Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation.

BACKGROUND: Cocaine-use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of neutrophil extracellular traps (NETs) and related intracellular signalling. We also investigated the role of early life stress in inflammatory profiles. METHODS: Blood samples, clinical data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. RESULTS: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1ß, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. CONCLUSION: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

Impact of social isolation on the oxytocinergic system: A systematic review and meta-analysis of rodent data.

Social isolation (SI) stress results from a combination of intrinsic and environmental factors and is associated with a variety of negative developmental outcomes. Oxytocin (OXT) might play a role in the consequences of SI in the brain and periphery. We conducted a systematic review and meta-analysis to compile data about the effects of SI in the oxytocinergic system of rats and mice, and its relation to behavioral alterations. Five databases (EMBASE, PsychNet, PubMed, Scopus, and Web of Science) were searched in March 2021, using ("Social Isolation" AND (mouse OR rat) AND (oxytocin OR oxytocin receptor)). This review followed the PRISMA guidelines, including registration in PROSPERO, and risk of bias assessment. The twelve articles included in this review indicated that SI was associated with decreased OXTR levels, resulting in behavioral alterations like increased aggression and anxiety-like behavior, hyperactivity, and diminished social behaviors and memory. No significant effects on OXT levels were observed. Administration of synthetic OXT or its agonists partially decreases those unwanted behaviors to similar levels of control animals.

Sex differences in risk behavior parameters in adolescent mice: Relationship with brain-derived neurotrophic factor in the medial prefrontal cortex.

Adolescence is as a period of development characterized by impulsive and risk-seeking behaviors. Risk behaviors (RB) involves exposure to dangerous or negative consequences to achieve goal-directed behaviors, such as reward-seeking. On the other hand, risk aversion/assessment behaviors allow the individual to gather information or avoid potentially threatening situations. Evidence has suggested that both behavioral processes, RB and risk assessment (RA), may have sex-differences. However, sex-specific behavioral patterns implicated in RB and RA are not fully understood. To address that, we investigated sex differences in risk-behavioral parameters in a decision-making task developed for rodents. In addition, we investigated the potential role of sex-dependent differences in gene expression of brain-derived neurotrophic factor (BDNF) exon IV in the medial prefrontal cortex (mPFC), which has been implicated to mediate PFC-related behavioral dysfunctions. Male and female C57BL/6J adolescent mice were evaluated in the elevated plus-maze (EPM) to assess anxiety-like behaviors and in the predator-odor risk taking (PORT) task. The PORT task is a decision-making paradigm in which a conflict between the motivation towards reward pursuit and the threat elicited by predatory olfactory cues (coyote urine) is explored. After behavioral testing, animals were euthanized and BDNF exon IV gene expression was measured by RT-qPCR. Comparative and correlational analyses for behavioral and molecular parameters were performed for both sexes. We observed that female mice spent more time exploring the middle chamber of the PORT apparatus in the aversive condition, which is an indicative of avoidance behavior. Female mice also had a higher latency to collect the reward than male mice and presented less time exploring the open arms of the EPM. BDNF exon IV gene expression was higher among females, and there was a positive correlation between the BDNF and PORT behavioral parameters. Our findings suggest sex-dependent effects in the PORT task. Females presented higher RA and avoidance behavior profile and expressed higher levels of BDNF exon IV in the mPFC. Moreover, higher BDNF expression was correlated with RA behaviors, which suggests that adolescent females tend to evaluate the risks more than adolescent males and that BDNF gene expression may be mediating decision-making processes.

Vulnerable and resilient cognitive performance related to early life stress: The potential mediating role of dopaminergic receptors in the medial prefrontal cortex of adult mice.

