Comparison of obsessions and compulsions in patients with anorexia nervosa and obsessive compulsive disorder.

Patients with anorexia nervosa (n = 18) and patients with obsessive-compulsive disorder (OCD) (n = 16) had similar scores on the Yale-Brown Obsessive Compulsive Scale (19 + or - 9 vs. 22 + or - 6). This suggests that these disorders have similar magnitude of impairment from obsessions and compulsions; however, OCD patients endorsed a wide variety of obsessions and compulsions, whereas anorexics tended to endorse symptoms that were related to symmetry and order.

Working memory as assessed by subject-ordered tasks in patients with obsessive-compulsive disorder.

We tested patients with obsessive-compulsive disorder (OCD) and normal subjects (n = 18 per group) on a self-paced, working memory task that, based on studies of patients with focal brain lesions and functional brain imaging studies of normals, is largely mediated by prefrontal cortex. The OCD patients had normal working memory spans and normal recognition memory for all types of material tested (abstract words, common objects, and novel nonsense objects). The patients, however, were slow (p < .005), and the time they took to complete the tasks was significantly correlated with ratings of OCD symptoms (r = .539, p < .05) and depression (r = .643, p < .01), but not anxiety. Slowed performance on this self-paced task was discussed in relation to normal response times by OCD patients under typical laboratory conditions. It was suggested that this discrepancy may be related to a broader dissociation between real-world and laboratory performance as seen in some patients with prefrontal lobe dysfunction.

Memory in sub-clinical obsessive-compulsive checkers.

In a series of experiments we extended the research on possible memory deficits in subclinical obsessive-compulsive Ss who reported excessive checking. Using a variety of memory tests we compared 20 subclinical checkers to 20 Ss without obsessive-compulsive symptomatology. Contrary to hypothesis, checkers remembered self-generated words better than read words just as much as did normals, but they were more likely than normals to report thinking they had studied words that, in fact, had not been on the study list. Further, they more often confused whether they read or generated the words at study. Checkers did not appear to perseverate on already-recalled words on repeated free recall tests any more than did normals. However, checkers remembered fewer actions overall and more often misremembered whether they had performed, observed, or written these actions. Such memory deficits may contribute to the development of excessive checking.

A comparison of the behavioral effects of oral versus intravenous mCPP administration in OCD patients and the effect of metergoline prior to i.v. mCPP.

In prior studies form three centers, an exacerbation of obsessive-compulsive disorder (OCD) symptoms was reported in some (55%-83%) patients with OCD receiving the serotonergic agonist m-chlorophenylpiperazine (m-CPP) orally, whereas intravenously administered mCPP produced anxiety but no OCD symptom exacerbation. In the present replication attempt, 27 OCD patients were given mCPP either orally (n = 17) or intravenously (n = 10) under double-blind conditions, using identical behavioral rating measures. OCD symptoms were significantly increased after intravenous mCPP (0.1 mg/kg), but not after oral mCPP (0.5 mg/kg). Anxiety and other ratings were markedly elevated after intravenous mCPP administration. After oral mCPP administration, anxiety and most other self-ratings were only slightly elevated in comparison to placebo administration, and behavioral rating increases were no different for the OCD patients compared to age-matched healthy controls. Pretreatment with the potent serotonin (5-HT) antagonist, metergoline, prior to intravenous mCPP was associated with essentially complete blockade of the exacerbation in OCD symptoms and the other behavioral responses in the OCD patients. These results suggest that the behavioral response of OCD patients to mCPP are variable and depend on the route and dose of mCPP. In addition, the ability of metergoline to antagonize the behavioral effects of intravenous mCPP suggests that these responses are mediated by 5-HT1/5-HT2 receptors.

A preliminary investigation of the lifetime prevalence of anorexia and bulimia nervosa in patients with obsessive compulsive disorder.

