Introduction
Every school day, Jennifer is late for her first period math class. And because of this, she is almost failing. Her teacher worries about her and wants to know if she is having trouble waking up or getting transportation to school. Jennifer shakes her head, too embarrassed to tell her teacher the truth.
Waking up on time and transportation to school are the least of Jennifer's worries. She wakes every morning at six, two hours before the first school bell rings. After her shower, Jennifer proceeds to dress herself - a task that takes nearly an hour for Jennifer to complete as she constantly dresses and undresses herself until her clothes feel "just right". As she proceeds downstairs from her bedroom, she undergoes a ritual in which a precise amount of time must be spent at each step as she descends. Jennifer soon realizes she is late for school and runs frantically to class. Halfway there, visions of a burning house persist in her mind and she runs back home to make sure the iron is turned off - which it always is. By the time she arrives at school, Jennifer is catching her breath only to find her classmates leaving for their next class.
Background information: definition, epidemiology, and symptoms
Jennifer suffers from a neuropsychiatric condition called obsessive-compulsive disorder (OCD). Jennifer is hardly an isolated case - studies have indicated that obsessive-compulsive disorder is more common than once thought. It has been estimated by the Cross-National Obsessive-Compulsive Disorder Group (CNCG) studies that the lifetime prevalence rate of OCD was a surprising 2.0-3.0 0n the United States (Weissman et al. 1994). This suggests that OCD is more than twice as prevalent as schizophrenia or panic disorder, representing the fourth most common psychiatric disorder in the United States. CNGG further confirmed prevalence rates in six other countries (Canada, Germany, Korea, New Zealand, Puerto Rico, and Taiwan) and found comparable rates of prevalence.
Obsessive-compulsive disorder was first described by French physician and psychologist Pierre Janet in his work Obsessions and Psychasthenia (1903). In it, Janet gives some of the most detailed clinical descriptions of the obsessive-compulsive condition. Many of Janet's observations have been integrated into the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) definition of OCD. Understanding the condition requires the acknowledgement of its two components: obsession and compulsion.
An obsession is a thought or image that is persistent and recurrent which causes great anxiety and distress. These thoughts are inappropriate and intrusive, going beyond the normal anxieties of everyday life. The most common obsessions is that of contamination through germs or dirt. Images of dirt, sickness, and human waste plague people with this obsession. Other obsessions include that of imagining having harmed self or others, losing control of aggressive urges, sexual thoughts and urges, religious doubt, forbidden thoughts, and a need to have things "just so". People with obsessions do not want to harbor these intrusive thoughts and often realize that these thoughts are absurd and senseless. It is often a source of great fear and embarrassment for the person. The person usually attempts to ignore such thoughts or neutralize them with some other action or thought.
In response to obsessions, people with OCD alleviate their anxiety by resorting to compulsions. Compulsions are characterized by being repetitive and clearly excessive. Though compulsions occur in response to a distressing obsession, the behaviors and mental acts do not give the sufferer any pleasure or gratification. There is only temporary relief from the anxiety caused by the obsession. In this sense, OCD should not be confused with, for example, compulsive gambling and other "compulsive" personalities because no pleasure is derived from the compulsive act in the case of OCD. Common compulsions include hand washing, checking, and ordering. Those that have obsessions about contamination respond by washing their hands until they become red and raw as a compulsive behavior. Those who obsess about the fear that they have harmed others will constantly stop at the side of the road while driving to make sure that they have not driven over anybody - a behavior known as checking. Compulsions can also be a mental exercise in repeating words silently, praying, or counting. These responses often have to adhere to rigid rules and unusual rituals that may or may not be realistically connected to the obsession. For example, a women who obsesses over the image of killing her baby must count to 10 forwards and backwards 100 times to alleviate her obsession.
In addition, the DSM-IV's criteria for OCD requires for the person to recognize that the obsessions or compulsions are excessive or unreasonable (this does not apply to children). The obsessions must also cause great distress and anxiety, interfering significantly with the person's occupational or social functioning. Often, clinicians will ask if obsessive thoughts and their behavioral responses consume more than 1 hour each day. The obsessive disturbances cannot be the direct physiological effects of a drug or general medical condition.
