Maternal separation induces long-term oxidative stress alterations and increases anxiety-like behavior of male Balb/cJ mice.

Early life stress (ELS) exposure is a well-known risk factor for the development of psychiatric conditions, including anxiety disorder. Preclinical studies show that maternal separation (MS), a classical model of ELS, causes hypothalamic-pituitary-adrenal (HPA) axis alterations, a key contributor to the stress response modulation. Given that HPA axis activation has been shown to induce oxidative stress, it is possible to hypothesize that oxidative stress mediates the relationship between chronic ELS exposure and the development of several disorders. Here, we investigate the effects of MS in the oxidative status [plasma and brain reduced glutathione, catalase and thiobarbituric acid reactive substances (TBARS)], metabolism (glucose, triglycerides and cholesterol) and anxiety-like behaviors in adult Balb/cJ mice. In short, we found that MS increased anxiety-like behaviors in the open field, light/dark test but not in the elevated-plus maze. Animals also presented increased circulating cholesterol, increased TBARS in the plasma and decreased catalase in the hippocampus. Our findings suggest that MS induces long-term alterations in oxidative stress and increased anxiety-like behaviors.

Maternal behavior of the mouse dam toward pups: implications for maternal separation model of early life stress.

Maternal care is essential for an adequate pup development, as well as for the health of the dam. Exposure to stress in early stages of life can disrupt this dam-pup relationship promoting altered neurobiological and behavioral phenotypes. However, there is a lack of consensus regarding the effects of daily maternal separation (MS) on the pattern of maternal behavior. The aim of this study is to compare the patterns of maternal behavior between mice exposed to MS and controls. BALB/c mice were subjected to MS for a period of 180 min/day from postnatal day 2-7 (n = 17) or designated to be standard animal facility reared (AFR) controls (n = 19). Maternal behaviors were computed as frequency of nursing, licking pups and contact with pups, and nonmaternal behaviors were computed as frequency of actions without interaction with pups and eating/drinking. A total of 18 daily observations of maternal behavior were conducted during these six days, and considering the proportion of maternal and nonmaternal behaviors, an index was calculated. There was no difference when comparing the global index of maternal behavior between the AFR and MS animals by the end of the observed period. However, the pattern of maternal behavior between groups was significantly different. While MS dams presented low frequency of maternal behavior within the first couple days of the stress protocol, but increasing over time, AFR dams showed higher maternal behavior at the beginning, reducing over time. Together, our results indicate that MS alters the maternal behavior of the dams toward pups throughout the first week of the stress protocol and provoked some anxiety-related traits in the dams. The inversion of maternal behavior pattern could possibly be an attempt to compensate the low levels of maternal care observed in the first days of MS.

Maternal separation induces hippocampal changes in cadherin-1 (CDH-1) mRNA and recognition memory impairment in adolescent mice.

In rodents, disruption of mother-infant attachment induced by maternal separation (MS) is associated with recognition memory impairment and long-term neurobiological consequences. Particularly stress-induced modifications have been associated to disruption of cadherin (CDH) adhesion function, which plays an important role in remodeling of neuronal connection and synaptic plasticity. This study investigated the sex-dependent effect of MS on recognition memory and mRNA levels of classical type I and type II CDH and the related ß -catenin (ß -Cat) in the hippocampus and prefrontal cortex of late adolescent mice. We provided evidence that the BALB/c mice exposed to MS present deficit in recognition memory, especially females. Postnatal MS induced higher hippocampal CDH-2 and CDH-8 mRNA levels, as well as an upregulation of CDH-1 in the prefrontal cortex in both males and females. MS-reared female mice presented lower CDH-1 mRNA levels in the hippocampus. In addition, hippocampal CDH-1 mRNA levels were positively correlated with recognition memory performance in females. MS-reared male mice exhibited higher ß -Cat mRNA levels in the hippocampus. Considering sex-specific effects on CDH mRNA levels, it has been demonstrated mRNA changes in CDH-1, ß -Cat, and CDH-6 in the hippocampus, as well as CDH-1, CDH-8 and CDH-11 in the prefrontal cortex. Overall, these findings suggest a complex interplay among MS, CDH mRNA expression, and sex differences in the PFC and hippocampus of adolescent mice.

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; R(2) = 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.

Vulnerability and resilience to prenatal stress exposure: behavioral and molecular characterization in adolescent rats.

