Association between DNA methyltransferase gene polymorphism and Parkinson's disease.

Parkinson's disease (PD) is a common and complex neurodegenerative disorder, the second most prevalent, only behind Alzheimer's disease. Recent studies suggest that environmental factors may contribute for neurodegeneration through induction of epigenetic modifications, such as DNA methylation, that is carried out by enzymes, such as DNMT1 and DNMT3B. This present study targeted to investigate the association among DNMT1 and DNMT3B polymorphisms with PD. Five hundred and twenty-two participants (214 PD patients following UK Brain Bank criteria and 308 healthy individuals) were evaluated. DNA was obtained from whole blood and genotypes were detected by an allelic discrimination assay using TaqMan® MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560 and rs759920 (DNMT1) and rs2424913, rs998382 and rs2424932 (DNMT3B). Was found association between DNMT3B rs2424913 in T allele carriers with PD. The presence of the T allele was associated with PD (OR=1.80, 95% CI 1.16-2.81, p=0.009). No significant difference was observed for others DNMT3B SNPs. Also, no association between PD and the control group were observed for DNMT1 polymorphisms. This is the first study addressing an association between DNMT3B polymorphism and PD. The polymorphism may play a role in the pathogenesis of PD.

Glucocorticoid receptor gene modulates severity of depression in women with crack cocaine addiction.

Crack cocaine addicted inpatients that present more severe withdrawal symptoms also exhibit higher rates of depressive symptoms. There is strong evidence that the identification of genetic variants in depression is potentialized when reducing phenotypic heterogeneity by studying selected groups. Since depression has been associated to dysregulation of the hypothalamic-pituitary-adrenal axis, this study evaluated the effects of SNPs in stress-related genes on depressive symptoms of crack cocaine addicts at early abstinence and over the detoxification treatment (4th, 11th and 18th day post admission). Also, the role of these SNPs on the re-hospitalization rates after 2.5 years of follow-up was studied. One hundred eight-two women were enrolled and eight SNPs in four genes (NR3C2, NR3C1, FKBP5 and CRHR1) were genotyped. A significant main effect of NR3C1-rs41423247 was found, where the C minor allele increased depressive symptoms at early abstinence. This effect remained significant after 10,000 permutations to account for multiple SNPs tested (P=0.0077). There was no effect of rs41423247 on the course of detoxification treatment, but a slight effect of rs41423247 at late abstinence was detected (P=0.0463). This analysis suggests that the presence of at least one C allele is worse at early abstinence, while only CC genotype appears to increase depressive symptoms at late abstinence. Also, a slight effect of rs41423247 C minor allele increasing the number of re-hospitalizations after 2.5 years was found (P=0.0413). These findings are in agreement with previous studies reporting an influence of rs41423247 on sensitivity to glucocorticoids and further elucidate its resulting effects on depressive-related traits.

Similarities between adult female crack cocaine users and adolescents in risky decision-making scenarios.

BACKGROUND: Although previous studies have shown that both adolescence and drug addiction can influence risk-taking and decision-making processes, the underlying mechanisms remain unclear. Specifically, there is a lack of evidence as to whether these conditions could affect deliberative and affective processes involved in risk taking, such as feedback learning and valuation of profits and risk. OBJECTIVES: The objectives were to compare the role of feedback and the use of information in risk-taking behavior between female crack cocaine users and adolescents. Additionally, we aimed to investigate whether sensation seeking, impulsivity, depressive and anxiety symptoms, executive functioning, and working memory performance could explain differences in risk-taking behavior. METHOD: This is a quasi-experimental study comparing 27 low-income adult female crack cocaine users (CU) to 18 female adolescents (AD) within two conditions (no-feedback or delayed-feedback) of the Columbia Card Task (CCT). In order to investigate CCT reference values for adult females, we also included 20 female non-drug-users with regular education and income as a reference group (RG). RESULTS: A similar pattern of risk-taking behavior was found between CU and AD within the CCT no-feedback condition. When delayed feedback was provided, AD exhibited a similar pattern of risk-taking behavior in the no-feedback condition, while CU showed a reduction of risk-taking behavior. Both groups exhibited higher risk taking than the RG within the CCT no-feedback condition, but only the AD group showed higher risk-taking behavior within the CCT feedback condition. Depressive symptom severity and working memory deficits were associated with higher risk-taking behaviors in CU. Executive functioning deficits were associated with higher risk-taking behavior in AD. CONCLUSIONS: Adult female crack cocaine users and female adolescents took similar risks during risky decision-making scenarios where feedback about their own performance was absent. However, when participants were provided with such feedback, it modulated risk-taking behaviors in crack cocaine users but not in adolescents.

