Cocaine-induced paranoia and psychotic symptoms (CIPPS) are associated with violence and greater morbidity in cocaine users. Since the phenotype appears only after chronic cocaine use, CIPPS provides a direct human example of cocaine-induced sensitization, an understanding of which is critical to addiction science. Genetic factors are important in CIPPS. CIPPS symptoms comprise a relatively homogeneous phenotypic spectrum. Thus, users who develop CIPPS, and those who do not, each represent more homogeneous groups of cocaine users, in whom genetic investigations are more likely to be fruitful than in those merely meeting dependence criteria. To examine the genetics of CIPPS, this work will: (1) Collect DNA samples from unrelated cocaine-using subjects in whom the CIPPS phenotype has been thoroughly evaluated, and from family trios containing probands carefully assessed for CIPPS. (2) Replicate and extend previous findings from this laboratory on the relationship of allelic variation at genes expressed in catecholamine neurons and CIPPS. (3) Determine relationships between genotypes, biochemical phenotypes, and behavioral phenotypes in African- and European-Americans. (4) Use methods previously developed for idiopathic psychoses to evaluate psychotic realm experiences and related psychological phenomena in abstinent cocaine users. Important strengths of the proposed work are (1) Development of unique DNA resources Suitable for extensive future study, including a first-of-its-kind family collection. (2) A focus on candidate genes supported by previous positive results and neurobiological considerations. (3) Use of haplotypes as well as single genotypes in genetic analysis. (4) Application of well-validated measures of psychosis: the Bell Object Relations and Reality Testing Inventory, the Scale for Assessment of Positive Symptoms, as well as the Cocaine Experience Questionnaire. (5) The use of a repeated measures design in phenotypic assessment. (5) Possible identification of phenotypes that do not depend on cocaine intoxication for expression. This program of research will improve our understanding of the genetics underlying human brain responses to chronic cocaine exposure, thus leading to better diagnosis and treatments for cocaine dependence and other addictive disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA012422-02
Application #
6378874
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Gordon, Harold
Project Start
2000-09-30
Project End
2004-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
2
Fiscal Year
2001
Total Cost
$284,986
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Denis, Cécile M; Gelernter, Joel; Hart, Amy B et al. (2015) Inter-observer reliability of DSM-5 substance use disorders. Drug Alcohol Depend 153:229-35
Tang, Yi-lang; Li, Wenbiao; Mercer, Kristina et al. (2010) Genotype-controlled analysis of serum dopamine ?-hydroxylase activity in civilian post-traumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 34:1396-401
Tang, Yi-lang; Kranzler, Henry R; Gelernter, Joel et al. (2009) Transient cocaine-associated behavioral symptoms rated with a new instrument, the scale for assessment of positive symptoms for cocaine-induced psychosis (SAPS-CIP). Am J Addict 18:339-45
Feinn, Richard; Gelernter, Joel; Cubells, Joseph F et al. (2009) Sources of unreliability in the diagnosis of substance dependence. J Stud Alcohol Drugs 70:475-81
Hodgkinson, Colin A; Yuan, Qiaoping; Xu, Ke et al. (2008) Addictions biology: haplotype-based analysis for 130 candidate genes on a single array. Alcohol Alcohol 43:505-15
Pierucci-Lagha, Amira; Gelernter, Joel; Chan, Grace et al. (2007) Reliability of DSM-IV diagnostic criteria using the semi-structured assessment for drug dependence and alcoholism (SSADDA). Drug Alcohol Depend 91:85-90
Tang, Yi-Lang; Kranzler, Henry R; Gelernter, Joel et al. (2007) Comorbid psychiatric diagnoses and their association with cocaine-induced psychosis in cocaine-dependent subjects. Am J Addict 16:343-51
Tang, Yi-lang; Epstein, Michael P; Anderson, George M et al. (2007) Genotypic and haplotypic associations of the DBH gene with plasma dopamine beta-hydroxylase activity in African Americans. Eur J Hum Genet 15:878-83
Herman, Aryeh I; Kranzler, Henry R; Cubells, Joseph F et al. (2006) Association study of the CNR1 gene exon 3 alternative promoter region polymorphisms and substance dependence. Am J Med Genet B Neuropsychiatr Genet 141B:499-503
Tang, Yilang; Buxbaum, Sarah G; Waldman, Irwin et al. (2006) A single nucleotide polymorphism at DBH, possibly associated with attention-deficit/hyperactivity disorder, associates with lower plasma dopamine beta-hydroxylase activity and is in linkage disequilibrium with two putative functional single nucleotide pol Biol Psychiatry 60:1034-8

Showing the most recent 10 out of 20 publications