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Problematic gambling is more common among people with alcohol use disorders (AUDs) (i.e., either alcohol abuse or dependence) compared with those without AUDs. This association holds true for people in the general population and is even more pronounced among people receiving treatment. No broadly accepted explanation for the link between problematic gambling and AUD currently exists. The available literature suggests that common factors may increase the risk for both conditions. For example, a defect of functioning in a particular brain system may underlie both conditions. This hypothesis should be further developed using brain imaging and psychopharmacological studies. Effective treatment and prevention will require additional research into relevant associations on both the event level (e.g., the effects of drinking on gambling behavior and vice versa) and the syndrome level (e.g., the relative onset and course of each condition among those who have either one or both disorders). A prudent interpretation of the available data suggests careful screening and treatment when necessary for problematic gambling among people with alcohol abuse and for alcohol abuse among people with gambling problems. [ABSTRACT FROM AUTHOR]

Exposure therapy is a first-line, empirically validated treatment for anxiety, obsessive-compulsive, and trauma-related disorders. Extinction learning is the predominant theoretical framework for exposure therapy, whereby repeated disconfirmation of a feared outcome yields fear reduction over time. Although this framework has strong empirical support and substantial translational utility, extinction learning is unlikely to be the sole process underlying the therapeutic effects of exposure therapy. In our clinic, we commonly treat obsessive-compulsive disorder (OCD) patients successfully with exposure therapy even when some or all of their feared outcomes are not amenable to disconfirmation and, by extension, to extinction learning. Herein, we present a generic clinical vignette illustrating a commonly encountered feared outcome in OCD that cannot be disconfirmed through exposure (damnation resulting from blasphemous thoughts). We describe two specific non-extinction-based strategies we commonly employ in such cases, and we associate these strategies with known change mechanisms that might account for their effectiveness: (1) non-associative habituation to aversive stimuli, and (2) fear-memory elicitation and subsequent reconsolidation. We discuss the limitations inherent in the reverse-translational approach taken and its opportunities for expanding the framework of exposure therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Berg, Webler, Klein and Kushner.)

Objective: Studies have demonstrated that reduced drinking without total abstinence is associated with improved outcomes in outpatients with alcohol use disorder (AUD). We sought to examine this question in AUD inpatients who have comorbid anxiety disorders, a common presentation in AUD., Method: This is a secondary analysis of data from a randomized controlled trial for N = 241 inpatients with AUD and comorbid anxiety disorders. Change from baseline drinking level was measured at 1-, 4-, and 12-months postdischarge, and psychological and functional outcomes were measured at 4- and 12-months postdischarge. Three groups were compared: abstinent, reduced (reduced drinking by 1-3 World Health Organization drinking risk levels without abstinence), or nonreduced (maintained or increased drinking risk level)., Results: At 1-, 4-, and 12-months posttreatment, most patients reported abstinence (83, 63, and 60%), and 11, 25, and 26% reported drinking at a reduced level. Drinking reductions achieved at 1-month posttreatment were maintained at 12-month posttreatment by 74% of participants. Overall, the abstinent group reported the best psychological and functional outcomes at follow-ups, followed by the reduced group. Few differences were observed between reducers and nonreducers, but reducers reported significantly better alcohol dependence severity and alcohol-related problems than nonreducers., Conclusions: Though abstinence was associated with the best outcomes in this abstinence-based treatment sample, we conclude that reduced drinking is also associated with significant improvements in alcohol-related outcomes in inpatients with AUD and comorbid anxiety disorders.At 1-, 4-, and 12-months posttreatment, most patients reported abstinence (83, 63, and 60%), and 11, 25, and 26% reported drinking at a reduced level. Drinking reductions achieved at 1-month posttreatment were maintained at 12-month posttreatment by 74% of participants. Overall, the abstinent group reported the best psychological and functional outcomes at follow-ups, followed by the reduced group. Few differences were observed between reducers and nonreducers, but reducers reported significantly (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Internalizing (anxiety and mood) disorders (INTD) commonly co-occur (are "comorbid") with alcohol use disorder (AUD). The literature suggests that excessive alcohol use aimed at coping with INTD symptoms is, at best, a partial explanation for the high comorbidity rates observed. We hypothesized that individuals with INTD experience greater susceptibility to developing AUD symptoms due to the partially shared neurobiological dysfunctions underlying both conditions. We probe this hypothesis by testing the prediction that, after accounting for the volume of alcohol intake, individuals with INTD experience higher levels of alcohol-related symptoms., Methods: Data from the National Epidemiological Survey on Alcohol-Related Conditions (NESARC) Wave 3 were used for the primary analyses, and NESARC Wave 1 data were used for independent replication analyses. Individuals who reported any alcohol use in the prior year were categorized as: (1) never having had an INTD diagnosis ("INTD-Never"); (2) having a remitted INTD diagnosis only ("INTD-Remitted"); or (3) having current INTD diagnosis ("INTD-Current"). Between-group contrasts of alcohol-related symptoms controlled for total alcohol intake (past year), drinking pattern (e.g., binging) and variables previously shown to mark exaggerated AUD symptoms relative to drinking amount (e.g., SES, gender, and family history)., Results: With all covariates in the model, individuals in the INTD-Current group and the INTD-Remitted group reported significantly greater alcohol-related symptoms than those in the INTD-Never group but did not themselves differ in level of alcohol-related symptoms. These results were replicated in the NESARC 1 dataset., Conclusions: Individuals with INTD experience more alcohol-related symptoms than those who drink at the same level. While considering other explanations, we argue that this "harm paradox" is best explained by the view that INTD confers a neurobiologically mediated susceptibility to the development of AUD symptoms., (© 2023 The Authors. Alcohol: Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