Exposure to stress can lead to long lasting behavioral and neurobiological consequences, which may enhance the susceptibility for the onset of mental disorders. However, there are significant individual differences in the outcome of stress exposure since only a percentage of exposed individuals may show pathological consequences, whereas others appear to be resilient. In this study, we aimed to characterize the effects of prenatal stress (PNS) exposure in rats at adolescence and to identify subgroup of animals with a differential response to the gestational manipulation. PNS adolescent offspring (regardless of sex) showed impaired emotionality in different pathological domains, such as anhedonia, anxiety, and sociability. However, using cluster analysis of the behavioral data we could identify 70% of PNS-exposed animals as vulnerable (PNS-vul), whereas the remaining 30% were considered resilient (PNS-res). At the molecular level, we found that PNS-res males show a reduced basal activation of the ventral hippocampus whereas other regions, such as amygdala and dorsal hippocampus, show significant PNS-induced changes regardless from vulnerability or resilience. Taken together, our results provide evidence of the variability in the behavioral and neurobiological effects of PNS-exposed offspring at adolescence. While these data may advance our understanding of the association between exposure to stress during gestation and the risk for psychopathology, the investigation of the mechanisms associated to stress vulnerability or resilience may be instrumental to develop novel strategies for therapeutic intervention.

Effects of early life stress on brain cytokines: A systematic review and meta-analysis of rodent studies.

Exposure to early life stress (ELS) may lead to long-lasting neurobiological and behavioral impairments. Alterations in the immune system and neuroinflammatory state induced by ELS exposure are considered risk factors for developing psychiatric disorders. Here, we performed a systematic review and meta-analysis of rodent studies investigating the short and long-term effects of ELS exposure on anti and pro-inflammatory cytokines in brain tissues. Our analysis shows that animals exposed to ELS present an increase in pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. On the other hand, no alteration was observed in the anti-inflammatory cytokine IL-10. Meta-regression revealed that alterations were more prominent in the hippocampus of adult animals that were exposed to more extended periods of ELS. These inflammatory effects were not permanent since few alterations were identified in aged animals. Our findings suggest that ELS exposure alters pro-inflammatory cytokines expression and may act as a primer for a secondary challenge that may induce lifelong immune alterations. Moreover, the actual evidence is insufficient to comprehend the relationship between anti-inflammatory cytokines and ELS fully.

Long-term Effects of Maternal Separation on Anxiety-Like Behavior and Neuroendocrine Parameters in Adult Balb/c Mice.

Introduction: Disruption of maternal care using maternal separation (MS) models has provided significant evidence of the deleterious long-term effects of early life stress. Several preclinical studies investigating MS showed multiple behavioral and biomolecular alterations. However, there is still conflicting results from MS studies, which represents a challenge for reliability and replicability of those findings. Objective: To address that, this study was conducted to investigate whether MS would affect anxiety-like behaviors using a battery of classical tasks, as well as central and peripheral stress-related biomarkers. Methods: Male Balb/c mice were exposed to MS from postnatal day (PND) 2 to 14 for 180-min per day. Two independent cohorts were performed to evaluate both baseline and anxiety-like behavior responses to MS at PND60. We performed composite scores to evaluate MS effects on anxiety and risk assessment phenotypes. Also, we assessed mRNA gene expression in the medial pre-frontal cortex (mPFC) of glucocorticoid and mineralocorticoid receptors (GR and MR) using real-time PCR and peripheral corticosterone levels (CORT) to investigate possible neurobiological correlates to anxiety behaviors. Results: We found increased anxiety-like behavior and decreased risk assessment and exploratory behaviors in MS mice. The animals exposed to MS also presented a decrease in MR mRNA expression and higher levels of CORT compared to controls. Conclusions: Our findings reinforce the body of evidence suggesting that long-term MS induces effects on anxiety and risk assessment phenotypes following the exposure to a standardized MS protocol. Moreover, MS affected the expression of MR mRNA and induced significant changes on CORT response. This data highlights that the reprograming MS effects on HPA axis could be mediate by MR gene expression in mPFC and chronic overactivity of peripheral CORT levels.

Neurotrophic Factor Levels in Preterm Infants: A Systematic Review and Meta-Analysis.

Objectives: Through a systematic review and meta-analysis of the literature we aimed to compare the levels of BDNF, NGF, NT-3, NT-4, and GDNF between human term and preterm infants, and investigate factors implicated in the variability of effect size estimates. Methods: The analysis was performed in three online databases, MEDLINE Complete, PsycINFO, and CINAHL. A random effects model was used to calculate the standardized mean difference (SMD) of neurotrophic factor levels in preterm infants vs. term within a 95% confidence interval (CI). To explore sources of heterogeneity meta-regression models were implemented. Results: Sixteen studies were included in this meta-analysis. A combined sample of 1,379 preterm and 1,286 term newborns were evaluated. We identified significant lower BDNF (SMD = -0.32; 95% CI: -0.59, -0.06; p = 0.014) and NT-3 (SMD = -0.31; 95% CI: -0.52, -0.09; p = 0.004) levels in preterm compared to term infants. No significant difference was observed in NGF and NT-4 levels between groups. Given that only two effect sizes were generated for GDNF levels, no meta-analytical model was performed. Meta-regression models revealed sample type (placental tissue, cerebrospinal fluid, peripheral blood, and umbilical cord blood) as a significant moderator of heterogeneity for BDNF meta-analysis. No significant associations were found for gestational week, birth weight, and clinical comorbidity of newborns with effect sizes. Conclusions: Our findings indicated that lower BDNF and NT-3 levels may be associated with preterm birth. Future studies with larger samples sizes should investigate neurodevelopmental manifestations resulting from neurotrophic factor dysregulation among preterm infants.

