Thiago Wendt Viola

Childhood maltreatment and inflammatory markers: a systematic review

Childhood maltreatment (CM) has been associated with several diseases in adult life, including diabetes, obesity and mental disorders. Inflammatory conditions have been postulated as possible mediators of this relationship. The aim was to conduct a systematic review regarding the association between CM and inflammatory markers in adulthood.

Childhood Trauma Questionnaire (CTQ) in Brazilian Samples of Different Age Groups: Findings from Confirmatory Factor Analysis

The Childhood Trauma Questionnaire (CTQ) is internationally accepted as a key tool for the assessment of childhood abuse and neglect experiences. However, there are relative few psychometric studies available and some authors have proposed two different factor solutions. We examined the dimensional structure and internal consistency of the Brazilian version of the CTQ. A total of 1,925 participants from eight different clinical and non-clinical samples including adolescents, adults and elders were considered in this study. First, we performed Confirmatory Factor Analysis to investigate the goodness of fit of the two proposed competitive factor structure models for the CTQ. We also investigated the internal consistency of all factors. Second, multi-group analyses were used to investigate measurement invariance and population heterogeneity across age groups and sex. Our findings revealed that the alternative factor structure as opposed to the original factor structure was the most appropriate model within adolescents and adults Brazilian samples. We provide further evidence for the validity and reliability of the CTQ within the Brazilian samples and report that the alternative model showed an improvement in fit indexes and may be a better alternative over the original model.

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.

Differential neuroendocrine and immune responses to acute psychosocial stress in women with type 1 bipolar disorder.

Bipolar disorder (BD) has been associated with immune imbalance, including lymphocyte activation and increased pro-inflammatory cytokines. Immune activation is part of stress response, and psychosocial stress has been implicated in the pathogenesis of psychiatric disorders. Here, we investigated the neuroendocrine and immune responses to acute psychosocial stress challenge in BD. Thirteen euthymic participants with type 1 BD and 15 healthy controls underwent the Trier Social Stress Test protocol (TSST). Blood samples were collected before and after TSST. Lymphocytes were isolated and stimulated in vitro to assess lymphocyte activation profile, lymphocyte sensitivity to dexamethasone, mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling by flow cytometry. Heart rate and salivary cortisol levels were monitored across the task. BD participants exhibited blunted stress responses as shown by reduced heart rate and salivary cortisol levels in comparison to healthy controls. BD was also associated with reduction in the percentage of regulatory T cells, but with expansion of activated T cells. When compared to controls, patients showed increased lymphocyte MAPK p-ERK and p-NF-κB signaling after the stress challenge, but exhibited a relative lymphocyte resistance to dexamethasone. In conclusion, stress-related neuroendocrine responses are blunted, associated with increased immune activation and lower sensitivity to glucocorticoids in BD. An inability in reducing NF-κB and MAPK signaling following TSST could be underlying the immune imbalance observed in BD.

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.

Childhood neglect and increased withdrawal and depressive severity in crack cocaine users during early abstinence

Studies have shown that environmental factors, such as exposure to childhood maltreatment, might shift the course of addiction. Little is known, however, about whether childhood physical neglect (PN) influences the severity of withdrawal and depressive symptoms during the detoxification period. This is a 3 weeks follow-up study. The participants were divided into 2 groups: those with a history of PN (PN+) (n=32) and those without a history of PN (PN-) (n=48). Clinical variables were assessed with the SCID-I, BDI-II, Childhood Trauma Questionnaire, Addiction Severity Index and Cocaine Selective Severity Assessment. Depressive symptom assessments were repeated at three time points. Withdrawal symptom assessments were repeated at five different points following detoxification. A repeated measures analysis of covariance indicated that the PN+ group exhibited a significantly lower reduction in the severity of withdrawal symptoms compared to the PN- group (p<0.05). Post hoc analyses showed that after 12 days of treatment, the severity of withdrawal symptoms in the PN+ group did not decrease in the same level as was observed in the PN- group. Moreover, a strong correlation was found between the severity of depression and the intensity of the abstinence symptoms during treatment. Patients who reported more depressive symptoms also exhibited more severe withdrawal symptoms. The ASI-6 indicated higher severity problems related to alcohol and psychiatric disorders in the PN+ groups. Our data support the role of childhood PN in the contingencies of the detoxification process of crack cocaine-dependent women.

The influence of geographical and economic factors in estimates of childhood abuse and neglect using the Childhood Trauma Questionnaire: A worldwide meta-regression analysis.

This multilevel meta-analysis examined the effects of geographical and economic factors on worldwide childhood maltreatment estimates measured by the Childhood Trauma Questionnaire (CTQ) short-form. The primary outcome extracted was continuous scores on the CTQ subscales - emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect - and total score. Geographical, economical and methodological variables were extracted for use as covariates in meta-regression models. A literature search identified 288 studies suitable for the CTQ total score analysis (N=59,692) and 189 studies suitable for maltreatment subtype analysis (N=44,832). We found that Europe and Asia were associated with lower CTQ estimates while South America presented the highest estimates among continents. Specifically, studies from China, Netherlands and United Kingdom presented the lowest maltreatment estimates. Furthermore, high-income countries presented lower CTQ physical neglect estimates in comparison to low- or middle-income countries, while per-capita gross domestic product of countries was negatively associated with childhood physical neglect estimates. Despite the influence of methodological covariates, these findings indicate that geographical and economic factors could influence variations of childhood maltreatment estimates around the world, particularly when assessed by a structured standardized questionnaire.

