Effects of childhood trauma on BDNF and TBARS during crack-cocaine withdrawal

Objective: To evaluate the association between childhood trauma (CT) and serum levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARS) during crack-cocaine withdrawal. Method: Thirty-three male crack-cocaine users were recruited at admission to a public addiction treatment unit. Serum BDNF and TBARS levels were evaluated at intake and discharge. Information about drug use was assessed by the Addiction Severity Index-6th Version (ASI-6); CT was reported throughout the Childhood Trauma Questionnaire (CTQ). CTQ scores were calculated based on a latent analysis model that divided the sample into low-, medium-, and high-level trauma groups. Results: There was a significant increase in BDNF levels from admission to discharge, which did not differ across CT subgroups. For TBARS levels, we found a significant time vs. trauma interaction (F2,28 = 6.357, p = 0.005,ηp 2 = 0.312). In participants with low trauma level, TBARS decreased, while in those with a high trauma level, TBARS increased during early withdrawal. Conclusion: TBARS levels showed opposite patterns of change in crack-cocaine withdrawal according to baseline CT. These results suggest that CT could be associated with more severe neurological impairment during withdrawal.

TBARS and BDNF levels in newborns exposed to crack/cocaine during pregnancy: a comparative study

Objectives: To compare levels of a marker of lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and brain-derived neurotrophic factor (BDNF) in umbilical cord blood (UCB) between newborns exposed to crack/cocaine in utero (exposed newborns [EN], n=57) and non-exposed newborns (NEN, n=99), as well as in maternal peripheral blood at delivery. Methods: This was a cross-sectional study. Potential confounders, including perinatal parameters, psychopathology, and use of other substances, were assessed. Results: After adjusting for potential confounders, adjusted mean BDNF was significantly higher in EN (3.86 ng/mL, 95% confidence interval [95%CI] 2.29-5.43) than in NEN (0.85 ng/mL, 95%CI 0.47-1.23; p < 0.001; Cohen effect size: 1.12), and significantly lower in crack/cocaine mothers than in control mothers (4.03 ng/mL, 95%CI 2.87-5.18 vs. 6.67 ng/mL, 95%CI 5.60-7.74; p = 0.006). The adjusted mean TBARS level was significantly lower in EN (63.97 µM MDA, 95%CI 39.43-88.50) than NEN (177.04 µM MDA, 95%CI 140.93-213.14; p < 0.001; effect size = 0.84), with no difference between mother groups (p = 0.86). Conclusions: The changes in TBARS levels observed in EN suggest that fetuses exposed to cocaine mobilize endogenous antioxidant routes since very early stages of development. The increase in BDNF levels in EN might indicate changes in fetal development, whereas the changes in BDNF levels in mothers provide evidence of the complex metabolic processes involved in drug use during pregnancy.

IL-6 and IL-10 levels in the umbilical cord blood of newborns with a history of crack/cocaine exposure in utero: a comparative study / Níveis de IL-6 e IL-10 no sangue de cordão umbilical de recém-nascidos com história de exposição intrauterina ao crack/cocaína: um estudo comparativo

Introduction Prenatal cocaine exposure (PCE) is associated with neurobehavioral problems during childhood and adolescence. Early activation of the inflammatory response may contribute to such changes. Our aim was to compare inflammatory markers (IL-6 and IL-10) both in umbilical cord blood and in maternal peripheral blood at delivery between newborns with history of crack/cocaine exposure in utero and non-exposed newborns. Methods In this cross-sectional study, 57 newborns with a history of crack/cocaine exposure in utero (EN) and 99 non-exposed newborns (NEN) were compared for IL-6 and IL-10 levels. Sociodemographic and perinatal data, maternal psychopathology, consumption of nicotine and other substances were systematically collected in cases and controls. Results After adjusting for potential confounders, mean IL-6 was significantly higher in EN than in NEN (10,208.54, 95% confidence interval [95%CI] 1,328.54-19,088.55 vs. 2,323.03, 95%CI 1,484.64-3,161.21; p = 0.007; generalized linear model [GLM]). Mean IL-10 was also significantly higher in EN than in NEN (432.22, 95%CI 51.44-812.88 vs. 75.52, 95%CI 5.64-145.39, p = 0.014; GLM). Adjusted postpartum measures of IL-6 were significantly higher in mothers with a history of crack/cocaine use (25,160.05, 95%CI 10,958.15-39,361.99 vs. 8,902.14, 95%CI 5,774.97-12,029.32; p = 0.007; GLM), with no significant differences for IL-10. There was no correlation between maternal and neonatal cytokine levels (Spearman test, p ≥ 0.28 for all measures). Conclusions IL-6 and IL-10 might be early biomarkers of PCE in newborns. These findings could help to elucidate neurobiological pathways underlying neurodevelopmental changes and broaden the range of possibilities for early intervention.

Introdução A exposição pré-natal à cocaína está associada a problemas neurocomportamentais durante a infância e adolescência. A ativação precoce da resposta inflamatória pode contribuir para tais alterações. Nosso objetivo foi comparar marcadores inflamatórios (IL-6 e IL-10) no sangue do cordão umbilical e no sangue periférico materno na hora do parto, entre recém-nascidos expostos ao crack intraútero e recém-nascidos não expostos. Métodos Neste estudo transversal, 57 recém-nascidos expostos ao crack intraútero (RNE) e 99 recém-nascidos não expostos (RNNE) foram comparados quanto aos níveis de IL-6 e IL-10. Dados sociodemográficos e perinatais, psicopatologia materna, consumo de nicotina e outras substâncias foram sistematicamente coletados em casos e controles. Resultados Após o ajuste para potenciais confundidores, a média de IL-6 foi significativamente maior nos RNE em comparação aos RNNE [10.208,54, intervalo de confiança (IC95%) 1.328,54-19.088,55 versus2.323,03, IC95% 1.484,64-3.161,21; p = 0,007; modelo linear generalizado (MLG)]. A média ajustada de IL-10 foi significativamente maior nos RNE do que nos RNNE (432,2189, IC95% 51,44-812,88 versus 75,52, IC95% 5,64-145,39, p = 0,014; MLG). Medidas pós-parto ajustadas de IL-6 foram significativamente maiores nas mães que usaram de crack/cocaína (25.160,05, IC95% 10.958,15-39.361,99 versus 8.902,14, IC95% 5.774,97-12.029,32; p = 0,007; MLG), sem diferenças significativas para IL-10. Não houve correlação entre níveis maternos e neonatais de citocinas (teste de Spearman, p ≥ 0,28 para todas as medidas). Conclusões IL-6 e IL-10 podem ser biomarcadores precoces da exposição pré-natal a cocaína em recém-nascidos. Esses resultados podem ajudar a elucidar as vias neurobiológicas subjacentes a alterações do desenvolvimento e aumentar a gama de possibilidades para intervenção precoce.

Histone deacetylase activity and brain-derived neurotrophic factor (BDNF) levels in a pharmacological model of mania

Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH) exposure, a well-accepted animal model of acute mania in bipolar disorder (BD), and histone deacetylase (HDAC) inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC) and peripheral blood mononuclear cells (PBMCs) of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF) protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li), 200 mg/kg sodium valproate (VPT), 2 mg/kg sodium butyrate (SB), or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity. .