Biomedical subjects
Publications and source records attributed to S A Rasmussen.
During the past decade, there has been rapid growth in understanding the clinical features, pathophysiology, and treatment of obsessive compulsive disorder (OCD). This article reviews the current state of knowledge of the epidemiology and clinical features of OCD with a focus on the disorder's phenomenologic heterogeneity and its comorbidity with other Axis I and Axis II syndromes.
Obsessive compulsive disorder is now recognized as a common psychiatric disorder. The lifetime prevalence of 2% to 3% found in the United States has also been found in epidemiologic studies in several other countries with diverse cultures. This disorder has previously been underestimated due to a number of factors that include patients' reluctance to spontaneously admit to obsessions and compulsions and the omission of screening questions about obsessive compulsive disorder on routine mental status examinations. Depression and other anxiety disorders frequently co-occur with obsessive compulsive disorder, which may contribute to misdiagnosis. Patients with eating disorders, Gilles de la Tourette's syndrome, and schizophrenia have a greater comorbid risk compared with the general population. Differential diagnosis of obsessive compulsive disorder includes generalized anxiety disorder, panic disorder, phobias, compulsive personality disorder, and hypochondriasis. While many of these syndromes are characterized by intrusive thoughts, few have associated rituals. The complex tics seen in some patients with Tourette's syndrome may be difficult to distinguish from the compulsions seen in obsessive compulsive disorder, and, in fact, there is significant overlap in symptoms between the two disorders. Currently, the impulse control disorders, such as compulsive gambling and the paraphilias, are not considered to be part of obsessive compulsive disorder. Although the phenomenology of obsessive compulsive disorder appears to be quite diverse, with many distinct kinds of obsessions and compulsions, there are three important core features: abnormal risk assessment, pathologic doubt, and incompleteness. These features cut across phenomenological subtypes and may be useful in defining homogeneous subgroups with distinct treatment outcomes.
During a seven-years period, 898 women (9.9% of all deliveries) had a cesarean section at the Department of Obstetrics and Gynecology, University Hospital of Tromsø. 29.3% of the women suffered one or more complications (8.5% intraoperative, 23.1% postoperative). The most common complication was infection (22.3%). The following factors were associated with the occurrence of complications: emergency operation, obesity, labor prior to surgery, increased duration of labor or rupture of fetal membranes prior to operation, low gestational age, and station of the presenting part of the fetus below the ischial spinal plane. The same tendency was found for intra- and postoperative complications. Hb levels less than 12.0 g/100 ml increased the risk of infection. We suggest ways of reducing both the number of cesarean sections and the number of complications.
To evaluate whether serotonin reuptake inhibition is critical to the treatment of obsessive-compulsive disorder, 40 outpatients with a principal diagnosis of obsessive-compulsive disorder were randomized in a double-blind fashion to 8 weeks of treatment with either the serotonin reuptake inhibitor fluvoxamine maleate (n = 21) or the norepinephrine reuptake inhibitor desipramine hydrochloride (n = 19). Fluvoxamine was significantly better than desipramine in reducing the severity of obsessive-compulsive symptoms, as measured by the Yale-Brown Obsessive Compulsive Scale and by the global response rate ("responder" equaling "much improved"). Eleven of 21 patients were responders with fluvoxamine compared with 2 of 19 patients with desipramine. Fluvoxamine, but not desipramine, was also effective in reducing the severity of "secondary" depression. Fluvoxamine-induced improvement in symptoms of obsessive-compulsive disorder was not correlated with the severity of baseline depressive symptoms. This study provides additional evidence that the acute serotonin reuptake properties of a drug are predictive of its anti-obsessive-compulsive efficacy. It is hypothesized that the mechanism of action of serotonin reuptake inhibitors in obsessive-compulsive disorder may be related to chronic treatment-induced adaptive changes in presynaptic serotonin receptor function (eg, autoreceptor desensitization) and/or indirect influences on dopaminergic function (eg, in the basal ganglia).
Here we report on 4 unrelated patients with reciprocal translocations which resulted in duplication of the distal portion of chromosome 1q. Although the patients had certain non-specific malformations in common, our investigation and a review of the literature do not suggest the existence of a distinct phenotype due to this chromosome abnormality. We think that the coexisting deletion present in each of these patients is responsible for most of the observed differences in clinical manifestations. The variable phenotype makes clinical recognition difficult and precludes making a long-term prognosis.
