Depression Severity Moderates Reward Learning Among Smokers with Current or Past Major Depressive Disorder in a Smoking Cessation Randomized Clinical Trial.

INTRODUCTION: Behavioral and pharmacological smoking cessation treatments are hypothesized to increase patients' reward learning to reduce craving. Identifying changes in reward learning processes that support effective tobacco dependence interventions among smokers who experience depression may guide patients towards efficient treatment strategies. The objective was to investigate the extent to which adult daily cigarette smokers with current or past major depressive disorder (MDD) learned to seek reward during 12 weeks of treatment combining behavioral activation and varenicline. We hypothesized that a decline in reward learning would be attenuated (least to most) in the following order: 1) Behavioral activation integrated with ST (BASC) + varenicline, 2) BASC + placebo, 3) Standard behavioral cessation treatment (ST) + varenicline, 4) ST + placebo. METHODS: We ran a Phase 4, placebo-controlled, randomized clinical trial with 300 participants receiving 12 weeks of one of four conditions across two urban medical centers. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI). Reward learning was ascertained at Weeks 1, 7, and 14 using the Probabilistic Reward Task (PRT), a laboratory task that uses an asymmetric reinforcement schedule to assess (a) learning to seek reward (response bias), (b) differentiate between stimuli, and (c) time to react to cues. RESULTS: There was a significant interaction of BDI group x PRT response bias. Response bias declined from Week 7 to 14 among participants with high baseline depression symptoms. The other two BDI groups showed no change in response bias. CONCLUSIONS: Controlling for baseline depression, participants showed a decrease in response bias from Week 1 to 14, and from Weeks 7 to 14. Treatment condition and abstinence status were unassociated with change in reward learning. IMPLICATIONS: Smokers who report greater depression severity show a decline in reward learning despite their participation in smoking cessation treatments, suggesting that depressed populations pose unique challenges with standard smoking cessation approaches.

Treatment-related changes in insomnia, anticipatory pleasure, and depression symptoms: A proof-of-concept study with cancer survivors.

OBJECTIVE/BACKGROUND: Cancer survivors have elevated rates of insomnia and depression. Insomnia increases risk for depression onset, and the Integrated Sleep and Reward (ISR) Model suggests that impairments in reward responding (e.g., ability to anticipate and/or experience pleasure) plays a central role in this relationship. Cognitive behavioral therapy for insomnia (CBT-I) is efficacious for treating chronic insomnia and reducing depression in cancer survivor populations. The effects of CBT-I on anticipatory and consummatory pleasure are theoretically and clinically meaningful, yet remain unexamined. PATIENTS/METHODS: This secondary analysis of a pilot RCT (N = 40 cancer survivors with insomnia) explicated changes in anticipatory and consummatory pleasure and depression symptoms following a 4-session, synchronous, virtual CBT-I program versus enhanced usual care (referral to a behavioral sleep medicine clinic + sleep hygiene handout). Linear mixed models examined changes in anticipatory and consummatory pleasure and depression symptoms as predictors of changes in insomnia severity from baseline to post-intervention and 1-month follow-up. RESULTS: CBT-I buffered against deterioration in anticipatory pleasure but not consummatory pleasure or depression symptoms. Across conditions, increased anticipatory pleasure was associated with insomnia reduction through 1-month follow-up, even after adjusting for changes in depression symptoms. CONCLUSION: CBT-I may improve reward processing deficits in cancer survivors with insomnia. Findings provide support for the ISR Model and implicate pleasure as an important target for insomnia and depression.

An evaluation of the construct validity of the Adult Rejection Sensitivity Questionnaire.

