Samantha J. Moshier

Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder

Background: Proinflammatory cytokines have been reported to be elevated in individuals experiencing chronic stress as well as in those with major depressive disorder. Much less is known about cytokines in anxiety disorders such as posttraumatic stress disorder (PTSD) and panic disorder (PD). We hypothesized that PD and PTSD would be associated with a generalized proinflammatory cytokine signature. Method: We utilized Luminex technology to examine 20 cytokines and chemokines in serum from 48 well‐characterized individuals with a primary DSM‐IV PD or PTSD diagnosis, and 48 age‐ and gender‐matched healthy controls. We conservatively employed a Bonferroni correction for multiple testing (α=.05/20=.0025). Results: Individuals with primary PTSD or PD had significantly elevated median peripheral cytokine levels for 18 of 20 different cytokines compared to age‐ and gender‐matched healthy controls (all P<.0025). To assess for the presence of a generalized proinflammatory state, we also examined the proportion of subjects with detectable levels of at least six of nine common proinflammatory cytokines and chemokines (IL‐6, IL‐1α, IL‐1β, IL‐8, MCP‐1, MIP‐1α, Eotaxin, GM‐CSF, and IFN‐α). For men and women, 87% of anxiety patients had six or more detectable levels of these proinflammatory cytokines, compared with only 25% of controls (Fishers Exact Test (FET) P=.000). Confirmatory analysis of the subset of individuals without current psychiatric medication use or comorbid depression was of comparable significance. Conclusions: These findings suggest that a generalized inflammatory state may be present in individuals with PD or PTSD. Depression and Anxiety, 2009.

Eszopiclone for the Treatment of Posttraumatic Stress Disorder and Associated Insomnia: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE The development of novel strategies for the treatment of posttraumatic stress disorder (PTSD) represents a critical public health need. We present the first prospective, randomized, double-blind, placebo-controlled trial of a non-benzodiazepine hypnotic agent for the treatment of PTSD and associated insomnia. METHOD Twenty-four patients with PTSD by DSM-IV criteria and sleep disturbance were treated in a randomized, double-blind, placebo-controlled crossover study of 3 weeks of eszopiclone 3 mg at bedtime compared to placebo. The primary outcome measures were changes in scores on the Short PTSD Rating Interview (SPRINT) and the Pittsburgh Sleep Quality Index (PSQI). The data were collected from April 2006 to June 2008. RESULTS Three weeks of eszopiclone pharmacotherapy was associated with significantly greater improvement than placebo on PTSD symptom measures including the SPRINT (P = .032) and the Clinician-Administered PTSD Scale (P = .003), as well as on measures of sleep including the PSQI (P = .011) and sleep latency (P = .044). Greater improvement with eszopiclone on PTSD measures was present even when specific sleep-related items were excluded. Adverse events were consistent with the known profile of the drug. CONCLUSIONS This study provides initial evidence that pharmacotherapy with eszopiclone may be associated with short-term improvement in overall PTSD severity as well as associated sleep disturbance. Longer, more definitive study of eszopiclone in PTSD is warranted. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00120250.

Cigarette smoking is associated with suicidality in bipolar disorder

OBJECTIVES Cigarette smoking in individuals with bipolar disorder has been associated with suicidal behavior, although the precise relationship between the two remains unclear. METHODS In this prospective observational study of 116 individuals with bipolar disorder, we examined the association between smoking and suicidality as measured by Linehans Suicide Behaviors Questionnaire (SBQ) and prospective suicide attempts over a nine-month period. Impulsivity was measured by the Barratt Impulsiveness Scale. RESULTS Smoking was associated with higher baseline SBQ scores in univariate and adjusted analyses, but was not significant after statistical adjustment for impulsivity in a regression model. A higher proportion of smokers at baseline made a suicide attempt during the follow-up period (5/31, 16.1%) compared to nonsmokers (3/85, 3.5%); p = 0.031, odds ratio = 5.25 (95% confidence interval: 1.2-23.5). Smoking at baseline also significantly predicted higher SBQ score at nine months. CONCLUSIONS In this study, current cigarette smoking was a predictor of current and nine-month suicidal ideation and behavior in bipolar disorder, and it is likely that impulsivity accounts for some of this relationship.

De novo fear conditioning across diagnostic groups in the affective disorders: evidence for learning impairments.

De novo fear conditioning paradigms have served as a model for how clinical anxiety may be acquired and maintained. To further examine variable findings in the acquisition and extinction of fear responses between clinical and nonclinical samples, we assessed de novo fear conditioning outcomes in outpatients with either anxiety disorders or depression and healthy subjects recruited from the community. Overall, we found evidence for attenuated fear conditioning, as measured by skin conductance, among the patient sample, with significantly lower fear acquisition among patients with depression and posttraumatic stress disorder. These acquisition deficits were evident in both the simple (considering the CS+only) and differential (evaluating the CS+in relation to the CS-) paradigms. Examination of extinction outcomes were hampered by the low numbers of patients who achieved adequate conditioning, but the available data indicated slower extinction among the patient, primarily panic disorder, sample. Results are interpreted in the context of the cognitive deficits that are common to the anxiety and mood disorders, with attention to a range of potential factors, including mood comorbidity, higher-and lower-order cognitive processes and deficits, and medication use, that may modulate outcomes in fear conditioning studies, and, potentially, in exposure-based cognitive behavioral therapy.