RATIONALE: Exposure to early life stress (ELS) is known to have pronounced effects on the prefrontal cortex (PFC). However, not all individuals exposed to ELS manifest the same neurobiological and cognitive phenotypes when adults. Dopamine signaling could be a key factor in understanding the effects of stress on PFC-related cognitive function. OBJECTIVES: We aimed to investigate the differential effects of ELS on cognitive performance of adult mice and the dopaminergic receptors expression in the PFC. METHODS: BALB/c males were exposed to the maternal separation (MS) procedure and their cognitive performance on the eight-arm radial maze (8-RAM) were assessed during adulthood. For molecular-level assessments, we performed mRNA expression analyses for dopamine receptors-DRD1, DRD2, DRD3-and Hers1 expression in the medial PFC. RESULTS: While MS produced an overall impairment on 8-RAM, the stressed animals could be divided in two groups based on their performance: those with impaired cognitive performance (vulnerable to maternal separation, V-MS) and those without any impairment (resilient to maternal separation, R-MS). V-MS animals showed increased DRD1 and DRD2 expression in comparison with other groups. Errors on 8-RAM were also positively correlated with DRD1 and DRD2 mRNA expression. CONCLUSIONS: Our findings suggest a potential role of the dopaminergic system in the programming mechanisms of cognitive vulnerability and resilience related to ELS.

Cocaine Use Disorder Is Associated With Changes in Th1/Th2/Th17 Cytokines and Lymphocytes Subsets.

Background: Cocaine is a psychostimulant drug with high addictive proprieties. Evidence suggests that cocaine use leads to critical changes in the immune system, with significant effects on T, B, and natural killer (NK) cells and influencing peripheral levels of cytokines. The presence of abstinence-related symptoms during detoxification treatment is known to influence the prognosis. Here, our aim was to investigate immune profiles in women with cocaine use disorder (CUD) according to withdrawal symptoms severity. Methods: Blood samples and clinical data were collected at onset of detoxification treatment of 50 women with CUD. The patients were stratified according to Cocaine Selective Severity Assessment (CSSA) scores in low withdrawal (L-W) and high withdrawal (H-W) categories. In addition, we also included a control group with 19 healthy women as reference to immune parameters. Peripheral blood was collected and lymphocyte subsets were phenotyped by multi-color flow cytometry (B cells, CD4+ T, CD8+ T, NK cells, and different stages of T-cell differentiation). PBMCs from patients and healthy controls were stimulated in vitro with phytohemagglutinin (1%) for 72 h to assess the production of Th1/Th2/Th17 cytokines. Results: Following stimulation, lymphocytes from women with CUD produced increased levels of Th1/Th2/Th17 cytokines. However, higher levels of IL-2 and IL-17 were observed only in the L-W group, while higher levels of IL-6 were detected in the H-W group compared to controls. H-W group showed lower percentage of early-differentiated Th cells (CD4+CD27+CD28+), elevated percentage of Th cells (CD3+CD4+), intermediate-differentiated Th cells (CD4+CD27-CD28+), and B cells (CD3-CD19+). Both CUD groups showed decreased percentages of naïve T cells (CD3+CD4+CD45RA+ and CD3+CD8+CD45RA+). Conclusion: Our data demonstrated that CUD can lead to increased production of Th1/Th2/Th17 cytokines and lymphocyte changes.

The DNA modification N6-methyl-2'-deoxyadenosine (m6dA) drives activity-induced gene expression and is required for fear extinction.

DNA modification is known to regulate experience-dependent gene expression. However, beyond cytosine methylation and its oxidated derivatives, very little is known about the functional importance of chemical modifications on other nucleobases in the brain. Here we report that in adult mice trained in fear extinction, the DNA modification N6-methyl-2'-deoxyadenosine (m6dA) accumulates along promoters and coding sequences in activated prefrontal cortical neurons. The deposition of m6dA is associated with increased genome-wide occupancy of the mammalian m6dA methyltransferase, N6amt1, and this correlates with extinction-induced gene expression. The accumulation of m6dA is associated with transcriptional activation at the brain-derived neurotrophic factor (Bdnf) P4 promoter, which is required for Bdnf exon IV messenger RNA expression and for the extinction of conditioned fear. These results expand the scope of DNA modifications in the adult brain and highlight changes in m6dA as an epigenetic mechanism associated with activity-induced gene expression and the formation of fear extinction memory.