Rejection sensitivity (RS), the predisposition to defensively expect, readily perceive, and react strongly to interpersonal rejection (Downey & Feldman, 1996; Feldman & Downey, 1994), may be a transdiagnostic trait associated with a range of psychiatric symptoms and psychosocial dysfunction. Valid and reliable assessment of vulnerability factors is essential for individualized treatment and improving clinical outcomes. Limited research has examined the factor structure of the predominantly used self-report measure of RS, the Adult Rejection Sensitivity Questionnaire (A-RSQ; Berenson et al., 2009). Across two studies (Study 1: N = 346, 57.2% female, 76.6% White; 16.8% Hispanic/Latinx; Study 2: N = 540; 43.7% female, 80.2% White; 16.7% Hispanic/Latinx), we examined the factor structure of the A-RSQ in samples of adult U.S. residents and investigated associations with mental health correlates, including neuroticism, social anxiety, anxiety, depression, anhedonia, somatic arousal, and psychological distress. Study 2 also evaluated relations with interpersonal correlates, including introversion, submissiveness, and anxious and avoidant attachment. A two-factor solution with rejection expectancy and rejection concern representing separate factors consistently fit the data best. Distinct patterns of associations emerged suggesting that concern was more strongly associated with indicators of negative affect while expectancy was uniquely associated with diminished positive affect. Both concern and expectancy were associated with indicators of interpersonal dysfunction. Findings suggest that the current operationalization, and perhaps conceptualization, of RS as measured by the A-RSQ requires revision. Additionally, RS may be a clinically relevant transdiagnostic phenotype that influences symptom manifestation and psychosocial functioning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effects of the COVID-19 pandemic on anhedonia, reward exposure and responsiveness, and sleep in college students.

Objective: The COVID-19 pandemic's effects on college student mental health and its underlying mechanisms are not fully understood. Although necessary, physical distancing abruptly restricts interaction with environmental rewards and disrupts sleep patterns, both of which may contribute to psychological symptoms (eg, depression and anhedonia). This study explored differences in psychological symptoms, reward exposure and responsiveness, and sleep before versus during the pandemic. Methods: Eighty-seven college students completed baseline questionnaires and a one-week daily diary paradigm. The sample was divided into two groups based on data collection before (pre-) or after (post-COVID-19) implementation of state-wide COVID-19 physical distancing measures. Results: Findings highlight higher anhedonia, decrements in exposure to social, professional, and exercise related rewards, lower aniticipatory reward responsiveness, and lower sleep efficiency among college students during the initial months of the pandemic. Conclusions: Findings suggest anhedonia, reward system functioning, and sleep may be important targets to mitigate against college student mental health sequelae during COVID-19.

Relationships Among Sleep Disturbance, Reward System Functioning, Anhedonia, and Depressive Symptoms.

Recent models propose reward system dysfunction as a key mediator of the relationship between sleep and depression and anhedonia. This study explored interrelationships among sleep disturbance, depressive symptoms, anhedonia, and reward responsiveness. Two-hundred and sixty undergraduate students completed questionnaires and a daily diary paradigm assessing sleep, reward responsiveness, depression, anhedonia, and positive affect over 1 week. Baseline sleep disturbance was associated with depressive symptoms, anhedonia, and reward responsiveness. Daily diary sleep parameters showed differential associations with anticipatory versus consummatory reward responsiveness and positive affect. Poorer sleep quality, shorter sleep duration, and longer awakening after sleep onset predicted blunted anticipatory and consummatory reward responsiveness, while increased sleep onset latency and lower sleep efficiency predicted only decreased consummatory reward responsiveness. All sleep indices, except sleep onset latency, were associated with positive affect. Findings demonstrate unique associations between disparate sleep disturbance and reward responsiveness elements, highlighting new treatment mechanisms for anhedonia and depression.

Social anxiety, rejection sensitivity, and theory of mind decoding ability.

OBJECTIVES: Recent initiatives have highlighted the importance of investigating clinically relevant variations in social processes that contribute to mental illness. Surprisingly little research has examined the associations between socially and clinically relevant transdiagnostic factors, such as social anxity (SA) and rejection sensitvity (RS), on theory of mind (ToM) decoding ability. METHODS: The Reading the Mind in the Eyes Task and self-report measures of SA and RS were completed by 199 adult participants. RESULTS: Linear regression analyses suggest a specific difficulty decoding positive emotion associated with SA and global decrements in ToM associated with RS that may reflect a negative interpretation bias. CONCLUSIONS: These findings may have important implications for understanding how those with SA and RS perceive and navigate social interactions, which may contribute to the maintenance of symptoms and decreased psychosocial functioning.

Suppression and acceptance in unipolar depression: Short-term and long-term effects on emotional responding.

