Mice With OCD Can Mean New Hope for Humans

A new study of mouse brains leads to new insights — and perhaps new treatments — for a common disorder

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There may be no torment quite like the sublime looniness that is obsessive-compulsive disorder (OCD). Your hands are clean, the door is locked, you didn’t insult a colleague at work or drive over someone on the way home or mishear the 17 doctors you’ve seen in the past month who told you that no, you really, truly don’t have whatever disease you think you’ve got. And yet you keep washing or locking or checking or worrying.

Most people think they understand OCD — and most people are wrong. It’s not just tidiness, it’s not just fretfulness, and it’s not a glib adjective (“You should see how neat my desk is. I’m so OCD!”). It is, instead, a profound malfunction in various regions of the brain — principally the amygdala, which processes fear, anxiety and other primal emotions — and the mere fact that it is exceedingly treatable with cognitive-behavioral therapy, medication or both does not make it any less awful if you’ve got a real case of it. Now, thanks to a new study just published in Science, people suffering with OCD have at least a little more hope of recovery than they did before — and people studying the disorder have a lot more insight into what causes it in the first place.

The fact that OCD can be expressed in so many different ways has always suggested that it is caused by idiosyncratic interactions among several different brain regions. The amygdala likely plays a role in all of them, but the best-known forms of OCD — contamination anxiety and the excessive washing that can follow — are thought to be governed by the orbital frontal cortex (OFC) and the ventromedial striatum (VMS). The OFC governs decisionmaking and volitional activity; the VMS governs how we experience fear and risk. It’s not hard to see how an alarm set off by the VMS can lead to a decision to wash by the OFC — even if that decision defies reason.

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To explore that circuitry — and the way it goes haywire — a team of researchers led by Dr. Susanne Ahmari, assistant professor of clinical psychiatry at Columbia University, turned to a new technology called optogenetics. The researchers first engineered a common adenovirus — usually associated with upper-respiratory infections — to carry the genetic coding for a light-sensitive pigment known as rhodopsin. They then injected the virus into the OFC of lab mice, where it could enter brain cells carrying its rhodopsin payload with it. That caused the otherwise normal cells to become light sensitive. Finally, the scientists inserted fiber optic strands into the mice’s brains and stimulated them with pulses of light. What they expected to see was an increase in grooming behavior, which is common among mice — and in their species-specific way is similar to hand washing in humans. But when they flicked the light on in the mice’s brains what they got was pretty much nothing — at least at first.

“When we hyperstimulated this specific circuit, we thought we were going to see an increase in abnormal behaviors,” Ahmari said in a video released along with the Science paper. “That stimulation did not lead directly to repetitive behavior, but if we repeatedly stimulated for several days in a row for just five minutes a day, what we got was the progressive evolution of grooming behavior.”

The mice, in effect, had been neurologically nudged to a full-blown case of OCD, and even when the researchers quit the stimulation, the behavior stuck around for at least a week. In some of the mice, small doses of fluoxetine — the generic form of Prozac and other selective serotonin reuptake inhibitors — hastened the disappearance of the behavior.

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All that reveals a lot. For one thing, it may help explain why some OCD patients can go for years or decades without the disorder and then experience a single traumatic event — a near accident on a highway, a legitimate disease scare that turns out to be nothing — and shortly after, develop OCD symptoms related to the experience. They may have been born with a predisposition to the disorder (the genetic roots of OCD are still not completely understood), but the triggering event, like the few days of light stimulation in the mice, tips them fully into it.

More important, the research maps the underlying neural wiring behind the disorder and could help in the development of better, more precisely targeted drugs. For people with intractable cases of OCD that resist both behavioral and pharmacological therapy, other researchers have looked at deep-brain stimulation (DBS), using fine wires to activate or deactivate trouble spots. This is already being used successfully to treat the tremors associated with Parkinson’s disease. What science learns from studying mice could eventually lead to improved DBS.

None of this fully explains the mysteries of OCD, and drilling into the heads of human patients to insert wires is clearly a last therapeutic resort, especially since the large majority of cases do respond so well to less invasive treatment. Still, for sufferers who long castigated themselves as weak-willed or otherwise responsible for their own suffering, it can be a relief to know that OCD is just a sickness like any other — and as with so many sicknesses, relief is increasingly possible.

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Interesting read for me. I have had  OCD since childhood I have struggled with it for near on forty years. Recently I have undergone numerous attempts at CBT and exposure, I have fully understood how this works and how CBT is meant to help. Alas, CBT has helped but certainly has not stopped or cured my OCD. I strongly believe it is genetic, my mother had it. I have it and one my children has it but the others don't. I was very careful not to let my children see me doing my compulsions so I don't believe my child learned the behavior from me. Equally, I did not learn the behavior from my mother as we were separated during my childhood and I was told by another relative that my mother had OCD.