The synergistic risk effect of apolipoprotein ε4 and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) haplotype for Alzheimer's disease.

Alzheimer's disease (AD) is a complex and multifactorial disease with the contribution of several genes and polymorphisms to its development. Among these genes, the APOEε4 is the best known risk factor for AD. Methylation is associated with APOE expression and AD development. Recently, we found an association of the TGG haplotype in the DNMT3B gene, one of the catalyst enzyme for methylation, with AD. Therefore, the objective of the study was to investigate whether APOEε4 and TGG haplotype have an synergistic effect on AD. The sample was composed of 212 Caucasian individuals (108 healthy controls and 104 with AD by NINCDS-ADRDA and DSM-IV-TR criteria) from southern Brazil. The genetic analyses were performed by real time PCR for TaqMan(®) assay. Multivariate logistic regression was performed categorizing groups according to presence of APOEε4 and/or TGG haplotype as an independent variable for outcome AD. The presence of TGG haplotype plus the allele APOEε4 were strongly associated with AD [OR 11.13; 95 % CI (4.25-29.16); P < 0.001]. This association had a higher risk than each risk factor alone. We found a strong association of the interaction of DNMT3B gene with the APOEε4 in this sample of AD patients. The presence of TGG haplotype and APOEε4 significantly increased the risk of developing the disease, showing an synergistic effect.

Post-traumatic stress disorder and substance use following traumatic brain injury: a clinical and neuropsychological case study / Transtorno de estresse pós-traumático e uso de substância após traumatismo crânio-encefálico: um estudo de caso clínico e neuropsicológico

The present study proposes to investigate the case of a patient with crack-cocaine use disorder from the occurrence of a neurological condition of traumatic brain injury (TBI) and development of Post-Traumatic Stress Disorder (PTSD). It is presumed that this is a case of crack and cocaine use disorder from the occurrence of two predisposing factors: TBI and the appearance of post-traumatic symptoms. Therefore, the present case discusses, clinically and based in neuropsychological assessment, the hypotheses of substance use as self-medication to attenuate the depressive symptoms related to the traumatic experience and/or as a consequence of a neuropsychological framework. Furthermore, the presence of a neurological condition may explain the subsequent progression to crack-cocaine use disorder.(AU)

O presente estudo se propôs a investigar o caso de uma paciente dependente de cocaína e crack, a qual desenvolveu o quadro de dependência após ter sido diagnosticada com Traumatismo Crânio-Encefálico (TCE) em decorrência de um acidente e Transtorno de Estresse Pós-Traumático. Este caso, em especial, por apresentar co-ocorrência de condições neurológicas e psiquiátricas foi alvo de uma avaliação clínica e neuropsicológica. A hipótese do uso de substância como forma de automedicação pode estar relacionada com o início e progressão para dependência de cocaína e crack, uma vez que foram reportados sintomas depressivos e pós-traumáticos acentuados. Além disso, a presença de um quadro neurológico com possíveis alterações neuropsicológicas associadas pode explicar a subsequente progressão para dependência de cocaína e crack.(AU)

Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment.