Cognitive impairment in rheumatoid arthritis: role of lymphocyte subsets, cytokines and neurotrophic factors.

To what extent the cognitive impairment of rheumatoid arthritis (RA) is modulated by autoimmune and/or inflammatory activity is largely unknown. The aim of this study was to investigate the role of peripheral inflammation on cognitive functions of patients with active (Ac-), controlled (Co-) RA and healthy controls. In a cross-sectional study, 102 RA patients and 30 matched healthy controls were recruited. B and T cell subsets were immunophenotyped by flow cytometry. Plasma cytokines and neurotrophins were measured by flow cytometry and ELISA, respectively. Cognitive performance, depression and stress were evaluated by structured clinical interviews. Generalized linear modeling (GzLM) was used to compare differences between groups and multiple linear regression models were used to explore the predictive value of immune variables on cognitive performance. RA patients had overall cognitive impairment. Of note, the Ac-RA had the poorest performance on digit span (DST) and N-back when compared to Co-RA and control group (DST 9.9 ± 2.1, 12.9 ± 4.2, 15.5 ± 4.7, respectively; N-back 49.2 ± 8.3, 55.5 ± 11.1, 60.8 ± 9.1, respectively, all p < 0.0001). RA patients had expansions of immature B cells (Ac-RA 11.2 ± 7.1, Co-RA: 9 ± 5.7, control 5.9 ± 2.1) and plasma cells (Ac-RA 5.2 ± 2.5, Co-RA 6.9 ± 3.7, control 2.8 ± 1.7) as compared to controls, all p < 0.05. RA patients (controlled and active disease) had higher plasma levels of TNF, IL-2, IL-4, IL-6 and IL-10 than controls (all p < 0.002). RA patients had higher BDNF levels (Ac-RA 17,354.4 ± 5357.3, Co-RA 13,841.2 ± 5953.7, control 11,543.3 ± 3772), but lower GDNF levels [median (interquartile range) Ac-RA 0 pg/ml (0.0), Co-RA 0 pg/ml (4.6) and control 4.7 pg/ml (18.1)] than controls (all p < 0.05). RA patients had global cognitive impairment, which was associated with disease activity and immune changes.

Corticotropin Releasing Factor in the Bed Nucleus of the Stria Terminalis in Socially Defeated and Non-stressed Mice with a History of Chronic Alcohol Intake.

Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated use to the development of alcohol dependence. Preclinical studies have shown that dysregulation of the corticotropin releasing factor (CRF) neurotransmission has been implicated in stress-related psychopathologies such as depression and anxiety, and may affect alcohol consumption. The bed nucleus of the stria terminalis (BNST) contains CRF-producing neurons which seem to be sensitive to stress. In this study, adult male C57BL/6 mice previously defeated in resident-intruder confrontations were evaluated in the elevated plus-maze and tail suspension test. Mice were also tested for sweet solution intake before and after social stress. After having had continuous access to ethanol (20% weight/volume) for 4 weeks, control and stressed mice had CRF type 1 (CRFR1) or type 2 (CRFR2) receptor antagonists infused into the BNST and then had access to ethanol for 24 h. In separate cohorts of control and stressed mice, we assessed mRNA levels of BNST CRF, CRFR1 and CRFR2. Stressed mice increased their intake of sweet solution after ten sessions of social defeat and showed reduced activity in the open arms of the elevated plus-maze. When tested for ethanol consumption, stressed mice persistently drank significantly more than controls during the 4 weeks of access. Also, social stress induced higher BNST CRF mRNA levels. The selective blockade of BNST CRFR1 with CP376,395 effectively reduced alcohol drinking in non-stressed mice, whereas the selective CRFR2 antagonist astressin2B produced a dose-dependent increase in ethanol consumption in both non-stressed controls and stressed mice. The 10-day episodic defeat stress used here elicited anxiety- but not depressive-like behaviors, and promoted an increase in ethanol drinking. CRF-CRFR1 signaling in the BNST seems to underlie ethanol intake in non-stressed mice, whereas CRFR2 modulates alcohol consumption in both socially defeated and non-stressed mice with a history of chronic intake.

