Abnormal intestinal milieu in posttraumatic stress disorder is not impacted by treatment that improves symptoms.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder, resulting from exposure to traumatic events. Current recommended first-line interventions for the treatment of PTSD include evidence-based psychotherapies, such as cognitive processing therapy (CPT). Psychotherapies are effective for reducing PTSD symptoms, but approximately two-thirds of veterans continue to meet diagnostic criteria for PTSD after treatment, suggesting there is an incomplete understanding of what factors sustain PTSD. The intestine can influence the brain and this study evaluated intestinal readouts in subjects with PTSD. Serum samples from controls without PTSD (n = 40) from the Duke INTRuST Program were compared with serum samples from veterans with PTSD (n = 40) recruited from the Road Home Program at Rush University Medical Center. Assessments included microbial metabolites, intestinal barrier, and intestinal epithelial cell function. In addition, intestinal readouts were assessed in subjects with PTSD before and after a 3-wk CPT-based intensive treatment program (ITP) to understand if treatment impacts the intestine. Compared with controls, veterans with PTSD had a proinflammatory intestinal environment including lower levels of microbiota-derived metabolites, such as acetic, lactic, and succinic acid, intestinal barrier dysfunction [lipopolysaccharide (LPS) and LPS-binding protein], an increase in HMGB1, and a concurrent increase in the number of intestinal epithelial cell-derived extracellular vesicles. The ITP improved PTSD symptoms but no changes in intestinal outcomes were noted. This study confirms the intestine is abnormal in subjects with PTSD and suggests that effective treatment of PTSD does not alter intestinal readouts. Targeting beneficial changes in the intestine may be an approach to enhance existing PTSD treatments.NEW & NOTEWORTHY This study confirms an abnormal intestinal environment is present in subjects with PTSD. This study adds to what is already known by examining the intestinal barrier and evaluating the relationship between intestinal readouts and PTSD symptoms and is the first to report the impact of PTSD treatment (which improves symptoms) on intestinal readouts. This study suggests that targeting the intestine as an adjunct approach could improve the treatment of PTSD.

Protocol for a multi-site randomized controlled trial of a stepped-care intervention for emergency department patients with panic-related anxiety.

BACKGROUND: Approximately 40% of Emergency Department (ED) patients with chest pain meet diagnostic criteria for panic-related anxiety, but only 1-2% are correctly diagnosed and appropriately managed in the ED. A stepped-care model, which focuses on providing evidence-based interventions in a resource-efficient manner, is the state-of-the art for treating panic disorder patients in medical settings such as primary care. Stepped-care has yet to be tested in the ED setting, which is the first point of contact with the healthcare system for most patients with panic symptoms. METHODS: This multi-site randomized controlled trial (RCT) aims to evaluate the clinical, patient-centred, and economic effectiveness of a stepped-care intervention in a sample of 212 patients with panic-related anxiety presenting to the ED of Singapore's largest public healthcare group. Participants will be randomly assigned to either: 1) an enhanced care arm consisting of a stepped-care intervention for panic-related anxiety; or 2) a control arm consisting of screening for panic attacks and panic disorder. Screening will be followed by baseline assessments and blocked randomization in a 1:1 ratio. Masked follow-up assessments will be conducted at 1, 3, 6, and 12 months. Clinical outcomes will be panic symptom severity and rates of panic disorder. Patient-centred outcomes will be health-related quality of life, daily functioning, psychiatric comorbidity, and health services utilization. Economic effectiveness outcomes will be the incremental cost-effectiveness ratio of the stepped-care intervention relative to screening alone. DISCUSSION: This trial will examine the impact of early intervention for patients with panic-related anxiety in the ED setting. The results will be used to propose a clinically-meaningful and cost-effective model of care for ED patients with panic-related anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT03632356. Retrospectively registered 15 August 2018.

Sleep quality and outcome of exposure therapy in adults with social anxiety disorder.

