Co-ocorrency between attention deficit hyperactivity disorder and psychoactive substances

Attention deficit/hyperactivity disorder (ADHD) is highly associated with substance use disorders (SUDs), both in clinical and community studies. Approximately 30% of subjects with SUDs present with comorbid ADHD, a prevalence rate significantly higher than that seen in the general population. The effect of ADHD on the development of SUDs have been subject to extensive studies. This article reviews the existing literature regarding: a) the nature of the association between ADHD and SUDs; b) the impact of ADHD on SUDs; c) the treatment of ADHD which co-occurs with SUDs. Finally an overview, from a predominantly clinical perspective, an integration of those data is proposed.Existe forte associação entre o transtorno de déficit de atenção/hiperatividade (TDAH) e o transtorno por uso de substâncias psicoativas (TUSP) em estudos clínicos e comunitários. Estimam-se que aproximadamente 30% dos sujeitos com TUSP apresentem comorbidade com o TDAH, taxa significativamente maior do que a vista na população geral. Vários estudos vêm analisando o possível efeito do TDAH no risco de desenvolvimento de TUSP. O presente artigo revisa a literatura disponível às seguintes questões: a) natureza da associação entre o TDAH e o TUSP; b) efeitos do TDAH no TUSP; c) tratamento do TDAH na concomitância do diagnóstico de TUSP. Por fim, é oferecida uma integração das diferentes informações, sob um enfoque predominantemente clínico.Universidade Luterana do BrasilUFRGS Hospital de Clínicas de Porto AlegreUniversidade Federal de São Paulo (UNIFESP) Unidade de Pesquisa em Álcool e DrogasUNIFESP, Unidade de Pesquisa em Álcool e DrogasSciEL

A review and analysis of the relationship between neuropsychological measures and DAT1 in ADHD

Contains fulltext : 69105.pdf (publisher's version ) (Closed access)Meta-analyses indicate that the gene coding for the dopamine transporter (DAT1 or SLC6A3) is associated with an increased risk for ADHD. The mechanisms of this gene for ADHD are unclear. We systematically reviewed studies linking the VNTR in the 3' UTR of the DAT1 to neurophysiological and neuropsychological measures. In addition, a broad set of executive/cognitive and motor tests was administered to 350 children (5-11 years) and adolescents (11-19 years) with ADHD and 195 non-affected siblings. Two VNTRs (in intron 8 and the 3' UTR) and four SNPs (two 5' and two 3') in DAT1 were genotyped. The effect of the polymorphisms on neuropsychological functioning was studied. The review indicated that the majority of studies did not find a relation between DAT1 and neurophysiological or neuropsychological measures. In our sample, several of the polymorphisms of DAT1 were associated with ADHD and ADHD was associated with impaired neuropsychological functioning. However, none of the DAT1 polymorphisms was convincingly associated with neuropsychological dysfunctioning. This suggests that the effect of DAT1 on ADHD was not mediated by neuropsychological performance. However, since DAT1 is mainly expressed in the striatum and not the prefrontal cortex, it may influence striatum-related functions (such as delay aversion) more heavily than prefrontal related functions (such as executive functions). Associations of DAT1 with ADHD were only found in adolescents, which may suggest that DAT1 mainly exerts its effect in adolescence, and/or that having a more persistent form of ADHD may mark a more severe or homogeneous genetic form of the disorder

Prenatal Cocaine Exposure and Its Influence on Pediatric Epigenetic Clocks and Epigenetic Scores in Humans

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale DNAm data availability and existing evidence regarding PCE as a risk for health problems later in life, we generated ES for tobacco smoking, psychosis, autism, diabetes, and obesity. A gene ontology (GO) analysis on the CpGs included in the ES with group differences was performed. PCE was associated with lower DNAmGA in newborns, and this effect remained significant when controlling for potential confounders, such as blood cell type composition predicted by DNAm and obstetric data. DNAmGA was negatively correlated with BDNF levels in the serum of UCB. Higher tobacco smoking, psychosis, and diabetes ES were found in the PCE group. The GO analysis revealed GABAergic synapses as a potential pathway altered by PCE. Our findings of decelerated DNAmGA and ES for adverse phenotypes associated with PCE, suggest that the effects of gestational cocaine exposure on the epigenetic landscape of human newborns are detectable at birth

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 versus 2.323,03, 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

