This action might not be possible to undo. Are you sure you want to continue?
Brittany Adler 11/14/05
Obsessive Compulsive Disorder
An obsessive compulsive individual engages in ritualistic behaviors in order to relieve anxiety caused by repeated, intrusive thoughts. Although she feels that the behaviors will attenuate her obsession, the behaviors are burdensome and often are not associated with the obsession in a realistic way. Obsessive Compulsive Disorder (OCD) has a lifetime prevalence rate in the US of 2.5% and is the fourth most common psychiatric disorder. No studies thus far have found any sex differences in the prevalence of OCD. Risk of developing OCD is elevated prior to puberty and from 4050 years of age (Husted et al.). The syndrome PANDAS, in which a child acquires OCD or tic symptoms after a streptococcal infection, suggests that these disorders may have an autoimmune basis. Only a small proportion of children develop a neuropsychiatric disorder following streptococcal infection. It is likely that OCD symptomatology in PANDAS patients is caused by targeting of the basal ganglia by antistreptococcalantineuronal antibodies (Husted et al.). PANDAS symptoms are caused by Group A Streptococcus (GAS) and are generally episodic or sawtooth. One study by Murphy et al. sought to determine a relationship between the symptom course (episodic, sawtooth, stable or remitting) and GAS antibody fluctuations. In this study, 25 referred children from 617 years of age
were diagnosed with a Tic disorder and/or OCD according to the CYBOCS and YGTSS. Over a 9 to 22 month period, changes in symptoms, severity of choreiform movements, and GAS titers (to measure streptococcal antibodies) within each subject were measured 6 to 15 times. The children were grouped according to their symptom course into a 15 person ESC (episodic/sawtooth) group and a 10person SRC (stable/remitting) group. The ESC group thus resembled the fluctuating symptom intensity observed in PANDAS syndrome. Similar to children with PANDAS, the ESC group was largely male and had a shorter duration of OCD, although there was no significant difference in duration for the Tic disorder. This study found neurologic criteria, measured by choreiform movements, unable to distinguish between ESC and SRC groups. Furthermore, PANDASlike ESC children had elevated streptococcal titers associated with symptom exacerbation (measured by a greater than 9point change on CYBOCS and 14point change on YGTSS). The titers rarely normalized in this group throughout the period of observation, suggesting that recent exposure to GAS may have lead to the drastic symptom fluctuations apparent in ESC (and PANDAS) children. This idea was further supported by the finding that Tic symptom exacerbations and titer increases occurred most frequently in the fall/winter, when GAS infections are at their peak (Murphy et al). OCD is a chronic illness and few afflicted individuals ever experience a complete remission of symptoms, even after treatment. Only a 2535% reduction in the patient’s score on the YaleBrown Obsessive Compulsive Scale (YBOCS) is considered an
adequate response to a treatment. 4060% of patients do not even experience this modest degree of symptom relief. Such nonresponsive patients are placed in two categories: 1) treatmentresistant patients, who do not respond to at least two SRI trials and 2) the more severe treatmentrefractory patients, who fail to respond to at least three SRI trials, two augmentation strategies, and behavioral therapy. 3040% of patients are treatment refractory (Husted et al.). Glutamatergic neurons in the orbitofrontal cortex are overactive in OCD patients. Because 5HT inhibits these neurons, drugs that increase 5HT release (such as SRIs) are often effective in treating OCD. Increased levels of dopamine in the corticostriatal thalamiccortical system are also implicated in OCD, which may explain why atypical antipsychotics (dopamine antagonists) are effective augmentation strategies. One double blind, placebocontrolled study found that risperidone combined with an SRI improved OCD symptoms compared to an SRI and placebo (Hustsed et al.). Several studies have shown clomipramine (an SRI) to be more effective than SSRIs in reducing OCD symptoms in adults. However, there is no consensus on responses in OCD children and adolescents to various drugs. In a metaanalysis by Geller et al. of 12 doubleblind, controlled studies totaling 1044 children and adolescents, the efficacies of 4 SSRIs (paroxetine, fluoxetine, fluvoxamine, and sertraline) and clomipramine were assessed. There was overall a significant (.46) mean difference between drug and placebo treatments that amounted to a 4 point difference on the Y
BOCS. Although significant, the response to drugs compared to placebo was modest, which suggests that more effective drugs or augmentation strategies are needed. Further analysis showed that differences between the drug and placebo groups were dependent on the test used to measure outcome and on the drug administered. Although the YBOCS, NIMH Global OCD Scale, and CGI were sensitive to treatment differences, the Leyton Obsessional Inventory did not show any change, which suggests that this test is not a good measure of changes in symptoms with treatment. Furthermore, while clomipramine was the most effective drug used, there was no difference in efficacy among the four SSRIs. Thus, an appropriate SSRI should be selected based on its sideeffects for the individual patient. Despite clomipramine’s efficacy, it should only be used in severe cases of treatmentresistant OCD because of its adverse sideeffects. Because clomipramine is a nonselective drug, it is effective in treating ADHD and tic disorders, and so may be useful for targeting comorbid symptoms (Geller & Biederman et al.). Neuroimaging studies have shown OCD patients to have neurological dysfunctions that are similar to those observed in related disorders, such as Tourette’s syndrome and body dysmorphic disorder (Rauch et al.). MRI studies of OCD patients have shown decreased volumes of the corticostriatalthalamocortical (CSTC) circuits, which includes the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the caudate nucleus (Husted et al.). The striatum of OCD patients also has volumetric abnormalities and has been implicated as the primary pathology responsible for CSTC