The Role of Anxiety Sensitivity and Eating Expectancy in Maladaptive Eating Behavior

Research has shown that anxiety sensitivity (AS), or the fear of somatic arousal, predicts distress and maladaptive coping in a range of psychiatric conditions. More recently, the role of AS has been examined in pathological eating. In the current investigation, a two-study design was employed to examine the role of AS and eating expectancies in both self-reported and actual eating behavior. For Study 1, 42 overweight/obese participants completed questionnaires assessing AS, as well as eating behaviors and attitudes. In Study 2, 60 participants representing all weight ranges completed the same questionnaire battery and underwent a negative mood induction task followed by food exposure. Results of this study revealed a 3-way interaction between Anxiety Sensitivity Index-mental concerns subscale, Eating Expectancy Inventory—eating leads to feeling out of control subscale, and BMI suggesting that those elevated on all 3 constructs consumed the most calories. Results are discussed in relation to better understanding the role of AS and eating expectancy and its utility in identifying a subset of overweight/obese individuals at risk for maladaptive eating behavior.

Clarifying the Link Between Distress Intolerance and Exercise: Elevated Anxiety Sensitivity Predicts Less Vigorous Exercise

Anxiety sensitivity, one measure of distress intolerance, has been increasingly shown to play a role in a variety of health behaviors. A number of reports now suggest that individuals with higher levels of anxiety sensitivity (AS) are less likely to engage in exercise. However, this finding has been inconsistent across sex and limited by measurement strategy. This study examined the relationship between AS and self-reported exercise in a mixed-sex sample of 233 individuals. Consistent with prediction, AS was negatively associated with engagement in vigorous-intensity exercise; however, the strength of this association when covarying for sex was dependent on the measurement strategy used (continuous vs. categorical ASI scores). Sex did not moderate the AS-vigorous exercise association. AS was not associated with moderate-intensity exercise or walking. Results suggest a role of distress intolerance in exercise behavior and confirm the importance of continued research on this topic.

Anxiety Sensitivity Uniquely Predicts Exercise Behaviors in Young Adults Seeking to Increase Physical Activity

Individuals with elevated levels of anxiety sensitivity (AS) may be motivated to avoid aversive emotional or physical states, and therefore may have greater difficulty achieving healthy behavioral change. This may be particularly true for exercise, which produces many of the somatic sensations within the domain of AS concerns. Cross-sectional studies show a negative association between AS and exercise. However, little is known about how AS may prospectively affect attempts at behavior change in individuals who are motivated to increase their exercise. We recruited 145 young adults who self-identified as having a desire to increase their exercise behavior. Participants completed a web survey assessing AS and additional variables identified as important for behavior change—impulsivity, grit, perceived behavioral control, and action planning—and set a specific goal for exercising in the next week. One week later, a second survey assessed participants’ success in meeting their exercise goals. We hypothesized that individuals with higher AS would choose lower exercise goals and would complete less exercise at the second survey. AS was not significantly associated with exercise goal level, but significantly and negatively predicted exercise at Time 2 and was the only variable to offer significant prediction beyond consideration of baseline exercise levels. These results underscore the importance of considering AS in relation to health behavior intentions. This is particularly apt given the absence of prediction offered by other traditional predictors of behavior change.

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 (Cohens 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.

A comparison of emotional approach coping (EAC) between individuals with anxiety disorders and nonanxious controls.

Emotional regulation deficits are described as a core component of anxiety disorders (ADs), yet there remains a paucity of data examining this issue in patients diagnosed with ADs. We hypothesized that help‐seeking individuals with ADs would report lower levels of emotional approach coping (EAC), which includes emotional processing (EP) and emotional expression (EE), than nonanxious controls. Diagnostic interviews and a validated self‐report scale assessing emotional approaches to coping (emotional approach coping scale [EACS]) were administered to 101 nonanxious controls and 92 patients with a primary AD (29 generalized anxiety disorder, 40 social anxiety disorder, and 23 panic disorder). Patients with each AD demonstrated significantly lower EAC, including both EP and EE, than nonanxious controls. Lower EAC was also associated with higher anxiety sensitivity and higher anxiety symptom severity. Overall, gender did not moderate the anxiety–EAC effect, but the results suggested that women utilize EAC to a greater degree than men. Clinical techniques designed to improve emotional coping may be beneficial to individuals with ADs.

Treatment Outcome and Predictors of Internet Guided Self-Help for Obsessive-Compulsive Disorder

Internet-guided self-help (iGSH) has amassed significant empirical support for a variety of psychiatric conditions; however, it is not known who responds best to these treatments. This open trial examined the clinical outcomes and predictors of a 17-week iGSH program for obsessive-compulsive disorder (OCD). Therapist support was provided either in person or by phone 9 times for an average of 13minutes per session. Twenty-four patients initiated treatment, and 17 of these (70.8%) completed. Results of the intent-to-treat sample indicated statistically significant improvements at posttreatment with large treatment effects for OCD symptoms as assessed by the Yale Brown Obsessive-Compulsive Scale (d=0.87), and small to moderate improvements in depression (d=0.19), functioning (d=0.53), and quality of life (d=-0.18). These outcomes were largely maintained over a 6-month follow-up. Readiness to reduce avoidance of OCD triggers and attendance to therapist sessions were moderately associated with posttreatment response, and correctly classified the responder status (defined as clinically significant change) of nearly 9 out of 10 patients at posttreatment. These same variables did not predict responder status at 6-month follow-up. These results lend further empirical support to iGSH as a treatment for OCD and provide direction on the development of predictor models to identify patients who are and are not likely to acutely respond to iGSH.