BACKGROUND: Obsessive compulsive disorder (OCD) is currently classified as an anxiety disorder although it possesses many characteristics that distinguish it from other anxiety disorders. Clinically and neurobiologically, OCD appears to overlap somewhat with the eating disorders. METHOD: To assess in a controlled fashion the lifetime prevalence of the eating disorders in patients with OCD, we administered portions of the Structured Clinical Interview for DSM-III-R, Patient Version (SCID-P), to 62 patients (31 men, 31 women) with a primary DSM-III-R diagnosis of OCD. RESULTS: Among the OCD patients, the lifetime prevalence of anorexia nervosa and/or bulimia nervosa was 12.9% (N = 8), and an additional 17.7% (N = 11) met subthreshold criteria for either anorexia or bulimia nervosa. Interestingly, unlike multiple epidemiologic studies that have reported a substantial female preponderance among patients diagnosed with anorexia or bulimia nervosa, there was no significant gender difference in the lifetime prevalence of eating disorders among the patients with OCD. Almost 13% (N = 4) of the men and 6.5% (N = 2) of the women with OCD met criteria for a lifetime diagnosis of anorexia nervosa and 3.2% (N = 1) of the men and 6.5% (N = 2) of the women with OCD met criteria at some time in their lives for bulimia nervosa. In addition, subthreshold criteria for anorexia nervosa or bulimia nervosa were met by an additional 12.9% (N = 4) of the men and 22.6% (N = 7) of the women. CONCLUSION: These data suggest that OCD patients, regardless of gender, have a substantial lifetime prevalence of anorexia and/or bulimia nervosa.

A double-blind, placebo controlled study of trazodone in patients with obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) have been shown to be preferentially responsive to serotonin (5-HT) uptake-inhibiting antidepressants including clomipramine, fluoxetine, fluvoxamine, and sertraline. The nontricyclic antidepressant, trazodone, also possesses serotonin reuptake inhibiting properties and has been reported to be efficacious in OCD in several case reports and open trials. In order to investigate trazodone's potential antiobsessive efficacy in a controlled fashion, 21 patients with OCD were entered into a double-blind, parallel design comparison of trazodone and placebo. There were no significant differences in baseline rating scores of OCD or depressive symptoms between those who entered the trazodone phase (N = 13) versus those who entered the placebo phase (N = 8). As measured by standardized OCD and depression rating scales, there was no significant difference in OCD or depressive symptoms in the 17 patients who completed 10 weeks of trazodone (N = 11, mean daily dose, 235 +/- 10 mg) versus 10 weeks of placebo (N = 6) administration. In comparison to clomipramine and fluoxetine treatment which we have found to be associated with greater than 95% reduction in platelet 5-HT concentration, there was only a 26% mean reduction in platelet 5-HT concentration after 10 weeks of trazodone administration. These results indicate that trazodone lacks substantial antiobsessive effects and is associated with only modest reductions in platelet 5-HT concentrations.

Teacher, parent, and child evaluative ratings of a school reintegration intervention for children with newly diagnosed cancer.

The disruption of school participation and accompanying social experiences because of cancer and its treatment has been related to major problems in adaptation to the disease. For the child with cancer, continuation of his/her social and academic activities provides an important opportunity to normalize as much as possible a very difficult experience. The present study reports on the children's, parents', and teachers' subjective evaluations of the benefits of a comprehensive school reintegration intervention. Forty-nine children, newly diagnosed with cancer, received comprehensive school reintegration consisting of supportive counseling, educational presentations, systematic liaison between the hospital and the school, and periodic follow-ups. Children parents, and teachers were asked to rate their perceptions of the utility and value of the intervention approach. Overall subjective evaluations were very positive, providing support for the social validity of the school reintegration approach for children with newly diagnosed cancer.

Symptoms of eating disorders in patients with obsessive-compulsive disorder.

