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.

Oxytocin Receptor Exon III Methylation in the Umbilical Cord Blood of Newborns With Prenatal Exposure to Crack Cocaine.

BACKGROUND: Prenatal cocaine exposure (PCE) is associated with behavioral, cognitive, and social consequences in children that might persist into later development. However, there are still few data concerning epigenetic mechanisms associated with the effects of gestational cocaine exposure, particularly in human newborns. AIMS: We investigated the effects of PCE on DNA methylation patterns of the Oxytocin Receptor (OXTR) gene in the umbilical cord blood (UCB). The relationship between UCB DNA methylation levels and the severity of the mother's cocaine use during pregnancy was also evaluated. METHODS: In this cross-sectional study, 28 UCB samples of newborns with a history of crack cocaine exposure in utero and 30 UCB samples of non-exposed newborns (NEC) were compared for DNA methylation levels at two genomic loci located in exon III of the OXTR gene (OXTR1 and OXTR2) through pyrosequencing. Maternal psychopathology was investigated using the Mini International Neuropsychiatric Interview, and substance use characteristics and addiction severity were assessed using the Smoking and Substance Involvement Screening Test (ASSIST). RESULTS: No differences between newborns with a history of PCE and NEC were observed in OXTR1 or OXTR2 DNA methylation levels. However, regression analyses showed that maternal addiction severity for crack cocaine use predicted OXTR1 DNA methylation in newborns. CONCLUSION: These data suggest that OXTR methylation levels in the UCB of children are affected by the severity of maternal crack cocaine usage. Larger studies are likely to detect specific changes in DNA methylation relevant to the consequences of PCE.

Increased cocaine and amphetamine-regulated transcript cord blood levels in the newborns exposed to crack cocaine in utero.

BACKGROUND: Cocaine and amphetamine-regulated transcript (CART) is an endogenous antioxidant present since the embryonic period. CART is activated by high levels of dopamine and might be of interested in understanding the changes in the REDOX system associated with crack/cocaine intake. The goal of this study was to determine whether exposure to crack in utero is associated with increased CART levels. METHODS: In this cross-sectional study with consecutive sampling, we compared the umbilical cord blood (UCB) CART levels (µg/mL) of newborns exposed to crack/cocaine in utero (EN, n = 57) to levels in non-exposed newborns (NEN, n = 99). In addition, we compared serum CART levels between EN and NEN mothers, in the immediate postpartum period. Potential confounders, such as perinatal data (e.g., weight, Apgar, etc.), psychopathology (DSM-IV), and use of drugs other than crack (ASSIST) were assessed. RESULTS: According to general linear model analysis, the adjusted mean CART was significantly higher in EN (0.180, 95% CI 0.088-0.272) than in NEN (0.048, 95% CI 0.020-0.076; p < 0.002; d = 0.68). The difference in CART levels between EN and NEN mothers was not significant (p ≥ 0.05). CONCLUSION: The increase in CART levels in EN UBC suggests a response to crack/cocaine-induced oxidative stress during gestational period, as a potential attempt of neuroprotection. In adult women in puerperium, however, this endogenous antioxidant recruitment does not seem to operate.

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.

Differences in biomarkers of crack-cocaine adolescent users before/after abstinence.

AIMS: To measure the variation in Brain-Derived Neurotrophic Factor (BDNF), Thiobarbituric Acid Reactive Substances (TBARS) and interleukin (IL) levels in crack-cocaine dependent adolescents after 21days of abstinence, comparing to levels found in a group of healthy controls. DESIGN: Cross-sectional nested on a short follow-up study. SETTING: Two inpatient treatment units for adolescents, and a low-income neighborhood. PARTICIPANTS: 90 adolescents, of both genders, with diagnosis of crack cocaine dependence, and 81 healthy adolescents. MEASUREMENTS: Serum levels of IL-6, IL-10, TBARS and BDNF were assessed on admission and discharge. Drug addiction severity was assessed by the Addiction Severity Index - Teen Version (T-ASI) and Cocaine Craving Questionnaire - Brief version (CCQ-b). Psychiatric comorbidities were assessed by the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL). Generalized Estimating Equations (GEE) were used to estimate the IL-6, IL-10, TBARS and BDNF levels, adjusted for confounders. Hedges' g was used to estimate effect size. FINDINGS: TBARS (p=0.005, d=0.04), IL-6 (p=0.027, d=0.40) and IL-10 (p=0.025, d=0.41) were elevated and BDNF (p<0.001, d=0.62) was reduced (p<0.001), in patients, in comparison to controls, at admission time. Variation in those levels between admission and discharge were not significant. CONCLUSIONS: Crack-cocaine use seems to be associated with inflammatory and oxidative imbalances in adolescents.

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.

