Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome.

BACKGROUND: The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families. METHOD: OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed. RESULTS: EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders). CONCLUSIONS: Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.

Moderators and mediators of the relationship between receiving versus being denied a pregnancy termination and subsequent binge drinking.

BACKGROUND: Women who terminate pregnancies drink more subsequent to the pregnancy than women who give birth, including women who give birth after seeking to terminate a pregnancy. METHODS: Data are from the Turnaway Study, a prospective, longitudinal study of 956 women who sought to terminate pregnancies at 30 U.S. facilities. This paper focuses on the 452 women who received terminations just below facility gestational limits and 231 who were denied terminations because they presented just beyond facility gestational limits. This study examined whether baseline characteristics moderate the relationship between termination and subsequent binge drinking and whether stress, feelings about the pregnancy, and number of social roles mediate the relationship. RESULTS: Only having had a previous live birth modified the termination-binge drinking relationship. Among women with previous live births, binge drinking was reduced among women carrying to term compared to terminating the pregnancy. Among women who had not had a previous live birth, however, the reduction in binge drinking among those denied termination was not sustained over time, and binge drinking of those who had and had not had terminations converged by 2.5 years. Neither stress, negative emotions, nor social roles mediated effects on binge drinking. Positive emotions at one week mediated effects on binge drinking at six months, although positive emotions at two years did not mediate effects on binge drinking at 2.5 years. CONCLUSIONS: Higher levels of binge drinking among those who terminate pregnancies do not appear due to stress or to negative emotions. Only parous women - and not nulliparous women - denied terminations experienced sustained reductions in binge drinking over time.

Gender differences among HIV-positive methadone maintenance patients enrolled in a medication adherence trial.

This study examined baseline gender differences among HIV-positive methadone maintenance outpatients currently prescribed antiretroviral medications. Participants were enrolled in a larger clinical trial, which included a 4-week observation period using electronic monitors to track medication adherence. Contrary to previous literature, no significant differences were detected between men (n = 42) and women (n = 36) on medication adherence or depression. Both groups showed remarkably poor adherence during baseline (M = 56% of doses taken on time), high overall prevalence of depression (47%) and illicit cocaine use (47%). Women reported significantly more medication side effects (M = 21.4 vs. 14.9), higher severity of ASI psychiatric problems (M = 0.50 vs. 0.40), and lower SF-36 health-related quality of life in physical (M = 42.1 vs. 63.3) and emotional functioning (M = 26.9 vs. 58.9) than men. Women tested positive for opioids at higher rates than men (53% vs. 29%, respectively), whereas men were more likely to be positive for benzodiazepines than women (26% vs. 6%, respectively). Findings suggest that gender differences between male and female methadone maintenance patients have relevance to treatment providers. Extensive assessment, specialized medical care and mental health services may be warranted in the treatment of HIV-positive female drug abusers.

Social support and abstinence from opiates and cocaine during opioid maintenance treatment.

Social support may play an important role in helping drug users achieve abstinence; however these benefits may depend on the type of support experienced. In this prospective observational study, we examined the extent to which general and abstinence-specific support, both structural and functional, predicted opiate and cocaine abstinence in 128 opioid maintenance patients receiving either methadone or LAAM. A new multidimensional self-report instrument assessing abstinence-specific functional support was developed for the study. Previously validated measures were used to assess the remaining types of support. With baseline abstinence and other statistically important covariates adjusted, hierarchical logistic regression analyses demonstrated that the associations between social support at study baseline and biochemically confirmed abstinence 3 months later varied by type of support and by drug. Greater abstinence-specific structural support (operationalized as fewer drug users in the social network) and decreases in three types of negative abstinence-specific functional support (Complaints about Drug Use, Drug Exposure, and Demoralization) predicted cocaine, but not opiate abstinence. There were no effects for general support, whether structural or functional, on abstinence from either drug. Interventions that focus on modifying patients' abstinence-specific support may be helpful in reducing the high rates of cocaine use disorders in this population.

