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.

Heritability of tic disorders: a twin-family study.

BACKGROUND: Genetic-epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample. METHOD: In an extended twin-family design, we analysed lifetime tic data reported by adult mono- and dizygotic twins (n = 8323) and their family members (n = 7164; parents and siblings) from 7311 families in the Netherlands Twin Register. We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes. Heritability was estimated by genetic structural equation modeling for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria. RESULTS: Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between 0.25 and 0.37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment or non-additive genetic effects. CONCLUSIONS: Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSM-IV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies.

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.

Partitioning the etiology of hoarding and obsessive-compulsive symptoms.

BACKGROUND: Until recently, hoarding was considered an obsessive-compulsive symptom (OCS). However, current evidence suggests that these two phenotypes may be clinically, and perhaps etiologically, distinct. Both hoarding and OCS have a genetic etiology, but the degree of unique and shared genetic contributions to these phenotypes has not been well studied. METHOD: Prevalence rates were assessed for hoarding and OCS in a sample of adult twin pairs (n = 7906 twins) and their family members from The Netherlands Twin Register (total sample = 15,914). Using Mplus, genetic analyses using liability threshold models were conducted for both phenotypes, for their co-morbidity, and for specific hoarding symptoms (cluttering, discarding and acquiring). RESULTS: Of the total sample, 6.7% met criteria for clinically significant hoarding; endorsement of all three hoarding symptoms was > or = 79%. Men had slightly higher rates than women. Also, 5.7% met criteria for clinically significant OCS; rates were similar in males and females. Genetic factors accounted for 36% of the variance for hoarding and 40% of the variance for OCS. The genetic correlation between hoarding and OCS was 0.10. There was no evidence of sex-specific genetic contributions for hoarding or OCS. There was evidence for a genetic contribution to all hoarding symptom subtypes. Only cluttering showed evidence of a contribution from the shared environment. CONCLUSIONS: OCS and hoarding are common in this population-based sample, have prevalence rates similar to those previously reported, and show significant heritability. Genetic factors contributed to the co-morbidity of both traits, although the genetic correlation between them was low.

Quitting smoking does not increase the risk of major depressive episodes among users of Internet smoking cessation interventions.

BACKGROUND: Limited evidence has suggested that quitting smoking increases the incidence of major depressive episodes (MDEs), particularly for smokers with a history of depression. Further evidence for this increase would have important implications for guiding smoking cessation. METHOD: Spanish- and English-speaking smokers without a current MDE (n=3056) from an international, online smoking cessation trial were assessed for abstinence 1 month after their initial quit date and followed for a total of 12 months. Incidence of screened MDE was examined as a function of abstinence and depression history. RESULTS: Continued smoking, not abstinence, predicted MDE screened at 1 month [smoking 11.5% v. abstinence 7.8%, odds ratio (OR) 1.36, 95% confidence interval (CI) 1.04-1.78, p=0.02] but not afterwards (smoking 11.1% v. abstinence 9.8%, OR 1.05, 95% CI 0.77-1.45, p=0.74). Depression history predicted MDE screened at 1 month (history 17.1% v. no history 8.6%, OR 1.71, 95% CI 1.29-2.27, p<0.001) and afterwards (history 21.7% v. no history 8.3%, OR 3.87, 95% CI 2.25-6.65, p<0.001), although the interaction between history and abstinence did not. CONCLUSIONS: Quitting smoking was not associated with increased MDE, even for smokers with a history of depression, although a history of depression was. Instead, not quitting was associated with increased MDE shortly following a quit attempt. Results from this online, large, international sample of smokers converge with similar findings from smaller, clinic-based samples, suggesting that in general, quitting smoking does not increase the incidence of MDEs.

Therapeutic drug monitoring of nortriptyline in smoking cessation: a multistudy analysis.

Multiple, controlled clinical trials support the efficacy of nortriptyline as a smoking cessation agent. Although therapeutic plasma nortriptyline concentrations (PNCs) are known for the treatment of depression, little is known about PNCs in smoking cessation treatment. PNCs from three randomized, placebo-controlled smoking cessation trials (N=244) were analyzed both separately and pooled. PNCs normalized for dose and weight were associated with cigarettes per day and race, but not with sex or age. Greater smoking was associated with decreased normalized PNCs. In addition, both Asian and black populations had significantly higher normalized PNCs than the white populations. Weak and inconsistent associations between PNCs and self-reported side effects were observed. PNCs were linearly related to end of treatment and long-term biochemically verified smoking abstinence. Maximum therapeutic effects were observed over a range of plasma concentrations somewhat lower than those found effective for the treatment of depression.

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.

Gender differences in income after substance abuse treatment.

This study asked whether men and women who enrolled in substance use treatment reported similar changes in income from work, public assistance, and crime over time. Income data were analyzed for 261 substance users (77 women, 184 men) who entered day or residential treatment, and completed Addiction Severity Index measures at treatment entry and up to 18 months later. Over time, respondents reported increases in employment income. People whose main source of income at baseline had been crime or public assistance showed significant decreases respectively in income from crime or public assistance. Men made greater gains in work income than women did. Across time, men were more likely to be employed than women were. Findings show the economic value of substance use treatment, but less improvement in employment outcomes for women than men.

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.

Adherence with referrals for outpatient follow-up from a VA psychiatric emergency room.

This study identifies patient characteristics associated with adherence to outpatient mental health treatment referrals from a VA psychiatric emergency department. Attendance of outpatient appointments was monitored for 12 weeks following emergency department visits (N = 241). Overall attendance of the first appointments was 53%, ranging from 34% of the homeless, to 82% of patients with alcoholism in remission. Characteristics associated with initial adherence included having a place to live and the diagnosis of depression. At twelve weeks, the diagnosis of substance abuse was associated with worse ongoing adherence. The results underscore the need to develop interventions targeting patients at highest risk of poor adherence.

A cost-effectiveness and cost-benefit analysis of contingency contracting-enhanced methadone detoxification treatment.

We examined treatment costs in an ongoing study in which 102 opioid-addicted patients had been randomly assigned to either 180-day methadone detoxification or the same treatment enhanced with contingency contracting. In the latter condition, study participants received regular reinforcers contingent on negative urine toxicology screens and breath analyses for a range of drugs and alcohol. Both conditions involved psychosocial treatment, and all participants were stabilized to a daily methadone dose of approximately 80 mg during the first 4 months, followed by a 2-month taper. Individuals participating in the enhanced condition were more likely to provide continuously drug-free urine samples and alcohol-free breath samples during the final month of treatment than were participants in the control condition. Cost of treatment was calculated individually for each participant based on actual services received. First, unit cost for each service was determined, including adjusted staff salaries for direct treatment and opportunity cost of facilities utilized during service delivery. Next, we valued each patient's use of services during the first 120 days of the study and then added the cost of methadone, laboratory work, and contingent reinforcers. A subsample (n = 45) also provided data on health care utilization during treatment, which we valued using standard Medicare unit costs. The marginal cost of enhancing the standard treatment with contingency contracting was approximately 8%. An incremental cost of $17.27 produced an additional 1% increase in the number of participants providing continuously substance-free urine and breath samples during month 4 of the study. For every additional dollar spent on treatment, a $4.87 health care cost offset was realized; however, this difference was statistically insignificant due to extreme variances and small subsample size.

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.