It is often difficult to clinically isolate and diagnose OCD because there are other conditions that have similar obsessive/compulsive-like symptoms. Though these symptoms suggest OCD, the context of the obsession/compulsion (e.g. preoccupation with body appearance in Body Dysmorphic Disorder, anxiety in the presence of a feared object or situation in phobias, hair pulling in Trichotillomania) must be recognized by an experienced clinician so that another diagnosis can be made. Furthermore, comorbidity is a common phenomenon that complicates matters even worse. A recent survey of patients at an OCD clinic found that 66% had major depression, 26uffered from panic attacks, 23% had body dysmorphic disorder, 20 0.000000e+00xhibited tics, and 5% had Tourette's Syndrome (WWW1).
Etiology: Proposed hypotheses
Though there is currently no single, proven cause of OCD, many hypotheses in the last several years have been advanced to explain the pathophysiology of this condition. These studies have reinforced the biological basis of OCD, replacing old theories that OCD was a "learned" behavior and a result of childhood experiences. Early researchers have long known that OCD had a strong hereditary component (Janet 1903). Parents with OCD have an elevated risk of transmitting the disorder to their offspring. One study showed that 190f those with OCD had first degree relatives with OCD (Riddle et al. 1990). The general nature of OCD is usually passed on and not the specific symptoms. This means that a mother with cleaning compulsions can just as likely have children with different symptoms like checking or counting compulsions. This is one argument against OCD as a "learned" behavior because the specific "learned" aspect is not conserved. Studies have also shown that the concordance rate of OCD is higher for monozygotic (identical) twins than it is for dizygotic (non-identical) twins.
Researchers of animal behavior agree on OCD's genetic basis. They argue that OCD may be a vestige of an evolutionarily conserved behavior, an innate action pattern like elaborate courtship dances among animals (WWW2). For example, grooming in dogs is a fixed action pattern that is analogous to compulsions. A disorder in dogs known as canine acral licking is characterized by compulsive licking of the leg, to the point of licking away fur and skin. Remarkably, symptoms disappear when dogs are given the same drugs used to treat OCD in people.
The use of magnetic-resonance imaging (MRI) and positron emission tomography (PET) have been integral in identifying the specific neurobiological factors in the onset and persistence of OCD. Most studies have shown that abnormalities linked to OCD lie in the pathway that connects the frontal cerebral cortex with the basal ganglia, the so-called orbitofronto-striatal-pallido-thalamic pathway (Modell et al. 1989). The frontal lobe is associated with decision making and judgement. The basal ganglia is acknowledged as the relay station where signals for the planning and execution of movements occurs. In 1987, Baxter et al. published PET results indicating significantly increased glucose metabolic rates in the left orbital gyrus of the frontal lobe in OCD patients (Baxter et al. 1987). This area of hypermetabolism was normalized once OCD patients were given effective pharmacological or behavior therapy treatment (Baxter et al. 1992). Further evidence implicating this pathway in OCD are the results of stimulation of the cingulate cortex, which is a key component in the proposed pathway. This stimulation done to normal brains induced stereotypic motions characteristic of OCD compulsions (Tailarach et al. 1973). Surgical evidence revealed that a limbic leukotomy, a procedure that affects the fronto-caudate-thalamic pathway by lesioning the cingulate and orbitomedial frontal areas, has been shown to be a successful surgical approach to alleviating OCD.
Obsessive thinking is thought to be connected to the dysfunction of the basal ganglia's ability to filter the messages relayed to the frontal cortex. MRI studies of untreated OCD patients show loss of tissue in the caudate nuclei, an important part of the basal ganglia (WWW3). Obsessive thoughts that are usually suppressed in normal individuals are "passing" through the defective caudate nucleus in OCD individuals. The seen hypermetabolism and hyperactivity of the orbital gyrus of the frontal lobe is the result because nothing prevents these thoughts from persisting. Researchers also believe that abnormalities in the caudate nucleus affect attention shifting, which would explain the "stuck" feeling that individuals get during an obsessive episode (WWW2).
There is further evidence that the basal ganglia and orbitofrontal cortex are implicated in OCD. Obsessive and compulsive symptoms can be caused by injuries to the basal ganglia or by diseases that cause their degeneration. Tourette's syndrome, Parkinson's disease, and Huntington's chorea are characterized by OCD symptoms due to their common link to the basal ganglia. OCD symptoms can also arise with carbon monoxide poisoning, which presumably causes extensive damage to the basal ganglia.