Statistical analysis of randomized trials in tobacco treatment: longitudinal designs with dichotomous outcome.

This article considers two important issues in the statistical treatment of data from tobacco-treatment clinical trials: (1) data analysis strategies for longitudinal studies and (2) treatment of missing data. With respect to data analysis strategies, methods are classified as 'time-naïve' or longitudinal. Time-naïve methods include tests of proportions and logistic regression. Longitudinal methods include Generalized Estimating Equations and Generalized Linear Mixed Models. It is concluded that, despite some advantages accruing to 'time-naïve' methods, in most situations, longitudinal methods are preferable. Longitudinal methods allow direct effects of the tests of time and the interaction of treatment with time, and allow model estimates based on all available data. The discussion of missing data strategies examines problems accruing to complete-case analysis, last observation carried forward, mean substitution approaches, and coding participants with missing data as using tobacco. Distinctions between different cases of missing data are reviewed. It is concluded that optimal missing data analysis strategies include a careful description of reasons for data being missing, along with use of either pattern mixture or selection modeling. A standardized method for reporting missing data is proposed. Reference and software programs for both data analysis strategies and handling of missing data are presented.

Violent traumatic events and drug abuse severity.

We examined the occurrence of violent traumatic events, DSM-III-R diagnosis of posttraumatic stress disorder (PTSD), and PTSD symptoms, and the relationship of these variables to drug abuse severity. One-hundred fifty opioid-dependent drug abusers who were participants in a randomized trial of two methadone treatment interventions were interviewed using the Diagnostic Interview Schedule, the Addiction Severity Index, and the Beck Depression Inventory. Twenty-nine percent met diagnostic criteria for PTSD. With the exception of rape, no gender differences in the prevalence of violent traumatic events were observed. The occurrence of PTSD-related symptoms was associated with greater drug abuse severity after controlling for gender, depression, and lifetime diagnosis of PTSD. The high rate of PTSD among these methadone patients, the nature of the traumatic events to which they are exposed, and subsequent violence-related psychiatric sequelae have important implications for identification and treatment of PTSD among those seeking drug abuse treatment.

Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial.

CONTEXT: Despite evidence that methadone maintenance treatment (MMT) is effective for opioid dependence, it remains a controversial therapy because of its indefinite provision of a dependence-producing medication. OBJECTIVE: To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment, psychosocially enriched 180-day methadone-assisted detoxification. DESIGN: Randomized controlled trial conducted from May 1995 to April 1999. SETTING: Research clinic in an established drug treatment service. PATIENTS: Of 858 volunteers screened, 179 adults with diagnosed opioid dependence were randomized into the study; 154 completed 12 weeks of follow-up. INTERVENTIONS: Patients were randomized to MMT (n = 91), which required 2 hours of psychosocial therapy per week during the first 6 months; or detoxification (n = 88), which required 3 hours of psychosocial therapy per week, 14 education sessions, and 1 hour of cocaine group therapy, if appropriate, for 6 months, and 6 months of (nonmethadone) aftercare services. MAIN OUTCOME MEASURES: Treatment retention, heroin and cocaine abstinence (by self-report and monthly urinalysis), human immunodeficiency virus (HIV) risk behaviors (Risk of AIDS Behavior scale score), and function in 5 problem areas: employment, family, psychiatric, legal, and alcohol use (Addiction Severity Index), compared by intervention group. RESULTS: Methadone maintenance therapy resulted in greater treatment retention (median, 438.5 vs 174.0 days) and lower heroin use rates than did detoxification. Cocaine use was more closely related to study dropout in detoxification than in MMT. Methadone maintenance therapy resulted in a lower rate of drug-related (mean [SD] at 12 months, 2.17 [3.88] vs 3.73 [6.86]) but not sex-related HIV risk behaviors and in a lower severity score for legal status (mean [SD] at 12 months, 0.05 [0.13] vs 0.13 [0.19]). There were no differences between groups in employment or family functioning or alcohol use. In both groups, monthly heroin use rates were 50% or greater, but days of use per month dropped markedly from baseline. CONCLUSIONS: Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors. Illicit opioid use continued in both groups, but frequency was reduced. Results do not provide support for diverting resources from MMT into long-term detoxification.