Background: Drinking to cope with negative affect confers a direct risk of alcohol problems independently of greater alcohol consumption (i.e., confers susceptibility to the alcohol harm paradox). However, it remains unclear whether this risk is common across gender and countries., Methods: The current study applied path analysis to two cross-sectional samples of 18-25-year-old undergraduate hazardous drinking students recruited from the UK (Study 1; N = 873) and internationally (Study 2; N = 4064 recruited in Argentina, Canada, South Africa, Spain, Uruguay, USA, and England). The Drinking Motives Questionnaire (DMQ) measured drinking to cope with negative affect and drinking to enhance positive affect (i.e., enhancement motives). The Alcohol Use Disorders Identification Test (AUDIT) measured alcohol consumption and problems., Results: In both studies, drinking to cope with negative affect had a direct effect on alcohol problems (S1: β  = 0.259, SE = 0.031, p  <.001; S2: β  = 0.255, SE = 0.017, p  <.001), and only a negligible proportion of this effect was mediated by alcohol consumption (S1: 2.58 %, p  =.550; S2: 0.79 %, p= .538). By contrast, drinking to enhance positive affect had a smaller direct effect on alcohol problems (S1: β  = 0.000, SE = 0.033, p  =.989; S2: β  = 0.044, SE = 0.017, p  =.009), and a substantial proportion of this effect was mediated by greater alcohol consumption (S1: 99.76 %, p  <.001; S2: 60.36 %, p  <.001). Crucially, in both studies, the direct effect of drinking to cope on alcohol problems was invariant across gender and countries., Conclusions: These findings suggest that individuals who endorse drinking to cope with negative affect are uniquely susceptible to the alcohol harm paradox, that is, greater alcohol problems which cannot be explained by greater alcohol consumption, and this susceptibility is common across gender and countries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Ltd.)

Background: Ecological momentary assessment (EMA) studies have provided conflicting evidence for the mood regulation tenet that people drink in response to positive and negative moods. The current study examined mood-to-alcohol relationships idiographically to quantify the prevalence and intensity of relationships between positive and negative moods and drinking across individuals., Method: We used two EMA samples: 96 heavy drinking college students (sample 1) and 19 young adults completing an ecological momentary intervention (EMI) for drinking to cope (sample 2). Mood and alcohol use were measured multiple times per day for 4-6 weeks. Mood-alcohol relationships were examined using three different analytic approaches: standard multilevel modeling, group causal modeling, and idiographic causal modeling., Results: Both multilevel modeling and group causal modeling showed that participants in both samples drank in response to positive moods only. However, idiographic causal analyses revealed that only 63% and 21% of subjects (in samples 1 and 2, respectively) drank following any positive mood. Many subjects (24% and 58%) did not drink in response to either positive or negative mood in their daily lives, and very few (5% and 16%) drank in response to negative moods throughout the EMA protocol, despite sample 2 being selected specifically because they endorse drinking to cope with negative mood., Conclusion: Traditional group-level analyses and corresponding population-wide theories assume relative homogeneity within populations in mood-alcohol relationships, but this nomothetic approach failed to characterize accurately the relationship between mood and alcohol use in approximately half of the subjects in two samples that were demographically and clinically homogeneous. Given inconsistent findings in the mood-alcohol relationships to date, we conclude that idiographic causal analyses can provide a foundation for more accurate theories of mood and alcohol use. In addition, idiographic causal models may also help improve psychosocial treatments through direct use in clinical settings., (© 2022 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.)

Theoretical models of addiction suggest that alterations in addiction domains including incentive salience, negative emotionality, and executive control lead to relapse in alcohol use disorder (AUD). To determine whether the functional organization of neural networks underlying these domains predict subsequent relapse, we generated theoretically defined addiction networks. We collected resting functional magnetic resonance imaging data from 45 individuals with AUD during early abstinence (number of days abstinent M = 25.40, SD = 16.51) and calculated the degree of resting-state functional connectivity (RSFC) within these networks. Regression analyses determined whether the RSFC strength in domain-defined addiction networks measured during early abstinence predicted subsequent relapse (dichotomous or continuous relapse metrics). RSFC within each addiction network measured during early abstinence was significantly lower in those that relapsed (vs. abstained) and predicted subsequent time to relapse. Lower incentive salience RSFC during early abstinence increased the odds of relapsing. Neither RSFC in a control network nor clinical self-report measures predicted relapse. The association between low incentive salience RSFC and faster relapse highlights the need to design timely interventions that enhance RSFC in AUD individuals at risk of relapsing faster., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Socioeconomic deprivation is associated with greater alcohol problems despite lower alcohol consumption, but the mechanisms underpinning this alcohol harm paradox remain obscure. Fragmented published evidence collectively supports a multistage causal risk pathway wherein socioeconomic deprivation increases the probability of exposure to aversive experience, which promotes internalizing symptoms (depression and anxiety), which promotes drinking alcohol to cope with negative affect, which in turn accelerates the transition from alcohol use to dependence. To evaluate this proposed risk pathway, 219 hazardous drinkers from an undergraduate population completed questionnaires assessing these constructs in a single, cross sectional, online survey. Partial correlation coefficients revealed that each variable showed the strongest unique association with the next variable in the proposed multistage model, when adjusting for the other variables. Bootstrapped serial mediation analysis revealed that the indirect pathway linking all the variables in the proposed serial order was significant, while all other permutations were non-significant. Network centrality analysis corroborated the serial order of this indirect path. Finally, risk ratios estimated by categorizing the variables suggested that socioeconomic deprivation increased the risk of aversive experience by 32%, which increased the risk of internalizing symptoms by 180%, which increased the risk of drinking to cope by 64%, which increased susceptibility to alcohol dependence by 59%. These preliminary findings need to be corroborated by future research, nevertheless, they call for prevention strategies founded on social justice and the minimization of aversive experience in socially deprived individuals to mitigate mental health problems, maladaptive coping and addiction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shuai, Anker, Bravo, Kushner and Hogarth.)

This article describes the University of Minnesota Medical School Proposal Preparation Program (P3). P3 is designed to develop grant-writing skills for assistant professors preparing their first K- or R-series application to the National Institutes of Health (NIH). Three 4-month P3 cycles are conducted annually. For each cycle, a cohort of around 10 assistant professor participants and 5 regular faculty mentors meet for ten ~2-hour group sessions. Participants receive iterative oral and written feedback on their proposals in development within a small, interdisciplinary, group mentoring setting providing structure, accountability, guidance, and support. Between sessions, 1 peer and 1 mentor are assigned (on a rotating basis) to critique each participant's developing application. The sessions include a brief mentor-led presentation on a particular grant section followed by discussion of each participant's application conducted by the assigned reviewers. The cycle concludes with a mock NIH review session, in which each participant is matched with a University of Minnesota faculty content expert who critiques their completed application using NIH guidelines. In a survey sent to all past P3 participants as of 2018 (n = 194), 88% of respondents reported having submitted their P3-developed NIH grant, and 35% of these submitters reported funding success. A separate analysis of institutional data for all past P3 participants as of 2016 (n = 165) showed that 73% submitted at least 1 NIH proposal since completing P3 and that 43% of these had acquired NIH funding, for a combined total of $193 million in funding awarded. The estimated rate at which participants obtained funding for their P3-developed grant application (~35%) exceeds the national annual NIH grant funding rates (~20%) by approximately 50%. This article provides the practical information needed for other institutions to implement a P3-like program and presents a cost-benefit analysis showing the advantages of doing so., (Copyright © 2021 by the Association of American Medical Colleges.)