Etiologic studies of birth defects often use family history information provided by parents of patients. The validity of this information has not been adequately assessed. Using data from the Atlanta Birth Defects Case-Control study, we evaluated sensitivity, specificity, and positive predictive value of mothers' responses regarding the presence of birth defects in their offspring. A total of 4929 mothers of infants with major structural defects ascertained by the Metropolitan Atlanta Congenital Defects Program and a total of 3,029 mothers of normal infants were asked whether their babies had had a birth defect or a health problem diagnosed during the first year of life. Interviewers and coders of maternal responses were blinded to the case-control status of infants. Sensitivity (the proportion of case mothers who gave responses that could be coded as denoting a major birth defect) was 61%. Specificity (the proportion of control mothers who gave responses that could not be coded as denoting a major birth defect) was 98%. The positive predictive value (the proportion of mothers who gave a major-birth-defect response who in fact had babies with major birth defects) was estimated as 47%. Sensitivity, specificity, and positive predictive value varied by maternal sociodemographic factors such as race and education, as well as by type of defect. These results suggest that family history data obtained through maternal interviews should be cautiously interpreted and, if not properly validated, may alter estimates of recurrence risks.
Until the early 1980s, the only estimate of the prevalence of obsessive compulsive disorder (OCD) in the general population was 0.05%. Data collected from the Epidemiology Catchment Area (ECA) survey have suggested that OCD is 50 to 100 times more common than previously believed and twice as common as schizophrenia or panic disorder in the general population. These results have been corroborated in a second, more carefully designed epidemiologic study. Several reasons account for the previous underestimation of the prevalence of the disorder: (1) reluctance of patients to divulge their symptoms; (2) lack of recognition of the diversity of presenting symptoms in OCD by professionals; (3) misdiagnosis; (4) failure to ask OCD screening questions in the routine mental status examination. Demographic and clinical characteristics of the disorder have been consistent across studies and time, supporting the validity of current nosologic criteria and the disorder's relative homogeneity. OCD appears to be familial, suggesting that genetic factors play a prominent role in the phenotypic expression of illness.
A six- to eight-week double-blind placebo-controlled trial of the potent and selective serotonin reuptake inhibitor fluvoxamine was conducted in 42 patients with primary obsessive-compulsive disorder (OCD). Approximately one half of the patients also had symptoms of major depression. Fluvoxamine was significantly better than placebo on all measures of obsessive-compulsive symptoms. Nine of 21 patients were responders ("much improved") with fluvoxamine compared with no responders with placebo, and fluvoxamine was effective in patients with OCD both with and without secondary depression. Response of OCD was not correlated with severity of baseline depression. These data lend partial support to the serotonin hypothesis of OCD. However, since a number of patients failed to respond to fluvoxamine, the role of other neurochemical systems in this disorder needs to be explored.
The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessive-compulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's alpha coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.
The development design and reliability of the Yale-Brown Obsessive Compulsive Scale have been described elsewhere. We focused on the validity of the Yale-Brown Scale and its sensitivity to change. Convergent and discriminant validity were examined in baseline ratings from three cohorts of patients with obsessive-compulsive disorder (N = 81). The total Yale-Brown Scale score was significantly correlated with two of three independent measures of obsessive-compulsive disorder and weakly correlated with measures of depression and of anxiety in patients with obsessive-compulsive disorder with minimal secondary depressive symptoms. Results from a previously reported placebo-controlled trial of fluvoxamine in 42 patients with obsessive-compulsive disorder showed that the Yale-Brown Scale was sensitive to drug-induced changes and that reductions in Yale-Brown Scale scores specifically reflected improvement in obsessive-compulsive disorder symptoms. Together, these studies indicate that the 10-item Yale-Brown Scale is a reliable and valid instrument for assessing obsessive-compulsive disorder symptom severity and that it is suitable as an outcome measure in drug trials of obsessive-compulsive disorder.