INTRODUCTION: Poor sleep is prevalent among individuals with social anxiety disorder (SAD) and may negatively affect exposure therapy outcomes. Poor sleep may impair memory and learning, and thus compromise fear extinction learning thought to take place in exposure therapy. We examined poor sleep as a predictor of exposure therapy outcomes for SAD and the moderating role of d-cycloserine (DCS) on this relationship. METHODS: Participants were 152 individuals with a primary diagnosis of SAD. As part of a randomized clinical trial evaluating the efficacy of DCS for enhancing the effects of exposure therapy, they completed self-report baseline measure of sleep quality, and self-report sleep diaries assessing sleep duration (total sleep time [TST]) and sleep quality the nights before and after treatment sessions. RESULTS: Poorer baseline sleep quality was significantly associated with slower improvement over time and worse symptom outcomes at the end of treatment and follow-up after controlling for baseline symptoms of depression and social anxiety. Greater TST the night before treatment predicted lower SAD symptoms at the next session, after controlling for symptoms at the previous session. There was no relation between prior or subsequent night sleep quality on symptoms at the next session. No associations were moderated by DCS. CONCLUSIONS: We replicated and extended findings indicating that poor sleep quality is associated with poorer exposure therapy outcomes for SAD. Assessing for sleep difficulties before treatment initiation and incorporating sleep interventions into treatment may enhance exposure therapy outcomes for SAD.

Examining Insomnia During Intensive Treatment for Veterans with Posttraumatic Stress Disorder: Does it Improve and Does it Predict Treatment Outcomes?

Previous research has demonstrated that sleep disturbances show little improvement with evidence-based psychotherapy for posttraumatic stress disorder (PTSD); however, sleep improvements are associated with PTSD treatment outcomes. The goal of the current study was to evaluate changes in self-reported insomnia symptoms and the association between insomnia symptoms and treatment outcome during a 3-week intensive treatment program (ITP) for veterans with PTSD that integrated cognitive processing therapy (CPT), mindfulness, yoga, and other ancillary services. As part of standard clinical procedures, veterans (N = 165) completed self-report assessments of insomnia symptoms at pre- and posttreatment as well as self-report assessments of PTSD and depression symptoms approximately every other day during treatment. Most veterans reported at least moderate difficulties with insomnia at both pretreatment (83.0%-95.1%) and posttreatment (69.1-71.3%). Statistically significant reductions in self-reported insomnia severity occurred from pretreatment to posttreatment; however, the effect size was small, d = 0.33. Longitudinal mixed-effects models showed a significant interactive effect of Changes in Insomnia × Time in predicting PTSD and depression symptoms, indicating that patients with more improvements in insomnia had more positive treatment outcomes. These findings suggest that many veterans continued to struggle with sleep disruption after a 3-week ITP, and successful efforts to improve sleep could lead to better PTSD treatment outcomes. Further research is needed to establish how adjunctive sleep interventions can be used to maximize both sleep and PTSD outcomes.

A Case Report of Cognitive Processing Therapy Delivered over a Single Week.

Although evidence-based treatments for posttraumatic stress disorder (PTSD), such as Cognitive Processing Therapy (CPT), have been developed and widely disseminated, the rate of veterans engaging in and completing these therapies is low. Alternative methods of delivery may be needed to help overcome key barriers to treatment. Delivering evidence-based therapies intensively may address practical barriers to treatment attendance as well as problems with avoidance. This report details the case of a combat veteran who received 10 sessions of Cognitive Processing Therapy delivered twice per day over a single, five-day work week (CPT-5). Post-treatment, the veteran reported large and clinically meaningful decreases in PTSD and depression symptom severity as well as in guilt cognitions, which is a purported mechanism of successful treatment. These effects persisted six weeks after treatment ended. Despite the intensive nature of the treatment, the veteran found CPT-5 tolerable and could cite many benefits to completing therapy in one work week. In conclusion, CPT-5 holds promise as a way to efficiently deliver an evidence-based therapy that is both clinically effective and acceptable to patients, although more rigorous clinical trials are needed to test this treatment delivery format.

