by Ian Osborn
In my brain, a basal ganglia behavioral program was activated. My mind’s eye featured a second image: me gently rubbing a soft, white, impenetrable cream on my hand. Now the needle couldn’t harm me. It worked! Little did I know that I had now put into action a fixed-action grooming ritual, negatively reinforced because it temporarily rid me of the distressing needle thought. Now I had a compulsion, too.
I didn’t know what to make of those obsessions and compulsions in medical school. I didn’t even figure out that I had diagnosable OCD. Mental compulsions were not recognized back then, and my whole approach to the problem was to think about it as little as possible (an odd lack of curiosity for a psychiatrist, perhaps, but an OCD sufferer’s normal minimizing and secreting of symptoms).
Little was understood about OCD back then, but now OCD sufferers can be helped to make sense of their senseless rituals and self-tormenting thoughts. Inasmuch as people with severe obsessions and compulsions are often demoralized by their symptoms, frequently fearing that they are going crazy, making sense of symptoms can be crucial.
9
OCD AS A BRAIN DISORDER
Twenty years ago, even members of the medical profession had a hard time accepting the idea that OCD was a bona fide medical disorder. The difficulty was that OCD, like many other psychiatric disorders, was thought to lack a physical cause. No matter what psychiatrists said, the average physician could not be altogether convinced that a problem without a demonstrable biological basis should be included in the proper domain of medicine.
In those days, OCD stood in apparent contrast to, say, coronary artery disease (CAD), the common cause of heart attacks. CAD’s symptoms, such as chest pain and shortness of breath, were caused by physical changes in the body that could be observed, fatty tissues that clogged the coronary blood vessels. OCD, on the other hand, was caused, according to the authoritative Comprehensive Textbook of Psychiatry, by “a defensive regression of the psychic apparatus to the preoedipal anal-sadistic phase.” The exact meaning of those Freudian terms was a mystery to everyone but psychiatrists, but it was clear that they did not refer to any sort of biological process. Coronary artery disease was a true medical disorder; OCD was something else.
But times have changed. Over the last two decades, our understanding of OCD has been revolutionized by a series of fascinating and totally unexpected research findings. It is now absolutely clear that OCD is caused not by vague conflicts in the unconscious but rather by measurable chemical abnormalities that occur in specific regions of the brain. OCD, it turns out, is every bit as much a biological process as CAD. No one should any longer doubt that OCD is a distinct medical disorder.
Viewing OCD in this way has profound personal and social implications for those who suffer from it. Talcott Parsons, founder of the field of medical anthropology, described these implications in the 1940s. Parsons noted that in every culture people who suffer from physical disorders are dealt with in a special manner. They are relieved of their normal duties, taken care of. They are not blamed for their condition. Their treatment is, all in all, very different from that accorded to people who are recognized as otherwise defective: slackers, weaklings, or criminals.
Yet, many OCDers still think of themselves in just those terms. A few even turn themselves in as criminals! This is because OCDers are so prone to guilt. I once asked Tina, whose severe OCD was discussed in the last chapter, what aspect of her treatment had been most helpful to her. She said that it was learning that she had a “chemical disorder.” Before this, Tina had unmercifully blamed herself for her condition. Her husband had only made matters worse by nagging her, assuming that if she tried harder she could overcome her ridiculous fears. A great weight was lifted from Tina’s shoulders when she learned that her problems were in fact due to a physical problem. The new explanation resonated at a deep level: The symptoms were not her fault. It is of the utmost importance for OCDers, along with their families and the general public, to fully grasp this fact.
BRAIN IMAGING AND OCD
Evidence that conclusively proves OCD’s physical, biological basis comes from a number of divergent fields of study, including radiology, pharmacology, neurochemistry, neurology, and genetics. The strongest evidence, if one assumes that seeing is believing, is from the burgeoning field of brain imaging.
