The Man Who Couldn’t Stop (19 page)

When the scientists tested the younger boy's blood, they found that levels of antibodies – a sign of the severity of the strep infection – tracked his OCD symptoms. As the antibodies dropped, so his obsessions and compulsions weakened. When his antibodies spiked to indicate renewed strep infection, his OCD symptoms became worse.

The psychiatrists started to track down other similar cases. They advertised nationally and at big medical conferences. Reports of cases started to trickle in, slowly at first, just one or two each month, but as word spread the team would investigate four or five a week. They kept the idea of a possible link to streptococcus to themselves, until they had fifty children who showed a similar pattern: a strep throat infection closely followed by a surge in obsessive-compulsive symptoms or tics. By 1998, the psychiatrists had enough to go public. They published a report in the
American Journal of Psychiatry
that described the fifty cases, and coined a term for what was wrong with them: ‘Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections'; ‘Pandas' for short.

The important word in that long title is ‘autoimmune'. Scientists think Pandas is down to the strep infection because it makes the body release antibodies against the foreign bacteria that in some people go on to mistakenly attack their own brain cells, probably in the basal ganglia. The exact mechanism, and its contribution to the OCD symptoms in the children, remains unclear and somewhat controversial, given that the idea suggests that common bacteria could provoke infectious outbreaks of OCD and perhaps other psychiatric disorders too.

The 1998 academic paper on Pandas caused a sensation. Patients and anxious parents of children with mysterious obsessions were handed an easy-to-understand explanation, and a possible cure: the scientists successfully treated some of the children by sucking out and replacing the plasma from their blood, so ridding them of the anti-brain antibodies. But the Pandas hypothesis left too many doctors and medical experts sceptical. Disagreement was bitter and polarized the field of child psychiatry for years. It still does. Some said the NIMH team was plain wrong and insisted they scrap the whole idea. A flurry of academic papers attacked and offered support to both camps. The biggest losers were acutely ill children and their parents, who did not know which experts to believe. The research and the controversy continue.

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It is not just studies of humans that link damage to the basal ganglia to ritualized and compulsive actions. Experiments with green anoles, a lizard sometimes called the American chameleon, have highlighted the crucial role of the basal ganglia in ritual in reptiles. Male anoles square off with each other for territory with a series of displays and repetitive actions; chiefly they strut and push themselves up and down on their front legs. We do this when we fight over territory too; look how a boxer behaves in the ring when he paces around a downed opponent.

In 2003, brain scientists at the University of Florida showed that anole territorial display routines associate with increased activity in distinct parts of their basal ganglia. The basal ganglia of the reptiles, they observed, seemed to activate to release the behaviour in the appropriate context. And while one part of the basal ganglia seemed to control dominant behaviour – the squats and struts – a separate part appeared to associate with a separate routine of submissive behaviour shown by the weaker anoles, which squeeze flat to the floor. The results of the Florida experiments supported other research on anoles in the 1970s, which showed that damage to their basal ganglia appeared to switch off control of these territorial rituals, but leave other behaviours intact.

We should be careful not to draw too many comparisons between lizard and human brains, but the anole study does raise an important question. We saw earlier how a capacity, or instinct, for ritual seems hardwired into the human brain, and how the contents of common human rituals are similar to the themes of OCD. We know from the work of van Economo – on sleepy sickness – and others that damage to the basal ganglia can force some people to perform involuntary and repetitive – ritualistic – movements. And now we see that the basal ganglia relates to ritualistic behaviour, fixed action patterns, in other species too. Is OCD what happens when a fault in the brain leads the basal ganglia to deploy ritual at the wrong time, in an inappropriate context?

Some neuroscientists think that it is. Those who study the basal ganglia, and the brain tissue that surrounds and interacts with it, have developed a model of how the OCD-brain might go wrong. Like all models of the brain, it's massively simplistic to a neuroscientist and maddeningly complex to almost everybody else. It goes something like this:

The basal ganglia works closely with the brain's orbitofrontal cortex (OFC), which sits just behind the eyebrows. The OFC processes sensory information from the eyes and elsewhere and passes signals to a region of the basal ganglia called the striatum. From there, the message goes to a separate brain structure called the thalamus, which controls motor systems. In response, the thalamus passes signals back to the OFC.