A placebo-controlled pilot study of a wearable morning bright light treatment for probable PTSD.

BACKGROUND: Evidence-based treatments for post-traumatic stress disorder (PTSD) have poor uptake and remission rates, suggesting that alternative treatments are needed. Morning bright light may be an effective treatment for PTSD given its established effects on mood and sleep, however, there are no published trials. METHODS: We conducted a placebo-controlled pilot trial of a wearable light device, the Re-timer®, for individuals with probable PTSD. Individuals were randomly assigned to the active Re-timer® (n = 9) or a placebo Re-timer® dimmed with neutral density filters (n = 6). Participants self-administered the treatment at home 1 hr each morning over 4 weeks. PTSD and depression symptoms were assessed at pre- and post-treatment. RESULTS: The Re-timer® was well tolerated and the perceived benefit was high, though treatment adherence was only moderate. Those in the active group were more likely to achieve a minimal clinically important change in PTSD and depression symptoms and had larger symptom reductions than those in the placebo group CONCLUSIONS: A wearable morning light treatment was acceptable and feasible for patients with probable PTSD. This study provides initial proof-of-concept that light treatment can improve PTSD. A larger trial is warranted to establish treatment efficacy. NCT#: 03513848.

An Open Trial of Morning Bright Light Treatment Among US Military Veterans with Chronic Low Back Pain: A Pilot Study.

OBJECTIVE: To examine the feasibility, acceptability, and effects of a home-based morning bright light treatment on pain, mood, sleep, and circadian timing in US veterans with chronic low back pain. DESIGN: An open treatment trial with a seven-day baseline, followed by 13 days of a one-hour morning bright light treatment self-administered at home. Pain, pain sensitivity, mood, sleep, and circadian timing were assessed before, during, and after treatment. SETTING: Participants slept at home, with weekly study visits and home saliva collections. PARTICIPANTS: Thirty-seven US veterans with medically verified chronic low back pain. METHODS: Pain, mood, and sleep quality were assessed with questionnaires. Pain sensitivity was assessed using two laboratory tasks: a heat stimulus and an ischemia stimulus that gave measures of threshold and tolerance. Sleep was objectively assessed with wrist actigraphy. Circadian timing was assessed with the dim light melatonin onset. RESULTS: Morning bright light treatment led to reduced pain intensity, pain behavior, thermal pain threshold sensitivity, post-traumatic stress disorder symptoms, and improved sleep quality (P < 0.05). Phase advances in circadian timing were associated with reductions in pain interference (r = 0.55, P < 0.05). CONCLUSIONS: Morning bright light treatment is a feasible and acceptable treatment for US veterans with chronic low back pain. Those who undergo morning bright light treatment may show improvements in pain, pain sensitivity, and sleep. Advances in circadian timing may be one mechanism by which morning bright light reduces pain. Morning bright light treatment should be further explored as an innovative treatment for chronic pain conditions.

Evaluating patterns and predictors of symptom change during a three-week intensive outpatient treatment for veterans with PTSD.

