Prepared by Michael B. First, M.D., DSM Consultant to the American Psychiatric Institute for Research and Education (APIRE), a subsidiary of the American Psychiatric Association
The second diagnosis-related research planning conference in the "Future of Psychiatric Diagnosis: Refining the Research Agenda" series, focusing on diagnostic issues in Substance Use Disorders in future diagnostic classifications (e.g., DSM-5 and ICD-11), was held on February 14-17, 2005, at the National Institute for Alcohol Abuse and Alcoholism in Rockville, MD. Conference co-chairs were Marc Schuckit, MD, from the San Diego VAMC in La Jolla, California, and John Saunders, M.D. from the Royal Brisbane Hospital in Herston, Australia, and invited participants included 43 scientists from the United States and abroad.
The conference began with a presentation by Bengt Muthén, PhD (Los Angeles, CA), who discussed methodological issues pertinent to determining whether substance use disorders are best represented as categorical or dimensional constructs. Traditionally, latent class analysis has been used to model categorical constructs whereas factor analysis looking for continuous latent variables is used for dimensional models. Dr. Muthén, recommended using newer methods, such as a hybrid analysis technique called latent class factor analysis (LCFA) and growth mixture modeling to allow both categories and dimensions to be derived from the same analysis. Colin Drummond, MD (London, UK) was the discussant.
Two presentations addressed the topic of whether the scope of addictive disorders should be broadened to include disorders such as pathological gambling which is currently included in the Impulse Control Disorders section of the DSM-IV. Marc Potenza, MD (New Haven, CT) noted that substance dependence and pathological gambling have high rates of co-occurrence, share similar clinical characteristics (e.g., loss of control, tolerance, and withdrawal), have a similar clinical course (e.g., high rates in adolescence, lower rates in older adults), similar biology (e.g., involving the mesocortical limbic dopamine system and frontal serotonin system) and similar treatments (e.g., cognitive-behavioral therapy, naltrexone). While agreeing that the two conditions do appear to share a number of features, Nancy Petry, PhD (Farmington, CT) cautioned that some of the similarities may be an artifact of the fact that substance dependence and pathological gambling share similar criteria sets which have never be adequately validated. She noted that there were other important differences as well (e.g., extremely high placebo response rates for pathological gambling in contrast to substance use disorders). Additional research is necessary to determine whether the benefits of expanding the construct of addiction (e.g., expanding treatment opportunities for pathological gambling) outweigh the increased risk of stigma. Mats Berglund, MD (Malmo, Sweden) was the discussant.
Anna-Rose Childress, PhD (Philadelphia, PA), gave the next presentation concerning whether biological criteria should be included in the definitions of substance use disorders. Although technical limitations suggest that diagnostically useful biological tests such as neuroimaging will not be available in time for DSM-V, neurobiological studies are crucial for future understanding of the pathophysiology of substance addiction. Most individuals exposed to rewarding drugs of abuse do not become addicted. Those who do might have a dysfunction in meso-cortico-limbic circuitry (i.e., "GO" systems) involved in seeking reward and/or a dysfunction in prefrontal cortical systems ("STOP") that allow individuals to pause and weigh the consequences of our actions. Evidence for problems in "GO" systems include low D2 dopamine receptors seen in neuroimaging studies of chronic cocaine users and blunted dopamine release to a stimulant challenge. Problems with "STOP" circuitry might be indicated by the poor performance of substance users on decision-making tasks. What is unclear is whether these abnormalities represent a vulnerability factor in susceptible individuals or else are a consequence of the substance use itself. Studying individuals early in the course (e.g., adolescents) will be crucial for solving this chicken-and-egg problem. Ming Tsuang, MD, PhD (San Diego, CA) was the discussant.
The next two presentations focused on the concepts of Dependence and Non-Dependence in DSM and ICD. John Saunders, M.D. (Herston, Australia) noted that although the DSM and ICD have very similar definitions of substance dependence (characterized by loss of control over substance use, and tolerance/withdrawal) historically the DSM and ICD have had different paradigms for less severe forms of maladaptive substance use which overlap only partially. DSM-IV defines Substance Abuse as a residual category (i.e., it can only be diagnosed if criteria are not met for dependence) characterized by negative consequences of recurrent or continued use: role impairment, legal problems, use when hazardous; and continued use despite social and interpersonal problems. ICD-10 includes a category for harmful use requiring demonstrable physical or psychological harm and in early drafts included a category for hazardous use that puts the individual at risk for future harm. Dr. Saunders called for additional research on the non-dependence end of the substance use spectrum in order to make DSM and ICD more concordant in the future. Deborah Hasin PhD (New York, NY) noted that both DSM and ICD had withdrawal criteria for each substance except for cannabis and hallucinogens, but that ICD generally required fewer symptoms to make a diagnosis. Dr. Hasin called for continued research to determine whether cannabis withdrawal should be added to DSM-V/ICD-11 given current evidence supporting its clinical significance in maintaining cannabis dependence. DSM and ICD also differ in their criteria for remission from substance dependence and in their definitions of substance-induced disorders. Dr. Hasin called for additional research regarding the validity of both abuse and dependence and noted that empirical data suggests that dependence and abuse are orthogonal concepts and should be both diagnosed if present. Kathleen Bucholz, PhD (St. Louis, MO) served as discussant.
