Acta Neuropsychiatrica 2007: 19: 118121 All rights reserved DOI: 10.1111/j.1601-5215.2006.00169.

# 2007 The Authors Journal compilation # 2007 Blackwell Munksgaard

ACTA NEUROPSYCHIATRICA

Brief report

Obsessive compulsive disorder in adults with rheumatic heart disease

Ashfaq-U-Rahaman, Janardhan Reddy YC, Prabhavathi, Pramod Kumar Pal. Obsessive compulsive disorder in adults with rheumatic heart disease. Objective: There are considerable data on the possible association between streptococcal infection and obsessive compulsive disorder (OCD), particularly the relation between Sydenhams chorea (SC) and OCD. However, neuropsychiatric sequelae related to streptococcal infection are mainly reported in children. In this preliminary study, we examined prevalence of OCD in a group of adult subjects with established rheumatic heart disease (RHD). We hypothesized that the rate of OCD would be higher than the known general population rates. Method: One hundred adult subjects with RHD were evaluated for OCD and other comorbid psychiatric disorders using well-known psychiatric assessment tools. A qualified psychiatrist conducted the assessments. The diagnoses were made according to DSM-IV criteria. Results: The rate of clinical OCD and subclinical OCD was 10% and 3%, respectively (n 13), a rate much higher than the 13% rate reported in general population. Of the 13 subjects, only three had a history of SC (23%). Conclusions: OCD could be a long-term sequel in adults with a history of rheumatic fever in childhood, even in the absence of frank chorea. The findings call for systematic research in this little explored area.

Ashfaq-U-Rahaman1, Y. C. Janardhan Reddy1, Prabhavathi2, Pramod Kumar Pal3

1 Department of Psychiatry, NIMHANS, Bangalore, India; 2Department of Cardiology, Sri Jayadeva Institute of Cardiology, Bangalore, India; and 3 Department of Neurology, NIMHANS, Bangalore, India

Keywords: comorbidity; obsessive compulsive disorder; rheumatic heart disease Dr Y. C. Janardhan Reddy, Obsessive Compulsive Disorder Clinic, Department of Psychiatry, NIMHANS, Bangalore 560029, India. Tel: 0091-80-26995278, 26995306; Fax: 0091-80-26564822; E-mail: jreddy@nimhans.kar.nic.in, ycjreddy@yahoo.com

The association between Sydenhams chorea (SC), a classic postinfectious autoimmune basal ganglia disorder, and obsessive compulsive disorder (OCD) is well documented (1). There is also considerable interest in the pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a subtype of pediatric OCD with distinctive course but no obvious chorea (2). OCD occurring in the context of streptococcal infections is attributed to autoimmunity (3) against basal ganglia (4). Support for autoimmune hypothesis comes from the presence of autoantibodies that bind to basal ganglia proteins in both SC and PANDAS (5). The role of basal ganglia involvement in OCD is well documented. Neuroimaging studies suggest involvement of orbitofrontal-subcortical circuitry that involves orbitofrontal cortex, anterior cingulum, basal ganglia (caudate in particular) and thalamic structures (6,7). It appears that involve118

ment of basal ganglia is critical to the development of OCD [for detailed review, see Saxena and Rauch and Whiteside et al. (6,7)]. In the background of this knowledge, we hypothesized that the rate of OCD would be higher in adults with a history of rheumatic fever (RF) in childhood than the rates known in general population because of the longterm sequelae of potential autoimmune insult to the basal ganglia even in the absence of history of SC. There is some evidence for increased prevalence of OCD in RF even in the absence of SC (8), leading to the speculation that there could be a subthreshold autoimmune insult to the basal ganglia, which results in behavioral sequelae instead of frank chorea (9). However, neuropsychiatric sequelae related to streptococcal infection are mainly reported in children, with the exception of one recent study that found no evidence for increased prevalence of OCD in adults with a history of RF (10). This study examined the