BACKGROUND: Intensive delivery of evidence-based treatment for posttraumatic stress disorder (PTSD) is becoming increasingly popular for overcoming barriers to treatment for veterans. Understanding how and for whom these intensive treatments work is critical for optimizing their dissemination. The goals of the current study were to evaluate patterns of PTSD and depression symptom change over the course of a 3-week cohort-based intensive outpatient program (IOP) for veterans with PTSD, examine changes in posttraumatic cognitions as a predictor of treatment response, and determine whether patterns of treatment outcome or predictors of treatment outcome differed by sex and cohort type (combat versus military sexual trauma [MST]). METHOD: One-hundred ninety-one veterans (19 cohorts: 12 combat-PTSD cohorts, 7 MST-PTSD cohorts) completed a 3-week intensive outpatient program for PTSD comprised of daily group and individual Cognitive Processing Therapy (CPT), mindfulness, yoga, and psychoeducation. Measures of PTSD symptoms, depression symptoms, and posttraumatic cognitions were collected before the intervention, after the intervention, and approximately every other day during the intervention. RESULTS: Pre-post analyses for completers (N = 176; 92.1% of sample) revealed large reductions in PTSD (d = 1.12 for past month symptoms and d = 1.40 for past week symptoms) and depression symptoms (d = 1.04 for past 2 weeks). Combat cohorts saw a greater reduction in PTSD symptoms over time relative to MST cohorts. Reduction in posttraumatic cognitions over time significantly predicted decreases in PTSD and depression symptom scores, which remained robust to adjustment for autocorrelation. CONCLUSION: Intensive treatment programs are a promising approach for delivering evidence-based interventions to produce rapid treatment response and high rates of retention. Reductions in posttraumatic cognitions appear to be an important predictor of response to intensive treatment. Further research is needed to explore differences in intensive treatment response for veterans with combat exposure versus MST.

Examining the Relationship Between Parent and Child Psychopathology in Treatment-Seeking Veterans.

This study aimed to examine: (1) the relationship between parental psychopathology and child psychopathology in military families and (2) parenting sense of competence as a mediator of the relationship between veteran psychopathology and child psychopathology. As part of their standard clinical evaluations, 215 treatment-seeking veterans who reported having a child between the ages of 4 and 17 were assessed for psychopathology (posttraumatic stress disorder, depression, anxiety, and stress), their sense of competence as a parent, and their child's psychopathology (internalizing, externalizing, and attentional symptoms). A path analysis model examining parenting sense of competence as a mediator of the relationship between veteran psychopathology and child psychopathology showed significant indirect effects of veteran depression on all child psychopathology outcomes via parenting sense of competence. Parental sense of competence may be a critical mechanism linking veteran depression and child psychopathology, and may therefore be an important target for intervention.

Negative Posttrauma Cognitions Mediate the Association Between Morally Injurious Events and Trauma-Related Psychopathology in Treatment-Seeking Veterans.

Exposure to potentially morally injurious events has been shown to be associated with posttraumatic stress disorder (PTSD) and depression symptoms in military personnel. Few studies have examined factors that help to explain how potentially morally injurious events may contribute to the development of trauma-related psychopathology. Negative posttrauma cognitions are thought to play a role in the etiology of PTSD and depression following trauma; however, it is unclear whether more global beliefs about the self, others, and world play a role in the development of PTSD and depression due to morally injurious events. Using structural equation modeling, we tested whether morally injurious experiences were indirectly related to trauma-related psychopathology (PTSD and depression) through negative posttrauma cognitions in a sample of veterans seeking treatment for PTSD. An indirect effects only model best fit the data and showed that morally injurious experiences, specifically perceived transgressions by oneself and perceived betrayal, were indirectly associated with trauma-related psychopathology through negative posttrauma cognitions, ß = .17; 95% CI [.04, .31] and ß = .25; 95% CI [.11, .41], respectively. Our findings suggest that negative posttrauma cognitions may be an important mechanism linking exposure to morally injurious events and trauma-related psychopathology.

RANDOMIZED TRIAL OF D-CYCLOSERINE ENHANCEMENT OF COGNITIVE-BEHAVIORAL THERAPY FOR PANIC DISORDER.

