Faculty Bibliography

OBJECTIVE: We aimed to examine whether pretreatment with escitalopram would be associated with reduced fear acquisition and enhanced extinction learning in a fear conditioning paradigm, compared with placebo. METHODS: Healthy volunteers were randomized in double-blind fashion, to 14 days of escitalopram 10 mg/day (n = 18) or placebo (n = 20) prior to a classical fear conditioning paradigm. RESULTS: Although escitalopram was associated with a smaller skin conductance (SC) orienting response during habituation, no medication effects on fear acquisition were found. Escitalopram was associated with faster extinction of SC responses, compared with placebo, as revealed by a significant drug x conditioned stimulus x trial interaction for early extinction (F(3, 30) = 3.26, p = 0.035) and late extinction (F(3, 30) = 3.27, p = 0.035) trials. After adjustment for age, orienting response, and acquisition, results from linear contrast remained significant for early extinction (F(1, 29) = 5.43, p = 0.027). CONCLUSIONS: Escitalopram administered for 14 days prior to a fear conditioning paradigm did not influence acquisition of a conditioned fear response but did facilitate extinction learning. Impairments in extinction learning have been identified as a key component of posttraumatic stress disorder; our preliminary findings suggest that additional experimental and clinical studies assessing the efficacy of selective serotonin reuptake inhibitors for posttraumatic stress disorder prevention are warranted.

This article profiles bereavement among traumatized Cambodian refugees and explores the validity of a model of how grief and post-traumatic stress disorder (PTSD) interact in this group to form a unique bereavement ontology, a model in which dreams of the dead play a crucial role. Several studies were conducted at a psychiatric clinic treating Cambodian refugees who survived the Pol Pot genocide. Key findings included that Pol Pot deaths were made even more deeply disturbing owing to cultural ideas about "bad death" and the consequences of not performing mortuary rites; that pained recall of the dead in the last month was common (76 % of patients) and usually caused great emotional and somatic distress; that severity of pained recall of the dead was strongly associated with PTSD severity (r = .62); that pained recall was very often triggered by dreaming about the dead, usually of someone who died in the Pol Pot period; and that Cambodians have a complex system of interpretation of dreams of the deceased that frequently causes those dreams to give rise to great distress. Cases are provided that further illustrate the centrality of dreams of the dead in the Cambodian experiencing of grief and PTSD. The article shows that not assessing dreams and concerns about the spiritual status of the deceased in the evaluation of bereavement results in "category truncation," i.e., a lack of content validity, a form of category fallacy.

The authors investigated the importance of dreams of the deceased in the experiencing of prolonged grief (PG) and posttraumatic stress disorder (PTSD) among Cambodian refugees who survived the Pol Pot genocide (1975-1979). Such dreams were frequent in the last month (52% of those surveyed), and most often involved a relative who died in the Pol Pot period. Past month frequency was correlated with PG severity (r = .59) and PTSD severity (r = .52). The dreams were almost always deeply upsetting because the dreams indicated the deceased to be in a difficult spiritual state. Dreams of the deceased as a central component of PG and PTSD among Cambodian refugees is discussed.

Little is known about the presence and role of subclinical anxiety symptoms and traits in complicated grief (CG). Data from adults with CG (n=28) suggest that they experience more panic-spectrum symptoms (PSS) than bereaved controls (n=44), and that the presence of greater PSS is independently associated with poorer quality of life.

