B. ACCOMPLISHMENTS B.1 WHAT ARE THE MAJOR GOALS OF THE PROJECT?

Transcription

1 B.1 WHAT ARE THE MAJOR GOALS OF THE PROJECT? B. ACCOMPLISHMENTS The aims of this study have not been modified. The application responds to PA , Epidemiology of Drug Abuse. It is a competing continuation of R01-DA This phase of a longitudinal study, Vulnerability to Drug Abuse, is called Pathways to Recovery. The increase in drug use and substance use disorders (SUD) across the teenage years and early 20s has been the focus of extensive research. The rate of desistance from the mid-20s into the 30s is equally dramatic, but little studied. Yet offset is at least as important as onset, from both scientific and public health viewpoints. Scientifically, stable desistance from SUD is hard to explain within a simplistic model of gene-driven brain structure or functioning, or within current risk models. If addiction is a chronic relapsing brain disorder (1) (p.170), how and why do so many recover? The public health implications spring from the idea that identification of pathways to stable desistance could inform secondary and tertiary prevention efforts. Substance Use Disorders (SUD) and stable desistance Researchers have differing views of recovery from SUD, which we encapsulate here as desistance and functional recovery. The desistance approach looks at rates of DSM-IV symptoms and diagnoses, either cross-sectionally or longitudinally. The functional recovery approach focuses on aspects of life and functioning that are important to clinicians and their patients in addition to absence of DSM-like SUD; for example, physical and mental health, work and educational attainments, relationships with family and co-workers, avoidance of crime and HIV/ADIS-risk behaviors, and contributions to the life of the community. We will test the relationship between the two definitions as predictors of stable recovery. We define stable recovery in this study as absence of SUD at 2 assessments 5 years apart. The goal of this application is to test the extent to which functioning at the time of SUD onset predicts desistance at age 26 and stable desistance at age 30. We also aim for the first time to chart the prevalence of different types of functional deficit persisting even in individuals who maintain stable desistance. We propose a developmental approach to understanding trajectories of SUD persistence and desistance using one of the very few transdisciplinary studies in the USA that can address these issues. The Great Smoky Mountains Study (GSMS) is a longitudinal, population based study of a sample (N=1420, mainly Anglos and American Indians), aged 9, 11 and 13 at intake in 1993, and now aged 25 to 29. GSMS is the core of an interlocking series of projects funded by NIDA, NIMH, and NARSAD. Repeated waves of data have helped to deepen understanding of the course and mechanisms of drug initiation, use, and addiction.(2-6) We propose to address the problem of understanding the epidemiology of SUD at age 30 in 2 ways: (1) predictors of course based on repeated assessments of phenotypes, risk, and protection; (2) Cognitive and stress-related markers of mechanisms underlying the different courses of SUD. Note: This application deals with SUD, for lack of space. Analyses and publications will also examine symptomatic and asymptomatic-risk substance use (7) and specific substances (nicotine, alcohol, cannabis, other illicit drugs). We propose to assess GSMS participants at age 30, from 2 points of view: (1) The epidemiology of desistance from SUD; Mechanisms that mediate patterns of desistance, and provide potential keys to intervention. H1: The probability of stable desistance, i.e., desistance from DSM-IV SUD at age 26 that persists to age 30, will be predicted by measures of functioning during the course of SUD, and functional recovery at age 26 (stable relationships, social engagement, employment, absence of crime). That is, functional recovery predicts stability. H2a: Those with persistent or unstable SUD, or desistance with poor functioning, will display deficits at age 30 in both prefrontal cortex attention/executive functions (initiating and sustaining attention, inhibiting irrelevant information, set shifting) as measured by neuropsychological tasks. H2b: Elevated stress susceptibility as measured by physiological stress markers (cortisol reactivity, DHEAS, CRP, and EBV titers) from age 9 to 26 will predict SUD persistence and instability of recovery, or desistance with poor functioning. This association will mediate the link between stressor exposure and SUD outcomes. H3a. Based upon the female preponderance of stress-related psychopathology in adulthood, (8, 9) it is likely that females with persistent SUD will be overrepresented in the stress susceptibility pathway. H3b. Similar rates of SUDs and persistence at age 26 between American Indians and non-indians suggest similar patterns and predictors of recovery and persistence, controlling for gender. H4a: With AIDS-risk behaviors (e.g., sex for drugs, multiple partners) as with SUD, The probability of stable desistance will be predicted by measures of functioning, and functional recovery at age 26 (stable relationships, social engagement, employment, absence of crime). That is, functional recovery predicts stability of recovery. H4b: With AIDS-risk behavior as with SUD, similar patterns and predictors of recovery and persistence will be seen in American- Indian and non-indian participants, controlling for gender and other predictors of AIDS-risk behaviors. References 1.Koob GF. Neurobiology of addiction. Toward the development of new therapies. Annals of the New York Academy of Sciences. 2000;909: Costello E, Erkanli A, Copeland W, Angold A. Association of family income supplements in adolescence with development of psychiatric and substance use disorders in adulthood among an American Indian population.. JAMA. 2010;303: PMCID: Costello EJ, editor. Effects of Puberty on the Development of Substance Abuse. Presented at the International Society for Research in Child and Adolescent Psychopathology Tenth Scientific Meeting, June 29, 2001; 2001 June 29, 2001; Vancouver, BC. 4.Costello EJ, Erkanli A, Federman E, Angold A. Development of psychiatric comorbidity with substance abuse in adolescents: Effects of timing and sex. Journal of Clinical Child Psychology. 1999;28: Federman EB, Costello EJ, Angold A, Farmer EMZ, Erkanli A. Development of substance use and psychiatric comorbidity in an epidemiologic study of white and American Indian young adolescents: The Great Smoky Mountains Study. Drug and Alcohol Dependence. 1997;44: Sung M, Erkanli A, Angold A, Costello E. Effects of age at first substance use and psychiatric comorbidity on the development of substance use disorders. Drug and Alcohol Dependence. 2004;75: Dawson DA, Grant BF, Stinson FS, Chou PS, Huang B, Ruan WJ. Recovery from DSM-IV alcohol dependence: United States, RPPR Page 2