BACKGROUND: Initial studies have provided a mixed perspective of the efficacy of d-cycloserine (DCS) for augmenting the efficacy of exposure-based cognitive behavioral therapy (CBT) for panic disorder. In this multicenter trial, we examine the magnitude of DCS augmentation effects for an ultra-brief program of CBT. METHODS: We conducted a double-blind, controlled trial at three treatment sites, randomizing 180 adults with a primary diagnosis of panic disorder to five sessions of treatment, with study pill (50 mg DCS or matching placebo) administered 1 hr prior to the final three sessions. Two booster sessions were subsequently provided, and outcome was assessed at posttreatment and 1-month, 2-month, and 6-month follow-up assessments. The primary outcome was the degree of reduction in the Panic Disorder Severity Scale. Additional analyses examined the role of severity and current antidepressant or benzodiazepine use as moderators of DCS augmentation effects. RESULTS: DCS augmentation resulted in significant benefit only early in the trial, with no beneficial effects of DCS augmentation evident at follow-up evaluations. We did not find that baseline severity or antidepressant or benzodiazepine use moderated DCS efficacy, but benzodiazepine use was associated with lower efficacy of CBT regardless of augmentation condition. CONCLUSIONS: Consistent with other recent multicenter trials, the benefit of DCS was less than indicated by pilot study and reflected an acceleration of treatment response evident at treatment endpoint, but no advantage in response over follow-up evaluation. Our results did not support severity or concomitant medication moderators observed in previous trials of DCS augmentation.

A Pilot Study of Tailored Cognitive-Behavioral Resilience Training for Trauma Survivors With Subthreshold Distress.

This pilot study evaluated the feasibility, acceptability, and preliminary effectiveness of tailored cognitive-behavioral resilience training (TCBRT) for trauma-exposed individuals with a variety of subsyndromal psychological symptoms. TCBRT is a brief, flexible intervention that allows individuals to select the areas they wish to target using common cognitive-behavioral change principles. There were 14 individuals (78.6% female) who were recruited from a major medical center and enrolled in the 5-session intervention. There were 12 (85.7%) who completed all TCBRT sessions, and 2 (14.3%) who dropped out after 3 sessions. All participants reported that they received benefit from, were engaged in, and were satisfied with the intervention. Of the 12 with postintervention data, 5 of the participants demonstrated reliable increases in resilience and 6 demonstrated reliable decreases in anxiety. These improvements appeared to be maintained at 2-month follow-up; of the 11 participants with follow-up data, 5 demonstrated reliable increases in resilience and 6 demonstrated reliable decreases in anxiety. Our findings suggested that TCRBT was acceptable to trauma-exposed individuals with varying types of subthreshold distress.

D-cycloserine augmentation of cognitive behavioral therapy for anxiety disorders: an update.

Although cognitive behavioral therapy (CBT) is a generally effective treatment for treating anxiety disorders, there is clearly still room for further improvements. Recent advances in neuroscience of extinction learning led to novel clinical strategies to augment exposure-based treatments with d-cycloserine (DCS), a partial agonist at the glycine recognition site of the glutamatergic N-methyl-D-aspartate receptor. This review provides an update on the current knowledge of DCS as an augmentation strategy of CBT for anxiety disorders. The adequacy of the CBT to be augmented, the dose of DCS, and the timing and duration of augmentation efforts all appear to be important moderating variables. Moreover, there is evidence that DCS may also augment fear memory reconsolidation if the fear level remains high after the exposure. Future studies need to examine whether DCS can augment CBT when administered after exposure in order to develop a tailored administration strategy to maximize its clinical utility.

ADULT ANXIETY DISORDERS IN RELATION TO TRAIT ANXIETY AND PERCEIVED STRESS IN CHILDHOOD.

It is well established that objective early life stressors increase risk for anxiety disorders and that environmental stressors interact with dispositional factors such as trait anxiety. There is less information on how subjective perception of stress during childhood relates to later clinical anxiety. This study tested whether childhood perceived stress and trait anxiety were independently and interactively associated with adult anxiety disorders. Forty-seven adults diagnosed with anxiety disorders (M age = 34 yr., SD = 11) and 29 healthy participants (M = 33 yr., SD = 13) completed the adult Perceived Stress Scale, the State-Trait Anxiety Inventory, and the Global Perceived Early Life Events Scale as a measure of perceived stress during childhood. In a logistic regression model, high childhood perceived stress (ß = 0.64) and trait anxiety (ß = 0.11) were associated with significantly greater odds of adult anxiety disorder. The association between childhood perceived stress and adult anxiety remained significant when controlling for adult perceived stress. These findings suggest that children's perception of stress in their daily lives may be an important target of intervention to prevent the progression of stress into clinically significant anxiety.