A nicotine antagonist, mecamylamine, reduces cue-induced cocaine craving in cocaine-dependent subjects.

We have previously shown that nicotine enhances cue-induced cocaine craving. In the present study, the effects of a nicotine antagonist, mecamylamine, on cue-induced cocaine craving were investigated. Twenty-three cocaine-dependent patients, all cigarette smokers, were randomly assigned to mecamylamine (2.5 mg tablet) or placebo in a single-dose, placebo-controlled, crossover, double-blind study. Craving and anxiety were measured before and after cocaine cues with visual analog scales for desire to use cocaine and mood. Skin conductance, skin temperature and heart rate were recorded before and during cocaine cues. Following exposure to cocaine cues, all patients reported an increase in cocaine craving and anxiety relative to the precue measures. Cue exposure also produced an increase in skin conductance and decrease in skin temperature. The cue-induced increase in cocaine craving was reduced, while the cue-induced skin conductance and temperature responses were unaffected, by mecamylamine. These findings show that cue-induced cocaine craving is attenuated by mecamylamine. Further study on the use of mecamylamine in relapse prevention programs are suggested.

Longitudinal course and predictors of continuing distress following critical incident exposure in emergency services personnel.

This study examines the longitudinal course and predictors of stress-specific and general symptomatic distress in emergency services personnel. A three-group quasi-experimental design was used to determine the responses of 322 rescue workers to the Loma Prieta earthquake Interstate 880 Freeway collapse and to unrelated control critical incidents. Self-report questionnaires, including measures of incident exposure, peritraumatic dissociation and emotional distress, and current symptoms, were administered 1.9 years (initial) and 3.5 years (follow-up) after the freeway collapse. Despite modest symptom improvement at follow-up, rescue workers were at risk for chronic symptomatic distress after critical incident exposure. Peritraumatic dissociation accounted for significant increments in current posttraumatic stress disorder symptoms, over and above exposure, adjustment, years of experience, locus of control, social support, and general dissociative tendencies. The results suggest that rescue workers, particularly those with more catastrophic exposure and those prone to dissociate at the time of the critical incident, are at risk for chronic symptomatic distress.

Sleep disturbances in the Vietnam generation: findings from a nationally representative sample of male Vietnam veterans.

OBJECTIVE: This study analyzed questionnaire items that address complaints about sleep from the National Vietnam Veterans Readjustment Study, a nationally representative sample of the 3.1 million men and women who served in Vietnam. This study compared the frequency of nightmares and difficulties with sleep onset and sleep maintenance in male Vietnam theater veterans with male Vietnam era veteran and male civilian comparison subjects. It focused on the role of combat exposure, nonsleep posttraumatic stress disorder (PTSD) symptoms, comorbid psychiatric and medical disorder, and substance abuse in accounting for different domains of sleep disturbance. METHOD: The authors undertook an archival analysis of the National Vietnam Veterans Readjustment Study database using correlations and linear statistical models. RESULTS: Frequent nightmares were found exclusively in subjects diagnosed with current PTSD at the time of the survey (15.0%). In the sample of veterans who served in Vietnam (N = 1,167), combat exposure was strongly correlated with frequency of nightmares, moderately correlated with sleep onset insomnia, and weakly correlated with disrupted sleep maintenance. A hierarchical multiple regression analysis showed that in Vietnam theater veterans, 57% of the variance in the frequency of nightmares was accounted for by war zone exposure and non-sleep-related PTSD symptoms. Alcohol abuse, chronic medical illnesses, panic disorder, major depression, and mania did not predict the frequency of nightmares after control for nonsleep PTSD symptoms. CONCLUSIONS: Frequent nightmares appear to be virtually specific for PTSD. The nightmare is the domain of sleep disturbance most related to exposure to war zone traumatic stress.

An acute dose of nicotine enhances cue-induced cocaine craving.