A substantial number of people who have problems with alcohol also experience strong anxiety and mood problems. This article provides an overview of the evolving perspectives of this association in the context of three related disciplines-psychiatry, psychology, and neuroscience. Psychiatric and epidemiological studies show that having either an anxiety- or alcohol-related diagnosis elevates the prospective risk for developing the other disorder. From the psychological perspective, behavioral research demonstrates that drinking to cope with negative affect is a potent marker for current and future problems with alcohol. Neuroscientific research implicates overlapping neurobiological systems and psychological processes in promoting the rise of negative affect and alcohol misuse. The psychiatric perspective that alcohol misuse and co-occurring anxiety represent neurobiologically distinct diagnostic conditions has dominated the field for many decades. However, recent research provides increasing support for the neuroscientific perspective that these conditions share underlying, mutually exacerbating, neurobiological processes., Competing Interests: Financial Disclosure The authors declare that they have no competing financial interests.

The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this "declining effect". We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Registration: The analysis plan for this manuscript was registered on Open Science Framework (https://osf.io/c39p8/)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to assess the potential of combining graph learning methods with latent variable estimation methods for mining clinically useful information from observational clinical data sets., Materials and Methods: The data set contained self-reported measures of psychopathology symptoms from a clinical sample receiving treatment for alcohol use disorder. We used the traditional graph learning methods: Graphical Least Absolute Shrinkage and Selection Operator, and Friedman's hill climbing algorithm; traditional latent variable estimation method factor analysis; recently developed graph learning method Greedy Fast Causal Inference; and recently developed latent variable estimation method Find One Factor Clusters. Methods were assessed qualitatively by the content of their findings., Results: Recently developed graphical methods identified potential latent variables (ie, not represented in the model) influencing particular scores. Recently developed latent effect estimation methods identified plausible cross-score loadings that were not found with factor analysis. A graphical analysis of individual items identified a mistake in wording on 1 questionnaire and provided further evidence that certain scores are not reflective of indirectly measured common causes., Discussion and Conclusion: Our findings suggest that a combination of Greedy Fast Causal Inference and Find One Factor Clusters can enhance the evidence-based information yield from psychopathological constructs and questionnaires. Traditional methods provided some of the same information but missed other important findings. These conclusions point the way toward more informative interrogations of existing and future data sets than are commonly employed at present., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Anxiety and depression disorders (internalizing psychopathology) occur in approximately 50% of patients with alcohol use disorder (AUD) and mark a 2-fold increase in the rate of relapse in the months following treatment. In a previous study using network modeling, we found that perceived stress and drinking to cope (DTC) with negative affect were central to maintaining network associations between internalizing psychopathology INTP and drinking in comorbid individuals. Here, we extend this approach to a causal framework., Methods: Measures of INTP, drinking urges/behavior, abstinence self-efficacy, and DTC were obtained from 362 adult AUD treatment patients who had a co-occurring anxiety disorder. Data were analyzed using a machine-learning algorithm ("Greedy Fast Causal Inference"[ GFCI]) that infers paths of causal influence while identifying potential influences associated with unmeasured ("latent") variables., Results: DTC with negative affect served as a central hub for 2 distinct causal paths leading to drinking behavior, (i) a direct syndromic pathway originating with social anxiety and (ii) an indirect stress pathway originating with perceived stress., Conclusions: Findings expand the field's knowledge of the paths of influence that lead from internalizing disorder to drinking in AUD as shown by the first application in psychopathology of a powerful network analysis algorithm (GFCI) to model these causal relationships., (© 2018 by the Research Society on Alcoholism.)

Research in the domain of psychopathology has been hindered by hidden variables-variables that are important to understanding and treating psychopathological illnesses but are unmeasured. Recent methodological advances in machine learning have culminated in the ability to discover and identify the influence of hidden variables that confound the observed relationships among measured variables. We apply a combination of traditional methods and more recent advances to a data set of alcohol use disorder patients with comorbid internalizing disorders, and find that the increasingly advanced methods produce increasingly informative and reliable results. These results include novel findings evaluated positively by our psychopathologists, as well as findings validated with knowledge from existing literature. We also find that advanced graph discovery methods can guide the use of latent variable modeling procedures, which can in turn explain the output of the graph discovery methods, resulting in a synergistic relationship between two seemingly distinct classes of methods.

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear., Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables., Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked., Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder., Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies., Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes., Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.