OCD in RHD prevalence of OCD in a group of adult subjects with established rheumatic heart disease (RHD). We chose subjects with RHD because presence of established RHD is a definite proof of a history of RF. (67%), with almost even distribution of subjects from rural (51%) and urban (49%) backgrounds. A majority was Hindus (89%) and married (85%). The mean number (SD) of years of education was 6.19 (4.81) years. A history of major Jones criteria other than carditis was as following: polyarthritis in 41%, SC in 9%, subcutaneous nodules in 3% and erythema marginatum in 1%. As determined by echocardiography, mitral stenosis was the commonest valvular lesion (81%). Seventy-one subjects were on regular penicillin prophylaxis, and 20 were not taking penicillin regularly. The remaining nine subjects were not on prophylactic penicillin. A lifetime diagnosis of clinical OCD or subclinical OCD was present in 13 subjects (13%), 10 of them being female (77%): current clinical OCD in 9, current subclinical OCD in 3, and a history of OCD in 1 subject. The mean age of onset (SD) of RF and OCD was 12.76 (4.88) and 25.87 (9.58) years, respectively. In all the 13 subjects, OCD postdated RF. Of the 13 subjects, only three had a history of SC (23%). Six subjects with a history of SC did not have OCD. Major depression was the commonest current comorbid condition (41%). Comorbidity profile in the 100 subjects with RHD and the symptom profile in the 13 subjects with obsessional symptoms are given in Table 1. The subjects with lifetime diagnosis of clinical OCD or subclinical OCD (n 13) did not differ from those without with regard to age, gender, religion, urban/rural background, occupational status and years of education. However, those with OCD had significantly higher rates of current major depression (77 vs. 36%, p .007) than those without OCD.

Methods

One hundred adult cases with RHD (.18 years) diagnosed by a senior cardiologist based on clinical and echocardiographic evidence formed the sample of this study. We recruited consecutively the patients receiving treatment at the Sri Jayadeva Institute of Cardiology, Bangalore, India, over a period of 6 months. Informed consent was obtained from all the patients. The study was conducted as per the Ethical Guidelines for Biomedical Research Involving Human Subjects of the Ethics Committee of National Institute of Mental Health and Neurosciences. Doppler echocardiography has emerged as a safe, sensitive and noninvasive method for the diagnosis of RHD; its findings correlate very closely to those of cardiac catheterization and, therefore, considered adequate to diagnose RHD (11). Psychiatric assessments were performed using the Mini International Neuropsychiatric Interview (MINI) (12), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (13) and the tics and attention deficit disorder subsections of the Schedule for Tourette and other Behavioral Syndromes (14). A detailed clinical neurological examination was also performed. The MINI is a short structured diagnostic interview for diagnosing major axis-I psychiatric disorders according to the current classificatory systems. The Y-BOCS has a symptom checklist, and a 10-item clinician administered scale widely used for assessing severity of OCD. The Schedule for Tourette and other Behavioral Syndromes has an exhaustive checklist of motor and phonic tics and assesses worst ever and current severity of tics. It also has a 21-item questionnaire that helps in diagnosing attention deficit hyperactivity disorder as per DSM-IV criteria. All psychiatric diagnoses were made according to DSM-IV criteria. The principal author was trained to administer the instruments and performed all the detailed psychiatric assessments. The final diagnoses were made by the consensus opinion of the two authors (AUR and YCJR).

Discussion

Results

The mean age [standard deviation (SD)] of the subjects was 33.09 (9.22) years. The sample consisted of predominantly female subjects

In the assessment of psychiatric morbidity, the most striking finding was the increased prevalence of OCD (10%) in the patients with RHD compared with the reported general population prevalence of about 13% in various epidemiological studies (1517). The overrepresentation of female subjects in those with OCD is somewhat consistent with the epidemiological data but is also reflective of the female preponderance in the sample. The 10% rate of OCD in this sample of patients with RHD is five-fold higher than the general population rate suggesting, a possible etiological relationship between RHD and OCD. The existing literature on neuropsychiatric complications of RF is largely confined to acute phases of RF in children with the exception of a recent 119