The present study examined whether the active component in tobacco, nicotine, can modulate cocaine craving in patients with a history of smoking crack cocaine when exposed to crack cocaine related environmental cues. Twenty patients, all cigarette smokers, were randomly assigned to nicotine (two 22 mg transdermal patches) or placebo in a single-dose, placebo-controlled, crossover, double-blind study. Craving and anxiety were measured before and after cocaine cues with visual analog scales for desire to use cocaine and mood. Skin conductance and skin temperature were recorded before and during cocaine cues. Following exposure to cocaine cues, all patients reported an increase in cocaine craving and anxiety relative to the pre-cue measures. Cue exposure also produced an increase in skin conductance and decrease in skin temperature. The cue-induced increase in cocaine craving was strongly enhanced by nicotine, while the increase in anxiety was slightly augmented. Cue-induced skin conductance and temperature responses were unaffected by nicotine. These findings show that cue-induced cocaine craving is enhanced by nicotine. This occurred in the absence of any tobacco smoking-related cues, suggesting that nicotine may have direct psychopharmacological effects on conditioned cocaine craving.

Measurement properties of quantitative urine benzoylecgonine in clinical trials research.

Psychometric data are presented which examine the validity of using the concentration of benzoylecgonine in urine, a major metabolite of cocaine, as a measure of drug use, in studies of drug abuse treatments. In such research the standard biological indicator of drug use is usually a qualitative urine drug test, which merely indicates the presence or absence of a drug or its metabolite. A quantitative (i.e. continuous) outcome measure, such as the concentration of a drug or its metabolite in a biological fluid, has substantially more statistical power than a dichotomous measure and should, therefore, prove a more sensitive measure of drug use when viewed from a measurement perspective. Data from two placebo-controlled clinical trials of fluoxetine as an adjunct to treatment for cocaine abuse are analyzed to address this issue. Results indicate that urine benzoylecgonine level is closely related to self-reports of drug use and is independent of levels of anxiety, depression and hopelessness.

The relationship of counselor and peer alliance to drug use and HIV risk behaviors in a six-month methadone detoxification program.

The purpose of this study was to examine the relationship of treatment outcomes in opioid detoxification to levels of counselor and peer alliance. Forty-one subjects were recruited from a larger, 180-day study of psychosocial treatment. Beginning at day 90, subjects completed monthly measures of alliance. Outcome measures included treatment retention, drug use and self-reported HIV risk. Measures of alliance were found to be internally consistent and moderately stable over time. During the final 30 days of the methadone taper, higher levels of both types of alliance were associated with less use of illicit opioids. Alliance with counselor was associated with less frequent needle sharing. For subjects who could be located for 30-day follow-up, greater alliance with peers was associated with more frequent HIV (sexual) risk behaviors. Results suggest that treatment outcome may be improved through approaches that address a patient's alliance with both counselor and peers.

Adherence to zidovudine (AZT) among HIV-infected methadone patients: a pilot study of supervised therapy and dispensing compared to usual care.

Twenty-seven HIV-infected methadone maintenance patients who demonstrated problems adhering to zidovudine (AZT) were randomly assigned to a group that received eight weeks of weekday supervised therapy and dispensing of AZT or a group that received usual care of the clinic. Adherence was assessed by self-report, erythrocyte mean corpuscular volume (MCV), Medication Event Monitoring Systems (MEMS), and pill counts. Subjects in the intervention group demonstrated significantly higher MCV levels during the intervention period than usual care subjects, with similar but non-significant trends for the three other adherence measures. MEMS percent indicated significant group differences on weekdays, but not weekend days. There were no differences at a one-month follow-up. Results suggest supervised therapy and dispensing may be an effective strategy for improving AZT adherence, but only while provided. Further research is needed to establish the effects of larger and longer lasting interventions.

Childhood trauma and posttraumatic stress disorder in substance abuse inpatients.