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Mr. Kluger,

Your writing is perhaps more pernicious than the so-called 'mental illneses', such as OCD, which are diagnostically classified in a tome based on social/scientific myth - the widely used DSM-IV book of such 'diseases'. The problem with your article is a too-common pitfall in behavioral science: The transition from facts to theory is 'seamless' misleading the reader into believing that what they're reading is all factual, as opposed to  what is true: some of it is factual, and some of it is extrapolated speculations (theory)  drawn, without any substantiation, from those facts. But the blurring of fact and theory, when repeatedly amplified by the press (i.e., you), leads the public to believe in theories that are speculative at best, and far too often, simply mythological.

Your article is full of caveats, as it should be - e.g.,  'scientists think (that).....', but there is no proof. Example: Equating grooming behavior in mice with OCD in humans requires a large leap of theoretical faith. Yet the headline that leads to your article appears to state this as fact "Mice with OCD Can Mean New Hope for Humans." 

The press commonly feeds this blurring of the distinction between fact and theory, which itself is encouraged by researchers, since overstating what is factually known helps them get grants to fund their salaries and operations. 

Let's take two quick examples: DSM IV (soon the be V) is based on  the *theory* that mental illnesses are just like physical illnesses, in that they have a biochemical substrate. Yet there is very little evidence to support this supposition that the entire field of psychiatry rests on. More specifically, as an example, the 'common wisdom' in the culture, created by just such articles as yours, is that depression is a 'chemical imbalance' that can be 'cured' (or ameliorated) with anti-depressant medications. Except for the facts of the matter: There is no study, not one, that demonstrates and explains how this 'biochemical substrate' works in the brain to cause depression. Yes, there are studies that show that there is some correlation between neurotransmitters such as serotonin and mood, but what that relationship is, and how it works exactly, including what areas of the brain are affected and how remains a mystery - and hence a theory, rather than a statement based on facts.

Yet writing such as yours simply fuels the commonly-accepted myths as facts, and as such, supports the unsupportable proclamations of special interest groups in their perpetuation of such theories, masquerading as facts, such as pharmaceutical companies and the AMA - since, if these are not physical diseases at base, why do we need an MD leading the parade in treating them?  Why are pharmaceutical therapies the therapies of choice?

There are analogous examples throughout the history of science: One such is, in the 18th century I believe, science was focused on the question of 'what is fire?'. An English scientist, Joseph Priestly, prominent in his time, proposed that the answer to this question was a substance called 'Phlogiston' - materials that contained phylogiston were able to burn, those without it could not. All the great scientific societies of the day came to accept this theory as 'fact' - Paris, Vienna, London, etc., and it was presumed that it was just a matter of time before phlogiston's discovery was confirmed. We are still waiting for that confirmation. The dangers of accepting theory as fact has plagued science for a long time.  Very much like psychiatrists' and neurobiologists' current contention that, given enough grant money, we can unlock the 'secrets' of the brain with scientific precision and certainty.

I say shame on you for spreading such theories as facts, and further polluting what becomes 'common wisdom' and misinformation in the general culture. The role of the press should be the discernment and dissemination of truth. Being a shill for special interests in the scientific community makes journalism more akin to humanity's oldest profession.

James Koretz, Ph.D.

Clinical Psychologist


Thank you for this article, which gives us more insight into this baffling disorder and also gives hope to all those who have treatment-resistant OCD. If nothing else, it validates, as the author says, the fact that OCD is a real illness. My son had OCD so severe he could not even eat, and with the right therapy, he has made a remarkable recovery. His OCD is now classified as mild. I talk about anything and everything to do with the obsessive-compulsive disorder on my blog at www.ocdtalk.wordpress.com.


Opposition to animal experimentation has a long history.  The American Anti-Vivisection Society (AAVS) was founded by Caroline Earle White in 1883...long before People for the Ethical Treatment of Animals (PETA), which was founded in 1980, and even longer than before the current debate over stem-cell research!  

An editorial in the now-defunct Animals' Agenda from the early '00s, noted that animal research goes on unquestioned, while debate rages over stem-cell research, for no other reason than the stem-cells have human chromosomes.  This is speciesism--discrimination on the basis of species...a term which has not caught on or become part of the American vernacular, even among progressives, the way words like "Ms." or "homophobia" have become part of the American lexicon.


"Ask the experimenters why they experiment on animals, and the answer is:  'Because the animals are like us.'   Ask the experimenters why it is morally acceptable to experiment on animals, and the answer is: 'Because the animals are not like us.'  Animal experimentation rests on a logical contradiction."

--Charles R. Magel, professor of philosophy