Saulo Gantes Tractenberg

An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review.

Early life stress (ELS) developmental effects have been widely studied by preclinical researchers. Despite the growing body of evidence from ELS models, such as the maternal separation paradigm, the reported results have marked inconsistencies. The maternal separation model has several methodological pitfalls that could influence the reliability of its results. Here, we critically review 94 mice studies that addressed the effects of maternal separation on behavioural outcomes. We also discuss methodological issues related to the heterogeneity of separation protocols and the quality of reporting methods. Our findings indicate a lack of consistency in maternal separation effects: major studies of behavioural and biological phenotypes failed to find significant deleterious effects. Furthermore, we identified several specific variations in separation methodological procedures. These methodological variations could contribute to the inconsistency of maternal separation effects by producing different degrees of stress exposure in maternal separation-reared pups. These methodological problems, together with insufficient reporting, might lead to inaccurate and unreliable effect estimates in maternal separation studies.

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.

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.

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.

Crack cocaine addiction, early life stress and accelerated cellular aging among women

BACKGROUND Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening. However, the role of telomere length (TL) in crack cocaine addiction remains unknown. The purpose of this study was to investigate the TL in a sample of crack cocaine dependent-women who reported an ELS history and in a community-based sample of elderly women as a reference group for senescence. METHODS This study included treatment seeking crack cocaine dependents women (n=127) and elderly women without a psychiatric diagnosis (ELD, n=49). The crack cocaine sample was divided in two groups according to their Childhood Trauma Questionnaire (CTQ) scores: presence of history of childhood abuse and neglect (CRACK-ELS) and absence of ELS history (CRACK). TL was assessed by T/S ratio obtained from peripheral blood DNA using quantitative PCR assay. RESULTS CRACK and CRACK-ELS subjects exhibited shortened TL in comparison to the ELD group, despite their younger age. Among crack cocaine sample, CRACK-ELS group had significantly shorter telomeres than the CRACK group. Correlation analysis within crack cocaine group indicated that TL was negatively correlated with emotional abuse scores. CONCLUSIONS These results support previous findings associating telomere shortening with both ELS and drug addiction. This study suggests new evidence of a distinct biological phenotype for drug-dependent women with ELS. The results support the biological senescence hypothesis underpinning ELS experience.

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.

Exposição a trauma e transtorno de estresse pós-traumático em usuárias de crack

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.

Brain-Derived Neurotrophic Factor and Delayed Verbal Recall in Crack/Cocaine Dependents.

Background/Aims: Considering the role of brain-derived neurotrophic factor (BDNF) in memory processes and its peripheral response during the detoxification of cocaine, the aim of this study was to investigate whether plasma BDNF levels could be related to memory performance in women with crack/cocaine dependence. Methods: Twenty-five abstinent female crack/cocaine users (CCD) and 25 unmedicated healthy women (HW), carefully matched for age and years of formal education, were assessed regarding memory performance. Logical Memory was used to assess the immediate verbal recall (IVR), delayed verbal recall (DVR) and memory retention. Plasma BDNF levels were measured by Elisa immunoassay. Beck Depression Inventory was used to assess the severity of depressive symptoms, and the Cocaine Selective Severity Assessment the severity of cocaine abstinence symptoms. Results: The CCD group had lower DVR scores and higher plasma BDNF levels when compared to HW group. In addition, a linear regression model showed that BDNF levels predicted DVR scores within CCD group independently of depressive symptoms (R = 0.51; R2 = 0.26; t(22) = 4.025, p = 0.03). Conclusion: Despite higher plasma BDNF levels, crack users exhibited memory impairments when compared to healthy women. Specifically, peripheral BDNF levels predicted better cognitive performance only within individuals who already had cognitive impairment.

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.

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults.

Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Methods: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. Results: BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). Conclusion: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.