The effect of perceived life stress on posttraumatic stress disorder treatment outcome.

Life stress following trauma exposure is a consistent predictor of the development of posttraumatic stress disorder (PTSD). However, there is a dearth of research on the effect of life stress on PTSD treatment outcomes. The current study examined the effects of pretreatment levels of perceived life stress on treatment outcome in a sample of 200 individuals with PTSD who were randomized to receive either prolonged exposure (PE) therapy or sertraline as part of a clinical trial. Life stress over the year prior to treatment significantly interacted with treatment type to predict higher residual PTSD symptom severity, as assessed using the PTSD Symptom Scale-Interview, among participants who received sertraline but not those who received PE, ß = .24, p = .017, ∆R2 = .03. These findings were similar for self-reported depression severity, ß = .27, p = .008, ∆R2 = .04. Adherence to either PE homework or sertraline compliance did not mediate this association nor did life stress predict treatment retention for either treatment arm. Higher levels of perceived life stress may serve as a prescriptive predictor of PTSD treatment outcome, with PE remaining efficacious regardless of heightened pretreatment life stress. These findings encourage clinician confidence when providing PE to individuals with higher levels of life stress. Future researchers should examine the impact of PTSD treatment on perceived and objective measures of life stress to improve treatment for individuals who experience chronic stress.

Duloxetine for the treatment of generalized social anxiety disorder: a preliminary randomized trial of increased dose to optimize response.

OBJECTIVE: This is the first trial examining duloxetine for generalized social anxiety disorder (GSAD) and the effect of increased dose for those without early remission. METHODS: Individuals (n=39) with GSAD received 6 weeks of open-label duloxetine 60 mg/day; those with a Liebowitz Social Anxiety Disorder Scale (LSAS) score >30 at week 6 were randomized in double-blind fashion to an additional 18 weeks of continued duloxetine 60 mg/day or to duloxetine 120 mg/day. RESULTS: Duloxetine was associated with a significant LSAS reduction at week 6 (91.3 [17.7] to 69.8 [28.5], paired t [df]=5.2 [38], P<.0001), and randomized participants overall continued to improve at week 24 (74.6 [23.9] to 60.3 [29.7]; paired t [df]=3.3 [27], P=.0026). Though the increased dose strategy was associated with a moderate effect size (Cohen's d=.57), there was no significant difference at week 24 endpoint in LSAS reduction (20.5 [26.0] versus 7.3 [17.2], t [df]=1.6 [26], P=.13) nor remission (33% versus 8%) for duloxetine with dose increased to 120 mg/day compared to duloxetine continued at 60 mg/day. Overall, 44% (17/39) discontinued prior to week 24. CONCLUSIONS: Though with limited power, these data provide preliminary support for the efficacy of duloxetine for GSAD, and suggest continued improvement but limited remission overall at 24 weeks for individuals remaining symptomatic at week 6. These observations warrant further controlled study.

Imaginal exposure exacerbation revisited: Deconstructing patient characteristics associated with worse reactions to the initiation of imaginal exposure in PTSD.

OBJECTIVE: This study examines whether imaginal exposure leads to symptom exacerbation, systematically comparing individuals who received prolonged exposure (PE) to those who received pharmacotherapy. The study also examined whether common clinical features increase the likelihood of symptom exacerbation. METHOD: In 151 men and women with PTSD, we examined rates of reliable exacerbation of PTSD and depression symptoms after initiation of imaginal exposure and compared it to those receiving sertraline. We also examined relationships between exacerbation, treatment outcome, dropout, imaginal distress, and specific clinical features, including co-occurring MDD, multiple co-occurring disorders, childhood sexual abuse as target trauma, and a history of childhood physical or sexual abuse. RESULTS: Symptom exacerbation was not more common in PE compared to sertraline, not associated with higher dropout, or predictive of worse outcome. Those with co-occurring depression or multiple disorders, a target trauma of child sexual abuse, or a history of child abuse reported functionally equivalent peak distress at onset of imaginal as those without these characteristics. These factors did not lead to more exacerbation or worse adherence. CONCLUSION: Exacerbation was not specific to PE and patients with and without symptom worsening showed comparable treatment gains, suggesting symptom exacerbation may reflect a common clinical process.