OBJECTIVES: Transdiagnostic treatments increasingly include emotion regulation training focused on use of emotional suppression and acceptance. Despite the frequent use of these treatments in depression, little is known about the effects of these strategies in this population. DESIGN: An experimental study. METHODS: Eighty Veterans with unipolar depression participated in a study examining effects of these strategies on emotional responding (subjective, behavioural, and physiological). Physiological measures included: heart rate (HR), respiration (Resp), skin conductance (SC), and corrugator electromyography. On Day 1, participants were randomised to one of three conditions (acceptance, suppression, or control) and underwent an autobiographical sad mood induction. On Day 2, participants underwent a similar mood induction one week later. RESULTS: The suppression group demonstrated reduced physiological reactivity (Resp and SC) on Day 1. However, the suppression group reported decreased positive affect on Day 2. CONCLUSIONS: Results support short-term effectiveness and longer term costs from suppression use among depressed individuals. Findings may inform application of transdiagnostic emotion regulation treatments and suggest suppression functions differently in depressed versus other clinical populations.

Associations between insomnia and reward learning in clinical depression.

BACKGROUND: Depression and insomnia commonly co-occur. Yet, little is known about the mechanisms through which insomnia influences depression. Recent research and theory highlight reward system dysfunction as a potential mediator of the relationship between insomnia and depression. This study is the first to examine the impact of insomnia on reward learning, a key component of reward system functioning, in clinical depression. METHODS: The sample consisted of 72 veterans with unipolar depression who endorsed sleep disturbance symptoms. Participants completed the Structured Clinical Interview for DSM-IV, self-report measures of insomnia, depression, and reward processing, and a previously validated signal detection task (Pizzagalli et al., 2005, Biological Psychiatry, 57(4), 319-327). Trial-by-trial response bias (RB) estimates calculated for each of the 200 task trials were examined using linear mixed-model analyses to investigate change in reward learning. RESULTS: Findings demonstrated diminished rate and magnitude of reward learning in the Insomnia group relative to the Hypersomnia/Mixed Symptom group across the task. Within the Insomnia group, participants with more severe insomnia evidenced the lowest rates of reward learning, with increased RB across the task with decreasing insomnia severity. CONCLUSIONS: Among individuals with depression, insomnia is associated with decreased ability to learn associations between neutral stimuli and rewarding outcomes and/or modify behavior in response to differential receipt of reward. This attenuated reward learning may contribute to clinically meaningful decreases in motivation and increased withdrawal in this comorbid group. Results extend existing theory by highlighting impairments in reward learning specifically as a potential mediator of the association between insomnia and depression.

Learning gains from a one-day training in acceptance-based behavior therapy.

The primary method of training for individual licensed mental health professionals is continuing education (CE). Despite the promise of CE as a vehicle for training clinicians in evidence-based practices, only a handful of studies have examined the efficacy of trainings delivered in the CE context. Moreover, these studies have focused on a few very specific therapeutic approaches. There is a growing body of evidence supporting Acceptance-based Behavior Therapy (ABBT) as a treatment for generalized anxiety disorder (GAD) and related disorders. Training workshops aimed at disseminating ABBT are regularly conducted across and outside the United States, yet the effectiveness of these trainings is unknown. The goal of this study was to examine learning outcomes among licensed mental health professionals following a six-hour CE training in ABBT. Data were collected at baseline, post-training, and at three-month follow-up. Participants demonstrated a statistically significant increase in learning on an ABBT Knowledge Questionnaire and in their coded responses to client scenarios from baseline to follow-up, although there was a significant decline in knowledge between post and follow-up. Beyond baseline ABBT knowledge, attitude towards evidence-based practice was the only predictor of change in knowledge over time.

A randomized controlled pilot study evaluating Worry Less, Live More: The Mindful Way Through Anxiety Workbook.

Effective interventions for generalized anxiety exist, but barriers to treatment prevent their broad dissemination. Commercially available self-help materials may help bridge this gap, but few have been empirically evaluated. This study compared self-reported change in generalized anxiety symptomology and associated problems between community members with excessive worry who were randomly assigned to receive the Worry Less, Live More: The Mindful Way through Anxiety Workbook (n = 35) and those in a delayed condition (n = 29). Participants in the workbook condition reported significantly greater reductions between baseline and 11-week follow-up in self-reported worry (η2 =.15), general anxiety/tension (η2 =.13), and anxiety (η2 =.24) than those in the delayed condition, although no statistically significant differences across condition on changes in depression, functional impairment or acceptance were detected. This pilot study provides support for continued research examining the efficacy of acceptance-based behavioral therapy delivered in a self-help format.