The studies reviewed here suggest that the potent and selective serotonin reuptake inhibitor fluvoxamine is an effective treatment for OCD. Response to the antiobsessional effects of fluvoxamine is independent of baseline levels of depression. Additional studies are currently underway to determine if fluvoxamine is actually more effective in OCD than less potent blockers of serotonin reuptake (e.g., desipramine) (Goodman et al. unpublished data). However, since the clinical response to potent serotonin reuptake blockers is often incomplete or, in as many as one-third of patients, absent, the precise relevance of the monoamine reuptake blocking properties of these medications to the pathogenesis of OCD remains unclear.
Fifty patients with the diagnosis of alcohol dependence or abuse who were admitted to a university-based alcohol rehabilitation program were screened for obsessions and compulsions. Six percent (3) of the patients met DSM-III-R criteria for obsessive compulsive disorder (OCD), which is three times the lifetime prevalence for OCD found in the general population. The diagnosis of OCD is easily overlooked, so screening questions should be asked of all alcoholics during the routine clinical interview. Identifying those patients with dual diagnoses is important because treatment of the underlying OCD should improve overall clinical outcome.
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To evaluate the role of serotonin (5-HT) function in obsessive-compulsive disorder (OCD), behavioral and biochemical responses to the 5-HT receptor agonist m-chlorophenylpiperazine (MCPP) and the 5-HT precursor tryptophan were examined in healthy subjects and patients with OCD. Baseline prolactin levels and the prolactin rise following MCPP were significantly reduced in female patients compared with female healthy subjects. In contrast, the increase in prolactin level following tryptophan administration was not significantly different between male or female patients with OCD and the respective sex-matched healthy subjects. The prolactin responses to MCPP and tryptophan were both significantly higher in female patients and healthy subjects than in their male counterparts. The cortisol and growth hormone responses to MCPP and tryptophan were similar in the patients and healthy subjects and were not related to gender. The behavioral responses to MCPP or tryptophan were not consistently different between patients and healthy subjects, and neither MCPP nor tryptophan had effects on obsessive or compulsive symptoms. These results lend only partial support to the hypothesis that 5-HT dysfunction may be linked to the pathophysiology of OCD and point to the need for the evaluation of other neurotransmitter systems in future investigations of OCD.
Bipedality not only frees the hands for tool use but also enhances tool use by allowing use of the trunk for leverage in applying force and thus imparting greater final velocity to tools. Since the weight and acceleration of the trunk and forelimbs on the hindlimbs must be counteracted by muscles such as m. gluteus maximus that control pelvic and trunk movements, it is suggested that the large size of the cranial portion of the human gluteus maximus muscle and its unique attachment to the dorsal ilium (which is apparent in the Makapan australopithecine ilium) may have contributed to the effectiveness with which trunk movement was exploited in early hominid foraging activities. To test this hypothesis, the cranial portions of both right and left muscles were investigated in six human subjects with electromyography during throwing, clubbing, digging, and lifting. The muscles were found to be significantly recruited when the trunk is used in throwing and clubbing, initiating rotation of the pelvis and braking it as trunk rotation ceases and the forelimb accelerates. They stabilize the pelvis during digging and exhibit marked and prolonged activity when the trunk is maintained in partial flexion during lifting of heavy objects.
The acrocephalosyndactylies are a group of conditions with a wide variability of expression. We report a patient with features of the Pfeiffer syndrome (acrocephalosyndactyly type V), initially believed to be a new mutation in her family. Further examination of her mother demonstrated abnormalities of her right thumb which we believe may represent mild expression of the Pfeiffer syndrome. This observation illustrates the variability of phenotypic expression in the Pfeiffer syndrome and underscores the importance of careful investigation of parents and other family members when evaluating individuals with this condition.
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The authors present a case of coexisting obsessive-compulsive disorder (OCD) and bipolar affective disorder in which the obsessive-compulsive symptoms disappeared during episodes of mania and reappeared during periods of depression. Although patients with coexisting bipolar disorder and OCD are relatively rare, careful study of those patients may increase our understanding of the complex relationship between obsessive-compulsive symptoms and mood. Abnormalities in serotonergic neurotransmission have been postulated in both affective disorders and OCD and may provide important clues to the pathophysiology of OCD.