Faculty Bibliography

OBJECTIVE: Although binge eating disorder is a common and distressing concomitant of obesity, it has not yet been established whether affected individuals presenting to behavioral weight control programs should receive specialized treatments to supplement standard treatment. This study was designed to examine the added benefit of two adjunctive interventions, individual cognitive behavioral therapy (CBT) and fluoxetine, offered in the context of group behavioral weight control treatment. RESEARCH METHODS AND PROCEDURES: One hundred sixteen overweight/obese women and men with binge eating disorder were all assigned to receive a 16-session group behavioral weight control treatment over 20 weeks. Simultaneously, subjects were randomly assigned to receive CBT+fluoxetine, CBT+placebo, fluoxetine, or placebo in a two-by-two factorial design. Outcome measures, assessed at the end of the 16-session acute treatment phase, included binge frequency, weight, and measures of eating-related and general psychopathology. RESULTS: Overall, subjects showed substantial improvement in binge eating and both general and eating-related psychopathology, but little weight loss. Subjects who received individual CBT improved more in binge frequency than did those not receiving CBT (p<0.001), and binge abstinence was significantly more common in subjects receiving CBT vs. those who did not (62% vs. 33%, p<0.001). Fluoxetine treatment was associated with greater reduction in depressive symptoms (p<0.05). The 54 subjects who achieved binge abstinence improved more on all measures than the 62 subjects who did not. In particular, these subjects lost, on average, 6.2 kg compared with a gain of 0.7 kg among non-abstainers. DISCUSSION: Adjunctive individual CBT results in significant additional binge reduction in obese binge eaters receiving standard behavioral weight control treatment

OBJECTIVE: Many studies have implicated prenatal infection in the etiology of schizophrenia. Cytokines, a family of soluble polypeptides, are critically important in the immune response to infection and in other inflammatory processes. The goal of this study was to determine whether second-trimester levels of four cytokines-interleukin-8 (IL-8), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)-are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects. METHOD: The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort, born 1959-1967. Cases (N=59) were subjects diagnosed with schizophrenia spectrum disorders (mostly schizophrenia and schizoaffective disorder) who had available second-trimester maternal serum samples. Comparison subjects (N=105) were members of the birth cohort, had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder, and were matched to subjects with schizophrenia for date of birth, gender, length of time in the cohort, and availability of maternal sera. Maternal second-trimester serum levels of IL-8, IL-1beta, IL-6, and TNF-alpha were determined by sandwich enzyme-linked immunosorbent assay. RESULTS: The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects. There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1beta, IL-6, or TNF-alpha. CONCLUSIONS: Using prospectively collected prenatal sera in a large and well-characterized birth cohort, the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring. These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia. Moreover, these results may have important implications for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder

OBJECTIVES/HYPOTHESIS: The traditional blind passage of a transesophageal echocardiography probe transorally through the hypopharynx is considered safe. Yet, severe hypopharyngeal complications during transesophageal echocardiography at several institutions led the authors to investigate whether traditional probe passage results in a greater incidence of hypopharyngeal injuries when compared with probe passage under direct visualization. STUDY DESIGN: Randomized, prospective clinical study. METHODS: In 159 consciously sedated adults referred for transesophageal echocardiography, the authors performed transesophageal echocardiography with concomitant transnasal videoendoscopic monitoring of the hypopharynx. Subjects were randomly assigned to receive traditional (blind) or experimental (optical) transesophageal echocardiography. The primary outcome measure was frequency of hypopharyngeal injuries (hypopharyngeal lacerations or hematomas), and the secondary outcome measure was number of hypopharyngeal contacts. RESULTS: No perforation occurred with either technique. However, hypopharyngeal lacerations or hematomas occurred in 19 of 80 (23.8%) patients with the traditional technique (11 superficial lacerations of pyriform sinus, 1 laceration of pharynx, 12 arytenoid hematomas, 2 vocal fold hematomas, and 1 pyriform hematoma) and in 1 of 79 patients (1.3%) with the optical technique (superficial pyriform laceration) (P =.001). All traumatized patients underwent flexible laryngoscopy, but none required additional intervention. Respectively, hypopharyngeal contacts were more frequent with the traditional than with the optical technique at the pyriform sinus (70.0% vs. 10.1% [P =.001]), arytenoid (55.0% vs. 3.8% [P =.001]), and vocal fold (15.0% vs. 3.86% [P =.016]). CONCLUSION: Optically guided trans-esophageal echocardiography results in significantly fewer hypopharyngeal injuries and fewer contacts than traditional, blind transesophageal echocardiography. The optically guided technique may result in decreased frequency of potentially significant complications and therefore in improved patient safety