Recently, researchers have looked into the possibility that many cases of childhood onset OCD may be associated with Sydenham's chorea, a disorder associated with group A,b-hemolytic streptococcal infections (GABHS). Murphy et al. theorized that an autoimmune reaction similar to rheumatic fever causes antibodies against the streptococcus to cross-react with neuronal tissue mainly in the basal ganglia. This causes inflammation and development of movement disorders and OCD symptoms (Murphy et al. 1997). Children who presented with these symptoms were given the name PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). It was hypothesized that this type of infection may cause or exacerbate some cases of childhood-onset OCD. Following up on this, the antigenic determinant D8/17 was used to detect the prevalence of group A,(-hemolytic streptococci in the plasma of PANDAS patients. In fact, Swedo et al. found significantly higher rates of D8/17 in PANDAS patients (89%) than in healthy individuals (17%) (Swedo et al. 1997). Another study confirmed that data and demonstrated that PANDAS and OCD patients also had higher amounts of circulating antibodies against the basal ganglia (Kiessling et al. 1994). Since then, immunoglobulin and immunosuppressive doses of prednisone have successfully treated many children with apparent infection-induced OCD.
Investigation into the role of serotonin and dopamine in the pathogenesis of OCD arose from the success of pharmacological treatments at the molecular level. By working backward from effective treatment to possible etiology, hypotheses on dysfunction at the neurotransmitter level were proposed. Research into the serotonergic system in the brain is one of the more complicated topics in neurobiology and there is much that still needs to be done to elucidate the serotonergic basis of OCD. Thus far, serotonin receptor subtypes 5-HT1A and 5-HT2 have been implicated in the affected neural pathway. These subtypes have been associated with the axons that project from the raphe nuclei to the cortex and the striatum. The 5-HT1A postsynaptic receptor appears to be isolated to areas of the limbic region, while the 5-HT2 receptor is predominantly found in the cerebral cortex and, to a lesser amount, in the amygdala, cingulate, and hypothalamus. (WWW4) Increasing serotonin levels by introducing serotonin reuptake inhibitors in this pathway has proved to be a breakthrough in treatment and may lead to possible discovery of the precise cause of OCD.
Treatment
The embarrassment and shame that individuals with OCD suffer from often deter them from seeking professional help. The average time between the onset of OCD symptoms and the receipt of appropriate treatment is estimated at 17 years (Hollander et al. 1998). It is the hope of the medical community that public education about new and effective treatments will mean a better life for OCD patients and their families.
Up until this past decade, neurosurgery was the only viable option for OCD sufferers to treat their symptoms. Soon clomipramine became widely available and the first article describing the effectiveness of modern behavior therapy was published. Since then, potent selective serotonin reuptake inhibitors (SSRI's) and behavior therapy involving exposure and ritual prevention have been established as the cornerstones to effective OCD treatment.
Pharmacotherapy
The discovery of clomipramine proved to be a breakthrough in the treatment of OCD. Clomipramine is a tricyclic compound with non-selective serotonergic reuptake-inhibiting properties. Though other pharmacotherapies have been introduced, clomipramine remains the gold standard by which they are compared. As SSRI's became available, their efficacy was quickly tested and confirmed. Currently, floxetine (Prozac(), fluvoxamine (Luvox(), paroxetine (Paxil(), and sertraline (Zoloft() are FDA approved SSRI's for the treatment of OCD.
The efficacy of SSRI's reinforces the prominent role that serotonin plays in the possible pathophysiology of the disorder. Other medications operating through different pathways and neurotransmitters have been found to be less effective. Desipramine, a tricyclic compound similar to clomipramine except without serotonin reuptake inhibition properties, was studied and compared to clomipramine in double blind trials (Leonard et al. 1989). Their study showed that clomipramine was much more effective in treating OCD symptoms. The researchers thus concluded that serotonin reuptake inhibition is the key mechanism of pharmacological benefit. Potent norepinephrine reuptake inhibitors like desipramine may exhibit antidepressive action and be useful in panic suppression, but are ineffective in the treatment of OCD.
