The Center for Education and Drug Abuse Research

School of Pharmacy

University of Pittsburgh

Development of CEDAR Constructs Since 2/15/06 to test the CEDAR Theory and to develop SUD Liability Index

Some Key Findings and Assessment Measures

• Data suggests an association between the liability to SUD, the DRD5 and the MAOA genes. For DRD5 gene the association is stronger in females than males; in the MAO-A gene the association is observed only in males.
• The DRD5 gene has been tentatively found to be associated with novelty seeking behavior in females but not in males.
• In prepubertal boys, parental genotype was shown to correlate with aggressivity, an important precursor of SUD liability.
• Significant similarity exists between liability phenotypes of spouses as well as for the personality traits associated with the risk for SUD.
• Diminished secretion of the stress hormone cortisol was observed in HAR subjects in an anticipated stress situation compared to LAR subjects.
• HAR youth demonstrated lower executive cognitive functioning than LAR youth (e.g. planning, attention control, thinking flexibility).
• No differences were observed between HAR and LAR subjects on plasma pHVA (dopamine metabolite), pMHPG (noradrenergic metabolite) and B-endorphin levels.
• No differences were found between HAR and LAR subjects on platelet monoamine oxidase level B (MAO-B).
• HAR subjects showed elevated behavioral activity level measured by actigraph during tasks requiring focused attention and behavior control.
• Substance use disorder (SUD) and bulimia were found to be transmitted independently although there is a high frequency of substance abuse among bulimics.
• HAR subjects revealed attenuated P300 ERP’s and longer alpha synchronization than LAR youth on the oddball task.
• Level of stress reactivity, measured by saliva cortisol, was found to partly moderate the association between paternal SUD and attenuated P300 in offspring.
• P300 latency and amplitude correlated with executive cognitive functioning (ECF) capacity.
• Significant elevation of scores on both externalizing and internalizing scales was found among HAR children only if the father’s drug use persisted after their offspring surpassed age 6, suggesting perhaps a "critical" developmental period on SUD liability.
• Male and female HAR youth demonstrated greater cognitive, affective and behavioral dysregulation compared to LAR youth on the Dysregulation Inventory developed at CEDAR.
• Dysregulation scores in youth were found to correlate with antisociality during childhood, as well as parental and peer antisociality; Level of parental involvement mediated the association between dysregulation and antisociality.
• Adolescent onset SUD was observed to be featured by higher lifetime rates of cannabis and hallucinogen disorders, a shorter duration between first exposure and dependence, and shorter interval between first and second drug dependence diagnoses than adult onset SUD.
• Low executive cognitive functioning capacity at age 10-12 was found to predict level of reactive aggression two years later in HAR but not LAR youth.
• Adolescent onset, early adult onset, and mid-adult onset SUD were shown to differ with respect to profile and natural history of SUD.
• Aggressivity in HAR but not LAR boys was found to covary with cognitive distortions or misattributions.
• Functional communication skills are lower in HAR than LAR subjects; this capacity is related to level of substance use measured two years later.
• The rate of DSM-III-R diagnosis of learning disability was revealed to be higher in HAR (11.7%) than LAR (5.7%) subjects.
• Parents of HAR youth exhibit higher levels of risk for child abuse than LAR parents. Psychopathology in offspring of SUD probands was found to be more strongly predicted by parental childhood than parental adult psychopathology.
• Conjoint conduct disorder and tobacco use predicted marijuana initiation with 80% specificity and 94% sensitivity.
• Proband fathers with SUD retrospectively reported a higher rate of disruptive behavior disorder than proband fathers without SUD (51% vs. 7%); the former subjects had a significantly higher rate of childhood anxiety disorders (15% vs. 1%).
• Research directed at multidimensional mapping of substance use topography during adolescence revealed that single latent traits could be derived for three dimensions: a) context of consumption, (b) expectancies, and, (c) reinforcing effects.
• Preliminary analyses using growth curve modeling indicated that the social environment best predicted alcohol and tobacco use whereas cannabis use was best predicted by conduct problems.
• Preliminary analysis suggest that initial cannabis and tobacco use status is predicted by IQ; initial status of tobacco use is predicted by SES; initial alcohol and cannabis use is predicted by father’s substance use status.
• At age 12-14, the odds ratio in HAR boys Were 4.1 for boys to have had sex with one or more opposite sex partners in the past year compared to LAR boys.
• At age 16, the odds ratio in HAR boys was found to be 6.76 to have had sex with one or more opposite sex partners in the past year.
• At age 19, based on a small sample (N=52), HAR boys compared to LAR boys, show a trend towards having had sex with someone they hardly know.
• At ages 16 (odds ratio trend = 1.97) and 19 (odds ratio = 9.18), HAR boys were found to be less likely to eat 3 meals a day compared to LAR boys.
• At age 19, HAR boys were more likely to have a poor diet compared to LAR boys (odds ratio = 2.98).
• At age 16, HAR boys exhibited a trend towards having suffered an accidental injury that continued to bother them compared to LAR boys (odds ratio = 2.45).
• At age 19, the odds ratio of HAR boys was observed to be 6.79 for having to face legal charges of assault.