Results from the Field: Development and Evaluation of a Psychiatry Residency Training Rotation in Cognitive-Behavioral Therapies.

OBJECTIVE: The goal of this project was to develop and evaluate a new residency training rotation focused on cognitive-behavioral therapies (CBT) and to assess outcomes across multiple domains. METHODS: Data are presented from 30 psychiatry residents. Primary learning-related outcomes included content knowledge, self-efficacy, and attitudes and behavioral intentions towards evidence-based psychotherapies (e.g., CBT). RESULTS: Residents reported significant increases in CBT knowledge, CBT-specific self-efficacy, overall psychotherapy self-efficacy, belief in patient benefit from CBT, and behavioral intention to use CBT. However, there were almost no changes in attitudes towards evidence-based practice more broadly, with one significant finding showing an increase in skepticism towards such practices. CONCLUSIONS: This empirically based example of training program development, implementation, and evaluation appears largely successful and represents one approach for addressing the CBT competency goals outlined by the Accreditation Council for Graduate Medical Education (ACGME) and Milestone Project Guidelines. Despite these initial, positive findings, conclusions should be tempered by limitations of the project design (e.g., the lack of comparison group, absence of objective measures of resident behavioral change, or assessment of the effect of such changes on patient outcomes). Findings highlight the need for continued development and evaluation of training methods in CBT for residency programs.

Associations Among Posttraumatic Stress Disorder Symptoms, Substance Use, and Affective Attentional Processing in OEF/OIF/OND Veterans.

The majority of research examining affective attentional bias in posttraumatic stress disorder (PTSD) has not examined the influence of co-occurring psychiatric disorders. This study examined the individual and interactive effects of PTSD symptoms and substance use disorders (SUDs) on affective attentional processing among 323 veterans deployed to Iraq or Afghanistan. Participants were divided into those with SUD (SUD+, n = 46) and those without (SUD-, n = 277). Substance use disorder was determined using the Structured Clinical Interview for DSM-IV. Posttraumatic stress disorder was measured using the Clinician Administered PTSD Scale. A computerized go/no-go task (Robbins et al., 1994, Robbins et al.,1998) assessed affective attentional processing. Relative to those without SUD, those with SUD showed a significant association between PTSD symptoms and increased omission and commission accuracy rates and decreased d prime. No effects of valence were found. Findings suggest the need to consider co-occurring SUD when investigating the effects of PTSD on attentional control.

Punishment Learning in U.S. Veterans With Posttraumatic Stress Disorder.

Learning processes have been implicated in the development and course of posttraumatic stress disorder (PTSD); however, little is currently known about punishment-based learning in PTSD. The current study investigated impairments in punishment-based learning in U.S. veterans. We expected that veterans with PTSD would demonstrate greater punishment-based learning compared to a non-PTSD control group. We compared a PTSD group with and without co-occurring depression (n = 27) to a control group (with and without trauma exposure) without PTSD or depression (n = 29). Participants completed a computerized probabilistic punishment-based learning task. Compared to the non-PTSD control group, veterans with PTSD showed significantly greater punishment-based learning. Specifically, there was a significant Block × Group interaction, F(1, 54) = 4.12, p = .047, η(2) = .07. Veterans with PTSD demonstrated greater change in response bias for responding toward a less frequently punished stimulus across blocks. The observed hypersensitivity to punishment in individuals with PTSD may contribute to avoidant responses that are not specific to trauma cues.

Associations among smoking, anhedonia, and reward learning in depression.

Depression and cigarette smoking co-occur at high rates. However, the etiological mechanisms that contribute to this relationship remain unclear. Anhedonia and associated impairments in reward learning are key features of depression, which also have been linked to the onset and maintenance of cigarette smoking. However, few studies have investigated differences in anhedonia and reward learning among depressed smokers and depressed nonsmokers. The goal of this study was to examine putative differences in anhedonia and reward learning in depressed smokers (n=36) and depressed nonsmokers (n=44). To this end, participants completed self-report measures of anhedonia and behavioral activation (BAS reward responsiveness scores) and as well as a probabilistic reward task rooted in signal detection theory, which measures reward learning (Pizzagalli, Jahn, & O'Shea, 2005). When considering self-report measures, depressed smokers reported higher trait anhedonia and reduced BAS reward responsiveness scores compared to depressed nonsmokers. In contrast to self-report measures, nicotine-satiated depressed smokers demonstrated greater acquisition of reward-based learning compared to depressed nonsmokers as indexed by the probabilistic reward task. Findings may point to a potential mechanism underlying the frequent co-occurrence of smoking and depression. These results highlight the importance of continued investigation of the role of anhedonia and reward system functioning in the co-occurrence of depression and nicotine abuse. Results also may support the use of treatments targeting reward learning (e.g., behavioral activation) to enhance smoking cessation among individuals with depression.

