences in biomarkers of crack-cocaine adolescent users before/after abstinence.

AIMS: To measure the variation in Brain-Derived Neurotrophic Factor (BDNF), Thiobarbituric Acid Reactive Substances (TBARS) and interleukin (IL) levels in crack-cocaine dependent adolescents after 21days of abstinence, comparing to levels found in a group of healthy controls. DESIGN: Cross-sectional nested on a short follow-up study. SETTING: Two inpatient treatment units for adolescents, and a low-income neighborhood. PARTICIPANTS: 90 adolescents, of both genders, with diagnosis of crack cocaine dependence, and 81 healthy adolescents. MEASUREMENTS: Serum levels of IL-6, IL-10, TBARS and BDNF were assessed on admission and discharge. Drug addiction severity was assessed by the Addiction Severity Index - Teen Version (T-ASI) and Cocaine Craving Questionnaire - Brief version (CCQ-b). Psychiatric comorbidities were assessed by the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL). Generalized Estimating Equations (GEE) were used to estimate the IL-6, IL-10, TBARS and BDNF levels, adjusted for confounders. Hedges' g was used to estimate effect size. FINDINGS: TBARS (p=0.005, d=0.04), IL-6 (p=0.027, d=0.40) and IL-10 (p=0.025, d=0.41) were elevated and BDNF (p<0.001, d=0.62) was reduced (p<0.001), in patients, in comparison to controls, at admission time. Variation in those levels between admission and discharge were not significant. CONCLUSIONS: Crack-cocaine use seems to be associated with inflammatory and oxidative imbalances in adolescents.

Postural changes in different stages of schizophrenia is associated with inflammation and pain: a cross-sectional observational study.

OBJECTIVES: To assess the relationship between posture and inflammatory response markers (C-reactive protein [CRP] and von Willebrand factor [vWF]) in schizophrenics. METHODS: Forty patients with stable schizophrenia were divided into early-stage (<10 years since first episode, n = 15) and late-stage (≥10 years since first episode, n = 25) groups. Both groups were compared to controls (n = 26). All participants underwent postural assessment by biophotogrammetry. Cases alone underwent blood collection. The significance level was set at 5%, and analyses were carried out in SPSS 18.0. RESULTS: In the early-stage group, 15 postural angles were significantly different from their reference ranges, whereas in the late-stage group, only seven angles were significantly different. In comparison with the control group, only six angles were significantly different. There was no difference in inflammation markers between the early- and late-stage groups. However, CRP levels were higher in cases with greater disease severity, and vWF was associated with forward head posture. Pain correlated with five postural angles, and late-stage patients reported more pain than early-stage cases. CONCLUSIONS: CRP was associated with disease severity, while vWF and pain were associated with forward head posture, hyperlordosis and scoliosis, suggesting an association between vascular inflammation and pain, with an influence on posture.

Comparação dos níveis séricos da Cocaine and Amphetamine Regulated Transcript (CART) entre sangue de cordão umbilical e sangue periférico em gestantes usuárias de crack / Comparison between serum levels of Cocaine and Amphetamine Regulated Transcript (CART) between umbilical cord blood and peripheral blood of pregnant crack users

INTRODUÇÃO: No Brasil, o uso de crack permanece um desafio à saúde pública devido à facilidade de aquisição da droga e sua elevada capacidade de induzir dependência. A exposição intrauterina (EIU) à cocaína está associada a alterações neurocomportamentais durante a infância e adolescência. Em estudo prévio do nosso grupo, achou-se menor nível de estresse oxidativo (EO) em recém-nascidos (RN) com EIU. Uma possível explicação pode ser a Cocaine and Amphetamine Regulated Transcript (CART), um antioxidante endógeno presente desde o período embrionário e ativado por maiores níveis de dopamina. OBJETIVO: Verificar a correlação entre os níveis de CART no sangue de cordão umbilical (SCU) e sangue periférico de 57 gestantes com exposição ao crack. MÉTODOS: Trata-se de um estudo transversal, com amostragem consecutiva, em que o desfecho primário foi a correlação entre os níveis de CART no SCU e sangue periférico materno no pós-parto imediato. Dados gestacionais e perinatais foram sistematicamente coletados. RESULTADOS: Houve correlação significativa entre os níveis de CART no sangue de cordão umbilical e sangue periférico materno (rs= 0,350 e p<0,05). CONCLUSÕES: Estes achados demonstram que os níveis de CART no sangue materno e no SCU se correlacionam. Todavia, não se pode afirmar de quem é a produção, ou se é produzida por ambos. O presente trabalho pode ajudar a elucidar os caminhos neurobiológicos responsáveis pelas alterações de neurodesenvolvimento, contribuindo para a ampliação das possibilidades de intervenções precoces.

