111 THE COURSE AND CLINICAL FEATURES OF OBSESSIVE- COMPULSIVE DISORDER STEVEN A. RASMUSSEN JANE L. EISEN Twenty years have passed since the landmark National Epi- to 3% of the general population in the United States meet demiology Catchment Area Survey first demonstrated the lifetime DSM criteria for OCD (4). In a World Health prevalence of obsessive-compulsive disorder (OCD) in the Organization study that determined the leading causes of general population to be 50 to 100 times greater than had mortality and morbidity in developed countries, OCDwas been previously believed (1). This unexpected finding was found to be the eighth leading cause of disability for any instrumental in the renewed interest in and rapid growth of medical or psychiatric condition for ages 15 through 44 (5). our understanding of the clinical features, pathophysiology, Total costs of the disorder in the United States have been and treatment of OCD. Epidemiologic studies in different estimated at $8 billion in 1990, including $2.1 billion in cultures have confirmed the findings that up to 1% to 2% of direct costs and $5.9 billion in indirect costs related to lost the general population worldwide suffer from the disorder at productivity (6). any given time (2). Widespread attention in the media, in However, despite the increased recognition of the public addition to growing recognition of the disorder among health significance of OCDduring the last decade, surpris- health care professionals, has resulted in improvements in ingly little is known about the long-term course and prog- the diagnosis and treatment of large numbers of patients nosis of the disorder. Most studies conducted thus far sug- with OCDwho would not even have presented for treat- gest that OCDis chronic and lifelong. For several reasons, ment before 1980. however, questions have been raised about the validity of Knowledge of the clinical features of the disorder has these findings. Previous studies have been hampered by a also expanded significantly in the last 10 years. Treatment number of methodologic limitations, including a lack of centers specializing in OCDhave succeeded in enrolling standardized assessments, small numbers of subjects, and a large cohorts of patients, so that a more sophisticated analy- sample bias toward more severely ill patients. The introduc- sis of the heterogeneity and comorbidity of OCDand the tion of effective treatments for OCDin the last 10 years relationship of these variables to treatment outcome has also raises the question of the relevance of course studies been possible. Prospective observational studies of the longi- conducted in a pretreatment era. tudinal course of OCDhave contributed further insights Obsessive-compulsive disorder spans the life cycle. It has into the clinical characteristics and prognosis of the illness been described in children as young as age 2 (7) and also (3). Improvements in methodology, including the develop- in the very elderly (8). Evidence supports the hypothesis ment of structured interviews with proven reliability and that OCDis a heterogeneous disorder with multiple causes validity, the application of survival analysis and other statis- (9). Neurobiologic studies have demonstrated abnormalities tical techniques to assess longitudinal variables, and more in frontostriatal–basal ganglia circuitry (10). Like any organ sophisticated database management systems, have been in- system, these neural circuits are susceptible to a variety of strumental in these advances. pathologic processes, including those associated with auto- Epidemiologic studies have consistently shown that 2% immune, infectious, developmental/genetic, and aging pro- cesses. Identifying homogeneous subgroups of patients with OCDshould help in unraveling its neurobiologic pathogen- Steven A. Rasmussen: Brown University, Butler Hospital, Providence, esis and developing more specific and effective treatment Rhode Island. Jane L. Eisen: Department of Psychiatry and Human Behavior, Brown strategies. Medical School, Providence, Rhode Island. This chapter reviews data related to the clinical features 1594 Neuropsychopharmacology: The Fifth Generation of Progress and course of OCDduring the lifespan. It focuses on the dren of parents with OCDfor subsequent development of heterogeneity and comorbidity of the disorder in relation the disorder is poorly defined. No data are available that to its course, and points to a new wave of studies that should would make it possible to predict this transition. Similarly, complement neurobiologic and genetic studies of the patho- almost no data are available relating the effect of continuing genesis of OCD, lead to fuller recognition of its impact on subthreshold symptoms during a period of remission to the