Effects of crack cocaine addiction and stress-related genes on peripheral BDNF levels.

This study examined the effects of glucocorticoid receptor (NR3C1), corticotropin-releasing hormone receptor 1 (CRHR1), and brain-derived neurotrophic factor (BDNF) genes on susceptibility to crack cocaine addiction and BDNF levels. Crack addicted patients who sought treatment (n = 280) and non-addicted individuals (n = 241) were assessed. Three SNPs in NR3C1 (rs6198, rs41423247, and rs10052957), three in CRHR1 (rs12944712, rs110402, and rs878886), and one in BDNF (rs6265) were genotyped. No significant effect was seen in the case-control analyses. Crack cocaine addicted patients showed significantly lower serum BDNF levels. Significant effects were observed for NR3C1 rs41423247 and rs10052957. These effects were restricted to non-addicted individuals and they were supported by significant gene-by-disease status interactions. For CRHR1, all SNPs were associated with BDNF levels. Although there were significant effects only in the analysis restricted to non-addicted individuals, the lack of significant results in the gene-by-disease status interaction analyses suggest a general effect on BDNF levels. The haplotype analyses presented the same effect seen in the single marker analyses. This study suggests that SNPs in the NR3C1 and CRHR1 genes may influence BDNF levels, but this effect is blunted in the context of crack cocaine addiction. Therefore, our data may be interpreted in light of several studies showing pronounced effects of crack cocaine on BDNF levels. Since peripheral BDNF is a biomarker for several psychiatric phenotypes, our results may be useful in interpreting previous associations between stress-related SNPs, drug addiction, and depression.

Association between the Intron 8 VNTR Polymorphism of the DAT1 Gene and Crack Cocaine Addiction.

BACKGROUND: This study aims to compare allele and genotype frequencies of a 30-bp variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene, located at intron 8, between adult crack cocaine users and nonaddicted individuals. Due to its involvement in drug addiction, this gene is a good candidate for molecular studies. METHODS: A cross-sectional sample of 239 current adult crack abusers or dependents from in- and outpatient clinics and 211 control individuals was collected in Brazil. They were evaluated using ASRS, ASI-6, WAIS-III, and MINI assessments. DNA samples extracted from whole blood were genotyped for the intron 8 VNTR in DAT1. RESULTS: Logistic regression analysis was performed and controlled for gender, age, ethnicity, educational level, and comorbidities of clinical interest (generalized anxiety disorder, suicide risk, major depressive episode, and attention deficit/hyperactivity disorder). This analysis showed that the 6R6R genotype was associated with crack cocaine addiction (OR = 1.844; CI = 1.101-3.089; p = 0.020). CONCLUSIONS: Our results are consistent with the role of DAT1 in the neurobiology of drug addiction. Nevertheless, the study of other genes, environmental factors, and their interactions is also important to gain a broader understanding of this condition.

Comparação dos níveis séricos da Cocaine and Amphetamine Regulated Transcript (CART) entre sangue de cordão umbilical e sangue periférico em gestantes usuárias de crack / Comparison between serum levels of Cocaine and Amphetamine Regulated Transcript (CART) between 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: The use of crack cocaine remains a public health challenge in Brazil, 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 in 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.

Crack Cocaine Use in Adolescents: Clinical Characteristics and Predictors of Early Initiation.

OBJECTIVE: To describe the clinical characteristics of adolescents with crack cocaine dependence and possible predictors of transition from drug experimentation to crack cocaine dependence. METHODS: This cross-sectional study enrolled a consecutive sample of 90 adolescents admitted to a psychiatric inpatient unit in the city of Porto Alegre in southern Brazil for crack cocaine detoxification between May 2011 and November 2012. Comorbid psychological conditions were assessed using the Kiddie-SADS-Present and Lifetime Version, and severity of drug use was assessed using the Teen Addiction Severity Index (T-ASI). Comorbidities were compared with those in a community sample of non-drug using controls (n = 81). RESULTS: Patients' mean age was 15.6 years (85.6% boys, 14.4% girls). Seventy-nine (93.2%) met criteria for cocaine dependence (DSM-IV-TR), while 78 (91.8%) had symptoms consistent with cocaine abuse. All patients had experimented with at least 1 other addictive substance before crack cocaine: 61.4%, tobacco (mean age at first use = 11.61 years); 44.3%, alcohol (age at first use = 12.43 years); and 54.5%, cannabis (age at first use = 12.15 years). Patients had used crack cocaine 23.2 days in the last month, and the mean age at first use of crack cocaine was 13.38 years. The most common psychiatric comorbidity was conduct disorder (81.8%), followed by oppositional defiant disorder (52.3%) and attention-deficit/hyperactivity disorder (44.3%), all of which were more prevalent in the patient population than in controls (P < .001). The T-ASI questionnaire showed severe consequences of drug use in most areas of life assessed. The mean time between onset of drug experimentation and crack cocaine dependence was 2.53 (SD = 1.96) years. When Cox regression models were applied, we found that predictors of earlier progression to using crack cocaine were age at first use of any drug (hazard ratio [HR] = 0.79 [95% CI, 0.71-0.88]; P < .001) and age at admission (HR = 0.7 [95% CI, 0.57-0.87]; P = .001). CONCLUSIONS: Patients were found to have a multitude of comorbid conditions, which supports the idea of treatment by a multidisciplinary health care team. For each year of delay in the age at first drug use, the chance of crack cocaine initiation is reduced by 18%. Prevention programs aimed at delaying experimentation with addictive substances, especially "gateway" drugs, could delay the progression to crack cocaine dependence.