Early life stress and tumor necrosis factor superfamily in crack cocaine withdrawal

BACKGROUND Both early life stress (ELS) and substance abuse, especially cocaine, have robust effects on the inflammatory system. Considering the role of the tumor necrosis factor system in inflammatory signaling and its association with ELS, the aim of the study was to compare plasma levels of TNF-alpha, its soluble receptors and ligands during early abstinence of crack cocaine. METHODS This study included 24 crack cocaine-dependent women with (CRACK-ELS) and 20 without (CRACK) a history of ELS. A healthy control group (HC), containing 25 participants, was included to provide reference values. The Childhood Trauma Questionnaire (CTQ) retrospectively assessed childhood maltreatment history of patients. Plasma levels of TNF-alpha, TNF-related weak inducer of apoptosis (TWEAK), TNF-related apoptosis-inducing ligand (TRAIL), soluble receptors TNFRI (sTNFRI) and TNFRII (sTNFRII) were assessed on the 18th day of treatment. RESULTS The CRACK-ELS group had higher TNF-alpha and lower TWEAK levels compared to the CRACK and HC groups. sTNFRII was increased, but only in comparison with the crack cocaine group and the controls. TRAIL levels were slightly higher in the CRACK-ELS group, while no differences were found for sTNFRI levels. Also, TNF-alpha plasma level was positively predicted by abstinence severity and childhood maltreatment severity, and TWEAK was negatively predicted by childhood maltreatment severity. CONCLUSIONS This is the first study to evaluate the newly secreted tumor necrosis factor superfamily ligands, TWEAK and TRAIL, during crack cocaine abstinence, supporting the association between early life stress and peripheral pro-inflammatory levels.

Pro-inflammatory cytokines and soluble receptors in response to acute psychosocial stress: Differential reactivity in bipolar disorder

Mounting evidence suggests a chronic pro-inflammatory state in individuals with bipolar disorder (BD). Stress exposure is known to exacerbate several inflammatory conditions as well as psychiatric disorders. Here, we analyzed plasma levels of pro-inflammatory cytokines and their soluble receptors to realistic acute psychosocial stress challenge in BD. Thirteen euthymic type 1 BD patients and 15 matched controls underwent the Trier Social Stress Test protocol (TSST). Blood samples were collected before and after TSST and plasma cytokines interleukin IL-2, IL-6, IL-33, and tumor necrosis factor alpha (TNF-α) were measured. In addition TNF-α soluble receptors TNFR1 and TNFR2, and IL-33 soluble receptor sST2 were assessed. Increased IL-33 and reduced sST2 levels were observed in BD subjects as compared to controls, independently of stress exposure. Following TSST, there were higher levels of IL-2 and reduced levels of sTNFR1 in both groups. However, the magnitude change for both cytokines was found higher in controls than BD subjects. Our data suggest that BD patients have differential stress reactivity as compared to controls, possibly related to an immunologic imbalance and failure of regulatory mechanisms.

Distinct behavioral and immunoendocrine parameters during crack cocaine abstinence in women reporting childhood abuse and neglect

AIM To assess plasma levels of cortisol and cytokines between cocaine-dependent women with and without childhood maltreatment (CM) history during cocaine detoxification treatment. METHOD We assessed immunoendocrine and clinical parameters of 108 crack cocaine female users during 3 weeks of inpatient detoxification treatment, and 24 healthy women to obtain reference values. Women with (CM+, n=53) or without (CM-, n=55) CM history were identified answering the Childhood Trauma Questionnaire (CTQ). Blood samples and clinical assessment were collected before lunch during the first, second and third week post-treatment admission. Flow cytometry was used to assess TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17A plasma levels and ELISA assay was used to measure plasma cortisol levels. RESULTS At baseline, lower Th1 and Th17-related cytokines levels and higher Th2 cytokines levels were observed in crack cocaine users compared with reference values. Cytokines levels of cocaine dependents gradually became closer to reference values along detoxification treatment. However, when CM+ and CM- groups were compared, increased levels of IL-6, IL-4 and TNF-α across time were observed in CM+ group only. Additionally, a Th1/Th2 immune imbalance was observed within CM+ group, which was negatively correlated with the severity of the crack withdrawal. Finally, loading trauma exposure severity, immunoendocrine and clinical parameters in factor analysis, we identified three clusters of observed variables during detoxification: (1) systemic immunity and trauma exposure, (2) pro-inflammatory immunity and (3) behavior CONCLUSION Our results suggest the existence of an immunological phenotype variant associated with CM exposure during crack cocaine detoxification of women.