This happens in a non-stop loop, and it might help us respond to external threats. Told about events in the world by the OFC, the striatum and thalamus select the appropriate motor response, the right programme, and tell the OFC to make it happen. I see a lion. Yikes. Run away. When the circumstances change, the danger passes, the OFC signals the all-clear and the thalamus stands down.

What's important for the model of OCD is that the OFC can pass these signals to the thalamus in two different ways. The signal to switch on passes through the striatum, and is called direct. The stand-down is indirect; it is sent to the thalamus through the striatum and then via other parts of the basal ganglia.

In this model of obsessive behaviour, OCD occurs when the thalamus runs out of control and sends inappropriate instructions back to the OFC. The instructions and the behaviour no longer suit the circumstance, and this puts the OFC in a bind. Information from the senses, updates from the outside world, indicates everything is fine. Yet signals from the thalamus suggest not. The consequent motor behaviour, the ritual, continues even while the senses tell the OFC that there is no danger, and no need for the behaviour. That's the paradox of OCD right there. The water shrew jumps the removed stone. The clean hands are washed. I check the fresh paper towel for blood.

That's a stripped-down version of the, itself simplified, model of the OCD brain. But here's an even more simplified one: The direct route that excites the thalamus is an accelerator pedal. The indirect route is a brake. In normal function, the accelerator and brake work together to control speed. In OCD, the brake fails.

From this model of the way an obsessive brain works it's clear why a common response from others − that someone with OCD just should not be so ridiculous − does not and will never work. Don't you think we might have tried that? You merely tell us what we can see with our own eyes, that our hands are clean, that the towel is free of blood. We see and yet we can't stop. A driver who points out that a speeding car is going too fast does not slow it down. We need to fix the brake.

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One way to try to fix the brake is to use drugs. The Leeds psychiatrist who gave me the rubber band had also convinced me to take Prozac. It was still a wonder drug back then, and Elizabeth Wurtzel's bestselling account of her depression,
Prozac Nation
, had made those little green and cream pills almost a fashion accessory. Prozac didn't help me much. I wasn't depressed, just unhappy. I told the psychiatrist that I didn't feel any better. He offered me an alternative drug. I don't remember what it was called, just that he said it would turn me into a happy zombie. I wasn't sure whether that was an endorsement or a warning. I still don't know. I turned it down.

Some fifteen years later, the first thing that the psychiatrists I went to see at the specialist OCD unit did was to put me back on drugs. Not Prozac, but something similar. This time, the chance they would turn me into a happy zombie wasn't discussed.

 

ELEVEN

Daddy's little helper

Sertraline hydrochloride is what chemists call a psychotropic medication. I call it a lifeline, a route back to the light from the darkest regions inside my head. I take 200 mg every morning. The two white tablets taste bitter, so it's best to swallow them with plenty of water. Here goes. Gulp.

Seconds after I swallow the pills, acidic juice in my stomach starts to eat away at the thin layer of polymer film that covers them; within minutes the film is weak enough to release the crystal powder inside. Some of this powder dissolves quickly in the water and drops into the small intestine, the inch-wide and several-feet-long hosepipe coiled somewhere under my belly button, where it will work gently for hours along my intestinal tract.

As these freed drug molecules rub up against the wall of the gut, they leak through its porous lining and into the blood held by the tributaries of thin vessels on the other side, which trickle and pool into my giant hepatic portal vein. Inside the vein and buffeted by blood cells, most of the dissolved drug binds to giant serum proteins. It must hold tight, because its next stop is the liver.

The armies of PhD chemists who design drugs like sertraline hate the liver, because the liver hates chemicals like sertraline. It's the liver's job to strip foreign bodies from the blood, and sure enough it tears into the sertraline with its most powerful weapons – enzymes to break it down and convert the drug to something else.