Balancing Automatic-Controlled Behaviors and Emotional-Salience States: A Dynamic Executive Functioning Hypothesis.

Recently, there has been growing interest in understanding how executive functions are conceptualized in psychopathology. Since several models have been proposed, the major issue lies within the definition of executive functioning itself. Theoretical discussions have emerged, narrowing the boundaries between "hot" and "cold" executive functions or between self-regulation and cognitive control. Nevertheless, the definition of executive functions is far from a consensual proposition and it has been suggested that these models might be outdated. Current efforts indicate that human behavior and cognition are by-products of many brain systems operating and interacting at different levels, and therefore, it is very simplistic to assume a dualistic perspective of information processing. Based upon an adaptive perspective, we discuss how executive functions could emerge from the ability to solve immediate problems and to generalize successful strategies, as well as from the ability to synthesize and to classify environmental information in order to predict context and future. We present an executive functioning perspective that emerges from the dynamic balance between automatic-controlled behaviors and an emotional-salience state. According to our perspective, the adaptive role of executive functioning is to automatize efficient solutions simultaneously with cognitive demand, enabling individuals to engage such processes with increasingly complex problems. Understanding executive functioning as a mediator of stress and cognitive engagement not only fosters discussions concerning individual differences, but also offers an important paradigm to understand executive functioning as a continuum process rather than a categorical and multicomponent structure.

Assessing Affective and Deliberative Decision-Making: Adaptation of the Columbia Card Task to Brazilian Portuguese.

UNLABELLED: The ability to predict reward and punishment is essential for decision-making and the ability to learn about an ever-changing environment. Therefore, efforts have been made in understanding the mechanisms underlying decision-making, especially regarding how affective and deliberative processes interact with risk behavior. OBJECTIVE: To adapt to Brazilian Portuguese the Columbia Card Task (CCT) and investigate affective and deliberative processes involved in decision-making. METHODS: This study had two main phases: (1) a transcultural adaptation and (2) a pilot study. RESULTS: The feedback manipulation among the three conditions of CCT had an effect on the risk-taking level (p < .005, ES = .201). In addition, the feedback manipulation among the three conditions of CCT had an effect on the information use at both the individual and group levels. Further, a linear regression suggested that the use of information, indicated by the advantageous level of the scenarios, predict the number of cards chosen R 2 = .029, p < .001, accounting for 17% of the variance. CONCLUSIONS: The Brazilian CCT performs well and is a versatile method for the assessment of affective and deliberative decision-making under risk according to different feedback manipulation scenarios. This study goes further, comparing electrodermal activity during hot and warm conditions and addressing an advantageous level index analysis to asses deliberative processing.

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.

Dual-memory processes in crack cocaine dependents: The effects of childhood neglect on recall.

Exposure to adversities during sensitive periods of neurodevelopment is associated with the subsequent development of substance dependence and exerts harmful, long-lasting effects upon memory functioning. In this study, we investigated the relationship between childhood neglect (CN) and memory using a dual-process model that quantifies recollective and non-recollective retrieval processes in crack cocaine dependents. Eighty-four female crack cocaine-dependent inpatients who did (N = 32) or did not (N = 52) report a history of CN received multiple opportunities to study and recall a short list composed of familiar and concrete words and then received a delayed-recall test. Crack cocaine dependents with a history of CN showed worse performance on free-recall tests than did dependents without a history of CN; this finding was associated with declines in recollective retrieval (direct access) rather than non-recollective retrieval. In addition, we found no evidence of group differences in forgetting rates between immediate- and delayed-recall tests. The results support developmental models of traumatology and suggest that neglect of crack cocaine dependents in early life disrupts the adult memory processes that support the retrieval of detailed representations of events from the past.

Early abstinence of crack-cocaine is effective to attenuate oxidative stress and to improve antioxidant defences.

