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

Searching for a Neurobiological Basis for Self-Medication Theory in ADHD Comorbid With Substance Use Disorders An In Vivo Study of Dopamine Transporters Using Tc-99m-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-99m-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.University and Hospital de Clinicas of Porto AlegreCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FIPE/HCPASENADNIDAFogartyUniversity of KentuckyAbbottBristol-Myers SquibbEli-LillyJanssen-CilagNovartisShireComplexo Hosp Santa Casa LAMENU, Lab Med Nucl, Porto Alegre, RS, BrazilHCPA, Child & Adolescent Psychiat Div PRODAH, ADHD Outpatient Program, BR-90035003 Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psychiat, LiNC, Sao Paulo, BrazilUniv Fed RGS UFRGS, HCPA, Ctr Drug & Alcohol Res, Porto Alegre, RS, BrazilUniv Luterana Brasil, Porto Alegre, RS, BrazilInst Nacl Psiquiatria Desenvolvimento, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psychiat, LiNC, Sao Paulo, BrazilWeb of Scienc

Methylphenidate DAT binding in adolescents with Attention-Deficit/Hyperactivity Disorder comorbid with substance use disorder - a single photon emission computed tomography with [Tc-99m] TRODAT-1 study

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. Objectives: To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). Methods: Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc-99m] TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale-version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. Results: After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (p<0.001), and similar to 52% reductions of DAT BP at the left and right caudate. Similar decreases were found at the left and right putamen (p<0.001 for all analyses). Discussion: This study shows that the magnitude of DAT blockade induced by MPH in this population is similar to what is found in ADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies. (C) 2008 Elsevier Inc. All rights reserved.Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Programa Deficit Atencao Hiperatividade, ADHD Outpatient Clin, BR-90035003 Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Ctr Drug & Alcohol Res, BR-90035003 Porto Alegre, RS, BrazilUniv Luterana Brasil, Canoas, RS, BrazilUniversidade Federal de São Paulo, LINC, São Paulo, BrazilIrmandade Santa Casa Misericordia, Porto Alegre, RS, BrazilInst Nucl Energy Res, Long Tan, TaiwanUniversidade Federal de São Paulo, LINC, São Paulo, BrazilWeb of Scienc

Molecular Imaging Genetics of Methylphenidate Response in ADHD and Substance Use Comorbidity

Purpose: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and dopamine transporter (DAT1) genes have a role in both disorders, little is known about how these genes influence brain response to MPH in individuals with ADHD/SUDs. the goal of this study was to evaluate whether ADHD risk alleles at DRD4 and DAT1 genes could predict the change in striatal DAT occupancy after treatment with MPH in adolescents with ADHD/SUDs. Methods: Seventeen adolescents with ADHD/SUDs underwent a SPECT scan with [Tc 99m] TRODAT-1 at baseline and after three weeks on MPH. Caudate and putamen DAT binding potential was calculated. Comparisons on DAT changes were made according to the subjects' genotype. Results: the combination of both DRD4 7-repeat allele (7R) and homozygosity for the DAT1 10-repeat allele (10/10) was significantly associated with a reduced DAT change after MPH treatment in right and left caudate and putamen, even adjusting the results for potential confounders (P <= 0.02; R(2) from 0.50 to 0.56). Conclusions: in patients with ADHD/SUDs, combined DRD4 7R and DAT1 10/10 could index MPH reduced DAT occupancy. This might be important for clinical trials, in terms of better understanding individual variability in treatment response. Synapse 65: 154-159, 2011. (c) 2010 Wiley-Liss, Inc.Univ Fed Rio Grande do Sul, HCPA, ADHD Outpatient Clin, Porto Alegre Poa, RS, BrazilUFRGS, HCPA, Ctr Drug & Alcohol Res, Poa, BrazilUniv Luterana Brasil, Posgrad Saude Colet, Canoas, RS, BrazilUFRGS, Dept Genet, Poa, RS, BrazilUniversidade Federal de São Paulo, LINC, São Paulo, BrazilIrmandade Santa Casa Misericordia, Poa, RS, BrazilUniversidade Federal de São Paulo, LINC, São Paulo, BrazilWeb of Scienc

Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans

Abstract 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

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 &#8805; 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