Brain GABA levels in patients with bipolar disorder.

PURPOSE: A growing body of research supports an important role for GABA in the pathophysiology of bipolar and other mood disorders. The purpose of the current study was to directly examine brain GABA levels in a clinical sample of bipolar patients. GENERAL METHODS: We used magnetic resonance spectroscopy (MRS) to examine whole brain and regional GABA, glutamate and glutamine in 13 patients with bipolar disorder compared to a matched group of 11 healthy controls. FINDINGS: There were no significant differences in GABA, glutamate or glutamine between patients and controls. CONCLUSIONS: Further research is needed to better characterize the GABAergic and glutamatergic effects of pharmacotherapy, anxiety comorbidity and clinical state in bipolar disorder.

Childhood maltreatment linked to greater symptom severity and poorer quality of life and function in social anxiety disorder.

BACKGROUND: There is a paucity of data examining the prevalence and impact of childhood maltreatment in patients presenting with a primary diagnosis of social anxiety disorder (SAD). We thus examined the presence of a broad spectrum of childhood maltreatment, including physical, sexual, and emotional abuse and neglect, in treatment-seeking individuals with the generalized subtype of SAD (GSAD). We hypothesized that a history of childhood maltreatment would be associated with greater SAD symptom severity and poorer associated function. METHODS: One hundred and three participants with a primary diagnosis of GSAD (mean age 37+/-14; 70% male) completed the well-validated, self-rated Childhood Trauma Questionnaire (CTQ), as well as measures of SAD symptom severity and quality of life. RESULTS: Fully 70% (n=72) of the GSAD sample met severity criteria for at least one type of childhood abuse or neglect as measured by the CTQ subscales using previously established thresholds. CTQ total score adjusted for age and gender was associated with greater SAD severity, and poorer quality of life, function, and resilience. Further, the number of types of maltreatment present had an additive effect, with specific associations for emotional abuse and neglect with SAD severity. CONCLUSIONS: Despite the use of validated assessments, our findings are limited by the retrospective and subjective nature of self-report measures used to assess childhood maltreatment. Nonetheless, these data suggest a high rate of childhood maltreatment in individuals seeking treatment for GSAD, and the association of maltreatment with greater disorder severity suggests that screening is clinically prudent.

Can't get it out of my mind: A systematic review of predictors of intrusive memories of distressing events.

Intrusive memories, when persistent and distressing, are theorized to underlie a range of transdiagnostic psychological symptoms and associated impairment. However, little is known about factors predicting the development and persistence of intrusive memories. The aim of this systematic review is to evaluate the literature on pre-event, event-based, and post-event predictors of intrusive memories. A systematic review was conducted, searching for studies that examined intrusive, event-based memories. One hundred and six articles were identified from PsycInfo, PubMed, and Medline databases. Experimental and prospective studies with clinical (N = 14) and nonclinical (N = 92) samples were critically reviewed, provided the inclusion of an analogue stressor with nonclinical samples, and that intrusive memories frequency and/or distress were assessed as primary dependent variables. Pre-existing psychopathology and pre-event appraisal style appear to predict intrusive memories (small to medium effects), whereas trait dissociation did not predict intrusive memories. Of studies examining event-based predictors, higher data-driven processing appears to predict intrusive memories with generally large effects. Post-event negative appraisals consistently predicted intrusive memories (medium to large effects), and preliminary evidence suggests higher post-event conceptual processing predicting fewer intrusive memories. This review synthesizes findings regarding a broad range of pre-event, event-based, and post-event factors that may influence the development of intrusive memories. Methodological issues of current paradigms and the lack of emphasis on memory retrieval processes limit our understanding of what predicts intrusive memory persistence. These limitations are particularly important given that individuals typically seek treatment for distressing intrusive memories once a memory has been fully consolidated, where retrieval processes are of utmost importance. (PsycINFO Database Record

Attenuating fearful memories: effect of cued extinction on intrusions.

