The triallelic serotonin transporter gene linked polymorphic region (5-HTTLPR) has been associated with alterations in thermal pain perception. The primary aim of this study was to investigate the associations between heat pain (HP) perception and the triallelic 5-HTTLPR in a large cohort of adults with chronic pain.
The cohort included 277 adults with chronic pain who met inclusion criteria, and were consecutively admitted to an outpatient pain rehabilitation program from March 2009 through March 2010. Individuals were genotyped for the triallelic 5-HTTLPR (including rs25531) and categorized as high, intermediate, or low expressors of the serotonin transporter. Standardized measures of HP perception were obtained using a validated quantitative sensory test method of levels.
The distribution of the high, intermediate, and low expressing genotypes was 61 (22%), 149 (54%) and 67 (24%), respectively. The Hardy-Weinberg P-value was 0.204 which indicated no departure from equilibrium. A significant effect of genotype was observed for values of HP threshold (P = 0.029). Individual group comparisons showed that values of HP threshold were significantly greater in the intermediate compared to the high expressing group (P = 0.009) but not the low expressing group (P > 0.1). In a multiple variable linear regression model, the intermediate group (P = 0.034) and male sex (P = 0.021) were associated with significantly greater values of HP 0.5, but no significant genotype-by-sex interaction effect was observed.
In this study that involved adults with chronic pain, the intermediate triallelic 5-HTTLPR expressing group, but not the low expressing group, was associated with greater HP thresholds compared to the high expressing group.
The purpose of the current study was to evaluate feasibility and efficacy of two promising approaches to indicated prevention of disordered gambling in a college population.
Randomized controlled trial with assignment to a Personalized Feedback Intervention (PFI), Cognitive-Behavioral Intervention (CBI), or Assessment-Only Control (AOC). PFI was individually delivered in a single session and included feedback regarding gambling behavior, norms, consequences, and risk-reduction tips, delivered in a motivational interviewing style. CBI was delivered in small groups over 4-6 sessions and included functional analysis, brief cognitive correction, as well as identification of and alternatives for responding to gambling triggers.
At-risk or probable pathological gamblers (N = 147; 65.3% male; group assignment: PFI, n = 52; CBI, n = 44; AOC, n = 51).
Self-reported gambling quantity, frequency, consequences, psychopathology, normative perceptions, and beliefs.
Relative to control, results at 6-month follow-up indicated reductions in both interventions for gambling consequences (PFI d = .48; CBI d = .39) and DSM-IV criteria (PFI d=.60; CBI d=.48), reductions in frequency for PFI (d = .48). CBI was associated with reduced illusions of control, whereas PFI was associated with reduced perceptions of gambling frequency norms. Reductions in perceived gambling frequency norms mediated effects of PFI on gambling frequency.
A single-session Personalized Feedback Intervention and a multi-session Cognitive-Behavioral Intervention may be helpful in reducing disordered gambling in US college students.
gambling; college students; brief interventions; cognitive behavioral; prevention
Adolescence is a time in which individuals are particularly likely to engage in health-risk behaviors, with marijuana being the most prevalent illicit drug used. Perceptions of others’ use (i.e., norms) have previously been found to be related to increased marijuana use. Additionally, low refusal self-efficacy has been associated with increased marijuana consumption. This cross-sectional study examined the effects of normative perceptions and self-efficacy on negative marijuana outcomes for a heavy using adolescent population. A structural equation model was tested and supported such that significant indirect paths were present from descriptive norms to marijuana outcomes through self-efficacy. Implications for prevention and intervention with heavy using adolescent marijuana users are discussed.
marijuana; adolescent substance abuse; social norms; social learning theory
Adenosine signaling has been implicated in the pathophysiology of several psychiatric disorders including alcoholism, depression, and anxiety. Adenosine levels are controlled in part by transport across the cell membrane by equilibrative nucleoside transporters (ENTs). Recent evidence showed that a polymorphism in the gene encoding ENT1 is associated with comorbid depression and alcoholism in women. We have previously shown that deletion of ENT1 reduces ethanol intoxication and elevates alcohol intake in mice. Interestingly, ENT1 null mice display decreased anxiety-like behavior compared to wild-type littermates. However, our behavioral studies were performed only in male mice. Here, we extend our research to include female mice, and test the effect of ENT1 knockout on other behavioral correlates of alcohol drinking, including depressive and compulsive behavior, in mice.