This pilot study examined: the prevalence of childhood trauma in a sample of male veteran substance abuse inpatients, and the relationship of childhood trauma to substance abuse in this sample, controlling for posttraumatic stress disorder (PTSD). Forty-six subjects were interviewed using the Traumatic Antecedents Questionnaire, Structured Clinical Interview for DSM-III-R (SCID)-P Psychoactive Substance Use Disorders module, the Addiction Severity Index, and the SCID-NP-V PTSD module. Seventy-seven percent of subjects had been exposed to severe childhood trauma. Fifty-eight percent had lifetime PTSD. The total number of lifetime substance dependence disorders was strongly positively associated with total childhood trauma exposure. This relationship remained significant after controlling for demographics, family history of alcohol problems, combat exposure, and lifetime PTSD, including combat-related PTSD. A substantial number of these subjects reported exposure to childhood trauma, which in turn was related to multiple substance dependence. This has important implications for the natural history and prevention of multiple substance dependence disorders.

Self-efficacy and illicit opioid use in a 180-day methadone detoxification treatment.

Self-efficacy ratings coincided with illicit opioid use across the 3 phases of a 180-day methadone detoxification treatment. Efficacy ratings increased after patients received their first dose of methadone, did not change while they were maintained on a stable dose of methadone, and declined during the taper as they attempted to face high-risk situations without the full benefit of methadone. Efficacy ratings measured at a point before a phase of treatment predicted illicit opioid use across that phase. For clarification of the relation between self-efficacy and illicit opioid use, 3 conceptual models proposed by J.S. Baer, C.S. Holt, and E. Lichtenstein (1986) were tested. Self-efficacy influenced subsequent drug use in parallel with previous behavior, but this influence was found only at the start of the stabilization phase and immediately before the start of the taper phase. These findings highlight the usefulness of the self-efficacy concept for the treatment of opioid addiction.

Methods for the analysis of binary outcome results in the presence of missing data.

An important, frequent, and unresolved problem in treatment research is deciding how to analyze outcome data when some of the data are missing. After a brief review of alternative procedures and the underlying models on which they are based, an approach is presented for dealing with the most common situation--comparing the outcome results in a 2-group, randomized design in the presence of missing data. The proposed analysis is based on the concept of "modeling our ignorance" by examining all possible outcomes, given a known number of missing results with a binary outcome, and then describing the distribution of those results. This method allows the researcher to define the range of all possible results that could have resulted had the missing data been observed. Extensions to more complex designs are discussed.

Low (40 mg) versus high (80 mg) dose methadone in a 180-day heroin detoxification program.

Methadone Transition Treatment (MTT) is a treatment program for opioid-addicted individuals that takes advantage of a 1989 change in federal guidelines permitting the establishment of 180-day detoxification programs. Thirty-eight subjects were assigned to either high-dose (80 mg) or low-dose (40 mg) methadone in a double-blind design. Both conditions showed initial dramatic decreases in illicit drug use and distress symptoms (opioid craving, withdrawal symptoms, and dysphoria). The high-dose condition showed a nonsignificant trend toward less frequent illicit drug use during the period of stable methadone dosing. We speculate that intensive psychosocial treatment, including weekly individual counseling and three-times a week group therapy, may have dampened outcome differences between high- and low-dose methadone conditions. Treatment retention was high for both dosage conditions.

Measurement properties of clinical simulation tests: hypertension and chronic obstructive pulmonary disease.

Reliability and validity of two clinical simulation tests were studied, using a multimethod approach. The instruments were originally tested in a project that compared ability of physicians, nurse practitioners, and public health nurses to provide primary care. Reliability was assessed by comparing test scores of the same subjects on two occasions. Validity was assessed by: 1) comparing test scores of two expert panels and of professional health groups (nurses and physicians) with preprofessional groups (nursing and medical students), 2) comparing test contents with authoritative literature on the disease, and 3) analyzing results of test evaluation by all subjects. Subjects of the original project were compared with those in this study. Both tests were found reliable and valid, corroborating the original project's findings that nurse practitioners and physicians are equally proficient in assessment and treatment of health problems. Findings also lend validity to the tests' developmental model and suggest the usefulness of such tests in nursing and medical education.