Comparison between serum levels of Cocaine and Amphetamine Regulated Transcript (CART) from umbilical cord blood and peripheral blood of pregnant crack users

Introdução: No Brasil, o uso de crack permanece um desafio à saúde pública devido à facilidade de aquisição da droga e sua elevada capacidade de induzir dependência. A exposição intrauterina (EIU) à cocaína está associada a alterações neurocomportamentais durante a infância e adolescência. Em estudo prévio do nosso grupo, achou-se menor nível de estresse oxidativo (EO) em recém-nascidos (RN) com EIU. Uma possível explicação pode ser a Cocaine and Amphetamine Regulated Transcript (CART), um antioxidante endógeno presente desde o período embrionário e ativado por maiores níveis de dopamina. Objetivo: Verificar a correlação entre os níveis de CART no sangue de cordão umbilical (SCU) e sangue periférico de 57 gestantes com exposição ao crack. Métodos: Trata-se de um estudo transversal, com amostragem consecutiva, em que o desfecho primário foi a correlação entre os níveis de CART no SCU e sangue periférico materno no pós-parto imediato. Dados gestacionais e perinatais foram sistematicamente coletados. Resultados: Houve correlação significativa entre os níveis de CART no sangue de cordão umbilical e sangue periférico materno (rs= 0,350 e p<0,05). Conclusões: Estes achados demonstram que os níveis de CART no sangue materno e no SCU se correlacionam. Todavia, não se pode afirmar de quem é a produção, ou se é produzida por ambos. O presente trabalho pode ajudar a elucidar os caminhos neurobiológicos responsáveis pelas alterações de neurodesenvolvimento, contribuindo para a ampliação das possibilidades de intervenções precoces.Introduction: In Brazil, the use of crack cocaine remains a public health challenge, due to easy drug acquisition and its high ability to induce dependence. Intrauterine exposure (IUE) to crack cocaine is associated with neurobehavioral changes during childhood and adolescence. In a previous study of our group, lower levels of oxidative stress (OS) were found in newborns with IUE. One possible explanation may be the Cocaine and Amphetamine Regulator Transcript (CART), an endogenous antioxidant present since the embryonic period activated by higher levels of dopamine. Objective: The aim of this study is to investigate the correlation of CART levels between umbilical cord blood (UCB) and peripheral blood samples of 57 pregnant women exposed to crack. Methods: This is a cross-sectional study with a consecutive sampling, in which the primary outcome was the correlation between CART levels at UCB and peripheral blood of their mothers in immediate postpartum. Gestational and perinatal data were systematically collected. Spearman correlation test was performed after checking the pattern of distribution, being considered a 0.05 significance level. Results: There was a significant correlation between CART levels in umbilical cord blood and peripheral blood (rs = 0.350 and p <0.05). Conclusions: These findings suggest a correlation between CART levels at UCB and mother´s blood. However, it remains unclear whether it is produced by the mother, the fetus, or both. This study may help to elucidate the neurobiological pathways responsible for neurodevelopmental changes, providing a rationale for early interventions

Socio-demographic and clinical characteristics of pregnant and puerperal crack-cocaine using women: preliminary data

Background: The literature provides several studies on the effects of cocaine when exposed to the fetus. However, the majority of these data comes from animal models. Objective: The objective of this study is to present socio-demographic and clinical data in crack-cocaine using pregnant women and their babies, as compared to non-users. Methods: Cross-sectional study, comprised by 56 dyads of crack-cocaine using mothers-babies and 89 control dyads. In addition to the socio-demographic data and the babies’ information, data collection was based on ABIPEMI for socioeconomic level, WAIS for IQ, MINI for psychopathology and ASSIST for drug use. Results: Most crack users, in comparison to non-users, did not have a partner (10.52% vs 4.4%, P = 0.001) and presented lower IQ (78.15, +/-8.07 vs 84.27 +/- 9.87; P = 0.002). The prevalence of antisocial personality disorder and suicide risk in users was higher than in non-users (24.44% vs none, P < 0.001; 28.26% vs 10.46% P = 0.01). Most of the users did not participate in prenatal care (75%). The babies that the crack-cocaine using mothers gave birth to weighed significantly less than the controls (2.858 g vs 3.240 g, P = 0.002). Discussion: Users had a higher degree of psychopathology and lower attendance in prenatal care. There was an overlap of adverse factors, both for exposed mothers and babies. The sum of these vulnerabilities could result in significant harm to the developing infant