Faculty Bibliography

Prolonged exposure (PE) effectively reduces negative cognitions about self, world, and self-blame associated with posttraumatic stress disorder (PTSD), with changes in posttraumatic cognitions being associated with reductions in PTSD symptoms (Foa & Rauch, 2004). Further, recent research has demonstrated that cognitive change is a likely mechanism for PTSD symptom reduction in PE (Zalta et al., 2014). The present study examines temporal sequencing of change in three domains of posttraumatic cognitions (i.e., negative cognitions about the self, negative cognitions about the world, and self-blame) and PTSD symptoms during the course of PE. Adult outpatients meeting diagnostic criteria for PTSD were recruited at 4 sites. Participants (N=46) received 8 sessions of PE over 4 to 6weeks. PTSD symptoms and posttraumatic cognitions were assessed at pretreatment and Sessions 2, 4, 6, and 8. PTSD symptom severity and negative cognitions about the self and the world each decreased significantly from pre- to posttreatment, while self-blame cognitions were unchanged. Examination of temporal sequencing of changes during the course of PE via time-lagged mixed effects regression modeling revealed that preceding levels of negative cognitions about the world drove successive severity levels of PTSD symptoms, whereas preceding PTSD symptom severity did not drive subsequent negative cognitions about the world. Reductions in negative cognitions about the self led to subsequent improvement in PTSD. Improvement in PTSD symptoms in prior sessions was related to later reduction in negative cognitions about the self, though the impact of negative cognitions in influencing subsequent symptom change demonstrated a stronger effect. Results support that reductions in negative cognitions about the self and world are mechanisms of change in PE, which may have valuable implications for maximizing treatment effectiveness.

Perceived cognitive impairment is a core clinical feature of posttraumatic stress disorder (PTSD) and may be an important determinant of quality of life (QOL) in those who suffer from this disorder. Using a clinical data repository, we evaluated this hypothesis in a cross-sectional sample of U.S. military service members and veterans who served after September 11, 2001, and were seeking mental health treatment at a tertiary outpatient clinic. A consecutive series of 117 patients with a clinical diagnosis of PTSD completed a battery of questionnaires at intake, including the PTSD Checklist (Weathers, Litz, Herman, Huska, & Keane, 1993), a 4-item Cognitive Symptom subscale of the Neurobehavioral Symptom Inventory (Cicerone & Kalmar, 1995), the Depression Anxiety Stress Scale-21 (Lovibond & Lovibond, 1995), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Endicott, Nee, Harrison, & Blumenthal, 1993). Cognitive symptom reporting was very high, even in the subgroup without a history of traumatic brain injury. In a regression analysis, cognitive symptom severity was independently associated with QOL (beta = -.204). This relationship was not explained by comorbid traumatic brain injury, but was restricted to patients with comorbid depression (beta = -.278 in the subgroup with an elevated Depression Anxiety Stress Scale-21 Depression subscale; n = 91). In conclusion, perceived cognitive impairment was common in this PTSD sample and helped to explain impairments in QOL, especially in patients with comorbid depression.

Importance: The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders. Objectives: To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity. Design, Setting, and Participants: This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015. Exposures: Two-day fear conditioning and extinction paradigm. Main Outcomes and Measures: Skin conductance responses, blood oxygenation level-dependent responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait Form, and functional connectivity. Results: This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women). P values reported for the neuroimaging results are all familywise error corrected. Skin conductance responses during extinction recall did not differ between individuals with anxiety disorders and healthy controls (etap2 = 0.001, P = .79), where etap2 is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (etap2 = 0.178, P = .02). A similar hypoactive pattern was found during early conditioning (etap2 = 0.106, P = .009). The vmPFC hypoactivation was associated with anxiety symptom severity (r = -0.420, P = .01 for conditioning and r = -0.464, P = .004 for extinction recall) and the number of co-occuring anxiety disorders diagnosed (etap2 = 0.137, P = .009 for conditioning and etap2 = 0.227, P = .004 for extinction recall). Psychophysiological interaction analyses revealed that the fear network connectivity differed between healthy controls and the anxiety group during fear learning (etap2 range between 0.088 and 0.176 and P range between 0.02 and 0.003) and extinction recall (etap2 range between 0.111 and 0.235 and P range between 0.02 and 0.002). Conclusions and Relevance: Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder.