Cortico-limbic responses to masked affective faces across ptsd, panic disorder, and specific phobia.

BACKGROUND: Exaggerated amygdala and reduced ventromedial prefrontal cortex (vmPFC) responsiveness during emotional processing have been reported in studies examining individual anxiety disorders. Studies are needed, however, which directly compare activation of amygdalo-cortical circuitry across multiple anxiety disorders within the same study. Here we compared cortico-limbic neurocircuitry across three different anxiety disorders using a well-validated emotional probe task. METHODS: Sixty-five adult volunteers, including 22 healthy controls (HC) and participants meeting DSM-IV criteria for either posttraumatic stress disorder (14 PTSD), panic disorder (14 PD), or specific animal phobia (15 SP), underwent functional magnetic resonance imaging (fMRI) at 3 T while passively viewing backward-masked images of faces expressing fear, happy, and neutral emotions. RESULTS: A group comprising all three anxiety disorders showed greater activation within the left amygdala and reduced activation within the vmPFC compared to the HC group during the masked fear versus neutral condition. Pairwise group comparisons showed that amygdala activation only reached significance for the PTSD versus HCs, whereas decreased vmPFC was only evident for SP and PD groups versus the HC group. Furthermore, activation did not differ among the anxiety groups when contrasted directly with one another. A similar pattern was observed for masked happy versus neutral faces. CONCLUSIONS: Exclusive of specific diagnostic category, anxiety disorders were generally associated with increased activation of the amygdala and reduced activation within vmPFC. Categorical distinctions were generally weak or not observed and suggest that functional differences may reflect the magnitude of responses within a common neurocircuitry across disorders rather than activation of distinct systems.

A randomized, controlled trial of the efficacy of an interoceptive exposure-based CBT for treatment-refractory outpatients with opioid dependence.

Many patients diagnosed with opioid dependence do not adequately respond to pharmacologic, psychosocial, or combination treatment, highlighting the importance of novel treatment strategies for this population. The current study examined the efficacy of a novel behavioral treatment focusing on internal cues for drug use (Cognitive Behavioral Therapy for Interoceptive Cues; CBT-IC) relative to an active comparison condition, Individual Drug Counseling (IDC), when added to methadone maintenance treatment (MMT) among those who had not responded to MMT. Participants (N=78) were randomly assigned to receive 15 sessions of CBT-IC or IDC as an adjunct to ongoing MMT and counseling. Oral toxicology screens were the primary outcome. Results indicated no treatment differences between CBT-IC and IDC and a small, significant reduction of self-reported drug use, but no change on toxicology screens. Tests of potential moderators, including sex, anxiety sensitivity, and coping motives for drug use, did not yield significant interactions. Among opioid-dependent outpatients who have not responded to MMT and counseling, the addition of IDC or CBT-IC did not result in additive outcome benefits. These results highlight the need for more potent treatment strategies for opioid dependence, particularly among those who do not fully respond to frontline treatment.

Brain derived neurotrophic factor and treatment outcomes among veterans attending an intensive treatment program for posttraumatic stress disorder.