OBJECTIVE: This study was designed to explore potential overlap of the symptoms of obsessive-compulsive disorder and eating disorders. METHOD: The authors administered a structured, self-rating scale, the Eating Disorder Inventory, to 59 outpatients at an obsessive-compulsive disorder clinic and to 60 sex-matched normal volunteers. The Eating Disorder Inventory has been previously validated as a reliable measure of the specific cognitive and behavioral dimensions of the psychopathology typical of patients with eating disorders. The scores of the patients with obsessive-compulsive disorder and of the healthy comparison subjects were compared with those of 32 female inpatients with anorexia nervosa (N = 10) or bulimia nervosa (N = 22) who had also been given the inventory. RESULTS: The patients with obsessive-compulsive disorder scored significantly higher than the healthy comparison subjects on all eight subscales of the Eating Disorder Inventory: drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness, and maturity fears. Relative to the healthy subjects, male patients with obsessive-compulsive disorder had more symptoms than female patients with obsessive-compulsive disorder. The scores of the female patients with obsessive-compulsive disorder were midway between those of the 32 female patients with eating disorders and those of the 35 female normal subjects. CONCLUSIONS: These results suggest that patients with obsessive-compulsive disorder display significantly more disturbed eating attitudes and behavior than healthy comparison subjects and that they share some of the psychopathological eating attitudes and behavior that are common to patients with eating disorders.

Cognitive functioning in long-term survivors of childhood leukemia: a prospective analysis.

Treatment-related cognitive impairments have been reported for survivors of childhood leukemia following prophylactic central nervous system (CNS) treatment with 2400 cGy craniospinal irradiation and intrathecal chemotherapy. The present study was designed to prospectively evaluate cognitive functioning of 24 children prior to CNS prophylaxis of 1800 cGy of craniospinal irradiation and intrathecal drugs, and at intervals of 1 and 4-5 years. At diagnosis, prior to CNS treatment, all 24 subjects performed in the average range of intelligence, as measured by the Wechsler Intelligence Scales. Subjects continued to perform in the average range with no significant declines at the 1-year follow-up. Significant declines in cognitive functioning, however, were found at the 4- to 5-year follow-up period, with five subjects (21%) performing in the low average or borderline levels of intelligence. Of the 19 subjects performing in the average range, five showed significant discrepancies between Verbal and Performance IQ scores. Nine subjects exhibited poor performance on a subtest cluster assessing perceptual and attentional processes. With regard to school experiences, 50% of the subjects had received some type of special education services. The findings indicate the need for annual evaluations of cognitive functioning in long-term survivors of childhood leukemia who received 1800 cGy craniospinal irradiation, to identify potential cognitive late effects of treatment requiring appropriate special education services.

Coronary heart disease morbidity and mortality in hypercholesterolemic men predicted from an exercise test: the Lipid Research Clinics Coronary Primary Prevention Trial.

A positive exercise electrocardiogram (ECG) has been proved to predict cardiovascular events in asymptomatic normolipidemic men. To study whether it is also predictive for hypercholesterolemic men, data from 3,806 asymptomatic hypercholesterolemic men in the Lipid Research Clinics Coronary Primary Prevention Trial were analyzed. All the men had performed a submaximal treadmill exercise test at baseline, before they were assigned to the cholestyramine or placebo treatment group. Because of missing or inconclusive data, 31 men were excluded from the analyses. A test was positive if the ST segment was displaced by greater than or equal to 1 mm (visual code) or there was greater than or equal to 10 microV-s change in the ST integral (computer code), or both. The prevalence of a positive test was 8.3%. During the 7 to 10 year (mean 7.4) follow-up period, the mortality rate from coronary heart disease was 6.7% (21 of 315) in men with a positive test and 1.3% (46 of 3,460) in men with a negative test (placebo and cholestyramine groups combined). The age-adjusted rate ratio for a positive test, compared with a negative test, was 6.7 in the placebo group and 4.8 in the cholestyramine group. With use of Cox's proportional hazards models, it was found that the risk of death from coronary heart disease associated with a positive test was 5.7 times higher in the placebo group and 4.9 times higher in the cholestyramine group after adjustment for age, smoking history, systolic blood pressure, high density lipoprotein cholesterol and low density lipoprotein cholesterol. A positive test was not significantly associated with nonfatal myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Smoking, physical activity, and other predictors of endurance and heart rate response to exercise in asymptomatic hypercholesterolemic men. The Lipid Research Clinics Coronary Primary Prevention Trial.