The aim of this study was to analyze hypotheses-driven gene-environment and gene-gene interactions in smoked (crack) cocaine addiction by evaluating childhood neglect and polymorphisms in mineralocorticoid and glucocorticoid receptor genes (NR3C2 and NR3C1, respectively). One hundred thirty-nine crack/cocaine-addicted women who completed 3 weeks of follow-up during early abstinence composed our sample. Childhood adversities were assessed using the Childhood Trauma Questionnaire (CTQ), and withdrawal symptoms were assessed using the Cocaine Selective Severity Assessment (CSSA) scale. Conditional logistic regression with counterfactuals and generalized estimating equation modeling were used to test gene-environment and gene-gene interactions. We found an interaction between the rs5522-Val allele and childhood physical neglect, which altered the risk of crack/cocaine addiction (Odds ratio = 4.0, P = 0.001). Moreover, a NR3C2-NR3C1 interaction (P = 0.002) was found modulating the severity of crack/cocaine withdrawal symptoms. In the post hoc analysis, concomitant carriers of the NR3C2 rs5522-Val and NR3C1 rs6198-G alleles showed lower overall severity scores when compared to other genotype groups (P-values ≤ 0.035). This gene-environment interaction is consistent with epidemiological and human experimental findings demonstrating a strong relationship between early life stress and the hypothalamic-pituitary-adrenal (HPA) axis dysregulation in cocaine addiction. Additionally, this study extended in crack/cocaine addiction the findings previously reported for tobacco smoking involving an interaction between NR3C2 and NR3C1 genes.

Propriedades psicométricas da Cocaine Selective Severity Assessment (CSSA) em mulheres usuárias de crack / Psychometric properties of Cocaine Selective Severity Assessment (CSSA) in crack users

Objetivo Este estudo teve como objetivo adaptar a Cocaine Selective Severity Assessment (CSSA) para o português do Brasil e verificar as propriedades psicométricas do instrumento em uma amostra de usuárias de crack. Métodos Após as etapas de tradução e adaptação, 125 mulheres usuárias de crack, internadas em uma unidade pública de desintoxicação, foram avaliadas. Para caracterização da amostra e análise das validades concorrente, de construto e preditiva, foram utilizados os seguintes instrumentos: SCID-I, ASI-6, BDI-II e CCQ-B. Resultados A análise fatorial exploratória identificou cinco fatores, com níveis adequados de consistência interna tanto para os fatores quanto para o escore geral da CSSA. Quanto à validade concorrente, a CSSA vai ao encontro de instrumentos já utilizados na clínica e em pesquisas. Em relação à validade de construto e preditiva, a CSSA pode ser sensível ao declínio dos sintomas de abstinência durante o processo de desintoxicação do crack. Conclusões Nossos achados foram além da tradução e adaptação da CSSA, proporcionando testes de validade e sugerindo que a CSSA é um instrumento confiável na avaliação dos sintomas de abstinência do crack. .

Objective This study aimed to describe the translation and adaptation of Cocaine Selective Severity Assessment (CSSA) into Brazilian Portuguese and verify the psychometric properties in a sample of crack cocaine users. Methods After the translation and adaptation steps, 125 female crack cocaine-dependent inpatients who were enrolled in an inpatient detoxification unit were evaluated. To characterize the sample and realize the analysis of concurrent validity, construct validity and predictive validity the following instruments were used: SCID-I, ASI-6, BDI-II e CCQ-B. Results The exploratory factorial analysis identified five factors and revealed appropriate levels of internal consistency, as well as the total score of the CSSA. The concurrent validity showed that CSSA was in line with instruments used in clinical practice and in researches. Further, both construct and predictive validity indicated adequate sensitivity to decline of withdrawal symptoms during the detoxification processes. Conclusions Our findings were beyond the translation and adaptation, providing the reliability and validity of CSSA regarding the evaluation of withdrawal symptoms in crack cocaine abstinence. .

Long-term cannabis abuse and early-onset cannabis use increase the severity of cocaine withdrawal during detoxification and rehospitalization rates due to cocaine dependence.

BACKGROUND: Long-term and early-onset cannabis consumption are implicated in subsequent substance- related problems. The aim of this follow-up study was to investigate whether these patterns of cannabis use could impact cocaine withdrawal severity and cocaine craving intensity during detoxification. In addition, we investigated their impact in the rehospitalization rates due to cocaine dependence 2.5 years after detoxification assessment. METHODS: The sample was composed of 93 female cocaine-dependent inpatients who were enrolled in an inpatient detoxification unit. Cocaine withdrawal symptoms were measured at the 4th, 9th and 14th days of detoxification using the cocaine selective severity assessment (CSSA). Data on the age of first years of drug use - alcohol, cannabis and cocaine - and the years of substance abuse were obtained using the Addiction Severity Index (ASI-6). Other relevant clinical variables were also investigated, including a 2.5 years follow-up assessment of number of rehospitalization due to cocaine dependence. RESULTS: Early-onset cannabis use and long-term cannabis abuse were associated with an increase instead of a reduction in the severity of cocaine withdrawal symptoms and craving intensity during detoxification. In addition, long-term cannabis abuse predicted higher number of rehospitalization due to cocaine dependence after 2.5 years of the first detoxification assessment. CONCLUSIONS: Early-onset cannabis use and long-term cannabis abuse are associated with a worse detoxification treatment response. Our findings may help to identify patients who will struggle more severely to control cocaine withdrawal syndrome during early drug abstinence, and indicate that cannabis use prior to cocaine withdrawal should be considered an adverse factor.