PTSD and reasons for living: associations with depressive symptoms and alcohol use.

Posttraumatic stress disorder (PTSD) is associated with suicidal ideation and behavior, and is found to frequently co-occur with other conditions that exacerbate the risk for suicidal behavior. Despite these findings, few individuals with PTSD engage in suicidal acts, and there has been little research to examine those factors that protect against such behaviors. The current study used path analysis to examine the association among PTSD, depression, hazardous alcohol consumption, and beliefs about suicide (i.e., reasons for living) in a community sample with motor vehicle accident related-PTSD (N=50). Reasons for living were inversely associated with PTSD, depression, and alcohol use. Further, depression symptom severity accounted for the association between PTSD symptom severity and reasons for living. In contrast, hazardous alcohol consumption only demonstrated a trend for accounting for the association between PTSD and reasons for living. Our findings highlight the importance of clinicians assessing co-occurring depression symptoms and suggest the potential use of interventions that promote adaptive cognitions about suicide among people with PTSD.

Psychophysiologic reactivity, subjective distress, and their associations with PTSD diagnosis.

Intense subjective distress and physiologic reactivity upon exposure to reminders of the traumatic event are each diagnostic features of posttraumatic stress disorder (PTSD). However, subjective reports and psychophysiological data often suggest different conclusions. For the present study, we combined data from five previous studies to assess the contributions of these two types of measures in predicting PTSD diagnosis. One hundred fifty trauma-exposed participants who were classified into PTSD or non-PTSD groups based on structured diagnostic interviews completed the same script-driven imagery procedure, which quantified measures of psychophysiologic reactivity and self-reported emotional responses. We derived four discriminant functions (DiscFxs) that each maximally separated the PTSD from the non-PTSD group using (1) psychophysiologic measures recorded during personal mental imagery of the traumatic event; (2) self-report ratings in response to the trauma imagery; (3) psychophysiologic measures recorded during personal mental imagery of another highly stressful experience unrelated to the index traumatic event; and (4) self-report ratings in response to this other stressor. When PTSD status was simultaneously regressed on all four DiscFxs, trauma-related psychophysiological reactivity was a significant predictor, but physiological reactivity resulting from the highly stressful, but not traumatic script, was not. Self-reported distress to the traumatic experience and the other stressful event were both predictive of PTSD diagnosis. Trauma-related psychophysiologic reactivity was the best predictor of PTSD diagnosis, but self-reported distress contributed additional variance. These results are discussed in relation to the Research Domain Criteria framework.

Association between smoking and heart rate variability among individuals with depression.

BACKGROUND: Both depression and smoking have been independently associated with lower heart rate variability (HRV), suggesting dysregulation of cardiac autonomic function. However, no studies have systematically explored the effects of smoking on HRV among depressed patients. PURPOSE: This study examined differences in HRV based on smoking status among depressed individuals. METHODS: Electrophysiological data were examined among 77 adult outpatients without a history of myocardial infarction, who met criteria for major depressive disorder or dysthymia. Frequency domain [low frequency (LF), high frequency (HF), LF/HF ratio, respiratory sinus arrhythmia (RSA)] parameters of HRV, and heart rate and inter-beat interval (IBI) data were compared between depressed smokers (n = 34) and depressed nonsmokers (n = 44). RESULTS: After controlling for covariates, depressed smokers, compared to depressed nonsmokers, displayed significantly lower LF, HF, and RSA. CONCLUSIONS: Among depressed patients, smoking is associated with significantly lower HRV, indicating dysregulated autonomic modulation of the heart.

Changes in posttraumatic stress disorder and depressive symptoms during cognitive processing therapy: evidence for concurrent change.