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.

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.

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.

Crack cocaine users show differences in genotype frequencies of the 3' UTR variable number of tandem repeats of the dopamine transporter gene (DAT1/SLC6A3).

BACKGROUND: Due to the mechanism of action of the dopamine transporter (DAT) in drug addiction, the DAT1 gene is a potential candidate for molecular studies. This paper aims to compare the prevalence of allele and genotype frequencies created by the 3' UTR variable number of tandem repeats (VNTR) of this gene between crack cocaine users and controls. METHODS: A cross-sectional sample of 237 current adult crack cocaine abusers or dependents (DSM-IV TR criteria) from in- and outpatient clinics in southern Brazil and 205 community controls were compared. The subjects were evaluated using the Adult ADHD Self-Report Scale, the Mini-International Neuropsychiatric Interview - short version, and the Wechsler Intelligence Scale. DNA samples were genotyped for the DAT1 3' VNTR. RESULTS: Logistic regression analysis was performed to compare the frequency of the 10.10 genotype (the putative risk genotype) to those of other genotypes. A significant difference (p = 0.04, OR = 1.758, CI = 1.026-3.012) indicating an increased frequency of the 10.10 genotype in the cases (59.9%) compared to the controls (49.3%) was verified using clinical and demographic covariates. CONCLUSIONS: This is one of the first genetic association studies on crack cocaine users in the literature. The results suggest an influence of the DAT1 gene, namely the 3' VNTR 10.10 genotype. However, more analyses will confirm and clarify its contribution as a possible risk factor for crack cocaine dependence.

Searching for a neurobiological basis for self-medication theory in ADHD comorbid with substance use disorders: an in vivo study of dopamine transporters using (99m)Tc-TRODAT-1 SPECT.

PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) frequently co-occur. Although several studies have shown changes in striatal dopamine transporter (DAT) density in these disorders, little is known about the neurobiological basis of the comorbidity. The aim of this study was to evaluate striatal DAT density in treatment-naive ADHD adolescents with SUD (ADHD + SUD) and without SUD (ADHD), compared to SUD adolescents without ADHD (SUD) and healthy control subjects (HC). PATIENTS AND METHODS: Sixty-two male age-matched subjects diagnosed with DSM-IV criteria were included: ADHD + SUD (n = 18), SUD (n = 14), HC (n = 19), and ADHD (n = 11). Urine tests confirmed participants' drug use. All subjects performed SPECT scans with Tc-TRODAT-1 to evaluate DAT density in the striatum. RESULTS: The mean right striatum specific binding were 1.68 (ADHD), 1.38 (ADHD + SUD), 1.19 (HC), 1.17 (SUD), and in left striatum 1.65 (ADHD), 1.39 (ADHD + SUD), 1.19 (HC), and 1.17 (SUD). The ADHD group presented significantly higher striatal DAT density compared with ADHD + SUD, SUD, and HC groups. Adolescents with ADHD + SUD had significantly lower DAT density than those with ADHD, but significantly higher DAT density than those with SUD only and no significant difference from the healthy control group. CONCLUSION: The ADHD + SUD group had lower striatal DAT density in comparison with ADHD without SUD. It is possible to speculate that the use of cannabis and cocaine is responsible for the lower striatal DAT density in this group which would help in understanding the neurobiological basis for the self-medication theory in ADHD adolescents.