DNA methyltransferase haplotype is associated with Alzheimer's disease.

Epigenetic mechanisms have been implicated in syndromes associated with neuropsychiatric disorders, but little is known about the role of epigenetics in Alzheimer's disease (AD). DNA methylation, one of the main epigenetic mechanisms, is a complex process carried out by specific enzymes, such as DNMT1 and DNMT3B. This study aimed to investigate the association between DNMT1 and DNMT3B polymorphisms and AD. Two hundred and ten elderly subjects (108 healthy controls and 102 with AD-NINCDS/ARDA, DSM-IV-TR criteria) were assessed. DNA was obtained from whole blood, and genotypes were detected by an allelic discrimination assay using TaqMan(®) MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560, rs759920 (DNMT1) and rs998382, rs2424913, rs2424932 (DNMT3B). For both genes, the polymorphisms were in strong linkage disequilibrium. Carriers of the DNMT3B TGG haplotype were associated with AD (OR=3.03, 95% CI 1.63 to 5.63, P<0.001). No significant difference between AD and the control group were observed for DNMT1 polymorphisms. This study is one of the first describing a significant association between DNMT3B polymorphisms and AD. This enzyme, which is responsible for methylation in a general way, may be involved in AD.

Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress.

BACKGROUND: Neurotrophic factors have been investigated in the pathophysiology of alcohol and drug dependence and have been related to early life stress driving developmental programming of neuroendocrine systems. METHODS: We conducted a follow-up study that aimed to assess the plasma levels of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5) in crack users during 3 weeks of early abstinence in comparison with healthy controls. We performed a comprehensive clinical assessment in female inpatients with crack cocaine dependence (separated into 2 groups: participants with (CSA+) and without (CSA-) a history of childhood sexual abuse) and a group of nonuser control participants. RESULTS: Our sample included 104 women with crack cocaine dependence and 22 controls; of the women who used crack cocaine, 22 had a history of childhood sexual abuse and 82 did not. The GDNF plasma levels in the CSA+ group increased dramatically during 3 weeks of detoxification. In contrast, those in the CSA- group showed lower and stable levels of GDNF under the same conditions. Compared with the control group, BDNF plasma levels remained elevated and NGF levels were reduced during early abstinence. We found no differences in NT3 and NT4/5 between the patients and controls. However, within-group analyses showed that the CSA+ group exhibited higher levels of NT4/5 than the CSA- group at the end of detoxification. LIMITATIONS: Some of the participants were using neuroleptics, mood stabilizers or antidepressants; our sample included only women; memory bias could not be controlled; and we did not investigate the possible confounding effects of other forms of stress during childhood. CONCLUSION: This study supports the association between early life stress and peripheral neurotrophic factor levels in crack cocaine users. During early abstinence, plasmastic GDNF and NT4/5 were the only factors to show changes associated with a history of childhood sexual abuse.

Childhood physical neglect associated with executive functions impairments in crack cocaine-dependent women.