2 2002. Addiction Mar;100(3): Moon DG, Hecht ML, Jackson KM, Spellers RE. Ethnic and gender differences and similarities in adolescent drug use and refusal of drug offers. Substance Use & Misuse. 1999;34: Clayton RR, Voss HL, Robbins C, Skinner WF. Gender differences in drug use: An epidemiological perspective. NIDA Research Monograph. 1986;65: B.1.a Have the major goals changed since the initial competing award or previous report? No B.2 WHAT WAS ACCOMPLISHED UNDER THESE GOALS? File uploaded: B2accomplished_33115.pdf B.3 COMPETITIVE REVISIONS/ADMINISTRATIVE SUPPLEMENTS For this reporting period, is there one or more Revision/Supplement associated with this award for which reporting is required? No B.4 WHAT OPPORTUNITIES FOR TRAINING AND PROFESSIONAL DEVELOPMENT HAS THE PROJECT PROVIDED? File uploaded: B4_TrainingReport_33115.pdf B.5 HOW HAVE THE RESULTS BEEN DISSEMINATED TO COMMUNITIES OF INTEREST? On January 17, 2015 the Economist published an article claiming that per-capita income supplements to American Indians from casino profits increased poverty rather than decreasing it. The ensuing blog discussion frequently cited work from GSMS, which showed the opposite. B.6 WHAT DO YOU PLAN TO DO DURING THE NEXT REPORTING PERIOD TO ACCOMPLISH THE GOALS? Continue to carry out the Specific Aims as described above. RPPR Page 3