The next presentations considered whether different criteria are needed for substance use disorders in specific cultures. Javier Escobar MD (Piscataway, NJ) provided a general introduction to the topic of cross-cultural diagnosis, noting that although the DSM has been used internationally, it has not been culturally tested. He noted problems with the concept of race and ethnicity, suggesting that country of origin and immigrant status may be preferable. Dr. Escobar raised two key questions related to ethnicity and psychopatholgy: do symptom clusters of psychiatric disorders differ across cultures and can these symptoms and syndromes be reliabily defined, understood, and elicited in all countries and ethnic groups? Robin Room, PhD (Stockholm, Sweden) discussed potential variations between cultures in the meaning and meaningfulness of dependence, abuse, harmful use, intoxication, and withdrawal. Dr. Room reviewed studies on the cross-cultural applicability of substance use disorder criteria, which provided evidence both for some level of cross-cultural generalizability as well as evidence of divergent thresholds being applied across different cultures. Dr. Room offered a number of proposals to improve the cross-cultural applicability of theses disorders, including avoiding the use of causally attributive language, avoiding references to feeling and affect states, avoiding the use of culturally specific circumstances and activities and specifying the thresholds contained in the items. Maristela Monteiro MD (Washington, DC) and Vladimir Poznyak MD, PhD (Geneva, Switzerland) were the discussants.
Tom Crowley, MD (Denver, CO) presented on whether specific criteria for substance use disorders are needed for adolescents. He noted that the current criteria for substance use disorders generally work well in adolescents, showing validity (i.e., clearly discriminating patients from controls); validly grouping adolescents based on severity; and having good interrater reliability. He suggested six areas for adolescent-relevant studies designed to improve their usefulness: 1) research to determine whether cannabis withdrawal should be added to DSM-V; 2) research into the relationship of substance use disorders and disruptive behavior disorders; 3) research into the possibility of rephrasing some of the substance abuse criteria to increase their reliability and validity in adolescents; 4) research to determine whether earlier onset of substance use disorders between age 14-18 is a severity marker predicting worse outcome; 5) research to determine whether substance use diagnoses in adolescents should take into account the total number of substances and number of diagnostic criteria met; and 6) research to develop procedures for developing classifications for new substances that emerge on the market after publication of DSM-V. David Reiss M.D. (Washington, DC) was the discussant.
The next two presentations focused on whether there should be substance-specific criteria sets for substance dependence rather than the current DSM/ICD approach of having generic substance dependence criteria that apply to all substances. Alan Budney, PhD (Burlington, VT) focused on cannabis dependence, arguing that since cannabis is considered to be a "soft" drug (distinguishing it from cocaine, heroin, and perhaps alcohol), if the DSM-IV criteria adequately characterize cannabis dependence, then one could argue that they work validly for all disorders. Findings from the literature on cannabis dependence converge to suggest that the DSM criteria do an admirable job of capturing the construct although a few abuse and dependence items do not perform well. Strategies that might improve diagnostic sensitivity and specificity include differential weighing of specific items and having the number of items that differentiate mild, moderate, and severe dependence differ across substances. John Hughes, MD (Burlington, VT) provided evidence that, at least as they apply to nicotine dependence (and possibly for hallucinogens and inhalants), the generic dependence criteria do not work very well. Dr Hughes noted that among researchers studying smoking and nicotine dependence, the DSM-IV criteria have been overwhelmingly rejected (e.g., in the last 100 randomized clinical trials, only two used the DSM-IV criteria nicotine dependence in the trial.). Several of the dependence criteria do not apply to nicotine, including tolerance and using more than intended. Possible nicotine-specific criteria include level of consumption, time-to-first use, automaticity, use for cognitive enhancement, use for weight control, use for affect control, and use for stimulation. Wilson Compton, MD (Bethesda, MD) was the discussant.