OBJECTIVE: Mindfulness meditation has met increasing interest as a therapeutic strategy for anxiety disorders, but prior studies have been limited by methodological concerns, including a lack of an active comparison group. This is the first randomized, controlled trial comparing the manualized Mindfulness-Based Stress Reduction (MBSR) program with an active control for generalized anxiety disorder (GAD), a disorder characterized by chronic worry and physiologic hyperarousal symptoms. METHOD: Ninety-three individuals with DSM-IV-diagnosed GAD were randomly assigned to an 8-week group intervention with MBSR or to an attention control, Stress Management Education (SME), between 2009 and 2011. Anxiety symptoms were measured with the Hamilton Anxiety Rating Scale (HAMA; primary outcome measure), the Clinical Global Impressions-Severity of Illness and -Improvement scales (CGI-S and CGI-I), and the Beck Anxiety Inventory (BAI). Stress reactivity was assessed by comparing anxiety and distress during pretreatment and posttreatment administration of the Trier Social Stress Test (TSST). RESULTS: A modified intent-to-treat analysis including participants who completed at least 1 session of MBSR (n = 48) or SME (n = 41) showed that both interventions led to significant (P < .0001) reductions in HAMA scores at endpoint, but did not significantly differ. MBSR, however, was associated with a significantly greater reduction in anxiety as measured by the CGI-S, the CGI-I, and the BAI (all P values < .05). MBSR was also associated with greater reductions than SME in anxiety and distress ratings in response to the TSST stress challenge (P < .05) and a greater increase in positive self-statements (P = .004). CONCLUSIONS: These results suggest that MBSR may have a beneficial effect on anxiety symptoms in GAD and may also improve stress reactivity and coping as measured in a laboratory stress challenge. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01033851.

Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p=.083); among women, the LKM practitioners had significantly longer RTL than controls, (p=.007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity.

IMPORTANCE: The death of a loved one is one of life's greatest, universal stressors to which most bereaved individuals successfully adapt without clinical intervention. For a minority of bereaved individuals, grief is complicated by superimposed problems and healing does not occur. The resulting syndrome of complicated grief causes substantial distress and functional impairment even years after a loss, yet knowing when and how to intervene can be a challenge. OBJECTIVE: To discuss the differential diagnosis, risk factors for and management of complicated grief based on available evidence and clinical observations. EVIDENCE REVIEW: MEDLINE was searched from January 1990 to October 2012. Additional citations were procured from references of select research and review articles. Available treatment studies targeting complicated grief were included. RESULTS: A strong research literature led to inclusion of complicated grief in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (termed persistent complex bereavement disorder as a subtype of other specified trauma and stressor-related disorders), although it is a condition for which more research is formally recommended, and there is still ongoing discussion about the optimal name and diagnostic criteria for the disorder. Reliable screening instruments are available, and the estimated prevalence rate is 7% of bereaved people. Randomized controlled data support the efficacy of a targeted psychotherapy including elements that foster resolution of complicating problems and facilitate the natural healing process. Preliminary studies suggest antidepressant medications may be helpful. CONCLUSION AND RELEVANCE: Individuals with complicated grief have greater risk of adverse health outcomes, should be diagnosed and assessed for suicide risk and comorbid conditions such as depression and posttraumatic stress disorder, and should be considered for treatment.

OBJECTIVE: The authors examined whether D-cycloserine, a partial agonist at the glutamatergic N-methyl-d-aspartate receptor, augments and accelerates a full course of comprehensive cognitive-behavioral therapy (CBT) in adults with generalized social anxiety disorder. METHOD: This was a multisite randomized placebo-controlled efficacy study with 169 medication-free adults with generalized social anxiety disorder, of whom 144 completed the 12-week treatment and 131 completed the three follow-up assessments. Patients were randomly assigned to receive 50 mg of D-cycloserine or placebo 1 hour before each of five exposure sessions that were part of a 12-session cognitive-behavioral group treatment. Response and remission status was determined at baseline, throughout treatment, at end of treatment, and at 1-, 3-, and 6-month follow-up assessments by assessors who were blind to treatment condition. RESULTS: D-Cycloserine-augmented and placebo-augmented CBT were associated with similar completion rates (87% and 82%), response rates (79.3% and 73.3%), and remission rates (34.5% and 24.4%) at the posttreatment assessment; response and remission rates were largely maintained at the follow-up assessments. Although D-cycloserine was associated with a 24%-33% faster rate of improvement in symptom severity and remission rates relative to placebo during the treatment phase, the groups did not differ in response and remission rates. CONCLUSIONS: D-Cycloserine did not augment a full course of comprehensive CBT for social anxiety disorder.