The association of known coronary risk factors with progressive submaximal treadmill exercise tolerance test performance was studied in 6,238 asymptomatic white 34-60-year-old hypercholesterolemic men screened between 1973 and 1976 for the Lipid Research Clinics Coronary Primary Prevention Trial. Cigarette smoking and habitual physical inactivity were each associated with a doubling of the rate of symptom-related discontinuation of the exercise test; the tests of sedentary smokers were discontinued at four times the rate observed for active nonsmokers. Smaller increases in heart rate were observed during exercise testing in physically active men and in smokers than in their sedentary and nonsmoking counterparts. Thus, smoking, like habitual physical activity, reduced the heart rate required to sustain a given external workload. However, the heart rates of smokers tended to remain elevated after exercise, while those of physically active men returned more rapidly toward resting levels. Age, Quetelet index, and low plasma levels of high density lipoprotein cholesterol were also strong predictors of decreased endurance, while resting heart rate and blood pressure levels were significant predictors of heart rate response. Comparison of these results with those previously reported for ischemic electrocardiographic changes in this cohort suggests that coronary risk factors may selectively influence specific aspects of exercise tolerance test performance.

Predictive value of the exercise tolerance test for mortality in North American men: the Lipid Research Clinics Mortality Follow-up Study.

More than 3600 white men, from 30 to 79 years old and without a history of myocardial infarction, underwent submaximal treadmill exercise tolerance tests as part of their baseline evaluation for the Lipid Research Clinics Mortality Follow-up Study. The exercise test was conducted according to a common protocol and coded centrally; depression of the ST segment by at least 1 mm (visual coding) and/or 10 microV-sec (ST integral, computer coding) signified a positive test. Concurrent measurements of age, blood pressure, history of cigarette smoking, and plasma levels of lipids, lipoproteins, and glucose, as well as other coronary risk factors, were obtained. Cumulative mortality from cardiovascular disease was 11.9% (22/185) over 8.1 years mean follow-up among men with a positive exercise test vs 1.2% (36/2993) over 8.6 years mean follow-up among men with a negative test. Three-quarters (43) of these deaths were due to coronary heart disease. The relative risk for cardiovascular mortality associated with a positive exercise test was 9.3 before and 4.6 after age adjustment. Cardiovascular mortality rates were especially elevated (relative risk 15.6 before and 5.1 after age adjustment) among the 82 men whose exercise tests were adjusted "strongly" positive based on degree and timing of the ischemic electrocardiographic response. A positive exercise test was also moderately associated with noncardiovascular mortality; the relative risk for all-cause mortality was 7.2 before and 3.4 after age adjustment. The relative risk for cardiovascular mortality associated with a positive exercise test was not appreciably altered by covariance adjustment for known coronary risk factors other than age. A positive exercise test was a stronger predictor of cardiovascular death than were high plasma levels of low-density lipoprotein cholesterol, low plasma levels of high-density lipoprotein cholesterol, smoking, hyperglycemia, or hypertension. Its impact on risk of cardiovascular death was equivalent to that of a 17.4 year increment in age.

Dyslipoproteinemias and manifestations of coronary heart disease. The Lipid Research Clinics Program Prevalence Study.

The Lipid Research Clinics Prevalence Study population underwent a noninvasive evaluation to assess the odds of coronary heart disease (CHD) among individuals with various types of dyslipoproteinemia (DLP) relative to the odds for individuals free of DLP in a nonselected population. The noninvasive evaluation included the Rose questionnaire for angina, a resting electrocardiogram, and a graded treadmill exercise test. The presence of manifestations of CHD was assessed by a combination of these findings. Multiple linear regression and multiple logistic regression analyses were used to evaluate associations between CHD and DLP, with adjustments for the following covariates: age, body mass, systolic blood pressure, alcohol consumption, and cigarette use. There were no consistent associations in women or in men 30 to 49 years old. In men 50 to 69 years old, the mean high-density lipoprotein cholesterol (HDL-C) values and HDL-C/cholesterol ratio were significantly lower in the definite CHD and angina categories, compared with the negative (no evidence of CHD) group. Higher odds ratios for CHD were present in those classified as having type IIa, type IV, and hypoHDL DLPs, relative to those classified as normal by the phenotyping algorithm. These associations were consistent across the several categories of CHD manifestations, but did not reach statistical significance after adjustment for multiple testing. A statistically significant lower odds ratio for CHD was observed in men 50 to 69 classified as having hyperHDL when compared with those without DLPs. The associations between CHD and the various forms of DLP were consistent with those observed between CHD and the plasma lipid and lipoprotein-cholesterol concentrations. The Lipid Research Clinics Prevalence Study confirmed the relationship between elevated low-density lipoprotein cholesterol, decreased HDL-C, and noninvasively determined CHD in a free-living asymptomatic population of older men.