INTRODUCTION: The use of crack cocaine remains a public health challenge in Brazil, due to easy drug acquisition and its high ability to induce dependence. Intrauterine exposure (IUE) to crack cocaine is associated with neurobehavioral changes during childhood and adolescence. In a previous study of our group, lower levels of oxidative stress (OS) were found in newborns with IUE. One possible explanation may be the Cocaine and Amphetamine Regulator Transcript (CART), an endogenous antioxidant present since the embryonic period activated by higher levels of dopamine. OBJECTIVE: The aim of this study is to investigate the correlation of CART levels between umbilical cord blood (UCB) and peripheral blood samples of 57 pregnant women exposed to crack. METHODS: This is a cross-sectional study with a consecutive sampling, in which the primary outcome was the correlation between CART levels in UCB and peripheral blood of their mothers in immediate postpartum. Gestational and perinatal data were systematically collected. Spearman correlation test was performed after checking the pattern of distribution, being considered a 0.05 significance level. RESULTS: There was a significant correlation between CART levels in umbilical cord blood and peripheral blood (rs = 0.350 and p <0.05). CONCLUSIONS: These findings suggest a correlation between CART levels at UCB and mother's blood. However, it remains unclear whether it is produced by the mother, the fetus, or both. This study may help to elucidate the neurobiological pathways responsible for neurodevelopmental changes, providing a rationale for early interventions.

Crack Cocaine Use in Adolescents: Clinical Characteristics and Predictors of Early Initiation.

OBJECTIVE: To describe the clinical characteristics of adolescents with crack cocaine dependence and possible predictors of transition from drug experimentation to crack cocaine dependence. METHODS: This cross-sectional study enrolled a consecutive sample of 90 adolescents admitted to a psychiatric inpatient unit in the city of Porto Alegre in southern Brazil for crack cocaine detoxification between May 2011 and November 2012. Comorbid psychological conditions were assessed using the Kiddie-SADS-Present and Lifetime Version, and severity of drug use was assessed using the Teen Addiction Severity Index (T-ASI). Comorbidities were compared with those in a community sample of non-drug using controls (n = 81). RESULTS: Patients' mean age was 15.6 years (85.6% boys, 14.4% girls). Seventy-nine (93.2%) met criteria for cocaine dependence (DSM-IV-TR), while 78 (91.8%) had symptoms consistent with cocaine abuse. All patients had experimented with at least 1 other addictive substance before crack cocaine: 61.4%, tobacco (mean age at first use = 11.61 years); 44.3%, alcohol (age at first use = 12.43 years); and 54.5%, cannabis (age at first use = 12.15 years). Patients had used crack cocaine 23.2 days in the last month, and the mean age at first use of crack cocaine was 13.38 years. The most common psychiatric comorbidity was conduct disorder (81.8%), followed by oppositional defiant disorder (52.3%) and attention-deficit/hyperactivity disorder (44.3%), all of which were more prevalent in the patient population than in controls (P < .001). The T-ASI questionnaire showed severe consequences of drug use in most areas of life assessed. The mean time between onset of drug experimentation and crack cocaine dependence was 2.53 (SD = 1.96) years. When Cox regression models were applied, we found that predictors of earlier progression to using crack cocaine were age at first use of any drug (hazard ratio [HR] = 0.79 [95% CI, 0.71-0.88]; P < .001) and age at admission (HR = 0.7 [95% CI, 0.57-0.87]; P = .001). CONCLUSIONS: Patients were found to have a multitude of comorbid conditions, which supports the idea of treatment by a multidisciplinary health care team. For each year of delay in the age at first drug use, the chance of crack cocaine initiation is reduced by 18%. Prevention programs aimed at delaying experimentation with addictive substances, especially "gateway" drugs, could delay the progression to crack cocaine dependence.

Physical Functional Capacity and C-Reactive Protein in Schizophrenia.