Exposure-based therapies for posttraumatic stress disorder are thought to reduce intrusive memories through extinction processes. Methods that enhance extinction may translate to improved treatment. Rat research suggests retrieving a memory via a conditioned stimulus (CS) cue, and then modifying the retrieved memory within a specific reconsolidation window may enhance extinction. In humans, studies (e.g., Kindt & Soeter, 2013; Schiller et al., 2010) using basic learning paradigms show discrepant findings. Using a distressing film paradigm, participants (N = 148) completed fear acquisition and extinction. At extinction, they were randomized to 1 of 3 groups: CS cue within reconsolidation window, CS cue outside window, or non-CS cue within window. Intrusions were assessed 24 hr after extinction. Participants receiving the CS cue and completing extinction within the reconsolidation window had more intrusions (M = 2.40, SD = 2.54) than those cued outside (M = 1.65, SD = 1.70) or those receiving a non-CS cue (M = 1.24, SD = 1.26), F(2, 145) = 4.52, p = .01, d = 0.55. Consistent with the reconsolidation hypothesis, presenting a CS cue does appear to activate a specific period of time during which a memory can be updated. However, the CS cue caused increased, rather than decreased, frequency of intrusions. Understanding parameters of preextinction cueing may help us better understand reconsolidation as a potential memory updating mechanism.

Mood regulation and quality of life in social anxiety disorder: an examination of generalized expectancies for negative mood regulation.

The present study examined negative mood regulation expectancies, anxiety symptom severity, and quality of life in a sample of 167 patients with social anxiety disorder (SAD) and 165 healthy controls with no DSM-IV Axis I disorders. Participants completed the Generalized Expectancies for Negative Mood Regulation Scale (NMR), the Beck Anxiety Inventory, and the Quality of Life Enjoyment and Satisfaction Questionnaire. SAD symptom severity was assessed using the Liebowitz Social Anxiety Scale. Individuals with SAD scored significantly lower than controls on the NMR. Among SAD participants, NMR scores were negatively correlated with anxiety symptoms and SAD severity, and positively correlated with quality of life. NMR expectancies positively predicted quality of life even after controlling for demographic variables, comorbid diagnoses, anxiety symptoms, and SAD severity. Individuals with SAD may be less likely to engage in emotion regulating strategies due to negative beliefs regarding their effectiveness, thereby contributing to poorer quality of life.

Understanding the relationship of perceived social support to post-trauma cognitions and posttraumatic stress disorder.

Poor social support in the aftermath of a traumatic event is a well-established risk factor for posttraumatic stress disorder (PTSD) among adult trauma survivors. Yet, a great deal about the relationship between social support and PTSD remains poorly understood. In this study, we analyzed data from 102 survivors of a serious motor vehicle accident (MVA) at 4 weeks (Time 1) and 16 weeks (Time 2) post-MVA. We assessed the role of perceived dyadic social support, positive dyadic interaction, and negative dyadic interaction in the development and maintenance of PTSD. In addition, we examined how these social support constructs work together with negative post-trauma cognitions to affect the maintenance of PTSD. Neither perceived social support nor the quality of social interaction (i.e., positive or negative) was associated with PTSD symptom severity at Time 1. However, among those with elevated PTSD symptom severity at Time 1, greater social support and positive social interaction and lower negative social interaction were each associated with reductions in PTSD symptom severity from Time 1 to Time 2. For social support and negative social interaction, this association ceased to be significant when jointly assessed with negative post-trauma cognitions, suggesting that perceived social support and negative dyadic interaction were associated with maintenance of PTSD symptom severity because of their association with negative post-trauma cognitions. These results provide support to models and treatments of PTSD that emphasize the role of negative post-trauma cognitions in maintenance of PTSD.