3 B.2 (B2accomplished_33115.pdf) B.2 WHAT WAS ACCOMPLISHED UNDER THESE GOALS? 1) For the past year we have been collecting data as described in B1. We have completed assessment of 1,138 participants, which constitutes 82.3% of the targeted sample of 1383 surviving subjects. 2) In this respect we are meeting the stated objectives of the project. 3) In the meanwhile we have been analyzing and publishing papers from the data collected so far. Publications are listed under the product section of this RPPR. 4) The grant application (R01 MH ) that we wrote with Edwin van den Oord and colleagues at Virginia Commonwealth University, entitled Developmental methylomics of childhood trauma and its health consequences, has been funded and is under way. Health consequences include substance use disorders (SUD). One goal will be to compare methylation patterns in participants with persistent versus adolescence-limited SUD. The first 50 sets of DNA have been extracted (3 samples per subject, from blood spots taken in childhood, adolescence, and adulthood). We are in the process of transferring all the GSMS blood samples from Emory University, where they have been stored since 1993, to VCU. We are doing this because VCU is working with the samples and it is safer to have them on site than to be mailing them from one place to another. There are about 10,000 cards of blood spots in all, with more still being collected. 5) Publications: Of the publications listed in this report, eight were newly published in the past year, and nine were reported in previous years but had not been associated yet with the grant in the system. RPPR Page 4

4 C. PRODUCTS C.1 PUBLICATIONS Are there publications or manuscripts accepted for publication in a journal or other publication (e.g., book, one-time publication, monograph) during the reporting period resulting directly from this award? Yes Publications Reported for this Reporting Period Public Access Compliance Citation Worthman CM, Costello EJ. Tracking biocultural pathways in population health: the value of biomarkers. Ann Hum Biol May-Jun;36(3): PubMed PMID: ; PubMed Central PMCID: PMC Worthman CM. Habits of the heart: life history and the developmental neuroendocrinology of emotion. Am J Hum Biol Nov-Dec;21(6): PubMed PMID: ; PubMed Central PMCID: PMC Copeland WE, Shanahan L, Worthman C, Angold A, Costello EJ. Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis. Biol Psychiatry Jan 1;71(1): PubMed PMID: ; PubMed Central PMCID: PMC Copeland WE, Angold A, Costello EJ, Egger H. Prevalence, comorbidity, and correlates of DSM-5 proposed disruptive mood dysregulation disorder. Am J Psychiatry Feb;170(2): PubMed PMID: ; PubMed Central PMCID: PMC Akee R, Simeonova E, Copeland W, Angold A, Costello EJ. Young Adult Obesity and Household Income: Effects of Unconditional Cash Transfers. Am Econ J Appl Econ Apr 1;5(2):1-28. PubMed PMID: ; PubMed Central PMCID: PMC Copeland WE, Wolke D, Angold A, Costello EJ. Adult psychiatric outcomes of bullying and being bullied by peers in childhood and adolescence. JAMA Psychiatry Apr;70(4): PubMed PMID: ; PubMed Central PMCID: PMC Aberg KA, Xie LY, Nerella S, Copeland WE, Costello EJ, van den Oord EJ. High quality methylome-wide investigations through next-generation sequencing of DNA from a single archived dry blood spot. Epigenetics May;8(5): PubMed PMID: ; PubMed Central PMCID: PMC Copeland WE, Adair CE, Smetanin P, Stiff D, Briante C, Colman I, Fergusson D, Horwood J, Poulton R, Costello EJ, Angold A. Diagnostic transitions from childhood to adolescence to early adulthood. J Child Psychol Psychiatry Jul;54(7): PubMed PMID: ; PubMed Central PMCID: PMC Stringaris A, Maughan B, Copeland WS, Costello EJ, Angold A. Irritable mood as a symptom of depression in youth: prevalence, developmental, and clinical correlates in the Great Smoky Mountains Study. J Am Acad Child Adolesc Psychiatry Aug;52(8): PubMed PMID: ; PubMed Central PMCID: PMC Costello EJ, Copeland WE, Shanahan L, Worthman CM, Angold A. C-reactive protein and substance use disorders in adolescence and early adulthood: a prospective analysis. Drug Alcohol Depend Dec 1;133(2): PubMed PMID: ; PubMed Central PMCID: PMC Sung M, Erkanli A, Costello EJ. Estimating the causal effect of conduct disorder on the RPPR Page 6