BACKGROUND: Studies that have investigated the executive functions (EFs) in crack cocaine-dependence have focused on differences between groups of drug users and non-user controls. In this study, however, we employ a promising additional approach that considers individual differences, such as exposure to childhood neglect that might be related to the degree of cognitive impairment associated with addiction. OBJECTIVE: We evaluated EFs in crack cocaine-dependent women who have reported a history of childhood physical neglect (CPN) and compared these measures with those of crack cocaine-dependent women who do not reported CPN. METHOD: The participants were divided into 2 groups: those with a history of CPN (CPN+) (n=37) and those without a history of CPN (CPN-) (n=48). Cold EFs were assessed with the Stroop Task, the Trail Making Test B, the Verbal Fluency Task, the N-Back Task and the Letter and Number Sequencing task. Hot EFs were assessed with the Iowa Gambling Task (IGT). RESULTS: The CPN+ group exhibited lower performance in all of the tasks except the IGT. A multivariate analysis of covariance indicated significant group differences in EFs (F(6,63)=2.51, p=0.030), regardless of craving severity and premorbid IQ. CONCLUSIONS: CPN is associated with cognitive impairments in crack cocaine-dependent women specifically regarding EFs and working memory tasks.

Hair cortisol and stressful life events retrospective assessment in crack cocaine users.

BACKGROUND: Some evidence suggests that altered hypothalamic-pituitary-adrenal (HPA) axis functioning in cocaine users might play a role in the pathophysiology of substance abuse. This study aimed to investigate the relationship between exposure to negative life events and cortisol hair concentrations in crack cocaine users during the 3 months prior to admission to a detoxification program. METHODS: A total of 23 treatment-seeking, crack cocaine-dependent women were selected for this study 1 week after admission to an inpatient treatment at a locked treatment facility. The Paykel Life Events Scale measured the occurrence of stressful life events 3 months before admission. Hair cortisol concentration was measured during these three previous months. RESULTS: The partial correlations, using severity of dependence as control variable, revealed that there is a positive association between hair cortisol concentration and the number of negative life events exposure 90 days (r = .56; p = .007) and 30 days (r = .42; p = .048) prior to admission at the hospital. One-way ANOVA suggests that hair cortisol levels and stress load significantly increase over 3 months prior to hospitalization. CONCLUSIONS: The results of this study indicate that there is a positive association between measures of long-term cumulative cortisol secretion and the number of stressful events reported by women receiving inpatient treatment for crack cocaine dependence. Therefore, this study suggests that stress load can be objectively quantified and noninvasively assessed. SCIENTIFIC SIGNIFICANCE: This study is the first to investigate HPA axis functioning using hair cortisol concentrations among crack cocaine-dependent users. It is a promising strategy to assess stress load in substance abusers.

Tomada de decisão em dependentes de crack: um estudo com o Iowa Gambling Task / Decision making in addiction to crack: a study with the Iowa Gambling Task

Este estudo investigou como ocorre o processo de tomada de decisão em dependentes de crack pelo instrumento Iowa Gambling Task (IGT). Foram selecionados 30 participantes para o grupo de dependentes de crack - GDC, e 15 controles não usuários - GNU, de ambos os sexos. Para avaliar a intensidade de craving utilizou-se o Cocaine Craving Questionnaire-Brief. Houve diferenças significativas entre os grupos tanto no cálculo total, como no cálculo por blocos. A curva de aprendizagem do GDCmanteve-se constante e negativa na maior parte do jogo, havendo apenas no final um indício de aprendizagem. Em relação à classificação do desempenho na tarefa, as análises evidenciaram que um significativo número de participantes controles obtiveram desempenho não-prejudicado, oposto ao desempenho do GDC. As diferenças entre os grupos investigadas no IGT corroboraram com achado de estudo anterior, que evidenciou prejuízo no processo de tomada de decisão associado à dependência de cocaína e de crack.

This study investigated how decision-making process occurs in crack dependents through the Iowa Gambling Task (IGT). 30 participants were selected to crack dependent group - GDC, and 15 non-users controls - GNU, from both sexes. We used the Cocaine Craving Questionnaire-Brief to assess the craving intensity. There were significant differences between groups both in the total-calculus score and in the blocks scores. The learning curve of the GDC was constant and negative during almost all game, except in the very ending when a suggestion of learning was observed. Regarding the task performance's classification, the analysis showed that a significant number of controls participants achieved a non-impaired performance, opposed to GDC performance. The differences between groups investigated in the IGT corroborate with a previous study finding, about a worse decision-making process associated with cocaine and crack addiction.