We sought to determine whether adults with obsessive-compulsive disorder (OCD) who respond to intensive exposure and response (ritual) prevention (EX/RP) with or without clomipramine (CMI) fare better 12 weeks after treatment discontinuation than responders receiving CMI alone. After receiving 12 weeks of treatment (EX/RP, CMI, EX/RP+CMI, or pill placebo [PBO] in a randomized clinical trial conducted at three outpatient research centers), 46 adults with OCD who responded to treatment (18 EX/RP, 11 CMI, 15 EX/RP+CMI, 2 PBO) were followed after treatment discontinuation for 12 weeks. Patients were assessed every 4 weeks with the Yale-Brown Obsessive-Compulsive Scale, the National Institutes of Health Global Obsessive-Compulsive Scale, and the Clinical Global Impressions scale by an evaluator who was blind to original treatment assignment. The primary hypothesis was that EX/RP and EX/RP+CMI responders would be less likely to relapse 12 weeks after treatment discontinuation than responders to CMI alone. Twelve weeks after treatment discontinuation, EX/RP and EX/RP+CMI responders, compared to CMI responders, had a significantly lower relapse rate (4/33 = 12% versus 5/11 = 45%) and a significantly longer time to relapse. The CMI relapse rate was lower than previously reported. Nonetheless, responders receiving intensive EX/RP with or without CMI fared significantly better 12 weeks after treatment discontinuation than responders receiving CMI alone

OBJECTIVE: Although the newer antidepressants are widely used, little is known about how long it takes to see their full effect. The authors sought to determine how many weeks a fluoxetine trial with no improvement should continue before treatment is changed. METHOD: The data involved 840 patients in a 12-week open trial of fluoxetine, 20 mg/day, followed by a blinded, placebo-controlled discontinuation study. Outcomes at 4, 6, 8, 10, and 12 weeks were classified as nonresponse, partial response, response, and remission and were based on Hamilton Depression Rating Scale scores. The rate of remission at week 12 was calculated for each group of patients without remission at the earlier time points. The time to relapse during weeks 13-26 of the discontinuation study was examined in patients taking placebo and fluoxetine in relation to status at week 6. RESULTS: Patients unimproved at week 6 had a remission rate at week 12 of 31%-41%. For patients with remission at week 12, level of improvement at week 6 did not affect prognosis in weeks 13-26. Of the unimproved patients at week 8, 23% had remissions by week 12. The week 12 remission rate for unimproved patients at week 4 was clearly high enough to justify continued treatment; the rate for unimproved patients at week 10 was too low. CONCLUSIONS: These data suggest that nonresponse to fluoxetine should not be declared until 8 weeks of treatment have elapsed. Practitioners should discuss trial length with patients at the beginning of treatment

Clinical subtypes of obsessive-compulsive disorder may have differing pathophysiological mechanisms and treatment outcomes. The subtypes identified by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Symptom Checklist, clustered by clinical consensus, have never been subject to statistical validation. A factor analysis using a sample of 160 patients with OCD was conducted to determine whether factor analytically derived categories are identical to extant clinically determined categories. Our analysis revealed that the contamination subtype of the Y-BOCS Symptom Checklist contains two distinct subgroups: one relating to discomfort and the other to fear of harm. If replicated on a larger scale, the finding of new subtype groupings would have important implications for future research in obsessive-compulsive disorder