Before 1980 there was no way to measure regional biochemical reactions as they occur in the brain. Indeed, it was not even known whether such measurements were possible. Today, however, techniques such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) can perform continuous surveys of chemical reactions in the brain and then display them on a screen. The development of these brain-imaging techniques represents the greatest advance in neuroscience in the last decade.
In both PET and SPECT, investigators label a substance with a radioisotope, inject it into the bloodstream, and then observe where the isotope shows up in the brain. Sophisticated radiation detectors provide the pictures. In PET, to date the most widely used technique, the labeled compound is usually sugar, the sole source of brain cell nourishment. The areas that light up on the PET scan screen are the brain regions that are absorbing the most sugar, those that are working the hardest.
The technology used in MRI is somewhat different. In this case the brain is imaged by measuring the energy that is emitted by subatomic particles. There is a clear advantage to MRI in that it involves neither radiation nor the drawing of blood. In addition, it is proving to be the most sensitive and versatile of the new brain-imaging techniques.
Using PET, SPECT, and MRI, researchers can see where in the brain the neurons are firing, which region is transmitting the most messages. If a person is scanned while studying a book, the visual center in the back of the brain lights up on the screen. If attention is turned to music, auditory centers located not far from the ears are highlighted. Solving a puzzle causes the frontal lobe to stand out. With the movement of a hand, activity is shifted to the motor cortex located at the top of the brain. Different perceptions, different feelings, different ways of thinking, show up on the screen like storms on a satellite weather map.
Since 1987, more than a dozen studies have looked at the local biochemistry of the brain in patients with obsessive-compulsive disorder. The researchers who have done the bulk of this work are Judith Rapoport and Susan Swedo at the National Institutes of Mental Health, Lewis Baxter and Jeffrey Schwartz at UCLA, and Michael Jenike and Scott Rauch at Harvard. What they have discovered is that in OCD sufferers two areas of the brain light up abnormally: the basal ganglia, a core of cells at the center of the brain resembling a small cluster of grapes; and the orbital frontal region, a large area behind the forehead. The unusual excitations of these two regions are apparent even in OCD patients at rest and are intensified when OCD patients are engaged in compulsive rituals. Furthermore, these abnormalities are diminished, indeed sometimes disappear, when OCD is effectively treated with either medication or behavioral modification. No other psychiatric or physical disorder involves simultaneous abnormalities in these two brain areas. What is observed is a unique, visible, pathological condition of the brain directly related to OCD’s symptoms: convincing proof that OCD is truly a neurobiological disorder of the brain.
In addition to regional biochemical abnormalities, there is mounting evidence of significant structural abnormalities in the brains of people with severe OCD. Using MRI, which can depict brain structure in great detail, investigators have observed anatomical irregularities in the ventricular system, frontal cortex, and basal ganglia in both adults and children with OCD.
The most interesting of these findings was reported in 1996 by researchers at Harvard, who examined serial MRI cross-sections of the brains of a group of OCD patients and controls, a painstaking procedure that takes over thirty hours per subject to complete. The crucial observation: The brains of OCD patients had significantly more gray matter (brain cells) and significantly
less white matter (myelin and connective cells) than did the brains of control subjects. This makes a certain amount of intuitive sense: OCD sufferers, it seems, think too much. There is also speculation that OCD may reflect a failure in brain maturation. For reasons not yet determined, we are all born with an excess of brain cells; as the normal brain matures, however, it streamlines, losing unnecessary cells. OCD may involve a lack of this normal “pruning.”
NEUROCHEMICAL ABNORMALITIES AND OCD
From a statistical point of view, the strongest evidence for OCD having a biological cause comes from studies involving the brain chemical serotonin. These studies number a hundred or more, and their findings are conclusive.
Serotonin is a neurotransmitter, one of over a hundred different substances found at the junctions of brain cells whose job it is to carry messages from one nerve cell to another. Serotonin is manufactured near the connection of the brain and the spinal cord by a cluster of uniquely specialized cells that stretch out from the base of the brain to distant parts of the cerebrum. Serotonin’s involvement in OCD is immediately suggested by the fact that these cells project especially to two areas: the basal ganglia and frontal cortex.