Though these drugs have revolutionized OCD treatment, they have several notable shortcomings. Clomipramine has been associated with increased risk of heart arrhythmia in children. It's properties as an anti-muscarinic and anti-histamine leads to the adverse side effects of dry mouth and sedation. Most SSRI's have lesser side effects and for this reason are often the first drug of choice in the pharmacotherapy of OCD. Common adverse effects include anxiety, nervousness, and insomnia. The benefits of the drug often does not arise until several weeks, and sometimes months, into treatment. Thus, it is imperative that OCD patients do not become discouraged and prematurely discontinue use. Acceptance and compliance can be a problem among patients as about 300f patients refuse treatment because of strict time requirements, stress involved, and lag of drug benefit. Many patients with OCD are also reluctant to take the drugs because of obsessive thoughts about contamination on the actual medication. For these people, behavior therapy or psychosurgery may be viable alternatives.
Clomipramine and SSRI's have been found to alleviate symptoms in approximately 2/3 of patients, compared to 7% who were given a placebo (WWW1). Most respondents report 50-80% reduction in symptoms. Unfortunately, complete response occurs in less than 200f patients. Maintenance of treatment gains is a major difficulty and relapse is more of a rule than an exception when medication is withdrawn. Most patients go on to take the medication for an indefinite period of time. This means that until a true cause is found for OCD, SSRI's merely represent a means for symptom alleviation and not a cure.
For the 1/3 who do not respond to clomipramine or SSRI medication, several other pharmacotherapy treatments have been proposed. In animal models of compulsive behavior, Pittman et al. hypothesized that basal ganglia hyperdopaminergic states may underlie compulsions (Pittman et al. 1989). These results agree with imaging studies of basal ganglia abnormalities and could suggest a primary role of dopamine in the pathology of OCD. Dopamine-blocking medications have been successful in trials of OCD-related disorders, including Tourette's syndrome and a subpopulation of OCD patients for whom clomipramine and SSRI's were ineffective (Goodman et al. 1992). However, it is acknowledged that the serotonergic and dopaminergic pathways are intimately related and isolating dopamine as the primary neurotransmitter of interest in OCD competes with the more acknowledged and studied serotonin model. Other studies have supported that monoamine oxidase inhibitors (MAOI) may be most effective in certain cases of OCD characterized by comorbid anxiety or depressive disorders (WWW1).
Exciting evidence recently published in the Canadian Journal of Psychiatry suggested morphine as an efficacious drug that showed dramatic effects in cases in which SSRI's, behavior therapy, and psychosurgery failed (Warnecke 1997). The author referenced several imaging studies showing a concentration of opioid receptors in the caudate nucleus, an aforementioned important region in the pathogenesis of OCD (Murin et al. 1980; Woo et al. 1985). Notably, none of the patients reported a euphoric response after each dose of morphine, which suggests that the mu subclass of opioid receptors may not be involved and the risk of addiction should be very low. Oral doses of morphine were given with doses ranging from 20 to 40 mg. Surprisingly, therapeutic effects lasted for at least 5 days following a single dose.
Behavior therapy
The behavioral approach to the treatment of OCD is the second cornerstone in the current treatment of OCD. This approach uses graduated exposure and response prevention to alleviate OCD symptoms. Success rates have ranged from 75% (Marks et al. 1975) to 85% (Foa and Goldstein 1978) of patients. Studies have shown that, unlike drug treatment, relapse following this treatment is not a major problem. Behavior therapy aims to teach individuals with OCD to change their thoughts and feelings by first changing their behavior. This therapy involves exposure and response prevention. Exposure treatment is based on the premise that anxiety will decrease after prolonged exposure with something feared. Thus, people with contamination obsessions are made to repeatedly hold "dirty" objects such as money or a used napkin until their anxiety eventually fades. Response prevention involves keeping OCD patients in contact with "germy" objects so that they may refrain from responding in their usual, ritualistic manner. Obsessive cleaners are told to stand next to a trashcan and ordered to stay and refrain from washing themselves. Together, exposure is acknowledged to be helpful in decreasing obsessions and anxiety, while response prevention is helpful in controlling compulsive behavior. Another similar technique is systematic desensitization where patients are asked to list situations that give them anxiety in ever-increasing order. Stepwise, each session involves exposing the patient to an anxiety-provoking stimuli and continuing up the list until each anxiety is conquered.