Tratamento psicoterápico para adolescentes usuários de substâncias psicoativas / Psychotherapeutic treatment for adolescents with substance abuse

O uso de álcool e demais substâncias psicoativas é um dos problemas de maior prevalência entre adolescentes. Todo adolescente que for avaliado por profissional de saúde deve ser questionado sobre seu uso de álcool e substâncias psicoativas. Em caso positivo, esse uso deve ser investigado clinicamente e, mesmo quando minimamente problemático, o adolescente deve ser encaminhado para tratamento específico. O tratamento deve levar em conta várias particularidades da adolescência para ser efetivo. Há indicação do uso de psicoterapias no atendimento a esses adolescentes. Entre elas, estão a Terapia de Família, a Terapia Cognitivo-Comportamental e a Entrevista Motivacional. Todas essas modalidades de terapia apresentam evidências de eficácia nessa faixa etária e podem ser usadas separadamente ou em conjunto. Essas modalidades de tratamento serão revisadas, sendo explicados seu método de ação e suas principais evidências de eficácia em adolescentes.(AU)

The use of alcohol and drugs in the adolescence is a common problem. Every teenager that goes through psychological evaluation should be asked about use of alcohol and drugs of abuse. If positive, this use should be clinically investigated and, referred to treatment at the slightest signs of problems. Treatment must take account of age-specific characteristics in order to be effective. There are many kinds of psychotherapies based on evidence for this age group. Among them, are Family Therapy, Cognitive Behavioral Therapy and Motivational Interviewing. Those treatment modalities are addressed, explaining their means of action and their main proofs of efficacy in adolescents.(AU)

Abordagem terapêutica de puérpera usuária de crack / Therapeutic approach of a crack-user puerperal woman

Este é o relato do atendimento de uma das mães dependentes do crack e de seu bebê, que frequentam o Ambulatório de Psiquiatria da Infância e da Adolescência do HCPA. Esta específica abordagem terapêutica visa atender a gestante e o bebê, ainda antes do nascimento, a fim de preservar um de seus direitos básicos, que é o de não ser intoxicado tão prematuramente.(AU)

This is the report of the treatment of one of the crack-dependent mothers and her baby who attended the Childhood and Adolescence Psychiatry outpatient clinic of the HCPA. This specific approach aims at attending the mother and the baby, even before birth, in order to preserve one of his/her basic rights, which is: not be intoxicated so prematurely.(AU)

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. .

The effects of ADHD in adult substance abusers.

The aim of this study was to evaluate the psychiatric comorbidities and different areas of life functioning in substance abusers with attention deficit hyperactivity disorder symptoms. A cross-sectional, multi-center study involving 285 adult substance abusers from outpatient and inpatient clinics was performed. The Adult ADHD Self-Report Scale, the sixth version of the Addiction Severity Index, and the Mini International Neuropsychiatry Interview were used for data collection. Individuals with comorbid attention deficit hyperactivity disorder and substance use disorders showed increased addiction severity when compared with individuals without attention deficit hyperactivity disorder (53.3 ± 7.3 vs. 48.4 ± 8.4, respectively). Our results suggest that comorbid attention deficit hyperactivity disorder and substance use disorders is associated with a more severe course of substance use and with social and psychiatric impairment.

Is ADHD a risk factor independent of conduct disorder for illicit substance use? A meta-analysis and metaregression investigation.

OBJECTIVE: To investigate meta-analytically if the association between ADHD and illicit substance use (ISU) is maintained when controlling for conduct disorder/oppositional-defiant disorder (CD/ODD). METHOD: A systematic literature review was conducted through Medline from 1980 to 2008. Data extracted and selections made by one author were reviewed by another. RESULTS: Fifteen articles presented odds ratios (ORs) for the development of ISU in individuals with ADHD controlling for CD/ODD. In total, the study covered results for more than 1,000 individuals. The combined OR for studies that included in their analysis exclusively ISU was 1.35 (0.90-2.03), p = .15, heterogeneity = 55%. Lack of control for socioeconomic status was related with a weaker association between ADHD and ISU. CONCLUSION: The existing data do not indicate that ADHD increases the risk of ISU beyond the effects of CD/ODD. However, the combination of all existing data is limited in power to detect a small increase in chance.

[Translation and adaptation of the Motorcycle Rider Behavior Questionnaire: a Brazilian version]. / Tradução e adaptação da escala Motorcycle Rider Behavior Questionnaire: versão brasileira.

Traffic accidents are a leading cause of death in young adults. In Brazil, traffic accidents are proportionally more prevalent among motorcyclists as compared to automobile drivers. Although numerous data indicate that individual characteristics are involved in traffic accident risk, there is no instrument in Brazil to assess motorcyclists' traffic behavior. The authors thus proposed to perform translation and cultural adaptation of the Motorcycle Rider Behavior Questionnaire (MRBQ) into Brazilian Portuguese. The translation process consisted of: two independent translations into Brazilian Portuguese; unification of the translations; back-translation into English; formal assessment of semantic equivalence; application of a summary version in a convenience sample of motorcyclists; generation of a final version; and back-translation and submission to the original author, who approved this version. The Brazilian version maintained its semantic equivalence and was accepted by the convenience sample, an important characteristic for a self-completed instrument. Further studies are necessary to evaluate the questionnaire's psychometric properties in the Brazilian cultural context.