The best evidence linking serotonin abnormalities to OCD comes from medication studies. Some thirty-two controlled trails involving thousands of patients have shown that medications which specifically affect serotonin activity—Anafranil (clomipramine), Prozac (fluoxetine), Luvox (fluvoxetine), Paxil (paroxetine), and Zoloft (sertraline)—are vastly superior to both placebo and all other psychiatric drugs in the treatment of OCD. In the largest of these studies, active medication was found to benefit 84 percent of OCD patients, while the corresponding number for placebo was 14 percent. These are extremely significant treatment results, similar, for instance, to the effectiveness of penicillin in the treatment of pneumonia. The ineffectiveness of placebo in these studies is in itself a strong indicator that OCD is a specific, biological disorder, since most psychiatric conditions respond to placebo at a rate of 20 to 30 percent.
Other studies add to this evidence. mCPP, a drug that affects serotonin in a manner opposite to Anafranil, has been shown by investigators in Israel and the United States to make obsessions and compulsions worse, unless a person first receives Anafranil, in which case it has no effect. Still other studies have demonstrated a link between OCD and two hormones that exert an indirect effect on serotonin activity, oxytocin and vasopressin.
A dozen studies have attempted to directly gauge serotonin activity in OCDers. Some studies have measured levels of serotonin and its by-products. Others have used more complicated techniques, such as assessing the binding of serotonin to blood cells, or measuring levels of the hormone prolactin (thought to be a general indicator of brain serotonin activity) in response to a dose of d-fenfluramine (a serotonin-releasing agent). The results of these studies demonstrate with certainty that OCD is associated with some sort of abnormal serotonin activity.
The exact nature of the abnormality, however, has proven frustratingly elusive—nothing so simple, it appears, as an increase or decrease in the total amount of serotonin in the brain. The leading theory at this time proposes that serotonin receptors (the molecules on the surface of brain cells that receive and bind serotonin) may be abnormal in OCD.
NEUROLOGICAL DISEASES AND OCD
A number of neurological diseases caused by damage to the basal ganglia are accompanied by obsessions and compulsions indistinguishable from those found in OCD. Research into the relationship between OCD and these disorders, especially when taken in conjunction with the other findings discussed in this chapter, suggest that OCD itself is caused by some sort of a primary basal ganglia abnormality. Currently, this is the leading theory on the cause of OCD.
Given these connections, shouldn’t OCD be removed from the purview of psychiatry and put into the field of neurology? The idea has some merit, especially given the stigma many people attach to the word “psychiatric.” In truth, after two decades of intensive brain research, the line between neurology and psychiatry has become permanently blurred.
Gilles de la Tourette Syndrome
OCD bears a close relationship to the unusual neurological disorder known as Tourette’s, a genetic disorder of the nervous system characterized by sudden jerks and twitches called tics. Simple tics, such as eye blinks and neck stretches, occur in 10 percent of children and not uncommonly in adults. Tourette’s, in contrast, is characterized by complex, highly abnormal tics. In its extreme form, a person so afflicted may, for no apparent reason, repeatedly stop in his tracks and make a series of quick jumps while walking down the street. Another may spin around, take a couple of steps backward, then abruptly turn forward again. Most attention-getting of all are the vocal tics: muffled grunts and even explosive, involuntary shouts of profanities.
OCD resembles Tourette’s in several ways. The most obvious is the subjective likeness between tics and compulsions, respective hallmarks of the two disorders. Both are experienced as senseless, repetitive acts that a person does not want to do but must do in order to relieve tension. Both are preceded by intrusions: In the case of OCD these are unwanted thoughts; in Tourette’s they are uncomfortable sensations. Epidemiological studies, too, confirm a close association between OCD and Tourette’s. At least 40 percent of people with Tourette’s also have OCD, and about 10 percent of people with OCD have Tourette’s. Such an association would be impossible if the two were not related in some way.