Enzymes to the right of them, enzymes to the left of them, enzymes in front of them,
*
boldly the sertraline charges my liver's metabolic guns. Much of the drug is hit, and changed by the biological defences into clumps of derivative molecules called N-desmethylsertraline – still useful, but weaker. Together with traces of the original drug that manage to slip through, these start to pour with the blood that carries them into the central circulatory system.

It takes about six hours after I swallow the sertraline for the drug to peak in my circulatory blood. After the liver it visits the heart, from where it is flung to all corners of the body – some sertraline uselessly bounces around my toes and floods through my eyes. Some, by chance, takes the route that passes the mouth, where its journey began, and reaches the top of my head. There, the drug molecules face a formidable challenge, to breach perhaps the best-defended wall in all of nature, the blood-brain barrier.

Some four times longer than the former Berlin Wall, the blood-brain barrier is a thin layer of tightly knit cells painted onto the outside of the blood vessels that deliver nourishment to the brain. Unlike the cells that line the small intestine, which make it as easy as possible for stuff to move from the gut into the blood, the brain barrier does the opposite. The job of this coating layer is to resist and to make it difficult for the same stuff to shift through it, out of the blood vessels and into the surrounding cells and tissue of the brain. (Picture the barrier as the lagging that surrounds and insulates hot water pipes. The pipe is the blood vessel, the space around it the brain.) There's a good reason for that resistance. Brain cells are fragile and sensitive. They must live a sheltered life, protected from possible poisons or the volatile spikes and dips in blood chemicals that follow food or exercise.

The chemistry of the barrier dictates what goes from the blood into the brain and what does not. Heroin, for instance, is much more addictive than morphine because a quirk of its structure makes heroin a hundred times more soluble in fat, and so more able to cross the fatty blood-brain barrier. Even expert drug designers who can safely guide their best medicines through the liver come up short when they try to access the brain. They discover to their great frustration that the blood-brain barrier blocks even useful molecules like antibiotics and anti-cancer drugs.

Drugs that do penetrate the barrier must either dissolve in its fatty centre, like the heroin, or Trojan horse–style must smuggle themselves in. Sertraline seems able to do the latter and sticks to gateway proteins on the barrier's surface, which confuse the drug with something they were expecting, and so let it pass.

The battle of the liver is tough for the sertraline, but the blood-brain barrier is tougher – most of the sertraline molecules are rebuffed by its defences. But, as each beat of my heart delivers fresh blood and renewed reinforcements, and the sertraline keeps up its assault, it edges into the barrier and eventually through to the other side. It enters my brain.

Just a tiny fraction of the original 200 mg, the two bitter tablets, will ever get near a brain neuron. But it is enough. When I swallow the pills, the sertraline hydrochloride renews its daily battle against my OCD. My brain starts to change and my mind changes with it.

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Sertraline, sold also as Zoloft and Lustral, is one of a class of widely prescribed antidepressant medicines known as the SSRIs – selective serotonin reuptake inhibitors. Prozac is another. The SSRI drugs are controversial, partly because of the huge quantity of them routinely dished out, and also because of a claimed association with increased suicide risk in teenagers. There are doubts about if and how they really do work for depression. But they are a popular front-line treatment for OCD.

Psychiatrists have thrown dozens of different drugs at OCD over the years, from LSD, lithium and amphetamines to nicotine patches and the horse tranquilizer ketamine. The only chemicals that seem to consistently help are those that work – like the SSRIs do − on serotonin, a hormone found mostly in the gut but usually recognized for its role in the brain.

Dozens of trials of OCD treatment with SSRIs – sertraline, Prozac and a handful of others – have now been carried out with hundreds of people, and a consistent picture has emerged. Patients with obsessions and compulsions who take the drugs are more likely to improve – measured as a significant decrease in their Yale-Brown scores of obsessive and compulsive symptoms over time – than those who do not. The drugs don't help everybody, but then nothing does.