OBJECTIVES: To examine the effect of mindfulness meditation on occupational functioning in individuals with Generalized anxiety disorder (GAD). METHODS: Fifty-seven individuals with GAD (mean (SD) age=39 (13); 56% women) participated in an 8-week clinical trial in which they were randomized to mindfulness-based stress reduction (MBSR) or an attention control class. In this secondary analysis, absenteeism, entire workdays missed, partial workdays missed, and healthcare utilization patterns were assessed before and after treatment. RESULTS: Compared to the attention control class, participation in MBSR was associated with a significantly greater decrease in partial work days missed for adults with GAD (t=2.734, df=51, p=0.009). Interestingly, a dose effect was observed during the 24-week post-treatment follow-up period: among MBSR participants, greater home mindfulness meditation practice was associated with less work loss and with fewer mental health professional visits. CONCLUSION: Mindfulness meditation training may improve occupational functioning and decrease healthcare utilization in adults with GAD.

There are well-documented associations between posttraumatic stress disorder (PTSD) symptoms and intimate relationship impairments, including dysfunctional communication at times of relationship conflict. To date, the extant research on the associations between PTSD symptom severity and conflict communication has been cross-sectional and focused on military and veteran couples. No published work has evaluated the extent to which PTSD symptom severity and communication at times of relationship conflict influence each other over time or in civilian samples. The current study examined the prospective bidirectional associations between PTSD symptom severity and dyadic conflict communication in a sample of 114 severe motor vehicle accident (MVA) survivors in a committed intimate relationship at the time of the accident. PTSD symptom severity and dyadic conflict communication were assessed at 4 and 16weeks post-MVA, and prospective associations were examined using path analysis. Total PTSD symptom severity at 4weeks prospectively predicted greater dysfunctional communication at 16weeks post-MVA but not vice versa. Examination at the level of PTSD symptom clusters revealed that effortful avoidance at 4weeks prospectively predicted greater dysfunctional communication at 16weeks, whereas dysfunctional communication 4weeks after the MVA predicted more severe emotional numbing at 16weeks. Findings highlight the role of PTSD symptoms in contributing to dysfunctional communication and the importance of considering PTSD symptom clusters separately when investigating the dynamic interplay between PTSD symptoms and relationship functioning over time, particularly during the early posttrauma period. Clinical implications for the prevention of chronic PTSD and associated relationship problems are discussed.

Few studies have examined potential differences between social anxiety disorder (SAD) and generalised anxiety disorder (GAD) in the sensitivity to detect emotional expressions. The present study aims to compare the detection of emotional expressions in SAD and GAD. Participants with a primary diagnosis of GAD (n = 46), SAD (n = 70), and controls (n = 118) completed a morph movies task. The task presented faces expressing increasing degrees of emotional intensity, slowly changing from a neutral to a full-intensity happy, sad, or angry expressions. Participants used a slide bar to view the movie frames from left to right, and to stop at the first frame where they perceived an emotion. The frame selected thus indicated the intensity of emotion required to identify the facial expression. Participants with GAD detected the onset of facial emotions at lower intensity of emotion than participants with SAD (p = 0.002) and controls (p = 0.039). In a multiple regression analysis controlling for age, race, and depressive symptom severity, lower frame at which the emotion was detected was independently associated and GAD diagnosis (B = -5.73, SE = 1.74, p < 0.01). Our findings suggest that individuals with GAD exhibit enhanced detection of facial emotions compared to those with SAD or controls.

INTRODUCTION: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. METHODS: Subjects aged 18-70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls ( n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1beta, IL-6, and tumor necrosis factor-alpha) and after Bonferroni correction for multiple comparisons (IL-1alpha, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN-gamma-inducible protein 10, Eotaxin, interferon-gamma, monotype chemoattractant protein-1, macrophage inflammatory protein-1alpha, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor). RESULTS: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p 0.05 and p 0.002, respectively). CONCLUSION: Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature.

Biomimetic crossreactive sensor arrays have been used to detect and analyze a wide variety of vapor and liquid components in applications such as food science, public health and safety, and diagnostics. As technology has advanced over the past three decades, these systems have become selective, sensitive, and affordable. Currently, the need for noninvasive and accurate devices for early disease diagnosis remains a challenge. This Opinion article provides an overview of the various types of biomimetic crossreactive sensor arrays (also referred to as electronic noses or tongues in the literature), their current use and future directions, and an outlook for future technological development.