5 time from first substance use to substance use disorders using g-estimation. Subst Abus. 2014;35(2): PubMed PMID: ; PubMed Central PMCID: PMC Costello EJ, He JP, Sampson NA, Kessler RC, Merikangas KR. Services for adolescents with psychiatric disorders: 12-month data from the National Comorbidity Survey-Adolescent. Psychiatr Serv Mar 1;65(3): PubMed PMID: ; PubMed Central PMCID: PMC Shanahan L, Copeland WE, Angold A, Bondy CL, Costello EJ. Sleep problems predict and are predicted by generalized anxiety/depression and oppositional defiant disorder. J Am Acad Child Adolesc Psychiatry May;53(5): PubMed PMID: ; PubMed Central PMCID: PMC Copeland WE, Wolke D, Lereya ST, Shanahan L, Worthman C, Costello EJ. Childhood bullying involvement predicts low-grade systemic inflammation into adulthood. Proc Natl Acad Sci U S A May 27;111(21): PubMed PMID: ; PubMed Central PMCID: PMC Copeland WE, Shanahan L, Egger H, Angold A, Costello EJ. Adult diagnostic and functional outcomes of DSM-5 disruptive mood dysregulation disorder. Am J Psychiatry Jun;171(6): PubMed PMID: ; PubMed Central PMCID: PMC Shanahan L, Zucker N, Copeland WE, Costello EJ, Angold A. Are children and adolescents with food allergies at increased risk for psychopathology?. J Psychosom Res Dec;77(6): PubMed PMID: ; PubMed Central PMCID: PMC In Process at NIHMS Costello EJ, Maughan B. Annual Research Review: Optimal outcomes of child and adolescent mental illness. J Child Psychol Psychiatry Mar;56(3): PubMed PMID: ; NIHMSID: In Process at NIHMS Copeland WE, Shanahan L, Davis M, Burns BJ, Angold A, Costello EJ. Increase in untreated cases of psychiatric disorders during the transition to adulthood. Psychiatr Serv Apr 1;66(4): PubMed PMID: ; NIHMSID: In Process at NIHMS Copeland WE, Shanahan L, Davis M, Burns BJ, Angold A, Costello EJ. Increase in untreated cases of psychiatric disorders during the transition to adulthood. Psychiatr Serv Apr 1;66(4): PubMed PMID: ; NIHMSID: C.2 WEBSITE(S) OR OTHER INTERNET SITE(S) C.3 TECHNOLOGIES OR TECHNIQUES C.4 INVENTIONS, PATENT APPLICATIONS, AND/OR LICENSES Have inventions, patent applications and/or licenses resulted from the award during the reporting period? No C.5 OTHER PRODUCTS AND RESOURCE SHARING RPPR Page 7

6 C.5.a Other products C.5.b Resource sharing RPPR Page 8

7 Inclusion Enrollment Report Inclusion Data Record (IDR) #: Study Title: Vulnerability to Drug Abuse: Effects of Stressors & Stres-PROTOCOL-002 Foreign/Domestic: Domestic Planned Enrollment Report Racial Categories Not Hispanic or Latino Ethnic Categories Hispanic or Latino American Indian/Alaska Native Asian Native Hawaiian or Other Pacific Islander Black or African American White More than One Race Total Total Cumulative Enrollment Report Comments: GSMS wave 18 (RST) as of March 25, 2015 Racial Categories Not Hispanic or Latino Unknown/ Not Reported Ethnic Categories Hispanic or Latino Unknown/ Not Reported Unknown/Not Reported Ethnicity Unknown/ Not Reported Total American Indian/Alaska Native Asian Native Hawaiian or Other Pacific Islander Black or African American White More than One Race Unknown or Not Reported Total RPPR Page 20