This study will examine neuropsychological dysfunction and hypermotility in adolescent Substance Use Disorder (SUD), which frequently are morbid with Conduct Disorder (CD) and Attention-Deficit Hyperactivity Disorder (ADHD). Among youth with SUD the applicants will determine whether those with CD+ADHD have more serious pathology: earlier onset of CD symptoms, neuropsychological abnormalities, hypermotility, and a more persistent course. The applicants will study circadian rhythms of motility and neuropsyhological assessments to clarify aspects of ADHD contributing to SUD severity. They will compare 200 male and female patients and 200 controls in 48-hour assessments of motility, as subjects engage in activities and testing. Neuropsychological tests will assess verbal performance skills, impulsivity, inattention, and risk-taking. Diagnoses and severity of CD, ADHD, depression, and anxiety will be determined. Subjects, parents, and teachers will contribute information. Hypotheses focus on contributions to SUD from aspects of ADHD and CD: (1) Adolescents boys with CD and SUD will differ (after controlling for age) from community controls in having (a) greater spontaneous motility levels, (b) poorer neuropsychological functioning, including more impulsivity, inattention, and risk-taking in a laboratory reward- punishment paradigm, (c) more experiences of abuse and neglect, and (d) higher prevalence of psychiatric disorders (in addition to CD and SUD). (2) There are almost no data from girls with CD and SUD on abnormalities of motility, inattention, impulsivity; or on deficits in executive function, verbal processing, or verbal memory; on risk-taking or abuse/neglect experiences; or on severity of depression and anxiety. The applicants propose to disprove the null hypotheses of no main effect of gender, no main effect of group (patient or control), and no interactions, of those variables. The paucity of data on CD+SUD girls prevents directional predictions regarding gender effects. (3) Among male and female patients referred for treatment of CD and Substance Dependence (after controlling for age, gender, and severity of CD), the severity of the substance involvement will associate separately and jointly with: (A) Measures associated with comorbid CD + ADHD: (1) Greater motility, (2) Poorer neuropsychological functioning in selected areas (impulsivity, inattention, and """"""""executive functions"""""""" including risk-taking). (B] Earlier onset of CD. (C) Greater depression. That is, we predict that among substance-dependent adolescents, those with earlier CD onset, more severe ADHD-related symptoms, more neuropsychological deficits, and more depression will have more substance involvement.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DA009842-05
Application #
2897973
Study Section
Special Emphasis Panel (SRCD (27))
Program Officer
Gordon, Harold
Project Start
1995-09-01
Project End
2000-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Psychiatry
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Crowley, Thomas J; Dalwani, Manish S; Sakai, Joseph T et al. (2017) Children's brain activation during risky decision-making: A contributor to substance problems? Drug Alcohol Depend 178:57-65
Boulos, Peter K; Dalwani, Manish S; Tanabe, Jody et al. (2016) Brain Cortical Thickness Differences in Adolescent Females with Substance Use Disorders. PLoS One 11:e0152983
Dalwani, Manish S; McMahon, Mary Agnes; Mikulich-Gilbertson, Susan K et al. (2015) Female adolescents with severe substance and conduct problems have substantially less brain gray matter volume. PLoS One 10:e0126368
Crowley, Thomas J; Dalwani, Manish S; Mikulich-Gilbertson, Susan K et al. (2015) Adolescents' Neural Processing of Risky Decisions: Effects of Sex and Behavioral Disinhibition. PLoS One 10:e0132322
Chumachenko, Serhiy Y; Sakai, Joseph T; Dalwani, Manish S et al. (2015) Brain cortical thickness in male adolescents with serious substance use and conduct problems. Am J Drug Alcohol Abuse 41:414-24
Dalwani, Manish S; Tregellas, Jason R; Andrews-Hanna, Jessica R et al. (2014) Default mode network activity in male adolescents with conduct and substance use disorder. Drug Alcohol Depend 134:242-250
Tanabe, J; York, P; Krmpotich, T et al. (2013) Insula and orbitofrontal cortical morphology in substance dependence is modulated by sex. AJNR Am J Neuroradiol 34:1150-6
Sakai, Joseph T; Dalwani, Manish S; Gelhorn, Heather L et al. (2012) A behavioral test of accepting benefits that cost others: associations with conduct problems and callous-unemotionality. PLoS One 7:e36158
Sakai, Joseph T; Crowley, Thomas J; Stallings, Michael C et al. (2012) Test of association between 10 single nucleotide polymorphisms in the oxytocin receptor gene and conduct disorder. Psychiatr Genet 22:99-102
Dalwani, Manish; Sakai, Joseph T; Mikulich-Gilbertson, Susan K et al. (2011) Reduced cortical gray matter volume in male adolescents with substance and conduct problems. Drug Alcohol Depend 118:295-305

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