Exposure to Prenatal Stress Is Associated With an Excitatory/Inhibitory Imbalance in Rat Prefrontal Cortex and Amygdala and an Increased Risk for Emotional Dysregulation.

Epidemiological studies have shown that environmental insults and maternal stress during pregnancy increase the risk of several psychiatric disorders in the offspring. Converging lines of evidence from humans, as well as from rodent models, suggest that prenatal stress (PNS) interferes with fetal development, ultimately determining changes in brain maturation and function that may lead to the onset of neuropsychiatric disorders. From a molecular standpoint, transcriptional alterations are thought to play a major role in this context and may contribute to the behavioral phenotype by shifting the expression of genes related to excitatory and inhibitory (E/I) transmission balance. Nevertheless, the exact neurophysiological mechanisms underlying the enhanced vulnerability to psychopathology following PNS exposure are not well understood. In the present study, we used a model of maternal stress in rats to investigate the distal effects of PNS on the expression of genes related to glutamatergic and GABAergic neurotransmissions. We inspected two critical brain regions involved in emotion regulation, namely, the prefrontal cortex (PFC) and the amygdala (AMY), which we show to relate with the mild behavioral effects detected in adult rat offspring. We observed that PNS exposure promotes E/I imbalance in the PFC of adult males only, by dysregulating the expression of glutamatergic-related genes. Moreover, such an effect is accompanied by increased expression of the activity-dependent synaptic modulator gene Npas4 specifically in the PFC parvalbumin (PV)-positive interneurons, suggesting an altered regulation of synapse formation promoting higher PV-dependent inhibitory transmission and increased overall circuit inhibition in the PFC of males. In the AMY, PNS more evidently affects the transcription of GABAergic-related genes, shifting the balance toward inhibition. Collectively, our findings suggest that the E/I dysregulation of the PFC-to-AMY transmission may be a long-term signature of PNS and may contribute to increase the risk for mood disorder upon further stress.

Maternal Separation Combined With Limited Bedding Increases Anxiety-Like Behavior and Alters Hypothalamic-Pituitary-Adrenal Axis Function of Male BALB/cJ Mice.

Early life stress (ELS) is considered a risk factor for the development of psychiatric conditions, including depression and anxiety disorder. Individuals that live in adverse environments are usually exposed to multiple stressors simultaneously, such as maternal neglect, maltreatment, and limited resources. Nevertheless, most pre-clinical ELS models are designed to explore the impact of these events separately. For this reason, this study aims to investigate the effects of a combined model of ELS on anxiety-like behavior and hypothalamic-pituitary-adrenal (HPA) axis related targets. From PND 2 to PND 15 BALB/cJ mice were exposed simultaneously to maternal separation (MS; 3 h per day) and limited bedding (LB; ELS group) or left undisturbed (CT group). Maternal behavior was recorded in intercalated days, from PND 1 to PND 9. Male offspring were tested for anxiety-like behavior from PND 53 to PND 55 in the open field test (OF), elevated plus-maze (EPM), and light/dark test (LD). After behavioral testing, animals were euthanized, and glucocorticoid receptor (Nr3c1), corticotrophin-releasing hormone (Crh), and its receptor type 1 (Crhr1) gene expression in the hypothalamus were measured. Moreover, plasma corticosterone levels were analyzed. We observed that ELS dams presented altered quality of maternal care, characterized by a decrease in arched-back nursing, and an increase in passive nursing. Stressed dams also showed an increase in the number of exits from the nest when compared to CT dams. Furthermore, ELS animals showed increased anxiety-like behavior in the OF, EPM, and LD. Regarding gene expression, we identified an increase in hypothalamus Crh levels of ELS group when compared to CT animals, while no differences in Nr3c1 and Crhr1 expression were observed. Finally, stressed animals showed decreased levels of plasma corticosterone when compared to the CT group. In conclusion, we observed an alteration in maternal behavior in ELS dams. Later in life, animals exposed to the combined model of ELS showed increased levels of anxiety-like behavior. Moreover, the central and peripheral HPA measures observed could indicate a dysregulation in HPA function provoked by ELS exposure.