Brain derived neurotrophic factor (BDNF) may play an important role in the success of treatment for posttraumatic stress disorder (PTSD). Pre- and post-treatment blood samples were analyzed for 40 veterans who completed a 3-week intensive outpatient treatment for PTSD. The treatment included Cognitive Processing Therapy, mindfulness, and yoga as core treatment components. PTSD symptoms were assessed at pre-treatment, post-treatment, and 3-month follow-up. Participants reported large decreases in PTSD symptoms from pre-to post-treatment (d = 1.46, p < 0.001) and pre-treatment to 3-month follow-up (d = 0.91, p < 0.001). Unexpectedly, participants demonstrated a decrease in BDNF from pre-to post-treatment (d = 0.64, p < 0.001). Changes in BDNF from pre-to post-treatment were not significantly associated with PTSD symptom improvement. However, higher levels of post-treatment BDNF were significantly associated with lower PTSD symptoms at 3-month follow-up (n = 27, r = -0.57, p = 0.002) and greater improvements in PTSD symptoms from pre-treatment to 3-month follow-up (n = 27, r = 0.50, p = 0.008). Higher levels of post-treatment BDNF may facilitate the long-term success of intensive PTSD treatment. Further research with larger samples is needed to evaluate the processes by which BDNF may affect consolidation of improvements after completion of PTSD treatment.

Loving-Kindness Meditation practice associated with longer telomeres in women.

Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p=.083); among women, the LKM practitioners had significantly longer RTL than controls, (p=.007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity.

Sleep quality predicts treatment outcome in CBT for social anxiety disorder.

BACKGROUND: Sleep quality may be an important, yet relatively neglected, predictor of treatment outcome in cognitive-behavioral therapy (CBT) for anxiety disorders. Specifically, poor sleep quality may impair memory consolidation of in-session extinction learning. We therefore examined sleep quality as a predictor of treatment outcome in CBT for social anxiety disorder and the impact of d-cycloserine (DCS) on this relationship. METHODS: One hundred sixty-nine participants with a primary diagnosis of DSM-IV generalized social anxiety disorder were recruited across three sites. Participants were enrolled in 12 weeks of group CBT. Participants randomly received 50 mg of DCS (n = 87) or pill placebo (n = 82) 1 hr prior to sessions 3-7. Participants completed a baseline measure of self-reported sleep quality and daily diaries recording subjective feelings of being rested upon wakening. Outcome measures including social anxiety symptoms and global severity scores were assessed at each session. RESULTS: Poorer baseline sleep quality was associated with slower improvement and higher posttreatment social anxiety symptom and severity scores. Moreover, patients who felt more "rested" after sleeping the night following a treatment session had lower levels of symptoms and global severity at the next session, controlling for their symptoms and severity scores the previous session. Neither of these effects were moderated by DCS condition. CONCLUSIONS: Our findings suggest that poor sleep quality diminishes the effects of CBT for social anxiety disorder and this relation is not attenuated by DCS administration. Therapeutic attention to sleep quality prior to initiation of CBT and during the acute treatment phase may be clinically indicated.

Two weeks of pretreatment with escitalopram facilitates extinction learning in healthy individuals.

OBJECTIVE: We aimed to examine whether pretreatment with escitalopram would be associated with reduced fear acquisition and enhanced extinction learning in a fear conditioning paradigm, compared with placebo. METHODS: Healthy volunteers were randomized in double-blind fashion, to 14 days of escitalopram 10 mg/day (n = 18) or placebo (n = 20) prior to a classical fear conditioning paradigm. RESULTS: Although escitalopram was associated with a smaller skin conductance (SC) orienting response during habituation, no medication effects on fear acquisition were found. Escitalopram was associated with faster extinction of SC responses, compared with placebo, as revealed by a significant drug × conditioned stimulus × trial interaction for early extinction (F(3, 30) = 3.26, p = 0.035) and late extinction (F(3, 30) = 3.27, p = 0.035) trials. After adjustment for age, orienting response, and acquisition, results from linear contrast remained significant for early extinction (F(1, 29) = 5.43, p = 0.027). CONCLUSIONS: Escitalopram administered for 14 days prior to a fear conditioning paradigm did not influence acquisition of a conditioned fear response but did facilitate extinction learning. Impairments in extinction learning have been identified as a key component of posttraumatic stress disorder; our preliminary findings suggest that additional experimental and clinical studies assessing the efficacy of selective serotonin reuptake inhibitors for posttraumatic stress disorder prevention are warranted.