INTRODUCTION: Schizophrenia is a severe, debilitating mental disorder that affects both the physical health and the functional capacity of patients, causing great impairment throughout the life course. Although physical and cognitive impairments may represent different expressions of a single systemic inflammatory process, little is known about the relationship between motor function and schizophrenia. OBJECTIVE: To evaluate physical functional capacity in patients with schizophrenia and ascertain whether it correlates with markers of inflammation, disease severity, and pharmacotherapy. METHODS: Cross-sectional study using a convenience sampling strategy. Forty patients with stable schizophrenia, undergoing treatment, were recruited from the Outpatient Program of Hospital de Clínicas de Porto Alegre, University Hospital linked to Public Health System. Physical functional capacity was assessed by the 6-min walk test (6MWT), and inflammatory markers were measured by C-reactive protein (CRP) and Von Willebrand factor. RESULTS: Mean functional capacity and clinical variables differed among patients and Brazilian population regarding heart rate (p = 0.004), diastolic (p = 0.001) and systolic (p < 0.001) blood pressure, respiratory rate (p < 0.001), CRP (p = 0.015), Borg Scale of Perceived Exertion scores (BSPE) (p < 0.001), and 6MWT both in men (p < 0.001) and women (p = 0.024). Additionally, 6MWT and dyspnea in BSPE were positively associated with CRP (r = -0.369, p = 0.019) and (r = -0.376, p = 0.017) and (r = 0.354, p = 0.025 and r = 0.535, p < 0.001, respectively). CONCLUSION: The present study detected significant association between measures of functional impairment and markers of inflammation, especially elevated CRP in a group of stable outpatients with DSM-IV and ICD10 diagnosis of schizophrenia. Possible explanations for the associations could be linked to continued use of antipsychotics, although underlying neuroinflammatory mechanisms directly related to illness (schizophrenia) could not be ruled out. The findings of this study expand evidences of neuroinflammation to systemic inflammation in schizophrenia linking it to alterations of physical functional capacity and point to the need of additional studies exploring general inflammation and novel therapeutic interventions.

IL-6 and IL-10 levels in the umbilical cord blood of newborns with a history of crack/cocaine exposure in utero: a comparative study.

INTRODUCTION: Prenatal cocaine exposure (PCE) is associated with neurobehavioral problems during childhood and adolescence. Early activation of the inflammatory response may contribute to such changes. Our aim was to compare inflammatory markers (IL-6 and IL-10) both in umbilical cord blood and in maternal peripheral blood at delivery between newborns with history of crack/cocaine exposure in utero and non-exposed newborns. METHODS: In this cross-sectional study, 57 newborns with a history of crack/cocaine exposure in utero (EN) and 99 non-exposed newborns (NEN) were compared for IL-6 and IL-10 levels. Sociodemographic and perinatal data, maternal psychopathology, consumption of nicotine and other substances were systematically collected in cases and controls. RESULTS: After adjusting for potential confounders, mean IL-6 was significantly higher in EN than in NEN (10,208.54, 95% confidence interval [95%CI] 1,328.54-19,088.55 vs. 2,323.03, 95%CI 1,484.64-3,161.21; p = 0.007; generalized linear model [GLM]). Mean IL-10 was also significantly higher in EN than in NEN (432.22, 95%CI 51.44-812.88 vs. 75.52, 95%CI 5.64-145.39, p = 0.014; GLM). Adjusted postpartum measures of IL-6 were significantly higher in mothers with a history of crack/cocaine use (25,160.05, 95%CI 10,958.15-39,361.99 vs. 8,902.14, 95%CI 5,774.97-12,029.32; p = 0.007; GLM), with no significant differences for IL-10. There was no correlation between maternal and neonatal cytokine levels (Spearman test, p ≥ 0.28 for all measures). CONCLUSIONS: IL-6 and IL-10 might be early biomarkers of PCE in newborns. These findings could help to elucidate neurobiological pathways underlying neurodevelopmental changes and broaden the range of possibilities for early intervention.

IL-6 and IL-10 levels in the umbilical cord blood of newborns with a history of crack/cocaine exposure in utero: a comparative study / Níveis de IL-6 e IL-10 no sangue de cordão umbilical de recém-nascidos com história de exposição intrauterina ao crack/cocaína: um estudo comparativo