To assess depression-like behavior, we used a forced swim test modified for mice. We examined anxiety-like behavior and locomotor activity in open field chambers, and perseverant behavior using the marble-burying test. Finally, we investigated alcohol consumption and preference in female mice using a two-bottle choice paradigm.
ENT1 null mice of both sexes showed reduced immobility time in the forced swim test and increased time in the center of the open field compared to wild-type littermates. ENT1 null mice of both sexes showed similar locomotor activity levels and habituation to the open field chambers. Female ENT1 null mice displayed increased marble-burying compared to female wild-types, but no genotype difference was evident in males. Female ENT1 null mice showed increased ethanol consumption and preference compared to female wild-types.
Our findings suggest that ENT1 contributes to several important behaviors involved in psychiatric disorders. Inhibition of ENT1 may be beneficial in treating depression and anxiety, while enhancement of ENT1 function may reduce compulsive behavior and drinking, particularly in females.
Adenosine; Depression; Anxiety; Alcohol; ENT1; Sex; Compulsivity
Cannabis use adversely affects adolescents and interventions that are attractive to adolescents are needed. This trial compared the effects of a brief motivational intervention for cannabis use with a brief educational feedback control and a no-assessment control.
Participants were randomized into one of three treatment conditions: Motivational Enhancement Therapy (MET), Educational Feedback Control (EFC) or Delayed Feedback Control (DFC). Those assigned to MET and EFC were administered a computerized baseline assessment immediately following randomization and completed assessments at the 3- and 12-month follow-up periods. Participants in the DFC condition were not assessed until the 3-month follow-up. Following the completion of treatment sessions, all participants were offered up to 4 optional individual treatment sessions aimed at cessation of cannabis use.
High schools in Seattle, WA, USA.
310 self-referred adolescents who smoked cannabis regularly.
Main outcome measures included days of cannabis use, associated negative consequences, and engagement in additional treatment.
At the 3-month follow-up, participants in both the MET and EFC conditions reported significantly fewer days of cannabis use and negative consequences compared to DFC. Frequency of cannabis use was less in MET relative to EFC at 3 months, but did not translate to differences in negative consequences. Reduction in use and problems were sustained at 12-months but there were no differences between MET and EFC interventions. Engagement in additional treatment was minimal and not different by condition.
Brief interventions can attract and have positive impacts on adolescent cannabis users, but the mechanisms of the effects are yet to be identified.
The present investigation examined the relationships between motives for cannabis use and negative consequences associated with cannabis use following a brief intervention. The sample consisted of 205 adolescent cannabis users (66.3% male), who were recruited in high schools and randomly assigned to a brief two-session motivational enhancement therapy (MET) or an educational feedback control (EFC). Results supported the hypothesis that using cannabis to cope with negative affect would predict the number of problems and dependence symptoms related to cannabis use, after controlling for age, gender, years and frequency of cannabis use, and internalizing and externalizing behavior problems. Significant interactions between internalizing behavior problems and the coping motive showed that using to cope was associated with a higher number of cannabis dependence symptoms among adolescents reporting lower levels internalizing behavior problems. Findings support the potential utility of conducting further research to explore the coping motive as an important indicator of problematic cannabis use.
cannabis; marijuana; adolescents; cannabis use motives; internalizing behavior problems
To preliminarily evaluate telephone-delivered motivational enhancement therapy (MET) in motivating unadjudicated and nontreatment seeking intimate partner violence (IPV) perpetrators, who also use substances, to self-refer into treatment.
124 adult men were recruited via a multimedia marketing campaign and were randomly assigned to the intervention (MET) or comparison group following a baseline assessment. Participants in the MET condition received a personalized feedback report on their IPV and substance-use behaviors, consequences, and social norms beliefs.
Results supported the likely effectiveness of MET in short-term reduction of IPV behavior, increasing motivation for treatment seeking, and changing perceived norms for IPV and substance abuse (SA).
Applications for brief MET interventions to facilitate voluntary treatment entry among substance-using IPV perpetrators are discussed.