How Early Life Stress Impact Maternal Care: A Systematic Review of Rodent Studies.

Background: Maternal care refers to the behavior performed by the dam to nourish and protect her litter during its early development. Frequent and high-quality performance of such maternal behaviors is critical for the neurodevelopment of the pups. Maternal exposure to stress during early development can impair maternal care and amplify the deleterious effects of poor maternal caregiving and neglect. As such, a thorough understanding of the effects caused by several models of early life stress on maternal care may yield more insights into the relationship between stress and maternal behavior. Methods: A systematic review was performed to identify and address the effects of early life stress on maternal behavior. The search was conducted using three online databases: PUBMED, Embase, and Web of Science. To provide clear evidence of the impact of stress on maternal care, in every study, the stress group was always compared to a control group. Outcomes were categorized into eight different behaviors: (1) licking/grooming; (2) arched-back nursing; (3) blanket-nursing/passive nursing; (4) nest building; (5) contact with pups; (6) harmful/adverse caregiving; (7) no contact; (8) nest exits. Additionally, the methodological quality of the studies was evaluated. Results: A total of 12 different early life stress protocols were identified from the 56 studies included in this systematic review. Our data demonstrate that different stress models can promote specific maternal patterns of behavior. Regarding the maternal separation protocol, we observed an overall increase in nursing and licking/grooming behaviors, which are essential for pup development. An increase in the number of nest exits, which represents a fragmentation of maternal care, was observed in the limited bedding protocol, but the total amount of maternal care appears to remain similar between groups. Conclusions: Each stress protocol has unique characteristics that increase the difficulty of rendering comparisons of maternal behavior. The increase in maternal care observed in the maternal separation protocol may be an attempt to overcompensate for the time off-nest. Fragmented maternal care is a key component of the limited bedding protocol. Moreover, the methodological approaches to evaluate maternal behavior, such as time, duration, and behavior type should be more homogeneous across studies.

Acute neuroinflammation elicited by TLR-3 systemic activation combined with early life stress induces working memory impairments in male adolescent mice.

Toll-like Receptors (TLRs) are implicated with the pathogenesis of cognitive impairment induced by inflammation. Early life stress is associated with altered trajectories of neuroimmune signaling with implications for cognitive development. However, effects of TLR-3 activation on early life stress-related cognitive outcomes are understudied. We investigated the effects of maternal separation (MS) during postnatal development and a viral immune challenge during adolescence on working memory performance. BALB/c mice exposed to MS were separated from their dams daily for 180-min from postnatal day (PND) 2 to 15. At PND 45, animals were challenged with a single i.p. injection of either Poly (I:C) or sterile saline, and then subjected to a spatial working memory test in a Y-maze apparatus. Gene expression was determined by qPCR. Protein levels of oxidative stress markers were also assessed. A single peripheral administration of a TLR-3 agonist was able to induce working memory impairments in adolescent mice exposed to MS. At a molecular level, exposure to MS was associated with lower mRNA levels of Tlr3 in the medial prefrontal cortex (mPFC). However, when MS animals were exposed to Poly (I:C), a more robust activation of Tlr3, Il6 and Nfkb1 gene transcription was observed in these mice compared with control animals. These modifications did not result in oxidative stress. Finally, higher mRNA levels of Nfkb1 in the mPFC were correlated with lower working memory performance, suggesting that altered NF-κB signaling might be related with poor cognitive functioning. These results have implications for how ELS affects neuroimmune signaling in the mPFC.

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.

A systematic review of cognitive rehabilitation for bipolar disorder.

INTRODUCTION: It has been shown that bipolar disorder (BD) has a direct impact on neurocognitive functioning and behavior. This finding has prompted studies to investigate cognitive enhancement programs as potential treatments for BD, primarily focusing on cognitive reinforcement and daily functioning and not restricted to psychoeducation and coping strategies, unlike traditional psychosocial treatments. OBJECTIVE: This study presents a systematic review of controlled trials of cognitive rehabilitation (CR) for BD. Our main objective is to describe the results of studies of rehabilitation programs for BD and related methodological issues. METHOD: Electronic database searches (MEDLINE, Web of Science, and Embase) were conducted to identify articles using terms related to BD and CR. The methodological quality of each article was measured using the 5-item Jadad scale. RESULTS: A total of 239 articles were initially identified, but after application of exclusion criteria, only four were retained for this review. An average of 17 hours of intervention sessions were conducted, distributed as 0.95 hours per week and three of the four studies reported better executive function performance after CR interventions. CONCLUSIONS: We did not find robust evidence to support cognitive rehabilitation as an effective treatment for BD, because of: 1) the variety of intervention designs; 2) the methodological limitations of the studies; and 3) the lack of studies in the field.

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.

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.

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.

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.