Thomas Babor PhD (Farmington, CT) gave a presentation on potential subtypes of Dependence and Abuse. After describing the various rationale for including subtypes (e.g., facilitating matching to optimal treatment modality, indicating differential prognosis) Dr. Babor reviewed the various subtypes for alcohol dependence that have been proposed in the past, including continuous vs. binge use, familial vs. non-familial, affiliative vs. schizoid, primary vs. secondary, milieu-limited vs. male-limited and late-onset vs. early-onset. He noted that there is good evidence in terms of construct and predictive validity for 2-4 subtypes of alcohol dependence, and even better evidence for individual vulnerability factors such age at onset, family history, and associated antisocial personality disorder. Victor Hasselbrock, PhD, (Farmington, CT) reported that individuals with alcohol dependence can be clustered into four types that are associated with differential outcomes at one and three year follow-up: an early-onset type (high severity of dependence symptoms), late onset type (low severity), internal type (high alcohol intake associated with anxiety and depression), external type (associated with comorbid antisocial personality disorder). Lutz Schmidt, MD (Mainz, Germany) was the discussant.
Marc Schuckit MD (La Jolla, CA) presented on the comorbidity between Substance Use Disorders and other psychiatric disorders and the importance of substance-induced disorders. He stressed the importance of the methodology of the studies that look at this type of comorbidity when interpreting data such as prevalence. Dr. Schuckit emphasized that it is important to consider whether the drug can be etiologically related to the psychiatric syndrome supposedly being mimicked (e.g., alcohol does not cause mania) and the importance of considering onset and offset of the psychiatric symptoms in relation to the substance use. There is convincing evidence that substance-induced disorders exist, particularly for substance-induced psychosis, mood, and anxiety disorders, that they are clinically significant, and that they respond to treatment (e.g., antidepressants work for depression occurring in the context of alcohol dependence). Bruce Rounsaville, MD (New Haven, CT) reviewed the existing criteria for Substance-Induced disorders in DSM and suggested considering revised guidelines for timing and severity of substance-induced psychiatric symptoms but recommended against making changes unless there are clear benefits. Edward Nunes, MD (New York, NY) was the discussant.
John Helzer MD (Burlington, VT) presented on whether there should be categorical (i.e., clinical) and dimensional (i.e., research) criteria for substance use disorders in DSM-V. Noting that both approaches have merit, he made a number of suggestions about how categorical and dimensional approaches could both be implemented, including determining the content of the dimension by using the DSM categorical definitions, summing the categorical criteria to create a dimensional scale and adding associated features to the categorical criteria to create a broader item pool for later statistical analysis. Somnath Chatterji MD (Geneva, Switzerland) served as discussant.
Bridget Grant PhD (Bethesda, MD) and Linda Cottler, PhD (St. Louis, MO) gave presentations reviewing the available epidemiological data sets that have been collected both in the United States and internationally that could useful for conducting secondary data analyses that might provide answers to some of the research questions raised at the meeting. A number of these (e.g., the National Epidemiological Survey on Alcohol and Related Conditions [NESARC]) are available to qualified researchers who request access.
The conference concluded with a discussion of the various research strategies that will enrich the empirical base for making future decisions about the classification of personality disorders.
Other participants included Sawitri Assanangkhornchai, MD (Hai Yai, Thailand), Glorisa Canino, MD (San Juan, Puerto Rico), Deborah Deas, MND (Charleston, SC), Susumu Higuchi, JD, PhD (Yokosuka, Japan), Bong Jin-Hahm, MD (Seoul, Korea), Bankote Johnson, MD, PhD (Charlottesville, VA), David Kavanagh, PhD (Herston, Australia), Evgeny Krupitsky, MD, PhD (St. Petersberg, Russia), Sam Kuperman, MD (Iowa City, IO), Jack Maser, PhD (San Diego, CA), Maria Elena Medina-Mora, PhD (Colonia Huipulco, Mexico), A. Olabisi Odejide, MD (Ibadan, Nigeria), Maree Teesson, MD (Randwick, Australia), Wim can den Brink, MD (Amsterdam, Netherlands), William Vega, PhD (Piscataway, NJ), George Woody, MD (Philadelphia, PA).
Papers based on these presentations have been published as a supplement to the September 2006 issue of Addiction (i.e., Addiction, September 2006 - Vol. 101 Issue s1 Pages 1-173) and can be viewed by clicking here. These papers were also published in a monograph by American Psychiatric Publishing, Inc., which can be purchased here.