Internalizing disorders co-occur with alcohol use disorder (AUD) at a rate that exceeds chance and compromise conventional AUD treatment. The "vicious cycle" model of comorbidity specifies drinking to cope (DTC) as a link between these disorders that, when not directly addressed, undermines the effectiveness of conventional treatments. Interventions based on this model have proven successful but there is no direct evidence for how and to what extent DTC contributes to the maintenance of comorbidity. In the present study, we used network analysis to depict associations between syndrome-specific groupings of internalizing symptoms, alcohol craving, and drinking behavior, as well as DTC and other extradiagnostic variables specified in the vicious cycle model (e.g., perceived stress and coping self-efficacy). Network analyses of 362 individuals with comorbid anxiety and AUD assessed at the beginning of residential AUD treatment indicated that while internalizing conditions and drinking elements had only weak direct associations, they were strongly connected with DTC and perceived stress. Consistent with this, centrality indices showed that DTC ranked as the most central/important element in the network in terms of its "connectedness" to all other network elements. A series of model simulations-in which individual elements were statistically controlled for-demonstrated that DTC accounted for all the relationships between the drinking-related elements and internalizing elements in the network; no other variable had this effect. Taken together, our findings suggest that DTC may serve as a "keystone" process in maintaining comorbidity between internalizing disorders and AUD. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: Epidemiological studies and theory implicate drinking to cope (DTC) with anxiety as a potent moderator of the association between anxiety disorder (AnxD) and problematic alcohol use. However, the relevance of DTC to the treatment of alcohol use disorder (AUD) in those with a co-occurring AnxD has not been well studied. To address this, we examined whether DTC moderates the impact of two therapies: (1) a cognitive behavioral therapy (CBT) designed to reduce DTC and anxiety symptoms; (2) a progressive muscle relaxation training (PMRT) program designed to reduce anxiety symptoms only., Methods: Patients undergoing a standard AUD residential treatment with a co-occurring AnxD (N=218) were randomly assigned to also receive either the CBT or PMRT. DTC in the 30 days prior to treatment was measured using the Unpleasant Emotions subscale of the Inventory of Drinking Situations., Results: Confirming the predicted moderator model, the results indicated a significant interaction between treatment group and level of pre-treatment DTC behavior. Probing this interaction revealed that for those reporting more pre-treatment DTC behavior, 4-month alcohol outcomes were superior in the CBT group relative to the PMRT group. For those reporting less pre-treatment DTC behavior, however, 4-month alcohol outcomes were similar and relatively good in both treatment groups., Conclusions: These findings establish a meaningful clinical distinction among those with co-occurring AUD-AnxD based on the degree to which the symptoms of the two disorders are functionally linked through DTC. Those whose co-occurring AUD-AnxD is more versus less strongly linked via DTC are especially likely to benefit from standard AUD treatment that is augmented by a brief CBT designed to disrupt this functional link., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Recent studies using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) have found that some personality disorders (PDs) increase the persistence of several Axis I disorders. However, these effects are potentially confounded with the data collection wave in which PDs were assessed. Our aim was to extend published analyses to the case of anxiety disorders and to determine the robustness of the associations to analyses examining time-of-measurement effects. Persistence of anxiety disorders was defined either as follow-up diagnosis among participants diagnosed at baseline ("prediction") or baseline diagnosis among participants diagnosed at follow-up ("post-diction"). Results revealed a robust pattern of higher odds ratios for post-diction among PDs assessed at baseline, and lower odds ratios for post-diction among PDs assessed at follow-up, suggesting a time of measurement artifact. Although only 4% of associations were robust to both predictive and post-dictive analyses, these were consistent with previous research., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: As part of the 75th anniversary edition of the Journal of Studies on Alcohol and Drugs, this article reviews research on the relationship between mental disorders and substance use disorders ("comorbidity") from 1940--the journal's inception--to the present., Method: First, a survey of the titles and abstracts of all articles published in the journal was used to identify those articles pertaining to comorbidity. Seminal and representative works from this set of articles and a limited selection of articles from other journals were included in the review., Results: The early psychosocial research emphasized psychoanalytic formulations of alcohol use as a defensive symptom, which informed the early experimental research on the tension-reducing properties of alcohol. The "cognitive revolution," occurring in the 1970s, enabled an expansion of the tension-reduction theory to include a central role for mental processes (e.g., alcohol expectancies) in promoting drinking to cope with negative affectivity. The early clinical research characterized mental conditions commonly co-occurring with alcohol disorders and considered their etiological relationship to alcohol disorders. The "neo-Kraepelinian revolution" in psychiatry, which also occurred in the 1970s, infused the clinical comorbidity research with a more rigorous diagnostic technology and a range of biomedical research methodologies to study the mechanistic linkages of co-occurring disorders., Conclusions: Although a substantial quantity of scientific information on comorbidity has accumulated over the past 75 years, a standard model(s) of comorbidity has yet to congeal. Barriers and opportunities related to achieving this important goal are discussed.

Background: Clinical trials are typically designed to test the effect of a specific treatment on a single diagnostic entity. However, because common internalizing disorders are highly correlated ('co-morbid'), we sought to establish a practical and parsimonious method to characterize and quantify changes in a broad spectrum of internalizing psychopathology targeted for treatment in a clinical trial contrasting two transdiagnostic psychosocial interventions., Method: Alcohol dependence treatment patients who had any of several common internalizing disorders were randomized to a six-session cognitive-behavioral therapy (CBT) experimental treatment condition or a progressive muscle relaxation training (PMRT) comparison treatment condition. Internalizing psychopathology was characterized at baseline and 4 months following treatment in terms of the latent structure of six distinct internalizing symptom domain surveys., Results: Exploratory structural equation modeling (ESEM) identified a two-factor solution at both baseline and the 4-month follow-up: Distress (measures of depression, trait anxiety and worry) and Fear (measures of panic anxiety, social anxiety and agoraphobia). Although confirmatory factor analysis (CFA) demonstrated measurement invariance between the time-points, structural models showed that the latent means of Fear and Distress decreased substantially from baseline to follow-up for both groups, with a small but statistically significant advantage for the CBT group in terms of Distress (but not Fear) reduction., Conclusions: The approach demonstrated in this study provides a practical solution to modeling co-morbidity in a clinical trial and is consistent with converging evidence pointing to the dimensional structure of internalizing psychopathology.

Objective: Treatment for alcohol use disorder (AUD) is far less effective for those with a co-occurring anxiety disorder. Surprisingly, adding an independent anxiety treatment to AUD treatment does not substantially improve the poor alcohol outcomes of these patients. This may reflect the lack of attention from independent treatments to the dynamic interaction of anxiety symptoms with alcohol use and drinking motivation. On the basis of this view, we assembled a cognitive behavioral therapy (CBT) program designed to both reduce anxiety symptoms and weaken the links between the experience of anxiety and the motivation to drink., Method: 344 patients undergoing residential AUD treatment with current social phobia, generalized anxiety disorder, or panic disorder were randomly assigned to receive either the CBT or an active comparison treatment, progressive muscle relaxation training (PMRT). Assessments took place immediately following treatment and 4 months later (n = 247)., Results: As predicted, the CBT group demonstrated significantly better alcohol outcomes 4 months following treatment than did the PMRT group. Although both groups experienced a substantial degree of anxiety reduction following treatment, there were no significant group differences immediately after treatment and only a slight advantage for the CBT group 4 months after treatment., Conclusions: These findings suggest that specific interventions aimed at weakening the association between the experience of anxiety and drinking motivation play an important role in improving the alcohol outcomes of these difficult-to-treat patients beyond that of anxiety reduction alone.