OBJECTIVE: Trauma-focused psychotherapies reduce both posttraumatic stress disorder (PTSD) and co-occurring depression. However, little is known about the relationship between changes in PTSD and depression during treatment. This study examined the association between changes in PTSD and depression during the course of cognitive processing therapy (CPT) and its treatment components. METHOD: Data were drawn from a dismantling trial investigating the comparative efficacy of the components of CPT (Resick, Galovski, et al., 2008). One hundred twenty-six women (mean age = 36.14 years) from the original randomized intent-to-treat sample (N = 150) who attended at least 1 treatment session were included in this study. Participants diagnosed with PTSD were assigned to 1 of 3 treatment conditions: the full CPT protocol (n = 44), the cognitive therapy component of CPT (n = 39), and the written account component of CPT (n = 43). The majority of the sample self-identified as Caucasian (67%; 29% African American and 4% Other). Primary outcome measures included the Posttraumatic Diagnostic Scale and Beck Depression Inventory-II, administered at 8 time points (baseline, weekly throughout 6 weeks of treatment, and posttreatment). RESULTS: Multilevel regression analyses were conducted to examine relationships between PTSD and depression during treatment. Results indicated that changes in PTSD and depression were strongly related. Multilevel mediation analyses revealed that changes in PTSD and depression occurred concurrently, with lagged analyses providing no evidence that changes in symptoms of 1 disorder preceded changes in the other. CONCLUSIONS: Results suggest that changes in PTSD and depression occur contemporaneously during CPT.

The relationship between reward-based learning and nicotine dependence in smokers with schizophrenia.

Cigarette smoking rates remain remarkably high in schizophrenia relative to smoking in other psychiatric groups. Impairments in the reward system may be related to elevated rates of nicotine dependence and lower cessation rates in this psychiatric group. Smokers with schizophrenia and schizoaffective disorder (SWS; n=15; M(age)=54.87, S.D.=6.51, 100% male) and a non-psychiatric control group of smokers (NCL; n=16; M(age)=50.38, S.D.=11.52; 93.8% male) were administered a computerized signal detection task to measure reward-based learning. Performance on the signal detection task was assessed by response bias, discriminability, reaction time, and hit rate. Clinician-assessed and self-reported measures of smoking and psychiatric symptoms were completed. SWS exhibited similar patterns of reward-based learning compared to control smokers. However, decreased reward-based learning was associated with increased levels of nicotine dependence in SWS, but not among control smokers. Nicotine withdrawal and urge to smoke were correlated with anhedonia within the SWS group. Among SWS, reduced reward responsiveness and increased anhedonia were associated with and may contribute to greater co-occurring nicotine dependence. These findings emphasize the importance of targeting reward system functioning in smoking cessation treatment for individuals with schizophrenia.

Generalized anxiety disorder within the course of major depressive disorder: examining the utility of the DSM-IV hierarchy rule.

BACKGROUND: The current Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) specifies that generalized anxiety disorder (GAD) should not be diagnosed if it occurs exclusively during an episode of a major depressive disorder (MDD) or another mood disorder. This hierarchy rule was intended to promote diagnostic parsimony, but may result in the loss of important clinical information. The goal of this study was to compare individuals with MDD, comorbid MDD and GAD, and GAD within the course of MDD at intake and 12-month follow-up on self-report measures, clinician ratings, and rates of comorbidity. METHODS: Participants were divided into three diagnostic groups: MDD without GAD (n=124), comorbid MDD and GAD (n=59), and GAD within the course of MDD (n=166). All the participants completed a semi-structured clinical interview and self-report measures assessing psychopathology, temperament, and functional impairment. A subset of the total sample completed a follow-up assessment of 12 months postintake. RESULTS: Individuals with comorbid MDD and GAD and GAD within the course of MDD reported more psychopathology, negative affect, and functional impairment at intake than individuals with MDD only. The presence of GAD at intake, however, did not differentially predict symptom severity, functional impairment, or the presence of comorbidity at 12-month follow-up. CONCLUSIONS: Cross-sectional findings indicate that individuals with GAD within the course of MDD experience levels of psychopathology, functional impairment, and comorbidity similar to those found in individuals with comorbid GAD and MDD. Preliminary longitudinal findings, however, suggest that the presence of GAD in patients with MDD does not have prognostic significance.