Richard G. Petty, MD

Obsessive-Compulsive Disorder and Inflammation

We have recently talked about the growing evidence that several types of mental illness are associated with inflammation. There are some odd neuropsychiatric illnesses that are known to be associated not just with inflammation, but with disturbances of the immune system. One of the most marked in the so-called PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) in which people may get a constellation of symptoms after a streptococcal infection. Amongst the symptoms are obsessive compulsive disorder (OCD)-like symptoms, and that has lead to the question whether OCD itself might be some kind of autoimmune illness.

OCD can be a debilitating illness in which people have obsessive, distressing, intrusive thoughts and related compulsions (tasks or “rituals“) with which they try to neutralize the obsessions. It is classified as an anxiety disorder, and it is listed by the World Health Organization as one of the top twenty most disabling illnesses in terms of lost income and diminished quality of life.

Jack Nicholson did a very good job of portraying someone with OCD in As Good As It Gets, and Tony Shalhoub’s Adrian Monk is close to reality, though few people have quite the number of different and ever-changing obsessions as the character in the show.

Now new research (NR239) presented last week at the 2007 Annual Meeting of the American Psychiatric Association in San Diego has found a link between inflammation and OCD.

Researchers from Zonguldak Karaelmas University in Turkey measured the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in 31 drug free outpatients with OCD.

Both TNF-α and IL-6 levels were significantly higher in people with OCD compared with healthy volunteers.

What this tells us is that there may well be some involvement of the immune system in the pathophysiology of OCD, and, if confirmed, that in itself might suggest some new approaches to treatment.

The next step will be to replicate the study with a larger number, and then to do a longitudinal study, to see if these inflammatory markers rise as people are getting worse, and go down as they improve.

Tourette’s Syndrome

No surprise here, but I was just sitting on a plane.


When I heard people sniggering.

Why? A young man in his thirties was walking along trying to find his seat. As he did so he was constantly grunting, saying partially intelligible words and jerking. As a clinician it was immediately obvious that he almost certainly had Tourette’s syndrome, a developmental disorder of the brain in which people have involuntary, stereotyped, repetitive motor and phonic tics. Some people with the disorder exclaim obscene words or socially inappropriate and derogatory remarks, which together are known as coprolalia.

The illness was originally named for Georges Albert Édouard Brutus Gilles de la Tourette, (1859–1904), a French physician and neurologist, who published an account of nine patients with the now classic clinical features in 1885.

You may not often see someone with this problem, but it is good to know what it is, and that it is an illness that can cause great distress.

We have recently made some interesting discoveries about Tourette’s syndrome.

  1. It is an illness involving the dopamine systems in the basal ganglia of the brain together with some regions of the midbrain and some very specific linked regions of the cerebral cortex, cerebellum and limbic system.
  2. In adults with Tourette’s syndrome, the prefrontal cortex is a little smaller than normal, and the corpus callosum linking the hemispheres is larger than expected. These findings correlate with problems in the way in which people transfer information between the hemispheres and modulate attention.
  3. Very recent evidence has shown us that there are small hyper-intense lesions in the deep regions of the brain in people with Tourette’s, obsessive-compulsive disorder and attention deficit disorder. These three problems seem to have a number of biological links and two or more may co-exist in the same person. In children and adolescents with Tourette’s, the tics tend to get better over time but obsessive-compulsive disorder symptoms become more severe and persistent as they get older.
  4. There is important evidence that in some people, Tourette’s is linked to a post-infectious autoimmune disorder, and many have antibodies directed against neurons in the brain.
  5. There is also a link between Tourette’s and having low iron stores. Low iron stores are common in people with many chronic inflammatory illnesses. Iron is crucially important in the development of key regions of the brain. We do not have any viable evidence that giving people iron supplements will reduce the severity of Tourette’s, but it is something that needs to be examined in a formal study.

People have typically been treated with antipsychotic medicines such as risperidone that block dopamine receptors in the brain, and they can certainly help. A more recent approach is to use medicines like aripiprazole that modulate dopamine activity in the brain. A recent study done by some colleagues in the United Kingdom have confirmed that aripiprazole seems to be very helpful in about half of patients with Tourette’s, though neurological side effects do sometimes occur.

There has recently been a lot of interest in Habit Reversal Therapy: a behavioral treatment for tics. The therapy takes a lot of time and effort, but it is very interesting that behavior therapy can help with a neurological illness.

There is no published data on the use of Integrated Medicine in the treatment of people with Tourette’s, but many experts have reported that some patients have been helped with homeopathy and acupuncture.

That guy in the next seat who is cursing may not just be mean and uncouth. He may be suffering.

But maybe not for much longer.

We are getting very close. Not just to discovering the physical basis of the illness, but perhaps its meaning and purpose as well.

New discoveries are coming thick and fast, and I shall keep posting about those that will help individuals and illuminate the principles of Integrated Medicine.

Psychiatric Illnesses and Fibromyalgia

There’s an interesting and important article in last month’s issue of the Journal of Clinical Psychiatry, by a group of investigators from the University of Cincinnati.

They have shed important new light on fibromyalgia. We’ve recently learned how it is linked to disturbances of the serotonin transporter, as well as anti-inflammatory proteins, and that is may respond best to the kind of comprehensive multi-leveled approaches that we use in Integrated Medicine.