Anatomic and neuroendocrine studies further strengthen the connection. A 1996 National Institutes of Health study found that Tourette’s symptoms could be traced to abnormally sensitive neurochemical receptors in the basal ganglia.
Lastly, a genetic link between OCD and Tourette’s has now been confirmed by family and twin studies. These findings lead some experts to speculate that OCD and Tourette’s are different expressions of one genetic, neurobiological disease.
Autoimmune Neurological Disorders
Today’s most exciting frontier of OCD research stems from a remarkable finding reported in 1997 by psychiatrists Susan Swedo, Judith Rapoport and colleagues at the National Institutes of Mental Health. What the NIMH researchers have discovered is that childhood OCD is frequently associated with group A beta hemolytic streptococcal infections—strep throat!
This research had its start a decade ago with the study of OCD’s link to Sydenham’s chorea, a now rare disease of childhood that was seen frequently before the age of antibiotics. Once known as Saint Vitus’ dance, Sydenham’s is characterized by the sudden onset of neurological symptoms ranging from mild clumsiness and a tendency to drop objects to unrestrained flailing of the arms and delirium. Sydenham’s, it has been discovered, is an autoimmune disease. As with rheumatic fever, infections with streptococcal bacteria lead to the production of antibodies that double-cross the body: They kill not only streptococci but normal cells as well. In rheumatic fever, the heart is attacked; in Sydenham’s chorea, the brain. Brain-imaging studies of people suffering Sydenham’s chorea demonstrate inflamed, bulging basal ganglias.
OCD has long been known to bear a relationship to Sydenham’s, which is characterized by obsessions and compulsions in over half of all cases. Exploring this relationship, Swedo and colleagues asked this question: Could some routine cases of childhood OCD be caused, like Sydenham’s, by autoimmune damage to the basal ganglia? They were astounded by the finding. It now appears possible that up to 25 percent of childhood OCD may, indeed, have this origin. On the horizon is the remarkable possibility that large numbers of children with OCD may be effectively treated with penicillin. University centers are already screening childhood OCDers for anti-streptococcal antibodies and treating some cases with antibiotics. The NIMH researchers, whose offices are located not far from the National Zoo, have given a name to these immune system disorders that attack the basal ganglia: pediatric autoimmune neurobiological disorders associated with streptococci, or PANDAS.
It is interesting to note tha
t Saint Therese of Lisieux, the Christian luminary who was discussed in Chapter 3, may well have had PANDAS. Therese suffered severe bouts of sore throat all of her life and finally died at twenty-four of a respiratory illness. As a child, just prior to developing obsessive-compulsive disorder, Therese was confined to bed for a period of two months with a disorder of intermittent delirium she later referred to as “my strange sickness.” The saint’s aunt remembered, “the little girl was seized with a nervous trembling, followed by seizures of fright and hallucinations that were repeated several times a day.” The family maid recalled that Therese had “propulsive seizures during which she made wheel-like movements that she would have been absolutely incapable of making in a state of health.” The doctor called on to treat the disorder diagnosed St. Vitus’ dance.
Von Economo’s Encephalitis and Huntington’s Disease
Two additional disorders of the basal ganglia are associated with OCD. Von Economo’s is the name given to cases of brain infection that developed with the worldwide flu pandemic of 1917 to 1926. It’s symptoms were rigidity, tremor, and obsessions and compulsions, counting rituals being particularly common. Huntington’s disease, the cruel neurological illness that struck folk singer Woody Guthrie, starts in midlife with twitches and jerks and then inevitably progresses to dementia and death. In its early stages, Huntington’s commonly includes obsessive cleaning and checking rituals. In both Von Economo’s encephalitis and Huntington’s disease, brain damage is restricted largely to the basal ganglia.