IPV perpetration; substance abuse; brief interventions; randomized controlled trials; motivational enhancement therapy; check-up model; voluntary treatment referral
Although voluntary enrollment by abusive men in domestic violence perpetrator treatment programs occurs, most men enter treatment only after they have injured a partner or family member and have been arrested, convicted and sentenced. This leaves a serious gap for those who engage in abusive behavior but who have not been served by the legal or social service systems. To address this gap, the researchers applied social marketing principles to recruit abusive men to a telephone-delivered pre-treatment intervention (the Men’s Domestic Abuse Check-Up—MDACU), designed to motivate non-adjudicated and untreated abusive men who are concurrently using alcohol and drugs to enter treatment voluntarily. This article discusses recruitment efforts in reaching perpetrators of intimate partner violence, an underserved population. Informed by McGuire’s communication and persuasion matrix, the researchers describe three phases of the MDACU’s marketing campaign: (1) planning, (2) early implementation, and (3) revision of marketing strategies based on initial results. The researchers’ “lessons learned” conclude the paper.
Abusive men; Social marketing; Recruitment; Early intervention; Prevention
Psychotherapy process research continues to be important in identifying within session client and therapist behaviors related to outcome. Motivational Interviewing (MI) assumes that the type of client language elicited within session is important. Client behavior was coded from 61 MI sessions with marijuana dependent adults. Sessions were coded for client language using the Client Language and Commitment Scale. Client statements indicating desire and reasons for change were significantly predictive of marijuana treatment outcome through the 34-month follow-up above and beyond baseline levels of marijuana use or motivation for change. Commitment language was not associated with outcomes. These findings suggest specific types of client language statements predict marijuana treatment outcome and are durable to a 34-month follow-up.
motivational interviewing; motivational enhancement therapy; commitment language; therapy process; marijuana; cannabis; process; outcome
The Sex Check is a brief, telephone-delivered, HIV-prevention intervention tailored for individuals who are at high risk of HIV infection or transmission but who are neither reducing their risk on their own nor seeking support for this purpose. Because the intervention is delivered on a one-to-one basis, permits anonymity, is marketed to “men who have sex with men,” and is brief, it may be particularly responsive to cultural, structural, and attitudinal barriers to serving Latino MSM. Because many Latino MSM continue to engage in high risk sexual behaviors, developing and testing prevention interventions with this population is a public health priority.
HIV prevention; Latino MSM; high-risk sexual behaviors; risk reduction
Brief and low-burden HIV risk reduction counseling interventions are needed for populations at greatest risk for HIV infection.
This randomized controlled trial tested a brief theory-based counseling intervention delivered entirely over the telephone for men who engage in unprotected intercourse with men.
Participants received either risk reduction counseling that included information, motivational enhancement and behavior skills building, or brief HIV education counseling. A total of 319 participants completed follow-up assessments over a 10-month period. Descriptive and random effects mixed models are used to evaluate findings.
Results demonstrate that a brief telephone intervention can reach and engage high-risk men in risk reduction counseling. Nearly one third of participants identified as men of color; the median age was 33 years. Participants in both counseling conditions increased their motivation and behavioral skills to practice safer sex and reduced their number of sex partners and frequencies of engaging in unprotected anal sex over the study observation period. However, there were few differences between intervention conditions.
The effects of repeated measurement reactivity and brief interpersonal consciousness raising may account for the lack of differences between counseling conditions and the decrease in risk for all participants over time.
Research examining intimate partner violence (IPV) has lacked a comprehensive theoretical framework for understanding and treating behavior. The authors propose two complementary models, a treatment approach (Motivational Interviewing, MI) informed by a theory (Self-Determination Theory; SDT), as a way of integrating existing knowledge and suggesting new directions in intervening early with IPV perpetrators. MI is a client-centered clinical intervention intended to assist in strengthening motivation to change and has been widely implemented in the substance abuse literature. SDT is a theory that focuses on internal versus external motivation and considers elements that impact optimal functioning and psychological well-being. These elements include psychological needs, integration of behavioral regulations, and contextual influences on motivation. Each of these aspects of SDT is described in detail and in the context of IPV etiology and intervention using motivational interviewing.