Paroxetine alone is not sufficient to decrease alcohol use in socially anxious alcoholics seeking anxiety treatment. We tested the hypothesis that adding a brief-alcohol-intervention (BI) to paroxetine would decrease alcohol use. All subjects (N=83) had a diagnosis of social anxiety disorder, endorsed drinking to cope with anxiety, were NIAAA-defined at-risk drinkers, and were randomized to either paroxetine alone, or paroxetine plus BI. Both groups showed significant improvement in both social anxiety severity (F(5,83)=61.5, p<0.0001) and drinking to cope (e.g. F(4,79)=23, p<0.0001) and these two constructs correlated with each other (B=3.39, SE=0.696, t(71)=4.88, p<0.001). BI was not effective at decreasing alcohol use (e.g. no main effect of group, all p values >0.3). Paroxetine decreased social anxiety severity in the face of heavy drinking and decreasing the anxiety was related to a concurrent decrease in coping related drinking. BI was not effective at decreasing drinking or drinking to cope., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Recent work shows that the time from the initial use of nicotine, cannabis, and alcohol to the onset of dependence on these substances is shorter ("telescoped") in anxiety-disordered individuals. Previously, we hypothesized that telescoping may result from a shared neurobiology underlying both anxiety disorders and dependence. This hypothesis implies that telescoping occurs because individuals with an anxiety disorder transition to dependence with less overall drug exposure ("dependence susceptibility"). To investigate this further, we examined an estimate of the amount smoked (rather than the time transpired) from smoking initiation milestones to the onset of nicotine dependence in those with and without an anxiety disorder., Method: We used the subset of respondents in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Wave 1 who reported having smoked at least 100 cigarettes (N = 18,013). All data were based on face-to-face interviews., Results: Individuals with any anxiety disorder transitioned to nicotine dependence after smoking fewer total cigarettes than did individuals with no anxiety disorder. Furthermore, those with more than one anxiety disorder transitioned to nicotine dependence after smoking fewer cigarettes than did those with one anxiety disorder only. Several potentially confounding covariates were controlled for in these analyses., Conclusions: Dependence susceptibility is a novel concept with the potential to inform theoretical accounts of and prevention strategies for substance dependence among those with an anxiety disorder. In addition to nicotine, our theory and past data suggest that dependence susceptibility for other addictive substances (e.g., alcohol) also would be found among those with an anxiety disorder.

Although recognized for over 100 years, there is a relative dearth of empirical research on obsessive compulsive personality disorder (OCPD). The goal of the current study is to present nationally representative findings on prevalence, sociodemographic correlates, and comorbidity of OCPD among men and women. The current study uses nationally representative data to examine sociodemographic correlates and comorbidity of OCPD. Face-to-face interviews were conducted with 43,093 adults in the United States. The prevalence of lifetime OCPD was 7.8%, with rates the same for men and women. OCPD was significantly less common in younger adults and in Asians and Hispanics but was significantly more common in individuals with a high school education or less. When sociodemographic variables and other comorbidities were controlled for, current associations remained significant for all mood and anxiety disorders as well as lifetime personality disorders among both men and women. OCPD is a prevalent personality disorder in the US population and is equally represented in men and women. The results highlight the need for further research to identify common pathophysiological elements common to OCPD and associated disorders., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Alcohol dependence is more prevalent among those with any one of several anxiety or depressive ("internalizing") disorders than among those in the general population. However, because internalizing disorders are highly intercorrelated, it is ambiguous whether alcohol dependence is related to internalizing psychopathology components that are: (i) unique to a particular internalizing disorder ("specific"); versus (ii) shared across a number of internalizing disorders ("general"). To clarify this ambiguity, we employed structural equation and logistic models to decompose the specific versus general components of internalizing psychopathology and then related these components separately to alcohol dependence., Methods: The data were based on face-to-face interviews of U.S. community residents collected in the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 43,093)., Results: Both analytic approaches demonstrated that increases in the general internalizing psychopathology load are accompanied by increases in the prevalence of alcohol dependence. Once the general internalizing psychopathology load is accounted for, knowing whether a particular internalizing disorder is present or absent provides little additional information regarding the prevalence of alcohol dependence., Conclusions: The components of internalizing psychopathology that are associated with alcohol dependence are shared and cumulative among common anxiety and depressive disorders. These findings have the potential to influence clinical and scientific conceptualizations of the association between alcohol dependence and internalizing psychopathology., (Copyright © 2011 by the Research Society on Alcoholism.)

Objective: The frequent co-occurrence of alcohol dependence and anxiety disorder is a long-standing clinical conundrum. An underdeveloped perspective on this issue concerns the impact of a co-occurring anxiety disorder on the sequence and developmental course of alcohol-related milestones. Extrapolating from the body of basic science indicating overlap in the neurobiological processes associated with both anxiety disorder and alcohol dependence-particularly those involving the hypothalamic-pituitary-adrenal axis and elements of the amygdala- we hypothesized that anxiety-disordered individuals are vulnerable to the rapid development of alcohol dependence. Specifically, we predicted that the time from pre-dependence alcohol milestones (e.g., age at which regular drinking began) to post-dependence alcohol milestones would be briefer ("telescoped") among those with an anxiety disorder., Method: Seventy-eight individuals with alcohol dependence who had recently begun a chemical dependency treatment program underwent a diagnostic interview to determine the presence of current anxiety disorders and to establish the age at which several alcohol use and dependence milestones were first achieved., Results: We found that, compared with others in the sample, anxiety-disordered individuals transitioned significantly more quickly from the time they first began drinking regularly and first began getting drunk regularly to the onset of alcohol dependence, as well as from most pre-dependence alcohol milestones to the point at which their alcohol dependence was most severe., Conclusions: Individuals with anxiety disorders transition from regular drinking to alcohol dependence more rapidly than do individuals without anxiety disorders. These findings contribute to an improved understanding of the etiology of comorbidity and suggest novel directions for future research.