RATIONALE: Preclinical studies have shown that cocaine exposure and withdrawal are associated with cellular oxidative stress damage. However, the impact of crack-cocaine dependence on oxidative stress biomarkers remains unclear. Here, we assessed peripheral oxidative stress and antioxidant defences during two periods of crack-cocaine detoxification treatment and associated these changes with psychological morbidity. METHODS: Thirty female inpatients were recruited, and plasma samples were collected at the 4th and 18th days of abstinence; 30 healthy controls were also recruited. Plasma levels of protein carbonyl, protein thiol content, superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced reduced (GSH) and total reactive antioxidant potential (TRAP) were measured by standard methods; the questionnaires Cocaine Selective Severity Assessment, Beck Depressive Inventory and the Addiction Severity Index were applied. RESULTS: We report higher oxidative stress damage after 4 days of detoxification, as shown by increased total thiol content and protein carbonylation when compared with control group and after 18 days of detoxification. After 18 days of treatment, we observed a recovery of the oxidative stress damage and increase of the antioxidant defences, as shown by higher levels of SOD, GPx, GSH and TRAP. There was a positive correlation between protein carbonylation and psychological variables; in contrast, there was a negative correlation between TRAP levels and clinical assessments. CONCLUSIONS: Taken together, these results suggest that drug rehabilitation treatment was effective in decreasing oxidative damage represented by the reduction in biological markers, which are closely related to the severity of withdrawal symptoms.

Assessing affective and deliberative decision-making: adaptation of the Columbia card task to Brazilian Portuguese

The ability to predict reward and punishment is essential for decision-making and the ability to learn about an ever-changing environment. Therefore, efforts have been made in understanding the mechanisms underlying decision- making, especially regarding how affective and deliberative processes interact with risk behavior. Objective: To adapt to Brazilian Portuguese the Columbia Card Task (CCT) and investigate affective and deliberative processes involved in decision-making. Methods: This study had two main phases: (1) a transcultural adaptation and (2) a pilot study. Results: The feedback manipulation among the three conditions of CCT had an effect on the risk-taking level (p < .005, ES = .201). In addition, the feedback manipulation among the three conditions of CCT had an effect on the information use at both the individual and group levels. Further, a linear regression suggested that the use of information, indicated by the advantageous level of the scenarios, predict the number of cards chosen R2 = .029, p < .001, accounting for 17% of the variance. Conclusions: The Brazilian CCT performs well and is a versatile method for the assessment of affective and deliberative decision-making under risk according to different feedback manipulation scenarios. This study goes further, comparing electrodermal activity during hot and warm conditions and addressing an advantageous level index analysis to asses deliberative processing (AU)

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Mothers who were sexually abused during childhood are more likely to have a child victim of sexual violence / Mães que sofreram abuso sexual na infância têm maior chance de ter um filho vítima de violência sexual

Introduction: Recurrent exposure to childhood sexual abuse (CSA) seems to be higher among victims of sexual abuse. In this sense, experiences related to sexual violence can perpetuate within the family context itself in various ways. Here, we investigate the association between being exposed to CSA and having a child victim of sexual abuse. Method: We used a sample with 123 mothers, who were divided into 2 groups: one consisting of 41 mothers of sexually abused children and another consisting of 82 mothers of non-sexually abused children. History of exposure to CSA was evaluated by means of the Childhood Trauma Questionnaire - Short Form (CTQ) and we used a logistic regression model to estimate the prediction values regarding having or not a child exposed to sexual violence. Results: Mothers of sexually abused children had significantly higher scores on CTQ, especially on the sexual abuse subscale (SA). According to our logistic regression model, higher scores on the CTQ significantly predicted the status of being a mother of children exposed to sexual violence in our sample (Wald = 7.074; p = 0.008; Exp(B) = 1.681). Years of formal education reduced the likelihood of having a child victim of sexual violence (Wald = 18.994; p = 0.001; Exp(B) = 0.497). Conclusion: Our findings highlight the importance of a possible intergenerational effect of sexual abuse. Family intervention and prevention against childhood maltreatment should take this issue in account (AU)