Surprisingly, little is known about how IPV perpetrators perceive the consequences of their violent behavior. This article describes the development and evaluation of the Perceived Consequences of Domestic Violence Questionnaire (PCDVQ). The PCDVQ is a 27-item self-report instrument designed to assess the consequences of intimate partner violence (IPV) as perceived by the perpetrator. Data from 124 nontreatment seeking, male, IPV perpetrators recruited from the community provided support for the internal consistency of the PCDVQ. Participants reported an average of 9.97 (SD = 4.57) consequences. Scores on the PCDVQ significantly predicted motivation for change, β = .19, t(113) = 2.03, p < .05, and treatment seeking, χ2(df = 1) = 10.79, p < .01, odds ratio = 1.27 (95% CI: 1.10-1.46). Clinical implications of this instrument are discussed.
consequences; assessment; domestic violence; intervention; motivational interviewing
The most potent outcomes for cannabis use disorders have been observed with a combination of three evidence-based interventions, motivational enhancement therapy (MET), cognitive-behavioral therapy (CBT), and abstinence-based contingency-management (CM). Access to this intervention remains limited because of cost and service availability issues. This report describes the initial stages of a project designed to develop and test a computer-assisted version of MET/CBT/CM that could address many of the current barriers to its dissemination. A nonrandomized, 12-week comparison study assigned 38 adults seeking treatment for a cannabis use disorder to either therapist-delivered (n=22) or computer-delivered (n=16) MET/CBT/CM. Attendance, retention, and cannabis use outcomes did not differ significantly between groups, and there were no indications of superior outcomes favoring therapist delivery. Participants provided positive ratings of the computer-delivered sessions. These preliminary findings suggest that computer-assisted delivery of MET/CBT/CM is acceptable to outpatients and does not adversely impact compliance or outcomes achieved during treatment with MET/CBT/CM for cannabis use disorders. Assessment of post-treatment outcomes and replication in randomized trials are needed to determine reliability and longer-term effects. As observed in a growing number of studies, computerized therapies have the potential to increase access to, reduce costs, and enhance fidelity of providing evidence-based treatments without sacrificing and possibly enhancing effectiveness.
cannabis; marijuana; treatment; computer delivered; contingency management; internet
Batterer intervention programs primarily work with individuals mandated to participate. Commonly, attrition is high and outcomes are modest. Motivational enhancement therapy (MET), most widely studied in the substance abuse field, offers a potentially effective approach to improving self-referral to treatment, program retention, treatment compliance, and posttreatment outcomes among men who batter and who abuse substances. A strategy for using a catalyst variant of MET (a “check-up”) to reach untreated, nonadjudicated perpetrators is described in detail. Unique challenges in evaluating the success of this approach are discussed, including attending to victim safety and determining indicators of increased motivation for change.
abusers; check-up; motivational
This research was designed to evaluate the applicability of social norms approaches to interventions with male perpetrators of intimate partner violence (IPV). Participants included 124 nonadjudicated IPV perpetrating men recruited from the general population who completed assessment of their own IPV behaviors via telephone interviews and estimated the prevalence of behaviors in other men. Results indicated that IPV perpetrators consistently overestimated the percentage of men who engaged in IPV and that their estimates were associated with violence toward their partner over the past 90 days. Findings provide preliminary support for incorporating social norms approaches into clinical applications.
domestic violence; motivational interviewing; social norms
Two studies examined the relationships among injunctive norms and college student gambling. In study 1 we evaluated the accuracy of perceptions of other students’ approval of gambling and the relationship between perceived approval and gambling behavior. In study 2 we evaluated gambling behavior as a function of perceptions of approval of other students, friends, and family. In study 1, which included 2524 college students, perceptions of other students’ approval of gambling were found to be overestimated and were negatively associated with gambling behavior. The results of study 2, which included 565 college students, replicated the findings of study 1 and revealed positive associations between gambling behavior and perceived approval of friends and family. Results highlight the complexity of injunctive norms and the importance of considering the reference group (e.g., peers, friends, family members) in their evaluation. Results also encourage caution in considering the incorporation of injunctive norms in prevention and intervention approaches.
Social norms; Attitudes; Injunctive norms; Gambling
CYP2D6 is a polymorphic gene. It has been observed to be deleted, to be duplicated and to undergo recombination events involving the CYP2D7 pseudogene and surrounding sequences. The objective of this study was to discover the genomic structure of CYP2D6 recombinants that interfere with clinical genotyping platforms that are available today.
Clinical samples containing rare homozygous CYP2D6 alleles, ambiguous readouts, and those with duplication signals and two different alleles were analyzed by long-range PCR amplification of individual genes, PCR fragment analysis, allele-specific primer extension assay, and DNA sequencing to characterize alleles and genomic structure.