Tomada de decisão em dependentes de crack: um estudo com o Iowa Gambling Task / Decision making in addiction to crack: a study with the Iowa Gambling Task

Este estudo investigou como ocorre o processo de tomada de decisão em dependentes de crack pelo instrumento Iowa Gambling Task (IGT). Foram selecionados 30 participantes para o grupo de dependentes de crack - GDC, e 15 controles não usuários - GNU, de ambos os sexos. Para avaliar a intensidade de craving utilizou-se o Cocaine Craving Questionnaire-Brief. Houve diferenças significativas entre os grupos tanto no cálculo total, como no cálculo por blocos. A curva de aprendizagem do GDCmanteve-se constante e negativa na maior parte do jogo, havendo apenas no final um indício de aprendizagem. Em relação à classificação do desempenho na tarefa, as análises evidenciaram que um significativo número de participantes controles obtiveram desempenho não-prejudicado, oposto ao desempenho do GDC. As diferenças entre os grupos investigadas no IGT corroboraram com achado de estudo anterior, que evidenciou prejuízo no processo de tomada de decisão associado à dependência de cocaína e de crack.(AU)

This study investigated how decision-making process occurs in crack dependents through the Iowa Gambling Task (IGT). 30 participants were selected to crack dependent group - GDC, and 15 non-users controls - GNU, from both sexes. We used the Cocaine Craving Questionnaire-Brief to assess the craving intensity. There were significant differences between groups both in the total-calculus score and in the blocks scores. The learning curve of the GDC was constant and negative during almost all game, except in the very ending when a suggestion of learning was observed. Regarding the task performance's classification, the analysis showed that a significant number of controls participants achieved a non-impaired performance, opposed to GDC performance. The differences between groups investigated in the IGT corroborate with a previous study finding, about a worse decision-making process associated with cocaine and crack addiction.(AU)

Peripheral chemokine levels in women with recurrent major depression with suicidal ideation.

OBJECTIVE: To compare serum levels of MCP-1/CCL2, RANTES/CCL5, and Eotaxin/CCL11 between female patients with recurrent major depressive disorder (MDD) and healthy controls, verifying if there is a difference in the levels of these mediators between those with or without current suicidal ideation. METHODS: Thirty female outpatients with recurrent MDD were divided in two groups accordingly the presence or absence of suicidal ideation. These groups were compared with 16 healthy controls. Serum levels of MCP-1/CCL2, RANTES/CCL5, and Eotaxin/CCL11 were determined. Depression severity was evaluated by Beck Depression Inventory (BDI). Suicidal ideation was assessed by SCID-I and BDI. RESULTS: Patients with recurrent MDD and healthy controls did not differ in age, socioeconomic status, and education. All patients reported high scores of BDI (mean, SD, n; 29.75, 10.55, 28). Multivariable analysis of covariance adjusted for age and BMI showed that MDD patients with suicidal ideation presented lower levels of MCP-1/ CCL2 and RANTES/CCL5 (p < 0.001) and higher levels of Eotaxin/CCL11 (p = 0.04) compared to healthy controls. These differences remained significant after adjusting for depression severity. CONCLUSION: The findings of this study indicated that the presence of recurrent MDD with suicidal ideation is associated with differences in inflammatory chemokines when compared to those without suicidal ideation.

Peripheral chemokine levels in women with recurrent major depression with suicidal ideation / Níveis periféricos de quimiocina em mulheres com depressão maior com ideação suicida

OBJECTIVE: To compare serum levels of MCP-1/CCL2, RANTES/CCL5, and Eotaxin/CCL11 between female patients with recurrent major depressive disorder (MDD) and healthy controls, verifying if there is a difference in the levels of these mediators between those with or without current suicidal ideation. METHODS: Thirty female outpatients with recurrent MDD were divided in two groups accordingly the presence or absence of suicidal ideation. These groups were compared with 16 healthy controls. Serum levels of MCP-1/CCL2, RANTES/CCL5, and Eotaxin/CCL11 were determined. Depression severity was evaluated by Beck Depression Inventory (BDI). Suicidal ideation was assessed by SCID-I and BDI. RESULTS: Patients with recurrent MDD and healthy controls did not differ in age, socioeconomic status, and education. All patients reported high scores of BDI (mean, SD, n; 29.75, 10.55, 28). Multivariable analysis of covariance adjusted for age and BMI showed that MDD patients with suicidal ideation presented lower levels of MCP-1/ CCL2 and RANTES/CCL5 (p < 0.001) and higher levels of Eotaxin/CCL11 (p = 0.04) compared to healthy controls. These differences remained significant after adjusting for depression severity. CONCLUSION: The findings of this study indicated that the presence of recurrent MDD with suicidal ideation is associated with differences in inflammatory chemokines when compared to those without suicidal ideation.

