Faculty Bibliography

Complicated grief (CG) is increasingly recognized as a debilitating outcome of bereavement. Given the intensity of the stressor, its chronicity, and its association with depression, it is important to know the impact CG may have on cognitive functioning. This exploratory and descriptive study examined global and domain-specific cognitive functioning in a help-seeking sample of individuals with CG (n = 335) compared to a separately ascertained control sample (n = 250). Cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA). Controlling for age, sex and education effects, CG participants had lower total MoCA, visuospatial and attention scores relative to control participants. The two groups did not differ significantly in the domains of executive function, language, memory or orientation. Age, sex, and education accounted for much of the variance in MoCA scores, while CG severity and chronicity accounted for a very small percentage of MoCA score variance. Major depression was not a significant predictor of MoCA scores. This study is consistent with previous work demonstrating lower attention and global cognitive performance in individuals with CG compared to control participants. This study newly identifies the visuospatial domain as a target for future studies investigating cognitive functioning in CG.

Current exposure-based therapies aimed to reduce pathological fear and anxiety are now amongst the most effective interventions for trauma and anxiety related disorders. Nevertheless, they can be further improved to enhance initial and long-term outcomes. It is now widely accepted that a greater understanding of the neurobiological mechanisms of fear extinction is needed to further develop and identify novel effective targeted treatments as well as prevention strategies for fear-based and anxiety-related disorders. Guided by elegant mechanistic, cellular, and molecular preclinical reports, data from imaging studies are beginning to shape our understanding of how fear is quelled in the human brain. In this article, we briefly review the neural circuits underlying fear extinction in rodents and healthy humans. We then review how these circuits may fail to extinguish fear in patients with anxiety disorders. We end with a discussion examining how fear extinction research may lead to significant advances of current therapeutics for anxiety disorders.

This paper discusses each of several potential consequences of bereavement. First, we describe ordinary grief, followed by a discussion of grief gone awry, or complicated grief (CG). Then, we cover other potential adverse outcomes of bereavement, each of which may contribute to, but are not identical with, CG: general medical comorbidity, mood disorders, post-traumatic stress disorder, anxiety, and substance use.

Oxytocin is associated with differences in the perception of and response to socially mediated information, such as facial expressions. Across studies, however, oxytocins effect on emotion perception has been inconsistent. Outside the laboratory, emotion perception involves interpretation of perceptual uncertainty and assessment of behavioral risk. An account of these factors is largely missing from studies of oxytocins effect on emotion perception and might explain inconsistent results across studies. Of relevance, studies of oxytocins effect on learning and decision-making indicate that oxytocin attenuates risk aversion. We used the probability of encountering angry faces and the cost of misidentifying them as not angry to create a risky environment wherein bias to categorize faces as angry would maximize point earnings. Consistent with an underestimation of the factors creating risk (i.e., encounter rate and cost), men given oxytocin exhibited a worse (i.e., less liberal) response bias than men given placebo. Oxytocin did not influence womens performance. These results suggest that oxytocin may impair mens ability to adapt to changes in risk and uncertainty when introduced to novel or changing social environments. Because oxytocin also influences behavior in non-social realms, oxytocin pharmacotherapy could have unintended consequences (i.e., risk-prone decision-making) while nonetheless normalizing pathological social interaction.

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.

Complicated grief (CG) is a bereavement-specific syndrome chiefly characterized by symptoms of persistent separation distress. Physiological reactivity to reminders of the loss and repeated acute pangs or waves of severe anxiety and psychological pain are prominent features of CG. Fear of this grief-related physiological arousal may contribute to CG by increasing the distress associated with grief reactions and increasing the likelihood of maladaptive coping strategies and grief-related avoidance. Here, we examined anxiety sensitivity (AS; i.e., the fear of anxiety-related sensations) in two studies of bereaved adults with and without CG. In both studies, bereaved adults with CG exhibited elevated AS relative to those without CG. In study 2, AS was positively associated with CG symptom severity among those with CG. These findings are consistent with the possibility that AS contributes to the development or maintenance of CG symptoms.

Only a minority of patients with social anxiety disorder (SAD) has a robust therapeutic response to evidence-based serotonin reuptake inhibitor (SSRI) treatment. To help improve the personalized medicine approach to psychiatric care, we evaluated several candidate genetic predictors of SSRI response in SAD. At the start of a randomized controlled trial (NCT00282828), 346 patients with SAD at three sites received protocol-driven, open-label treatment with sertraline, up to 200. mg/d over 10 weeks. Efficacy was determined using a continuous measure of outcome (Liebowitz Social Anxiety Scale (LSAS)) and dichotomous indicators of response (LSAS