Ashfaq-U-Rahaman et al.
Table 1. Clinical characteristics of the sample Psychiatric comorbidity (N 100) Major depressive disorder, current Major depressive disorder, past Dysthymia OCD, current OCD, past Subclinical OCD Panic disorder, current Agoraphobia without panic disorder, current Social phobia, current Generalized anxiety disorder, current Bipolar disorder Psychosis Tics disorder Attention deficit hyperactivity disorder Profile of obsessive compulsive symptoms* (N 13) Obsessions, n (%) Aggressive Contamination Sexual Religious Symmetry, ordering Hoarding Somatic Miscellaneous Compulsions, n (%) Washing, cleaning Checking Repeating Counting Ordering, arranging Hoarding Miscellaneous Y-BOCS score in current OCD, mean (SD) Y-BOCS score in subclinical OCD, mean (SD)

41 9 1 9 1 3 2 4 1 1 1 1 1 3

1 7 0 2 4 1 3 7

(8) (54) (15) (31) (8) (23) (54)

5 (38) 1 (8) 3 (23) 2 (15) 3 (23) 1 (8) 3 (23) 18.00 (3.71) 10.00 (4.58)

*Symptom profile in the subjects with clinical and subclinical OCD (clinical 10, subclinical 3).

study that reported high rates of OCD and related spectrum disorders in a sample of nonacute subjects with RF that consisted mainly children (18). Literature on long-term neuropsychiatric complications in adults with a history of RF is scarce. This is surprising considering that RF has long-term complications related to other systems such as heart and joints. A recent study examined OC symptoms in a small sample of adults with a history of RF and found no increased propensity for OCD in adulthood (10). The study concluded that the neuropsychiatric manifestations possibly occur only in acute RF phases. However, in support of our hypothesis, there is an intriguing case report of an adult who developed OCD following a group-A beta hemolytic streptococcal infection after a latent period of 3 years (19). The case report has two main implications relevant to this study. First, the case report shows that poststreptococcal neuropsychiatric disorders are not limited to children. Second, the report shows that they can develop even after a relatively long latent period. 120

It is postulated that children might exhibit only tics or OCD if the dose of a presumed etiologic agent was not sufficient to cause frank chorea (9). This hypothesis implies that neuropsychiatric manifestations are dose dependent and that the manifestations lie on a continuum of impairment, ie psychiatric manifestations such as OCD occur at lower doses and SC occurs at higher doses. Our study does not support this hypothesis unequivocally. For example, three patients had both SC and OCD, whereas the other six subjects who had SC did not have OCD. However, our finding is supportive of the speculation that there could be basal ganglia damage even in the absence of frank chorea and that OCD could be a long-term sequel of such damage (9). It has been suggested that immunologic stress may result in compromised blood-brain barrier that results in influx of antineuronal antibodies into the central nervous system (20). Imaging studies of children with PANDAS have shown reduced caudate nucleus volumes in those with chronic OCD, suggesting that repeated bouts of inflammation could be the cause of shrinkage in the volume of caudate nuclei (4). It is possible that repeated bouts of infections could result in further damage to caudate nuclei in subjects with RHD too resulting in increased risk for OCD. Considering that basal ganglia involvement is crucial in the current neuroanatomic model of OCD (6,7), we speculate that RF results in the development of antibodies that cross-react with basal ganglia proteins and increase the vulnerability to develop OCD in the long run. The study provides preliminary clinical evidence that OCD could be a sequel of RF. The study has several shortcomings including the absence of a control group and unblind assessments. It could also be argued that a high prevalence of major depression in the subjects with OCD may have confounded the assessment of OCD. Despite its limitations, the study explores a little studied area and provides directions for more systematic studies in the future. The findings of the study need to be replicated by studies with a more robust methodology including a larger sample, a matched medically ill control group with commensurate rate of depression and, if feasible, blind assessments. Further, it would be prudent for future studies to collect immunological, neuroimaging and family genetic data to validate the concept.
Acknowledgements
This study was conducted as a part fulfillment toward the completion of MD course in Psychiatry by the first author. The

OCD in RHD
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