Approximately half of those receiving treatment for an alcohol use disorder (AUD) also suffer with an anxiety or depressive (internalizing) disorder. Because all internalizing disorders mark a poor alcohol treatment outcome, it seems reasonable to supplement AUD treatment with a psychiatric intervention when these disorders co-occur with AUD. However, this conclusion may be faulty given that the various possible interrelationships between AUD and internalizing disorders do not uniformly imply a high therapeutic yield from this approach. Unfortunately, the studies conducted to date have been too few and too small to resolve this important clinical issue with confidence. Therefore, we used a meta-analytic method to synthesize the effects from published randomized controlled trials examining the impact of supplementing AUD treatment with a psychiatric treatment for co-occurring internalizing disorder (N = 15). We found a pooled effect size (d) of .32 for internalizing outcomes and .22 for a composite of alcohol outcomes; however, the alcohol outcomes effect sizes were greater than this for some specific outcome domains. Subgroups that differed in terms of internalizing outcomes included treatment type (medication vs. cognitive behavioral therapy) and treatment focus (anxiety vs. depression). There was also a trend for the studies with better internalizing disorder outcomes to have better alcohol outcomes. These results indicate that clinical outcomes (both psychiatric and alcohol-related) could be somewhat improved by supplementing AUD treatment with psychiatric treatment for co-occurring internalizing disorder., (© American Academy of Addiction Psychiatry.)

Alcohol dependence (AD) is more likely to occur among individuals with rather than without an anxiety disorder. Self-medication theory (SMT) holds that drinking behavior is negatively reinforced when alcohol temporarily reduces anxiety and that the resulting escalation of drinking increases the risk for AD. We set out to empirically scrutinize SMT using the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) dataset. We found that only a minority (about 20%) of anxiety disordered individuals endorsed drinking to control anxiety symptoms. This minority drank more alcohol, had a higher cross-sectional rate of AD, and was at higher risk for developing new AD over four years compared to anxiety disordered non-self-medicators and individuals with no anxiety disorder. Consistent with SMT, increased prospective risk for AD among self-medicators is partially mediated by an increased level of alcohol use. Understanding the processes that promote and inhibit self-medication should be a priority for anxiety disorder researchers., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Anxiety disorders commonly co-occur with alcohol use disorders and reliably mark a poor response to substance abuse treatment. However, treating a co-occurring anxiety disorder does not reliably improve substance abuse treatment outcomes. Failure to account for individual differences in the functional dynamic between anxiety symptoms and drinking behavior might impede the progress and clarity of this research program. For example, while both theory and research point to the moderating role of tension-reduction alcohol outcome expectancies (TR-AOEs) in the association between anxiety symptoms and alcohol use, relevant treatment studies have not typically modeled TR-AOE effects. We examined the impact of a hybrid cognitive-behavioral therapy (H-CBT) treatment for panic disorder (independent variable) on response to a community-based alcohol dependence treatment program (dependent variable) in patients with higher vs. lower TR-AOEs (moderator). The H-CBT treatment was generally effective in relieving participants' panic symptoms relative to controls. However, TR-AOEs interacted with study cohort (H-CBT vs. control) in predicting response to substance abuse treatment. As expected, the H-CBT was most effective in improving alcohol use outcomes among those with the highest TR-AOEs. The study's primary methodological limitations are related to the quasi-experimental design employed.

Objective: Clinical practice and open-label studies suggest that quetiapine (an atypical anti-psychotic) might improve symptoms for individuals with social anxiety disorder (SAD). The purpose of this study was to provide a rigorous test of the acute impact of a single dose of quetiapine (25mg) on SAD symptoms., Method: Individuals with SAD (N=20) were exposed to a 4-min virtual reality (VR) public speaking challenge after having received quetiapine or placebo (double-blind) 1h earlier. A parallel VR challenge occurred 1 week later using a counter-balanced cross-over (within subject) design for the medication-placebo order between the two sessions., Result: There was no significant drug effect for quetiapine on the primary outcome measures. However, quetiapine was associated with significantly elevated heart rate and sleepiness compared with placebo., Conclusion: Study findings suggest that a single dose of 25mg quetiapine is not effective in alleviating SAD symptoms in individuals with fears of public speaking.

The feasibility of using virtual reality (VR) technology to induce a physiological response to stress was assessed in 12 volunteers during a laboratory session in which each participant completed a speech task within a VR environment and a math task outside the VR environment. Both tasks were effective in eliciting a physiological response with significant increases observed in response to each stress task in systolic and diastolic blood pressure and heart rate. Increases in plasma epinephrine and norepinephrine concentrations were observed during the speech task and in plasma epinephrine concentrations during the math task although these differences did not reach statistical significance. The use of VR technology may be a viable alternative to methods currently employed in presenting stressful tasks with the potential advantage of decreased variability in the audience response to the participants' performance.

Background: D-cycloserine (DCS), a glutamatergic partial N-methyl-d-aspartate (NMDA) agonist, can facilitate extinction learning related to cued fear in animals and humans. We predicted that DCS would accelerate obsession-related distress reduction in patients with obsessive-compulsive disorder (OCD) undergoing extinction-based exposure therapy., Methods: We administered DCS (125 mg) or placebo in a double-blind fashion to individuals with OCD approximately 2 hours before each exposure session., Results: D-cycloserine decreased both the number of exposure sessions required to achieve clinical milestones and the rate of therapy dropout. After four exposure sessions, patients in the DCS group reported significantly greater decreases in obsession-related distress compared with the placebo group; however, after additional sessions, the placebo group tended to catch up., Conclusions: D-cycloserine augmentation has the potential to increase the efficiency, palatability, and overall effectiveness of standard exposure therapy for OCD.

Cue-reactivity has received increased attention in addiction research, though not for gambling in particular. We examined cue reactivity in 18 problem gamblers by accompanying them to a gaming casino and measuring their subjective urge to gamble over a 1-h period. Half of the sample was additionally exposed to a gambling-specific negative mood induction (NMI) manipulation via guided imagery. Overall, about two-thirds of the sample reported moderate to high-gambling urges during the casino exposure. Additionally, the NMI reduced cue-reactivity. Finally, gambling urges in both groups decreased over the course of the exposure sessions. These findings suggest that a majority of problem gamblers experience the urge to gamble when exposed to gambling cues and that the intensity of these urges decrease with time, especially in the presence of a gambling-relevant NMI. Cue exposure should be studied further as a potential tool in the treatment of problem gambling.