Coronary risk factors and exercise test performance in asymptomatic hypercholesterolemic men: application of proportional hazards analysis.

The association of established coronary risk factors with submaximal graded treadmill exercise test performance was examined in 6,850 asymptomatic, white 34--59-year-old hypercholesterolemic men screened between 1973 and 1976 at 12 North American Lipid Research Clinics for participation in their Coronary Primary Prevention Trial. The prevalence of ischemic electrocardiographic responses (greater than or equal to 1 mm S-T segment depression) was 8.6%. The Cox proportional hazards method was adapted so as to take into account the level of exercise at which ischemic responses occurred and to which subjects without ischemic responses were exposed. The results were compared with those obtained by standard logistic regression. In both models, age, blood pressure, plasma cholesterol, and (inversely) plasma high-density lipoprotein cholesterol and alcohol consumption were significant independent predictors of an ischemic response to exercise. Surprisingly, ischemic responses were less frequent in smokers than in nonsmokers. However, when the proportional hazards method was used, cigarette smoking was weakly but significantly (p less than 0.01) predictive of an ischemic response on the treadmill. Results from this model differed from those of the logistic model because the former takes into account the reduced exercise capacity of smokers, which renders them less likely to reach workloads sufficient to induce myocardial ischemia. The proportional hazards model similarly demonstrated a possible beneficial effect of habitual physical activity which was not apparent in the logistic model. Quetelet index and plasma triglyceride were only weakly associated with the probability of an ischemic response, and did not contribute significantly to either model.

Predictors of systolic blood pressure response to treadmill exercise: the Lipid Research Clinics Program Prevalence Study.

We used multiple linear regression to study predictors of systolic blood pressure response (SBPR), i.e., the increase in pressure above baseline after 3, 6, and 9 min of treadmill exercise, in 4262 men and women. Predictors considered were usual SBP, the difference (delta SBP) between resting SBP and SBP immediately before exercise, age, education, obesity index, alcohol consumption, cigarette smoking, preexercise heart rate and, in women, gonadal hormone use. In men, age, obesity index, and cigarette smoking were positively associated with SBPR and in women 20 to 49 years old, age, obesity index, and alcohol consumption were positively associated with SBPR. In women 50 years old or older, usual SBP was negatively associated with SBPR. In both men and women a larger delta SBP was associated with a smaller SBPR. These results help explain the considerable variation in SBPR, and the delta SBP results suggest that potential SBPR may, to certain extent, have a specific, finite range. The similarity of predictor variables for SBPR to predictor variables for hypertension is concordant with the previous observation that a high SBPR may foreshadow subsequent hypertension.

A lysine-absorbable plasminogen activator is elevated in conditions associated with increased fibrinolytic activity.

A plasminogen activator, or class of activators, that absorbs to lysine-agarose is present in human plasma. We have developed a quantitative assay for this plasminogen activator. The assay involves removal of the activator from plasma with lysine-agarose affinity columns and subsequent measurement of the activity by the conversion of plasminogen to plasmin on standardized fibrin agar plates. Using this assay, we investigated three physiologic conditions that have in the past been associated with increased fibrinolytic activity to determine whether elevation of the LAPA was involved. Normal individuals undergoing strenuous physical exercise and others subjected to venous occlusion as well as patients with cirrhosis of the liver were examined. Treadmill exercise to maximal exertion produced up to 15-fold increases in the level of LAPA; venous occlusion produced similar elevation. Certain individuals did not show increase fibrinolytic activity in response to exercise or venous occlusion, as indicated by unchanged euglobulin lysis times. These fibrinolytic hyporesponders did not show an elevation of their LAPA levels. In the third group examined, patients with cirrhosis, 24 of 62 had elevated levels of LAPA. Supplementation of plasma from normal individuals with this plasminogen activator from exercised individuals and cirrhotics resulted in increased rates of clot lysis.