OBJETIVO: Comparar os níveis séricos de MCP-1/CCL2, RANTES/CCL5 e Eotaxin/CCL11 entre pacientes do sexo feminino com transtorno depressivo maior (TDM) recorrente e controles saudáveis, verificando se há diferença nos níveis desses mediadores entre os indivíduos com ou sem ideação suicida. MÉTODOS: Trinta pacientes do sexo feminino com TDM recorrente foram divididas em dois grupos de acordo com a presença ou ausência de ideação suicida. Esses grupos foram comparados com 16 controles saudáveis. Os níveis séricos de MCP-1/CCL2, RANTES/CCL5 e Eotaxin/CCL11 foram determinados. A gravidade da depressão foi avaliada usando o Beck Depression Inventory (BDI) e a ideação suicida foi avaliada usando o SCID-I e o BDI. RESULTADOS: As pacientes com TDM recorrente e os controles saudáveis não diferiram em idade, status socioeconômico e educação. Todas as pacientes relataram altas pontuações no BDI (média, SD, n; 29,75, 10,55, 28). A análise de covariância multivariada ajustada para idade e de IMC mostrou que as pacientes com TDM e ideação suicida apresentaram níveis mais baixos de MCP-1/CCL2 e RANTES/CCL5 (p < 0,001) e níveis mais elevados de Eotaxin/CCL11 (p = 0,04) em comparação com os controles saudáveis. Essas diferenças permaneceram significantes após o ajuste para gravidade da depressão. CONCLUSÃO: Os resultados deste estudo indicaram que a presença de TDM recorrente com ideação suicida está associada a diferenças nas quimiocinas inflamatórias na comparação com os indivíduos sem ideação suicida.

Exposição a trauma e transtorno de estresse pós-traumático em usuárias de crack / Trauma exposure and posttraumatic stress disorder in crack cocaine users

OBJETIVO: Verificar a ocorrência de trauma e transtorno de estresse pós-traumático (TEPT) em uma amostra de mulheres dependentes de cocaína tipo crack. MÉTODO: A amostra foi composta por 99 mulheres, entre 18 e 52 anos, internadas em uma unidade de desintoxicação e extensamente avaliadas por meio da SCID-I e a ASI-6. RESULTADOS: Verificou-se uma taxa de exposição a trauma de 86,9% entre mulheres dependentes de cocaína tipo crack. A taxa de TEPT na amostra foi de 15,1%. Os clusters de revivescência e hiperexcitabilidade foram os mais frequentes - 24,4% e 20,9% respectivamente. Entre os tipos de eventos relatados, os mais frequentes foram sofrer agressão/abuso físico e ser testemunha de violência a outros. CONCLUSÃO: Os resultados sugerem uma frequente exposição a eventos traumáticos. Com relação à idade da experiência traumática, sugere-se que as usuárias expostas a trauma durante a infância e adolescência apresentam um início do uso de drogas em idades mais precoces que aquelas cujo trauma ocorreu na vida adulta.

OBJECTIVE: To determine the occurrence of trauma and posttraumatic stress disorder (PTSD) in a sample of women addicted to crack cocaine type. METHOD: The sample comprised 99 women, between 18 and 52 years admitted to a detoxification unit and extensively assessed by SCID-I and ASI-6. RESULTS: There was a trauma exposure rate of 86.9% among women addicted to crack cocaine type. The rate of PTSD in the sample was 15.1%. The clusters of reexperiencing and hyperarousal were the most frequent, 24.4% and 20.9% respectively. Among the types of events reported most frequently were suffering assault/physical abuse and witnessing violence to others. CONCLUSION: The results suggest a frequent exposure to traumatic events. With regard to age of the traumatic experience, it is suggested that users exposed to trauma during childhood and adolescence showed a beginning drug use at earlier ages than those whose trauma occurred in adulthood.