Novel alleles, genomic structures, and the DNA sequence of these structures are described. Interestingly, in 49 of 50 DNA samples that had CYP2D6 gene duplications or multiplications where two alleles were detected, the chromosome containing the duplication or multiplication had identical tandem alleles.
Several new CYP2D6 alleles and genomic structures are described which will be useful for CYP2D6 genotyping. The findings suggest that the recombination events responsible for CYP2D6 duplications and multiplications are because of mechanisms other than interchromosomal crossover during meiosis.
allele; CYP2D6; CYP2D7; CYP2D8; cytochrome P450; drug metabolism; pharmacogenetics; polymorphism; recombinant
Large DNA rearrangements account for about 8% of disease mutations and are more common in duplicated genomic regions, where they are difficult to detect. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2. PKD1 is located in an intrachromosomally duplicated region. A tuberous sclerosis gene, TSC2, lies immediately adjacent to PKD1 and large deletions can result in the PKD1/TSC2 contiguous gene deletion syndrome. To rapidly identify large rearrangements, a multiplex ligation-dependent probe amplification assay was developed employing base-pair differences between PKD1 and the six pseudogenes to generate PKD1-specific probes. All changes in a set of 25 previously defined deletions in PKD1, PKD2 and PKD1/TSC2 were detected by this assay and we also found 14 new mutations at these loci. About 4% of the ADPKD patients in the CRISP study were found to have gross rearrangements, and these accounted for about a third of base-pair mutation negative families. Sensitivity of the assay showed that about 40% of PKD1/TSC contiguous gene deletion syndrome families contained mosaic cases. Characterization of a family found to be mosaic for a PKD1 deletion is discussed here to illustrate family risk and donor selection considerations. Our assay improves detection levels and the reliability of molecular testing of patients with ADPKD.
ADPKD; PKD1/TSC2-CGS; MLPA; deletions; mosaic; PKD2
When Caenorhabditis elegans encounters an unfavourable stimulus at its anterior, it responds by initiating an avoidance response, namely reversal of locomotion. The amphid neurons, ASHL and ASHR, are polymodal in function, with roles in the avoidance responses to high osmolarity, nose touch, and both volatile and non-volatile repellents. The mechanisms that underlie the ability of the ASH neurons to respond to such a wide range of stimuli are still unclear. We demonstrate that the inositol 1,4,5-trisphosphate receptor (IP3R), encoded by itr-1, functions in the reversal responses to nose touch and benzaldehyde, but not in other known ASH-mediated responses. We show that phospholipase Cβ (EGL-8) and phospholipase Cγ (PLC-3), which catalyse the production of IP3, both function upstream of ITR-1 in the response to nose touch. We use neuron-specific gene rescue and neuron-specific disruption of protein function to show that the site of ITR-1 function is the ASH neurons. By rescuing plc-3 and egl-8 in a neuron-specific manner, we show that both are acting in ASH. Imaging of nose touch–induced Ca2+ transients in ASH confirms these conclusions. In contrast, the response to benzaldehyde is independent of PLC function. Thus, we have identified distinct roles for the IP3R in two specific responses mediated by ASH.
In order to avoid potential hazards, animals detect and discriminate between a wide range of aversive stimuli. To detect some of these stimuli, animals use polymodal sensory neurons, that is neurons of a single type that can detect a range of different stimuli and transmit an appropriate signal to the downstream nervous system. Pain-sensing nociceptors in humans and the ASH neurons in C. elegans are both polymodal. The ASH neurons mediate responses to high osmotic strength, nose touch, high ambient oxygen, and volatile and non-volatile compounds. It remains unclear how these cells detect and discriminate between these different stimuli. We show that signalling through the second messenger inositol 1,4,5-trisphosphate (IP3) and its receptor (IP3R) is required in ASH for animals to respond to nose touch. We also show that IP3Rs are required for the response to the volatile compound benzaldehyde. However, these signalling components are not required for a range of other ASH-mediated responses. Thus, we have identified a signalling mechanism that is specific to a small subset of ASH-mediated responses. These results add to our understanding of how ASH discriminates between a variety of stimuli and thus to our understanding of polymodal neurons in general.
