Understanding Obsessive-Compulsive and Related Disorders
OCD is a common mental disorder, and is often disabling. The past few decades, however, have seen the emergence of many effective treatments, both pharmacological and psychotherapeutic. The challenges for the 21st century are two-fold: first, to make these effective treatments available to all sufferers; and, second, to unravel the biology of this disorder sufficiently so that we can cure its symptoms, and ultimately, prevent its occurrence. In order to tackle these challenges, it is essential that we understand the etiology of OCD.
Prevailing theories indicate that OCD is a biological disease. Functional brain imaging studies have produced a model for pathophysiology of OCD which involves hyperactivity in certain subcortical and cortical regions. On the basis of imaging studies, Insel has proposed that inappropriately increased activity in the head of the caudate nucleus inhibits globus pallidus fibers that ordinarily dampen thalamic activity. The resulting increase in thalamic activity produces increased activity in orbitofrontal cortex, which, via the cingulate gyrus, completes the circuit to the caudate and produces increased activity in the head of the caudate. Hypothetically, primitive cleaning and checking behaviors are "hard-wired" in the thalamus. Insel's hypothesis is supported by evidence from MRI (magnetic resonance imaging) studies, which have found an abnormally small caudate in some OCD patients, and by positron emission tomography (PET scan) studies, which have found increased metabolism in orbital frontal cortex, cingulate gyrus, and caudate, with decreases following successful treatment. The association of OCD with Tourette's syndrome and Sydenham's chorea, which are believed to involve basal ganglia pathology, is also consistent with this model.
In the section below, we have outlined a more detailed description of the various theories and hypotheses involved in the biological basis of OCD. As will be noted by many readers, the information provided here is more suited for clinicians, medical professionals, or others who are more familiar with medical terminalogy. For this reason, readers are encouraged to seek further information from their physicians/psychiatrists and/or other OCD resources.
Etiology: Biological Models
Many investigators have contributed to the hypothesis that OCD involves dysfunction in a neuronal loop running from the orbital frontal cortex to the cingulate gyrus, striatum (cuadate nucleus and putamen), globus pallidus, thalamus and back to the frontal cortex. Organic insult to these regions can produce obsessive and compulsive symptoms. The results of neurosurgical treatment of OCD strongly support this hypothesis. Surgical interruption of this loop by means of cingulotomy, anterior capsulotomy or subcaudate tractotomy brings about symptomatic improvement in a large proportion of patients unresponsive to all other treatments. Cingulotomy interrupts this loop at the anterior cingulate cortex, thereby disrupting frontal cortical input into the Papez circuit and limbic system, which are believed to mediate anxiety and other emotional symptoms. Anterior capsulotomy (lesions within the anterior limb of the internal capsules) and subcaudate tractotomy (lesions in the substantia innominata, just under the head of the caudate nucleus) interrupt fronto-thalamic fibers, which may mediate the obsessive and compulsive components of OCD. Baxter et al. in 1992 hypothesized that the hyperactivity observed in this neuronal loop arises because of imparied caudate nucleus function. The impariment allows "worry inputs" from the orbitofrontal cortex to inhibit excessively the inhibitory output from the globus pallidus to the thalamus. The resulting excess in thalamic output then impinges on various brain regions involved in the experience of OCD symptoms, including the orbital frontal region, thus reinforcing hyperactivity in the neuronal loop. However, Baxter et al. caution that the abnormal neurophysiology underlying OCD symptoms may involve structures as yet undetected. Decreased metabolic activity can be missed by current scanning techniques. Alternately, the metabolic hyperactivity of small neuronal fields can be missed when surrounding structures exhibit no change or mask the increase behind compensatory decreases.
Serotonin and Other Neurotransmitters
The hypothesis that an abnormality in serotonergic neurotransmission underlies OCD arose out of the observation that clomipramine, which inhibits both serotonin and norepinephrine reuptake, relieved symptoms, whereas noradrenergic reuptake inhibitors did not. The unique efficacy of clomipramine and the SSRIs remains the strongest support for this hypothesis. Studies of peripheral markers of serotonergic function in blood and cerebrospinal fluid have not conclusively demonstrated an abnormality. Pharmacological challenge studies with serotonergic agonists have suggested dysregulation within the serotonin system, with behavioral hypersensitivity and neuroendocrinological hyposensitivity to the activation of serotonin receptors, but numerous inconsistencies remain to be resolved. The beneficial effects of enhanced serotonergic neurotransmission do not prove that abnormalities in this system are the root cause of OCD symptoms. Serotonergic neurons modulate the function of many other systems, where the primary cause or causes may lie. In patients with comorbid Tourette's syndrome, tics and schizotypal personality disorder, treatment studies indicate a role for dopaminergic neurons.
Twin studies and family studies strongly suggest that vulnerability to OCD can be inherited, but a positive family history is absent in many patients. Older studies of monozygotic twins show a 65% concordance for OCD, but no control groups were included. One study found an 87% concordance for "obsessional features" (OCD symptoms that may not have caused significant distress or social impairment) in monozygotic twins; the concordance of dizygotic twins was only half as large. On the other hand, none of eight monozygotic twin pairs in another study were concordant for OCD, according to Andrews et al. in 1990. A recent review notes that in Pauls' study in 1992, 10% of the parents of children and adolescents with OCD themselves had the disorder, and in another study, OCD was present in 25% of fathers and 9% of mothers. The symptoms of parents and children usually differed, arguing aginst social or cultural transmission. A study by Black et al. in 1992 however, found no increase in OCD prevalence in first degree relatives of OCD patients compared to those of control group. The recent finding, by Murphy et al. in 1997 and Swedo et al. in 1997, that an antigen which is a genetic marker for rheumatic fever susceptibility is also a marker for susceptibility to an autoimmune form of childhood onset OCD will undoubtedly spur progress in unraveling genetic contributions to the pathogenesis of OCD.