OBJECTIVE: The study examined a large data set to determine whether patients' sex affected the outcome of antidepressant treatment. METHOD: Data for 1,746 patients aged 18-65 years who had been treated with tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), fluoxetine, or placebo were examined in a retrospective analysis to determine whether men and women differed in their responses to antidepressants. To examine the effect of menopausal status in the absence of data on individual patients' menopausal status, results for female patients younger or older than age 50, 52, 54, and 56 were compared. RESULTS: Men and women both younger and older than age 50 had equivalent response rates to tricyclics and fluoxetine. Women had a statistically superior response to MAOIs. Placebo response was equivalent across all groups. CONCLUSIONS: Neither sex nor menopausal status may be relevant in antidepressant treatment of adult depressed patients up to 65 years of age. Although women had a statistically superior response to MAOIs, this difference may not be clinically relevant

OBJECTIVE: To examine the association between menstrual functioning and depressive disorder symptoms (DDS), obsessive-compulsive disorder symptoms (OCDS), and eating disorder symptoms (EDS) in high school girls. METHOD: Survey data from a county-wide high school population (completion rate 91%) were used. Associations between menstrual indices and scores above clinical cutoff on the Beck Depression Inventory, Leyton Obsessive-Compulsive Inventory-Child Version, and Eating Attitudes Test were examined by using logistic regression ( = 2,547 girls). RESULTS: Controlling for chronological age and other risk factors, late menarche was associated with DDS (odds ratio [OR] = 2.26, 95% confidence interval [CI] = 1.16-4.18). Gynecological year 1 (GY1) was associated with DDS (OR = 3.13, CI = 1.23-7.33), EDS (OR = 3.11, CI = 1.00-8.09), and OCDS, both number (OR = 5.75, CI = 1.79-15.74) and interference (OR = 12.55, CI = 3.20-41.4). Secondary amenorrhea was associated with DDS (OR = 1.94, CI = 11.30-2.84) and EDS (OR = 2.32, CI = 1.51-3.49); polymenorrhea with EDS (OR = 1.92, CI = 1.27-2.86); and irregular cycles with EDS (OR = 1.70, CI = 1.11-2.54) and DDS (OR = 1.76, CI = 11.21-2.53). CONCLUSIONS: In high school girls, late menarche, GY1, and menstrual cycle abnormalities are associated differentially with DDS, OCDS, and EDS

OBJECTIVE: This study examined the relationships of dissociation and childhood trauma with ataque de nervios. METHOD: Forty Puerto Rican psychiatric outpatients were evaluated for frequency of ataque de nervios, dissociative symptoms, exposure to trauma, and mood and anxiety psychopathology. Blind conditions were maintained across assessments. Data for 29 female patients were analyzed. RESULTS: Among these 29 patients, clinician-rated dissociative symptoms increased with frequency of ataque de nervios. Dissociative Experiences Scale scores and diagnoses of panic disorder and dissociative disorders were also associated with ataque frequency, before corrections were made for multiple comparisons. The rate of childhood trauma was uniformly high among the patients and showed no relationship to dissociative symptoms and disorder or number of ataques. CONCLUSIONS: Frequent ataques de nervios may, in part, be a marker for psychiatric disorders characterized by dissociative symptoms. Childhood trauma per se did not account for ataque status in this group of female outpatients

OBJECTIVE: This article discusses broad statistical issues common to much medical research: intent-to-treat analysis vs. completers analysis; clustered hierarchical and repeated-measures data; missing data and dropouts; and assessment of direct, indirect, and total effects. Traditional approaches and statistical techniques are reviewed and contrasted with modern methods for analysis of medical studies. METHOD: The concepts are introduced and discussed in general terms; they are illustrated with an example. The example comes from a study of the effect of residence in special care units (SCUs) for demented elderly on the daily function of nursing homes residents. More than 700 residents from 22 nursing facilities, residing in either an SCU or a non-SCU were assessed three times at approximate 6-month intervals. RESULTS: Results from both the application of traditional statistical techniques and modern methods for the analysis of repeated-measures of hierarchical multicenter data are presented, interpreted, and compared. Advantages and shortcomings of these approaches are discussed. CONCLUSION: This article advocates the use of mixed models and proper causal reasoning and terminology in the analysis and publication of results from studies on aging and life course