Caveolins are plasma membrane–associated proteins that colocalize with, and stabilize caveolae. Their functions remain unclear although they are known to be involved in specific events in cell signaling and endocytosis. Caenorhabditis elegans encodes two caveolin genes, cav-1 and cav-2. We show that cav-2 is expressed in the intestine where it is localized to the apical membrane and in intracellular bodies. Using the styryl dye FM4-64 and BODIPY-labeled lactosylceramide, we show that the intestinal cells of cav-2 animals are defective in the apical uptake of lipid markers. These results suggest parallels with the function of caveolins in lipid homeostasis in mammals. We also show that CAV-2 depletion suppresses the abnormal accumulation of vacuoles that result from defective basolateral recycling in rme-1 and rab-10 mutants. Analysis of fluorescent markers of basolateral endocytosis and recycling suggest that endocytosis is normal in cav-2 mutants and thus, that the suppression of basolateral recycling defects in cav-2 mutants is due to changes in intracellular trafficking pathways. Finally, cav-2 mutants also have abnormal trafficking of yolk proteins. Taken together, these data indicate that caveolin-2 is an integral component of the trafficking network in the intestinal cells of C. elegans.
Given the prevalence of regular marijuana use among adolescents and associated risks for adverse consequences to functioning, effective interventions are needed that are tailored for this population. To date, most such counseling approaches have relied on non-voluntary participation by adolescent marijuana smokers and the outcomes have been only modestly successful. The Teen Marijuana Check-Up is a brief motivational enhancement intervention publicized as a non-pressured and confidential opportunity for the teen marijuana smoker to “take stock” of his/her use. The intervention is designed for in-school implementation and intended to elicit the teen's voluntary participation. This paper highlights the manner in which adolescents are recruited, key intervention elements, the nature of the counseling style utilized, and clinical challenges. The outcomes of two trials with this intervention are briefly discussed.
cannabis; marijuana; adolescent; brief intervention; check-up
This study's aims were (a) to investigate the feasibility of a school-based motivational enhancement therapy (MET) intervention in voluntarily attracting adolescents who smoke marijuana regularly but who are not seeking formal treatment and (b) to evaluate the efficacy of the intervention in reducing marijuana use. Ninety-seven adolescents who had used marijuana at least 9 times in the past month were randomly assigned to either an immediate 2-session MET intervention or to a 3-month delay condition. Two thirds of the sample characterized themselves as in the precontemplation or contemplation stages of change regarding marijuana use. Participants’ marijuana use and associated negative consequences were assessed at baseline and at a 3-month follow-up. Analyses revealed that both groups significantly reduced marijuana use at the 3-month follow-up ( p < .001); however, no between-group differences were observed. Despite the absence of a clear effect of MET, this study demonstrated that adolescents could be attracted to participate in a voluntary marijuana intervention that holds promise for reducing problematic levels of marijuana use.
motivational enhancement therapy; adolescents; cannabis; marijuana; school based
The prevalence of marijuana abuse and dependence disorders has been increasing among adults and adolescents in the United States. This paper reviews the problems associated with marijuana use, including unique characteristics of marijuana dependence, and the results of laboratory research and treatment trials to date. It also discusses limitations of current knowledge and potential areas for advancing research and clinical intervention.
Countless barriers come between people who are struggling with substance abuse and those charged with providing substance abuse treatment. The check-up, a form of motivational enhancement therapy, is a harm reduction intervention that offers a manner of supporting individuals by lowering specific barriers to reaching those who are untreated. The check-up was originally developed to reach problem drinkers who were neither seeking treatment nor self-initiating change. The intervention, marketed as an opportunity to take stock of one's experiences, involves an assessment and personalized feedback delivered with a counseling style termed motivational interviewing. Check-ups can be offered in care settings to individuals who, as a result of screening, manifest risk factors for specific disorders such as alcoholism. They can also be free-standing and publicized widely to the general public. This paper will discuss illustrations of in-person, computerized, in-school, and telephone applications of the free-standing type of check-up with reference to alcohol consumers, adult and adolescent marijuana smokers, and gay/bisexual males at risk for sexual transmission of HIV. The paper's major focus is to highlight how unique features of each application have the potential of reducing barriers to reaching specific at-risk populations. Also considered are key policy issues such as how check-up services can be funded, which venues are appropriate for the delivery of check-up interventions, pertinent competency criteria in evaluating staff who deliver this intervention, how marketing can be designed to reach contemplators in untreated at-risk populations, and how a check-up's success ought to be defined.