Interleukin-6 and verbal memory in recurrent major depressive disorder.

OBJECTIVE: To evaluate the possible association between peripheral levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) with immediate and delayed verbal recall in a group of recurrent depressed women. METHODS: Logical Memory Subtests of the Wechsler Memory Scale - Revised was administered to 30 patients with recurrent major depressive disorder with no clinical and psychiatric comorbidities. Blood samples were collected from 8:00 am to 9:00 am, before memory assessments.Plasma was stored and ELISA assay was used to detect IL-6 and TNF-alpha levels. RESULTS: There was a statistically significant association between IL-6 levels and immediate verbal recall (IVR) (B=-0.787, p=0.000) and delayed verbal recall (DVR) (B=-0.695, p=0.001) even after controlling for age, depression severity and body mass index. CONCLUSION: The results of this study indicated that low performances in IVR and DVR are associated with higher IL-6 levels in women with recurrent MDD. The results of this study suggest the existence of an association between inflammatory imbalance and cognitive impairment in MDD.

6­Sulfatoxymelatonin as a predictor of clinical outcome in depressive patients.

OBJECTIVES: This study established the value of the 6­sulfatoxymelatonin (aMT6s) urine concentration as a predictor of the therapeutic response to noradrenaline reuptake inhibitors in depressive patients. METHODS: Twenty-two women aged 18-60 years were selected. Depressive symptoms were assessed by using the Hamilton Depression Scale. Urine samples were collected at 0600-1200 h, 1200-1800 h, 1800-2400 h, and 2400-0600 h intervals, 1 day before and 1 day after starting on the nortriptyline treatment. Urine aMT6s concentration was analyzed by a one-way analysis of variance/Bonferroni test. Spearman's rank correlation coefficient was used to analyze the correlation between depressive symptoms after 2 weeks of antidepressant treatment and the increase in aMT6s urine concentration. RESULTS: Higher and lower size effect groups were compared by independent Student's t-tests. At baseline, the 2400­ to 0600­h interval differed from all other intervals presenting a significantly higher aMT6s urine concentration. A significant difference in aMT6s urine concentrations was found 1 day after treatment in all four intervals. Higher size effect group had lower levels of depressive symptoms 2 weeks after the treatment. A positive correlation between depressive symptoms and the delta of aMT6s in the 2400-0600 h interval was observed. CONCLUSION: Our results reinforce the hypothesis that aMT6s excretion is a predictor of clinical outcome in depression, especially in regard to noradrenaline reuptake inhibitors.

Increased soluble tumor necrosis factor-alpha receptors in patients with major depressive disorder.

AIM: Several lines of evidence suggest that major depressive disorder is associated with an inflammatory status. Tumor necrosis factor-alpha has been investigated as a potential molecular target in mood disorders. Tumor necrosis factor-alpha exerts its activity through binding to specific cell membrane receptors named as TNFR1 and TNFR2. The aim of the present study was to investigate soluble plasma TNFR1 (sTNFR1) and TNFR2 levels (sTNFR2) in major depressive disorder patients. METHODS: Female outpatients with major depressive disorder (n = 30) were compared with a healthy control group (n = 19). Severity of depressive symptoms was evaluated on Beck Depression Inventory; post-traumatic stress disorder (PTSD) symptoms were evaluated on PTSD Checklist-Civilian Version; and childhood abuse and neglect on the Childhood Trauma Questionnaire. Plasma tumor necrosis factor-alpha and its soluble receptors were measured by ELISA. RESULTS: Patients had no changes in tumor necrosis factor-alpha concentrations but did have increased sTNFR1 (P < 0.001) and sTNFR2 (P < 0.001) levels compared to controls. Plasma level of sTNFR1 was positively predicted by age (B = 0.25, P = 0.05) and PTSD-like symptoms (B = 0.41, P = 0.002) and plasma levels of sTNFR2 by depression severity (B = 0.67, P < 0.001). CONCLUSIONS: Soluble tumor necrosis factor-alpha receptors could be reliable markers of inflammatory activity in major depression.