Introduction Prenatal cocaine exposure (PCE) is associated with neurobehavioral problems during childhood and adolescence. Early activation of the inflammatory response may contribute to such changes. Our aim was to compare inflammatory markers (IL-6 and IL-10) both in umbilical cord blood and in maternal peripheral blood at delivery between newborns with history of crack/cocaine exposure in utero and non-exposed newborns. Methods In this cross-sectional study, 57 newborns with a history of crack/cocaine exposure in utero (EN) and 99 non-exposed newborns (NEN) were compared for IL-6 and IL-10 levels. Sociodemographic and perinatal data, maternal psychopathology, consumption of nicotine and other substances were systematically collected in cases and controls. Results After adjusting for potential confounders, mean IL-6 was significantly higher in EN than in NEN (10,208.54, 95% confidence interval [95%CI] 1,328.54-19,088.55 vs. 2,323.03, 95%CI 1,484.64-3,161.21; p = 0.007; generalized linear model [GLM]). Mean IL-10 was also significantly higher in EN than in NEN (432.22, 95%CI 51.44-812.88 vs. 75.52, 95%CI 5.64-145.39, p = 0.014; GLM). Adjusted postpartum measures of IL-6 were significantly higher in mothers with a history of crack/cocaine use (25,160.05, 95%CI 10,958.15-39,361.99 vs. 8,902.14, 95%CI 5,774.97-12,029.32; p = 0.007; GLM), with no significant differences for IL-10. There was no correlation between maternal and neonatal cytokine levels (Spearman test, p ≥ 0.28 for all measures). Conclusions IL-6 and IL-10 might be early biomarkers of PCE in newborns. These findings could help to elucidate neurobiological pathways underlying neurodevelopmental changes and broaden the range of possibilities for early intervention.

Introdução A exposição pré-natal à cocaína está associada a problemas neurocomportamentais durante a infância e adolescência. A ativação precoce da resposta inflamatória pode contribuir para tais alterações. Nosso objetivo foi comparar marcadores inflamatórios (IL-6 e IL-10) no sangue do cordão umbilical e no sangue periférico materno na hora do parto, entre recém-nascidos expostos ao crack intraútero e recém-nascidos não expostos. Métodos Neste estudo transversal, 57 recém-nascidos expostos ao crack intraútero (RNE) e 99 recém-nascidos não expostos (RNNE) foram comparados quanto aos níveis de IL-6 e IL-10. Dados sociodemográficos e perinatais, psicopatologia materna, consumo de nicotina e outras substâncias foram sistematicamente coletados em casos e controles. Resultados Após o ajuste para potenciais confundidores, a média de IL-6 foi significativamente maior nos RNE em comparação aos RNNE [10.208,54, intervalo de confiança (IC95%) 1.328,54-19.088,55 versus2.323,03, IC95% 1.484,64-3.161,21; p = 0,007; modelo linear generalizado (MLG)]. A média ajustada de IL-10 foi significativamente maior nos RNE do que nos RNNE (432,2189, IC95% 51,44-812,88 versus 75,52, IC95% 5,64-145,39, p = 0,014; MLG). Medidas pós-parto ajustadas de IL-6 foram significativamente maiores nas mães que usaram de crack/cocaína (25.160,05, IC95% 10.958,15-39.361,99 versus 8.902,14, IC95% 5.774,97-12.029,32; p = 0,007; MLG), sem diferenças significativas para IL-10. Não houve correlação entre níveis maternos e neonatais de citocinas (teste de Spearman, p ≥ 0,28 para todas as medidas). Conclusões IL-6 e IL-10 podem ser biomarcadores precoces da exposição pré-natal a cocaína em recém-nascidos. Esses resultados podem ajudar a elucidar as vias neurobiológicas subjacentes a alterações do desenvolvimento e aumentar a gama de possibilidades para intervenção precoce.

Pesquisa em psicoterapia psicanalítica de adultos: uma revisão sistemática de ensaios clínicos / Research in psychoanalytic psychotherapy for adults: a systematic review of clinical trials

O objetivo deste estudo é reunir os ensaios clínicos que envolveram alguma modalidade de Psicoterapia Psicanalítica publicados no período compreendido entre julho de 2008 e julho de 2013. Pretendemos identificar quais as modalidades contempladas, qual a população mais estudada, quais os fatores de interesse mais estudados, que localidades apresentam maior produção e quais os principais resultados encontrados. A revisão foi realizada em julho de 2013, através das bases de dados PsycINFO, Embase e Pubmed. Foram selecionados 27 estudos. O número de ECRs em PP encontrado nesta revisão pode ser considerado pequeno, o que possivelmente reflete uma preferência por outros delineamentos de pesquisa na avaliação dos resultados das técnicas psicanalíticas. A pesquisa em PP parece ser veiculada predominantemente através de periódicos acessados muitas vezes apenas por outros pesquisadores. Porém, o difícil acesso pode não ser a única razão por trás da reconhecida dissociação entre academia e prática clínica: a linguagem utilizada nos artigos encontrados nesta revisão pressupõe amplo conhecimento de termos de uso restrito de pesquisadores. Acreditamos que esta revisão pode ser útil para uma geração de terapeutas e pesquisadores que desejam trabalhar em sincronia com o avanço do conhecimento científico.(AU)