society, and help to measure the effectiveness of behavioral likelihood of relapse in adults. Prospective quantitative lon- and pharmacologic treatment strategies that have been de- gitudinal assessment of probands with subthreshold symp- veloped during the past two decades. toms is needed in child and adult populations. SUBTHRESHOLD SYMPTOMS DEVELOPMENTAL PSYCHOPATHOLOGY It is generally agreed that it is the frequency of obsessions Little systematic study of the developmental antecedents of and compulsions, in addition to the degree with which they OCDhas been carried out since Janet. In his Obsessions interfere with function, that distinguishes normal from ab- and Psychasthenia, Janet (19) postulated that obsessions and normal. A patient must have had an hour of obsessive-com- compulsions are the most severe stage of an underlying pro- pulsive symptoms daily for a period of 6 months that inter- dromal state that he called psychasthenia, a syndrome charac- fere with social or occupational function to meet DSM-IV terized by feelings of incompleteness and imperfection. He criteria for the disorder (11). This requirement has tradi- hypothesized that all patients in whom obsessions and com- tionally been thought to translate to a score of 16 or higher pulsions develop pass through a prodromal stage of psychas- on the Yale–Brown Obsessive-Compulsive Scale (Y- thenia. His clinical descriptions of the temperamental fea- BOCS). Like symptoms of anxiety, obsessive-compulsive tures of psychasthenics coincide remarkably well with our symptoms are present to some degree in most people. Rach- preliminary findings of the prodromal symptoms of patients man and Hodgson (12) found that a high percentage of the with OCD. His description of the patient who ‘‘finds on normal population report some obsessions and compul- the stairway the word that needed to be said in the parlor’’ sions. Similarly, after screening 861 Israeli military recruits is an astute clinical description and close analogue of the at 16 years of age, Apter et al. (13) concluded that obsessive- independent variable chosen by Kagan et al. (20) to measure compulsive phenomena appear on a continuum, with few behavioral inhibition (i.e., speech latency in a novel social symptoms and minimal severity at one end and many symp- situation). It is worth noting that Janet included three of the toms and severe impairment on the other. The receiver op- five elements of DSM-III compulsive personality disorder in erating characteristics that would best distinguish the clini- his description of the psychasthenic state: perfectionism, cal from the subthreshold syndrome of OCDhave yet to restricted emotional expression, and indecisiveness. Previ- be delineated. Using Angst’s longitudinal follow-up sample, ous studies have shown that a considerable portion if not Degonda et al. (14) found a weighted lifetime prevalence the majority of patients with OCDdo not meet the DSM- for subthreshold obsessive-compulsive symptoms at age 30 III-R criteria for compulsive personality disorder. The Euro- of 5.5%. Goodman (15) screened 958 college students and pean diagnostic schema for anacastic personality is more identified 23 subjects with subclinical OCD. At follow-up directly related to Janet’s original definition of psychasthe- 1 year later, 87% continued to have significant symptoms. nia and is consistent with the idea of an obsessive spectrum It has been recognized for many years that most normal that ranges from normal obsessional behavior through ob- children go through developmental stages characterized by sessional personality to OCD. obsessive-compulsive or superstitious behavior (16). Deter- A retrospective study of 90 of our OC probands in which mining where the clinical syndrome begins and ends is im- a semistructured format was used was designed to elicit pro- portant for pharmacologic and genetic studies. For example, dromal personality traits or temperamental factors com- the multicenter collaborative studies of the selective seroto- monly found in OCD(22). Duringthis study, we identified nin reuptake inhibitors (SSRIs) in OCDnoted a higher 10 factors commonly found in our adult OC probands as rate of response to placebo in patients with Y-BOCS scores children (Table 111.1). These traits tended to vary mini- between 16 and 20, a finding that prompting some investi- mally during the childhood and adolescent years. gators to suggest that patients with Y-BOCS scores below The developmental antecedents of OCDoverlap signifi- 20 be excluded from controlled trials (17). Family genetic cantly with the behavioral inhibition syndrome in children studies have shown a higher risk for both subthreshold and that Kagan et al. (20) described. Four of the developmental clinical OCDin OCDprobands