Though behavior therapy may be the most effective treatment in terms of long term management of OCD, these sessions may produce more anxiety for the patient and be quite a traumatic experience for them. Many patients are unwilling to endure short-term discomfort in exchange for long-term gains. Another drawback is that behavior therapy services are not as readily available as medications and can be time consuming and expensive. Qualified therapists for OCD can be difficult to find. This treatment is also not advised for children and adolescents. But again, the long lasting benefits of behavior therapy is one of its clear advantages, and this long-lasting improvement is partial compensation for the steady efforts needed to benefit from therapy. In an uncontrolled study (Foa 1995), a comparison was made between intensive exposure/response prevention treatment with 10 weeks of clomipramine, fluvoxamine, and placebo pill. Treatment improved obsessions in 850f patients receiving behavior therapy, 520f those receiving medication, and 19 0n those taking the placebo. Corresponding compulsions were improved in 100%, 43%, and 120f patients. A follow up sixteen months later found those that were taking medication were doing as well as those who had received behavior therapy. However, patients on medication lost all gains when the medication was discontinued.
The current recommendation for individuals who present with OCD symptoms is a combination therapy of an SSRI and behavior therapy. Early studies have shown in this common sense approach that medication improved compliance to behavior therapy and that patients treated with combined therapy were more successful in eventually discontinuing the medication.
Last resort
A small minority of patients respond to neither medication nor behavior therapy and are left with psychosurgery as their last option. If symptoms are severe and the OCD patient is deemed totally incapacitated by the disorder, anterior cingulotomy, anterior capsulotomy, and occasionally, subcaudate tractotomy surgical procedures are prescribed as a last resort. These procedures attempt to interrupt fibers that connect the frontal lobe with the basal ganglia. For one-third of patients who are resistant to all other treatments, this option derives some benefits (Baer et al. 1995). With current stereotactic techniques used in psychosurgery, the risk of these operations are relatively insignificant.
Conclusion
Individuals who suffer from OCD often feel trapped by their condition. Having to scrub until hands are red and raw or always having to tap on the wall three times before entering a room are absurd acts to the individual, but little can be done to stop the incessant thoughts that invade their minds. A sense of shame develops and life must be altered to accommodate these distressing actions. With onset of symptoms occurring in childhood or adolescence, often years and decades go by before treatment is sought.
In the meantime, researchers have elucidated the pathophysiology of the OCD condition. Implicated in imaging studies and surgical trials are the neural pathways that connect the basal ganglia and the frontal cortex. Abnormalities in the basal ganglia, which essentially acts as a filter for obsessive thoughts, lead to hypermetabolism in the frontal lobe - the probable key as to why obsessive thoughts persist and remain. Serotonin is a key neurotransmitter in this pathway and the discovery of SSRI's has revolutionized the pharmacological treatment of OCD. More research is being done to isolate the specific serotonin receptors and pathways involved in the pathology of the disease. Efficacy of drugs affecting dopamine and opioid neurotransmission only complicate matters and dispel the assertion that the pathophysiology of OCD can be based solely on a serotonergic model. In combination with the proven success of behavior therapy, these SSRI's and related medications provide hope to those suffering from this chronic and often debilitating disorder.