This systematic review aims at gathering all the psychoanalytic psychotherapy clinical trials published in the period between July 2008 and July 2013. We intend to identify which modalities were contemplated, the most studied population, the most studied factors of interest, the locations with higher production and the main results. The search was conducted in July 2013 on the following databases: Embase, Pubmed, and PsycINFO. Twenty-seven studies were selected. The number of RCTs in PP found in this review can be considered small, which may reflect a preference for other research designs in evaluating the results of psychoanalytic techniques. Research in PP seems to be conveyed predominantly through journals which are often only accessed by other researchers. However, the difficult access may not be the only reason behind the recognized dissociation between academia and clinical practice: the language used in the articles found in this review requires extensive knowledge of terms of restricted use by researchers. We believe that this review may be useful for a generation of therapists and researchers who wish to work in synchrony with the advancement of scientific knowledge.(AU)

Impaired endoplasmic reticulum stress response in bipolar disorder: cellular evidence of illness progression.

Bipolar disorder (BD) is a severe chronic psychiatric disorder that has been associated with cellular dysfunctions related to mitochondria, neurotrophin levels, and oxidative stress. Evidence has shown that endoplasmic reticulum (ER) stress may be a common pathway of the cellular changes described in BD. In the present study we assessed unfolded protein response (UPR) and the effects of this cellular process on lymphocytes from patients with BD. We also evaluated whether the stage of chronicity of BD was associated with changes in UPR parameters. Cultured lymphocytes from 30 patients with BD and 32 age- and sex-matched controls were treated with tunicamycin, an ER stressor, for 12 or 24 h to measure levels of UPR-related proteins (GRP78, eIF2α-P, and CHOP) using flow cytometry, and for 48 h to analyse ER stress-induced cell death. In healthy controls but not in patients we found an increase in levels of GRP78, eIF2α-P, and CHOP after ER stress induction. In addition, tunicamycin-induced cell death was significantly higher in patients compared to controls. More importantly, early-stage patients did not differ from controls while the late-stage patients showed an impaired ER stress response. Thus, dysfunction in ER-related stress response may be associated with decreased cellular resilience in BD and illness progression.

Expression of matrix metalloproteinases in patients with bipolar disorder

Objective: High cardiovascular mortality rates have been reported in patients with bipolar disorder (BD). Studies indicate that matrix metalloproteinases (MMPs) are implicated in cardiovascular diseases. We evaluated the expression pattern of MMP-2 and MMP-9 in blood from patients with BD during acute mania and after euthymia, in comparison with healthy controls. Methods: Twenty patients and 20 controls were recruited and matched for sex and age. MMP messenger RNA (mRNA) levels were measured using real-time quantitative polymerase chain reaction (PCR). Body mass index (BMI) was calculated for all subjects. Results: There were no significant differences in MMP-2 and MMP-9 mRNA expression between patients and controls. mRNA levels were not significantly different during mania and euthymia. However, MMP-2 mRNA levels were negatively associated with BMI in BD patients and positively associated with BMI in controls. There was no difference in the pattern of MMP-9 expression between patients and controls. Conclusions: Our results suggest a different pattern of association between MMP-2 and BMI in BD patients as compared with controls. Despite some study limitations, we believe that the role of MMPs in BD should be further investigated to elucidate its relationship with cardiovascular risk. .

Homocysteine and other markers of cardiovascular risk during a manic episode in patients with bipolar disorder.

OBJECTIVE: To evaluate serum levels of different biomarkers associated with cardiovascular disease in patients with bipolar disorder (BD). Patients were prospectively evaluated in two separate instances: during acute mania and after remission of manic symptoms. All measurements were compared with those of healthy controls. METHODS: The study included 30 patients with BD and 30 healthy controls, matched for gender and age. Biochemical parameters evaluated included homocysteine (Hcy), folic acid, vitamin B12, ferritin, creatine kinase (CK) and C-reactive protein (CRP). RESULTS: Hcy levels were significantly higher in the BD patients, both during mania and after achieving euthymia. When Hcy was adjusted for body mass index, there was no significant difference between patients and controls. Ferritin was the only marker that showed a significant decrease during mania when compared to both euthymic patients and controls. There were no significant differences for folate, vitamin B12, CK and CRP. CONCLUSIONS: These findings do not show an association between alterations of markers of cardiovascular risk during manic episodes. Further studies are necessary to determine factors and mechanisms associated with cardiovascular risk in patients with BD.