The new research compared people with fibromyalgia with people with rheumatoid arthritis, and it found that fibromyalgia, but not rheumatoid, may be associated with a range of psychiatric illnesses:

  1. Major depressive disorder
  2. Bipolar disorder
  3. Comorbid anxiety disorders including panic disorder, social phobia, posttraumatic stress disorder and obsessive-compulsive disorder
  4. Eating disorders and
  5. Substance abuse

What was particularly important in this study was that the psychiatric problems usually preceded the onset of fibromyalgia. So it wasn’t that people were developing psychological problems because they were in chronic pain.

It’s beginning to look as if fibromyalgia is part of a larger group of disorders that all share common etiologies or causes. Family studies have indicated that fibromyalgia and mood disorders share some of the same – perhaps genetic – determinants.

The study also confirms what we have said before: fibromyalgia is not only associated with some psychiatric problems, but also with other medical disorders, several of which may also co-exist with the same psychiatric problems. They include:

  1. Chronic fatigue syndrome
  2. Irritable bowel syndrome
  3. Interstitial cystitis
  4. Multiple chemical sensitivities and
  5. Migraine

Not only does this research highlight the need to check people with fibromyalgia to see if they might also be struggling with a psychiatric problem, but it is helping us home in on some of the mechanisms linking these apparently separate problems.

This particular study was done mainly in white women, and the investigators knew who had fibromyalgia, so there’s more work to be done.

But if you or a loved one is struggling with fibromyalgia, it is good news to know that we are making rapid progress in unraveling this horrible illness.

New Clues to Obsessive Compulsive Disorder

In this month’s edition of the Journal of Neuroscience, a team from the University of Michigan has published a very interesting report. Every one of us has made a mistake at some stage in our lives, whether it is something trivial like dropping the groceries, or something more serious, like deleting a crucial computer file. What the researchers did was use functional MRI (fMRI) to peer inside the brain at the instant of making a mistake. While in the scanner, people were forced into making an error that carries consequences – for instance, losing money. When that happened, a particular part of the brain called the rostral anterior cingulate cortex, or rACC, became much more active when the person realized that he or she had erred and there was a penalty attached to the mistake. This part of the brain is involved in deciding what kinds of emotional responses are appropriate.

What is so interesting about this work is that in a previous study on a small group of people with obsessive compulsive disorder (OCD), the same team has shown that the rACC region of the brain became much more active in response to a no-penalty error in the brains of OCD patients, compared to people without the condition. One of the characteristics of OCD is fear and anxiety about errors or failures in certain aspects of everyday life. As a result, many begin repetitive patterns of behavior to ward off or to prevent such events.

So it looks as if people struggling with OCD have a hyperactive response to making errors, after which they begin to get more and more worried that they may have made a mistake. OCD can be a terribly incapacitating condition. We think of mild cases like Melvin Udall in As Good as it Gets, or Adrian Monk, but in reality it can cause much suffering.

I was once asked to see a seventy five year old man who had suffered from a bizarre case of OCD since the age of fourteen. He had traveled the country trying to get help, and it was an extraordinary tribute to him that despite his problem he had built a successful business and family life. He came to see me for acupuncture, but left with a prescription for a medicine that was at the time relatively new. His improvement over the next few months, as we used medication, psychological and social work and then some energetic techniques was just extraordinary.

Research like that from the University of Michigan may well bear important fruit in the future.

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The Ethical Brain

There is a nice blog, Brainethics, that discusses an interesting new book Hardwired Behavior by Laurence Tancredi. This really is an outstanding piece of work. The author is both a psychiatrist and a lawyer who argues that Society’s assumptions about free will and individual responsibility must be drastically revised in the light of scientific discoveries about the brain.

This is part of a large debate that is going on within psychiatry and psychology and within the legal profession. As an example, at what age should a young person be able to drive a car or be legally liable for their decisions? The driving question comes up because the brain and nervous system of a fifteen-year-old is still far from being fully mature, and may lead to poor coordination and decision-making. Can an eighteen-year-old be held liable for his behavior, at a time that his brain is not fully formed? Yet he is able to fight for his country. You will see that your answers to those questions are likely to be a mixture of political positions and personal experience. But there is also no doubt that the explosion of knowledge about the brain will be factored into some future legal decisions.

In Tancredi’s book, he applies knowledge derived from recent research to such traditional moral concerns as violence, sexual infidelity, lying, gluttony and sloth, and even financial fraud and gambling. For anybody working in the field, it is very clear that hormones, nutritional status, drugs, genetic abnormalities, injuries and traumatic experiences all have profound effects on the structure and functioning of the brain. Therefore they may all have an impact on our moral choices. Some experimental work implies that our actions are initiated by pre-conscious and unconscious processes in the brain before we are consciously aware of them. Does that mean that our sense of moral agency is a retrospective illusion? And what about free will?? Is that an illusion too?

I like this book, and also the recent book by Michael Gazzaniga, entitled The Ethical Brain. But I need to sound a note of caution: we are bewilderingly complex creatures, and there is powerful evidence for the existence of systems that can over-ride some of the neurological ones. So even after reading and studying hundreds of books and scientific papers and talking to hundreds of scientists around the world, I remain convinced that free will is not an illusion, and that there really is a genuine morality which is a great deal more than the firing of neurons in the brain.

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