Bibliography
Baer L., Rauch, S.L., Ballantine, H., Martuza, R., Cosgrovew, R., Cassem, E., Giriunas, I., Manzo, P.A., Dimino, C., Jenike, M.A. Cingulotomy for intractable obsessive-compulsive disorder: prospective long-term follow-up of 18 patients. Archives of General Psychiatry, 52, 384-392 (1995)
Baxter, L., Phelps, M., Mazziotta, J., Guze, B., Schwartz, J., Selin, C. Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Archives of General Psychiatry 44, 211-218 (1987)
Baxter, LR Jr; Schwartz, JM; Bergman, KS; Szuba, MP; Guze, BH; Mazziotta, JC; Alazraki, A; Selin, CE; Ferng, HK; Munford,P; et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Archives of General Psychiatry, 1992 Sep, 49(9):681-9. (1992)
Foa, E., Goldstein, A. Continuous exposure and complete response prevention in the treatment of obsessive compulsive neurosis. Behaviour Therapy, 9, 821-829 (1979)
Goodman WK, McDougle CJ, Price LH. The role of serotonin and dopamine in the pathophysiology of obsessive compulsive disorder. Internat Clin Psychopharmacol;7(Suppl 1):35-8. (1992)
Hollander, E; Kwon, J; Weiller, F; Cohen, L; Stein, DJ; DeCaria, C; Liebowitz, M; Simeon, D. Serotonergic function in social phobia: comparison to normal control and obsessive-compulsive disorder subjects. Psychiatry Research, 1998 Jul 13, 79(3):213-7 (1998)
Janet, Pierre Les obsessions et la psychasthenie [Obsessions and Psychasthenia] Vol.1 Paris: Felix Alcan (1903)
Kiessling, LS; Marcotte, AC; Culpepper, L. Antineuronal antibodies: tics and obsessive-compulsive symptoms. Journal of Developmental and Behavioral Pediatrics, 1994 Dec, 15(6):421-5 (1994)
Leonard, HL; Swedo, SE; Rapoport, JL; Koby, EV; Lenane, MC; Cheslow, DL; Hamburger, SD. Treatment of obsessive-compulsive disorder with clomipramine and desipramine in children and adolescents. A double-blind crossover comparison. Archives of General Psychiatry, 1989 Dec, 46(12):1088-92. (1989)
Marks, I., Hodgson, R., Rachman, S. Treatment of chronic obsessive-compulsive disorder 2 years after in vivo exposure. Brit Journal of Psychiatry, 127, 349-364 (1975)
Modell SC, Mountz JM, Curtis GC, Greden JF. Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessivecompulsive disorder. J Neuropsychiatry Clin Neurosci 1989;1:27-36. (1989)
Murin LC et al. Striatal opiate receptors:pre- and post- synaptic localization Life Sci 1980:27:1175-83. (1980)
Murphy, TK; Goodman, WK; Fudge, MW; Williams, RC Jr; Ayoub, EM; Dalal, M; Lewis, MH; Zabriskie, JB. B lymphocyte antigen D8/17: a peripheral marker for childhood-onset obsessive-compulsive disorder and Tourette's syndrome? American Journal of Psychiatry, 1997 Mar, 154(3):402-7. (1997)
Pittman RK, Green RC, Jenike MA, Mesulam MM. Clinical comparison of Tourette's disorder and obsessivecompulsive disorder. Am J Psychiatry 1989;144:1166-71. (1989)
Riddle, M.A., Scahill, L., King, R. Obsessive-compulsive disorder in children and adolescents: Phenomology and family history. Journal of the American Academy of Child and Adolescent Psychiatry, 29, 766-772 (1990)
Swedo, SE; Leonard, HL; Mittleman, BB; Allen, AJ; Rapoport, JL; Dow, SP; Kanter, ME; Chapman, F; Zabriskie,J. Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever. American Journal of Psychiatry, 1997 Jan, 154(1):110-2. (1997)
Talairach J, Bancaud J, Geier S, Bordas-Ferrer M, Bonis A, Szikla G, et al. The cingulate gyrus and human behavior. Electroencephalogr Clin Neurophysiol 1973;34:45-52 (1973)
Warneke, L. A possible new treatment approach to obsessive-compulsive disorder. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie, 1997 Aug, 42(6):667-8. (1997)
Weissman, M., et al. The cross-national epidemiology of obsessive-compulsive disorder. Journal of Clinical Psychiatry , 55, 5-10 (1994)
Woo SK. et al. Specific opioid-amphetamine interactions in the caudate putamen. Psychopharmacology 1985:85:271-6. (1985)
(WWW1) http://www.mhsource.com/advocacy/narsad/ocd.html
(WWW2) http://www.mentalhealth.com/mag1/p5h-ocd4.html
The New Biology of Obsessive Compulsive Disorder
By Judith L. Rapoport, MD
The Harvard Medical School Mental Health Letter, January 1989
(WWW3) http://www.mentalhealth.com/mag1/p5h-ocd2.html
(WWW4) http://www.cma.ca/jpn/vol-24/issue-1/0015.htm
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