Cognitive-behavioral therapy (CBT) refers to a group of therapeutic techniques that can be categorized broadly as psychoeducation, cognitive restructuring, and behavioral exposure. Unlike other psychotherapeutic approaches, CBT is derived from learning laboratory experimentation rather than conjecture and theorizing. This article provides background information concerning the origins and practice of cognitive and behavioral therapies and summarizes findings from a recently completed research project at the University of Minnesota that integrates new neuroscientific findings and CBT.

Objective: Findings showing that individuals with panic disorder (PD) are prone to experience panic attacks when inhaling CO2-enriched air have given rise to the hypothesis that physiological systems underlying the experience of suffocation may be important in the etiology of PD. In this study, we tested several predictions stemming from this view., Methods: Forty individuals with PD and 32 controls underwent both a breath-holding challenge and a CO2 rebreathing challenge. A wide array of physiological and psychological responses, including continuous measurements of subjective suffocation, was recorded., Results: Individuals with PD experienced elevated physiological reactivity to both challenges and greater levels of suffocation sensations during the rebreathing challenge. Furthermore, PD individuals who experienced a panic attack in response to the rebreathing challenge exhibited faster but shallower breathing during the challenge than did other PD individuals., Conclusion: Findings are consistent with theories linking PD to hypersensitive brain systems underlying the experience of suffocation. The possibility that subjective suffocation was in part mediated by peripheral interoceptive disturbances (vs. brainstem dysregulation) is discussed.

Recently researchers have posited a "respiratory" subtype of panic disorder (PD), which differs from "nonrespiratory" subtypes in phenomenology and perhaps treatment response. This study was designed to further examine evidence for the existence of a respiratory subtype in PD. Individuals with PD with prominent respiratory symptoms (PD-R; n=10) and without prominent respiratory symptoms (PD-NR; n=23), as well as healthy controls (n=27), underwent a standardized 5% CO(2) rebreathing challenge. Ventilatory response and subjective sensation of suffocation were continuously recorded. The PD-R group exhibited greater subjective suffocation levels, rates of respiration, and propensity to terminate the procedure voluntarily than did the other two groups, which in turn did not differ on these measures. Findings are consistent with the existence of a respiratory subtype of PD, which differs from nonrespiratory subtypes in CO(2) sensitivity., (Published 2006 Wiley-Liss, Inc.)

Recent research has made it clear that problematic gambling is often accompanied by problematic alcohol use. Unfortunately, little is known about the nature of this association, especially as it relates to gambling treatment outcome. The purpose of this study is to explore the effect of current alcohol use level and previous substance abuse treatment on the symptoms of a large cohort of pathological gamblers as well as on their response to treatment for pathological gambling. The sample included 464 men and 301 women recruited at six gambling treatment programs in Minnesota. Gambling treatment patients were assessed on a number of gambling problem severity and related clinical variables using the Gambling Treatment Outcome Monitoring System (GAMTOMS). Patients with frequent alcohol use had greater gambling involvement at baseline than infrequent alcohol users. Patients with a previous history of substance abuse treatment had more severe psychosocial problems, ostensibly resulting from their gambling behavior, than patients without past substance abuse treatment. A MANOVA with repeated measures showed that neither pretreatment alcohol use, nor past substance abuse treatment exerted significant effects on gambling treatment outcome. While the level of pretreatment alcohol use and a history of substance abuse treatment are markers for greater gambling problem severity, treatment outcome for pathological gambling was not adversely impacted by these variables.

It has long been recognized that gambling is an activity that is often combined with alcohol intake. Not only do the behaviors of drinking and gambling frequently co-occur, alcohol use disorders and pathological gambling are also commonly co-morbid conditions in both clinical and non-clinical samples. This article introduces a special issue of the Journal of Gambling Studies focusing on cutting edge findings on the relations between gambling and alcohol use behaviors and their associated disorders. We set the stage for the following series of six novel empirical papers and integrative commentary by reviewing the theoretical pathways through which alcohol use and gambling disorders may be linked. We conclude by describing some of the novel contributions of each of the empirical studies from within the context of these theoretical models.

Background: Anxiety disorders are present in a high percentage of alcoholism treatment patients. We tested the prediction that having a comorbid anxiety disorder increases the prospective risk for relapse to drinking after alcoholism treatment. We also explored the prospective associations of specific anxiety syndromes (and depression) with drinking and anxiety outcomes., Methods: We assessed the diagnostic status and daily drinking patterns of 82 individuals approximately one week after they entered alcoholism treatment (baseline) and again approximately 120 days later (follow-up) (n=53)., Results: Consistent with study predictions, those with a baseline anxiety disorder (approximately 55%) were significantly more likely than others to meet various definitions of drinking relapse over the course of the follow-up. Regression models showed that baseline social phobia was the single best predictor of a return to any drinking after treatment, whereas panic disorder was the single best predictor of a relapse to alcohol dependence after treatment. Having multiple anxiety disorders (versus any specific anxiety disorder) at the baseline was the strongest predictor of having at least one active ("persistent") anxiety disorder at the follow-up. Cross-sectional analysis at the follow-up showed that anxiety disorder persisted in the absence of a relapse to alcohol dependence far more often than relapse to alcohol dependence occurred in the absence of a persistent anxiety disorder., Conclusions: Screening for comorbid anxiety disorder in alcoholism treatment patients is warranted and, where found, should be considered a marker of high relapse risk relative to that of noncomorbid patients. The capacity of specific anxiety treatment to mitigate relapse risk among comorbid patients remains an open question.

Background: Depression and anxiety are common disorders and have substantially overlapping symptom complexes. Not surprisingly, treatment approaches are similar for both conditions with the selective serotonin reuptake inhibitors (SSRIs) as the initial therapy of choice. However, after first line treatments have been deployed, residual symptoms are often problematic. Augmentation strategies to address these difficulties are an area of active investigation. This study assessed aripiprazole as adjunctive therapy to SSRIs for patients with persistent anxiety symptoms complicating a depression or anxiety disorder., Methods: Ten patients who had been receiving SSRIs for at least 6 weeks, but still had clinically significant anxiety symptoms, were enrolled in an open label, flexibly-dosed study of adjunctive aripiprazole. Clinical status was assessed with the Hamilton Anxiety Rating Scale (HAM-A), Montgomery Asberg Rating Scale (MADRS), and Sheehan Disability Scale (SDS)., Results: Eighty percent of the subjects had a greater than 50% reduction of symptoms on these outcome measures by week 2 of therapy, and continued with further decrements in symptoms throughout the course of the study., Conclusions: The results of this trial provide preliminary evidence that aripiprazole may be an effective adjunctive treatment in individuals on SSRIs with residual symptoms of anxiety or depression. More rigorous double-blind studies are warranted to confirm and elucidate the potential role of aripiprazole in these conditions.

