Faculty Bibliography
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287
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.
PMCID:4593618
PMID: 23861215
ISSN: 1520-6394
CID: 2281262
Influence of RGS2 on sertraline treatment for social anxiety disorder
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
PMCID:3988537
PMID: 24154666
ISSN: 1740-634x
CID: 2281312
A double-blind randomized controlled trial of augmentation and switch strategies for refractory social anxiety disorder
OBJECTIVE: Most patients remain symptomatic after an initial intervention with approved treatments for generalized social anxiety disorder. This randomized controlled trial provides systematic, prospectively derived data on the relative benefits of "next-step" pharmacotherapies to improve outcomes for individuals with generalized social anxiety disorder who remain symptomatic after initial treatment. METHOD: This three site, 12-week, double-blind randomized controlled trial compared the relative benefits of three strategies for patients remaining symptomatic (Liebowitz Social Anxiety Scale [LSAS] score >50) after a 10-week trial of sertraline alone: the addition of up to 3.0 mg/day of clonazepam (sertraline plus clonazepam), a switch to up to 225 mg/day of venlafaxine, or prolonged sertraline treatment with placebo (sertraline plus placebo). RESULTS: A total of 397 participants received at least one dose of sertraline; 181 nonresponders (LSAS score >50) at week 10 were randomly assigned to sertraline plus clonazepam, switch to venlafaxine, or sertraline plus placebo. Overall, 21% of patients achieved remission (LSAS score
PMID: 24399428
ISSN: 1535-7228
CID: 2281322
The human ortholog of acid-sensing ion channel gene ASIC1a is associated with panic disorder and amygdala structure and function
BACKGROUND: Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide, possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that carbon dioxide-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid-sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. METHODS: We conducted a case-control analysis (n = 414 PD cases and 846 healthy controls) of ACCN2 single nucleotide polymorphisms and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n = 1048) or task-evoked reactivity to emotional stimuli (n = 103) in healthy individuals. RESULTS: Two single nucleotide polymorphisms at the ACCN2 locus showed evidence of association with PD: rs685012 (odds ratio = 1.32, gene-wise corrected p = .011) and rs10875995 (odds ratio = 1.26, gene-wise corrected p = .046). The association appeared to be stronger when early-onset (age
PMCID:4103972
PMID: 24529281
ISSN: 1873-2402
CID: 2281332
Gender differences in oxytocin-associated disruption of decision bias during emotion perception
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.
PMCID:4086323
PMID: 24814142
ISSN: 1872-7123
CID: 2281342
Gender moderates the effect of oxytocin on social judgments
OBJECTIVE: The neuropeptide oxytocin is implicated in social processing, and recent research has begun to explore how gender relates to the reported effects. This study examined the effects of oxytocin on social affective perception and learning. METHODS: Forty-seven male and female participants made judgments of faces during two different tasks, after being randomized to either double-blinded intranasal oxytocin or placebo. In the first task, "unseen" affective stimuli were presented in a continuous flash suppression paradigm, and participants evaluated faces paired with these stimuli on dimensions of competence, trustworthiness, and warmth. In the second task, participants learned affective associations between neutral faces and affective acts through a gossip learning procedure and later made affective ratings of the faces. RESULTS: In both tasks, we found that gender moderated the effect of oxytocin, such that male participants in the oxytocin condition rated faces more negatively, compared with placebo. The opposite pattern of findings emerged for female participants: they rated faces more positively in the oxytocin condition, compared with placebo. CONCLUSIONS: These findings contribute to a small but growing body of research demonstrating differential effects of oxytocin in men and women.
PMID: 24911580
ISSN: 1099-1077
CID: 2281352
Anxiety sensitivity in bereaved adults with and without complicated grief
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.
PMCID:4118557
PMID: 25075646
ISSN: 1539-736x
CID: 2281362
A Cross-sectional Examination of Telomere Length and Telomerase in a Well-Characterized Sample of Individuals with Major Depressive Disorder Compared to Controls [Meeting Abstract]
ISI:000209477100527
ISSN: 1740-634x
CID: 2725622
MINDFULNESS MEDITATION FOR GENERALIZED ANXIETY DISORDER: EFFECTS ON RESILIENCE, ANXIETY, AND HYPOTHALAMIC PITUITARY ADRENAL (HPA) AXIS [Meeting Abstract]
ISI:000330467400004
ISSN: 1534-7796
CID: 2725812
Gray Matter Correlates of Posttraumatic Stress Disorder - A Voxel-Based Morphometry Study [Meeting Abstract]
ISI:000318671800231
ISSN: 0006-3223
CID: 2725802