Introdução: A recorrência da exposição ao abuso sexual na infância (ASI) parece ser maior entre vítimas de abuso sexual. Nesse sentido, experiências relacionadas à violência sexual podem perpetuar-se dentro do próprio contexto familiar por diversas maneiras. Aqui, investigamos a associação entre ser exposto a ASI e ter um filho vítima de abuso sexual. Método: Usamos uma amostra com 123 mães, que foram divididas em 2 grupos: um composto por 41 mães de filhos abusados sexualmente e outro composto por 82 mães de filhos não abusados. O histórico da exposição à ASI foi avaliado por meio do Childhood Trauma Questionnaire - Short Form (CTQ) e usamos um modelo de regressão logística para estimar os valores preditivos em relação a ter ou não um filho exposto a violência sexual. Resultados: Mães de crianças vítimas de abuso sexual obtiveram maiores escores no CTQ, especialmente na subescala de abuso sexual (SA). Segundo nosso modelo de regressão logística, escores maiores no CTQ foram capazes de predizer significativamente a categoria de ser ou não mãe de uma criança vítima de violência sexual em nossa amostra (Wald = 7,074; p = 0,008; Exp(B) = 1,681). O número de anos de escolaridade reduziu a chance de ter um filho vítima de violência sexual (Wald = 18,994; p = 0,001; Exp(B) = 0,497). Conclusão: Nossos achados ressaltam a importância de um possível efeito intergeracional do abuso sexual. Intervenções familiares e preventivas contra maus-tratos na infância deveriam levar em consideração essa problemática (AU)

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.

Mothers who were sexually abused during childhood are more likely to have a child victim of sexual violence.

INTRODUCTION: Recurrent exposure to childhood sexual abuse (CSA) seems to be higher among victims of sexual abuse. In this sense, experiences related to sexual violence can perpetuate within the family context itself in various ways. Here, we investigate the association between being exposed to CSA and having a child victim of sexual abuse. METHOD: We used a sample with 123 mothers, who were divided into 2 groups: one consisting of 41 mothers of sexually abused children and another consisting of 82 mothers of non-sexually abused children. History of exposure to CSA was evaluated by means of the Childhood Trauma Questionnaire - Short Form (CTQ) and we used a logistic regression model to estimate the prediction values regarding having or not a child exposed to sexual violence. RESULTS: Mothers of sexually abused children had significantly higher scores on CTQ, especially on the sexual abuse subscale (SA). According to our logistic regression model, higher scores on the CTQ significantly predicted the status of being a mother of children exposed to sexual violence in our sample (Wald = 7.074; p = 0.008; Exp(B) = 1.681). Years of formal education reduced the likelihood of having a child victim of sexual violence (Wald = 18.994; p = 0.001; Exp(B) = 0.497). CONCLUSION: Our findings highlight the importance of a possible intergenerational effect of sexual abuse. Family intervention and prevention against childhood maltreatment should take this issue in account.

Adipokines during early abstinence of crack cocaine in dependent women reporting childhood maltreatment.

Childhood maltreatment has been associated with addiction and immune dysregulation, although neurobiological substrates underlying this association remain largely unknown. The aim of the study was to compare plasma levels of adipokines during early abstinence in crack cocaine dependent women with (CM+) and without history of childhood maltreatment (CM-). One hundred four crack cocaine female users were followed for 20 days in a detoxification inpatient treatment unit. Plasma levels of adiponectin, resistin and leptin were assessed every 7 days during 3 weeks of follow-up. The Childhood Trauma Questionnaire (CTQ) retrospectively assessed childhood maltreatment history. A healthy control group was included to provide adipokines reference values (HC). All crack users increased leptin plasma levels during early abstinence despite concentrations remained lower in comparison with non-users group. Crack users reporting childhood maltreatment exhibited a significant reduction in plasma levels of adiponectin and resistin when compared to CM- group. In addition, only CM- participants increased plasma levels of adiponectin during detoxification. This is the first study evaluating adipokines during crack cocaine abstinence. Our results suggest a modulator effect of childhood maltreatment on inflammatory status in treatment-seeking crack cocaine dependents during early abstinence.