dysfunctions. Reduced levels of Nacetyl aspartate (NAA), a marker of healthy neurons, are found in the striatum of OCD patients but not in the lenticulate, which suggests neural degeneration of the striatum. Some findings suggest that OCD patients experience intruding (and often noxious) information that should otherwise be unconscious because they are unable to involve the striatum in thalamic gating. OCD patients also tend to have increased baseline activity in the orbitofrontal cortex, cingulate gyrus, caudate nucleus, and thalamus, possibly because of an imbalance in the direct and indirect pathways. There is a correlation between activity in these regions and symptom expression. Symptom reduction of OCD after therapy is associated with decreased activity (normalization) in the OFC, ACC, and caudate. Interestingly, brain activity in OCD patients can often predict the patient’s response to therapy. For instance, OFC hyperactivity predicts poor response to SRI treatment and positive response to behavioral therapy (Rauch et al.). There are other possibilities for OCD patients who are unresponsive to SRI monotherapy. Behavioral therapy exposes the patient to an anxietyproducing stimulus and the compulsive response is suppressed until the stimulus is no longer feared. This therapy is extremely effective and symptoms improve in 7080% of patients, especially when SSRI treatment is concurrent. Furthermore, unlike pharmacological treatment, patients do not relapse after the treatment is discontinued. However, such therapy is very stressful and over 25% of OCD patients cannot tolerate it. For these patients, cognitive
therapy is often used, in which the patient is encouraged to reflect on the perceived threat and her controlling thoughts. However many studies have shown cognitive therapy to be ineffective (Husted et al.). Psychosurgery is an extreme measure if all other treatments fail. Little is known about the biological explanations for the efficacy of some psychosurgeries. One study found anterior cingulotomies, or the ablation of the anterior cingulate cortex and the fibers of the cingulum, to improve symptoms in 43% of patients. Interestingly, there is a delay in symptom relief after surgery, which suggests that neural pathway reorganization as well as neural interruption is responsible for the observed improvements (Husted et al.). Subcaudate tractotomies and bilateral orbitomedial leucotomies are also effective because they interrupt fibers between the OFC/ACC and the thalamus and therefore decrease overactivity. Limbic leucotomies, anterior capsulotomies, vagus nerve stimulation, and deep brain stimulation are also effective treatments for treatment refractory OCD patients (Rauch et al.). OCD has a high comorbidity rate with other psychiatric disorders. There is a significant overlap between ADHD and OCD, with an estimated 30% of OCD children also afflicted with ADHD. Understanding ADHD and OCD comorbidity is important because comorbid children often have poorer drug responses and so may need different treatments. ADHD symptoms usually occur several years before the onset of OCD symptoms, which suggests that ADHD may be a distinct disorder in OCD children and is
not misdiagnosed simply because obsessions make children inattentive. It is possible that childhood OCD may be a distinct subtype of OCD that is often accompanied by comorbid ADHD. One study by Geller et al. determined how comorbid ADHD affects the expression of OCD. By comparing referred OCD children with and without ADHD, the authors found the two groups to be very similar, even in the prevalence and severity of symptoms (as measured by the CYBOCS). With the exception of a higher frequency of somatic obsessions in the comorbid children, OCD+ADHD and OCD children had identical obsessivecompulsive symptoms. The OCD+ADHD children performed worse in school compared to the OCD children, but this is consistent with studies in pure ADHD children. The finding that ADHD does not impact the expression of OCD, combined with a past finding that OCD does not affect the expression of ADHD, suggests that comorbid children have two distinct disorders. Interestingly, the rate of CD in the OCD+ADHD children was strikingly low considering the high comorbidity rate of CD and ADHD. This suggests that the symptoms of CD are attenuated by the presence of OCD in OCD+ADHD children (Geller & MBBS et al.). OCD is an extremely debilitating disorder that requires further attention such that symptom relief can be maximized in patients. We are just beginning to understand the neurochemical basis of OCD, and new drug therapies look promising and are improving many OCD patients’ lives. Unfortunately, the high comorbidity rate of OCD with other psychiatric disorders tends to decrease responsiveness to drug therapy. New
developments in drugs, behavioral therapies, and even psychosurgeries can help the many OCD patients who are currently unresponsive to the numerous options of OCD therapy.