We conjectured that individual differences in tension-reduction alcohol outcome expectancies (TR-AOEs) could produce widely varying responses to manipulations in alcohol-placebo studies and tested this idea by having individuals with social phobia give speeches in front of a group. One speech occurred before and one after participants consumed either a placebo beverage or a control beverage (i.e., a nonalcoholic drink described as containing no alcohol). Study results indicate that the placebo manipulation reduced cognitive and affective symptoms of anxiety to a greater extent for males with high TR-AOEs than for males with low TR-AOEs. This pattern was not found for women in the placebo group or for individuals in the control group. These findings demonstrate a moderating effect of TR-AOEs on the association between the consumption of a placebo beverage and response to an anxiety challenge and highlight the importance of accounting for gender and outcome expectancies when evaluating psychoactive substances.

Alcohol, administered acutely, is known to cause CO(2) hyposensitivity. CO(2) hypersensitivity associated with anxiogenic hyperventilation (HV) could reasonably be expected to emerge as an opponent process upon withdrawal from chronic alcohol use. To test this hypothesis, we applied two well-known methods to quantify CO(2) sensitivity in recently detoxified alcohol-dependent individuals and never alcohol-disordered individuals who are social drinkers. We found that the alcoholic group exhibited significantly greater CO(2) sensitivity than did controls in response to both challenges. Indirect evidence of chronic HV was also obtained. These findings implicate the effect of chronic alcohol use on CNS-based CO(2) sensitivity in heightening the vulnerability to disturbing anxiety symptoms and syndromes exhibited by alcoholic individuals. Future work must verify that pathological drinking actually causes the dysregulated respiratory responding observed in this study as is inferred in our conclusions.

Treatment of depression and anxiety disorders with selective serotonin reuptake inhibitors (SSRIs) has been shown by numerous studies to be generally effective. Less well understood is how clinically to address the residual anxiety symptoms a significant minority of such patients treated with SSRIs continue to experience. We assessed quetiapine as adjunctive therapy to SSRIs for patients with anxiety symptoms complicating a depressive or anxiety disorder. Patients receiving a stable dosage of an SSRI for at least 6 weeks who also had persistent anxiety symptoms (Hamilton Anxiety scale [HAM-A] > or =16), were enrolled in a 9-week, open-label, variable dose study. Changes in clinical status were assessed with the Hamilton Depression Rating Scale (HAM-D), HAM-A, and State Anxiety Inventory (SAI). Statistically and clinically significant reductions of > or =50% in the HAM-D and HAM-A occurred by the second week of treatment in 10 of the 11 patients. These improvements continued throughout the study along with a significant improvement on the SAI scale. The most frequent side effects reported were mild dry mouth, constipation, and transient drowsiness with dose escalation. The results provide evidence that quetiapine may be an effective adjunctive treatment for recalcitrant anxiety symptoms in individuals treated with SSRIs for either anxiety or depressive disorders. Given the open-label design of the trial, more rigorous studies are clearly indicated., (Copyright 200 Wiley-Liss, Inc.)

Evidence of an increased risk for various psychiatric disorders among pathological gamblers far exceeds our understanding of the impact that this psychiatric comorbidity has on the outcome of treatment for pathological gambling. One major source of the problem is that treatment efficacy and effectiveness studies for pathological gambling typically have not addressed comorbidity's impact on outcome. This paper discusses epidemiological, clinical, health service delivery, and research issues pertaining to the intersection of pathological gambling treatment outcome and comorbid psychiatric disorders. It is argued that this topic suffers from major knowledge gaps in terms of the nature of comorbidity of pathological gambling and other psychiatric disorders and the role of client characteristics on treatment outcome for pathological gambling. Research priorities are identified.

Objective: To identify predictors of treatment response to 8 weeks of cognitive-behavioral therapy (CBT) among anxious-depressed adolescents with school refusal, half of whom received imipramine plus CBT and half of whom received placebo plus CBT., Method: A hierarchical multiple regression analysis was used to evaluate the following variables as potential predictors of treatment response as measured by school attendance at the end of treatment: baseline severity (school attendance at baseline), drug group (imipramine versus placebo), presence of separation anxiety disorder (SAD), and presence of avoidant disorder (AD)., Results: Baseline attendance, CBT plus imipramine, SAD, and AD were significant predictors of treatment response and accounted for 51% of the variance in outcome. Specifically, a higher rate of attendance at baseline and receiving imipramine predicted a better response to treatment whereas the presence of SAD and AD predicted a poorer response to treatment. The relationship between sociodemographic variables and treatment outcome was also evaluated. Age and socioeconomic status were unrelated to school attendance after treatment. Males had significantly higher rates of attendance after treatment than females., Conclusions: Adolescents with school refusal are a heterogeneous population and require individualized treatment planning. Variables such as diagnosis and severity at the start of treatment should be taken into consideration when planning treatment.

The carbon dioxide (CO(2)) challenge paradigm has been useful for modeling panic in the laboratory. While showing promise as a technique able to promote a better understanding of the etiology of panic disorder (PD), this goal has been impeded by the lack of standardization of the challenge methodology and by uncertainty concerning the optimal definition and assessment of laboratory panic. The purpose of this paper is to highlight the impact of method variance on laboratory findings and to present recommendations for future challenge research. We begin by reviewing studies that have employed CO(2) as a stimulus for panic provocation focusing on the status of key methodological parameters between the studies and the relationship of these parameters to findings. We then make pragmatic and theoretically-based recommendations concerning approaches to methodological standardization, the establishment of a valid laboratory panic definition and the desirability of using of additional outcome measures. We conclude that although further work is needed to improve the CO(2) challenge laboratory model of panic, this paradigm can play an important role in understanding the psychopathology of PD.