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.

(MORE: Sexual and Emotional Abuse Scar the Brain in Different Ways)

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.

(MORE: Avatar Therapy Helps Schizophrenia Sufferers Silence Their Demons)

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.

MORE: Brain’s Own Valium Discovered

16 comments
cordial
cordial

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.

VasuMurti
VasuMurti

John Stuart Mill observed, "The reason for legal intervention in favor of children apply not less strongly to the case of those unfortunate slaves — the animals." 

People for the Ethical Treatment of Animals

501 Front StreetNorfolk, VA  23510

(757) 622-PETA (7382)

(757) 622-0457 (fax)

In Defense of Animals

3010 Kerner Blvd.San Rafael, CA  94901

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415) 454-1031 (fax)

Compassion Over Killing

PO Box 9773

Washington, DC  20016

(301) 891-2458

info@cok.net

Physicians Committee for Responsible Medicine

5100 Wisconsin Avenue, NW

Suite 400Washington, DC  20016

(202) 686-2210

pcrm@pcrm.org

jkoretz
jkoretz

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





JanetSinger
JanetSinger

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.

VasuMurti
VasuMurti

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.

VasuMurti
VasuMurti

"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

MelBaum
MelBaum

Dr Koretz,

I appreciate your clear articulation demonstrating the lack of definitive evidence for a physical basis for mental disorders such as OCD.  However, I wonder how then would you explain the causes of the psychological misery of OCD as elaborated in the opening paragraphs of the accompanied article?

JenniferBonin
JenniferBonin

@VasuMurti I don't have a problem eating cows, or chickens, or basil plants.  I don't have a problem riding horses or training my cat or enslaving herbs on my porch.  Is this "speciesism"? 

If so, I'm okay with that.  Because when you get down to it, like most humans, I DO believe we have a bigger responsibility to ourselves than other lifeforms.  And I'm also aware that all life harms other life, simply by existing.  Animals eat other plants and animals.  Even plants crowd each other out, killing their neighbors if at all possible.  While life isn't always cruel, it isn't always kind either.  I see no reason to get excited when scientists try to help people at the expense of mice.

(If you're really anti-speciesism, I seriously hope you don't plan to eat anytime soon, and I hope you don't live in a house which is build where plants and animals used to be.  You know, maybe you should just kill yourself now, to keep from bothering any non-humans, come to think of it...)

jkoretz
jkoretz

@MelBaum 

(Please note 2 parts, due to length) Part 1

MelBaum, As promised, let me respond to your question. On the symptomatic level, the 'psychological misery of OCD' is just as it is experienced by the patient: The anguish that comes with the continual interruption of the flow of life and enjoyment in it by obsessive thoughts or compulsive behaviors, rituals (of any form, such as endlessly repetitive handwashing due to fear of omnipresent 'contamination' from the environment if one does not succumb to the urgency with which one feels harm will befall them, should they fail to perform whatever 'ritual' seems demanded as the price of safety.)

My experience with patients, and hence my view, is similar to Mr. Klugar's reportage only in the sense that while the symptoms themselves are absolutely problematic (let us dispense with the superfluous issues of 'are they realistic?' - each person's internal reality is absolutely realistic to them, and the suffering that goes with it all too real, also), to consider such symptoms alone as what comprises 'the problem' from which they arise is a short-sighted view. Mr. Klugar goes on to elaborate all the brain regions which may be malfunctioning as the primary cause of this disorder. And as you know, I take issue with this unproven speculation, masquerading as 'scientifically' verified 'fact.'

I do not pretend that the explanation I've experienced of 'initial causes' is scientific, only that in my treatment of many patients with what is called OCD, I find that there has been, uniformly, a disturbance in the relationship between the patient and others, and/or with his (or her) environment, and the symptoms of OCD may be seen as the visible results of a struggle within the patient to resolve this disturbance - most often unsuccessfully, as the 'relational' disturbance can never be solved nor mastered by means of external 'rituals', and only increases one's problems and suffering.

Let me make a concrete example to illustrate: A man comes to me with 'germaphobia', i.e., the fear of contamination from all kinds of sources in the environment - door handles, keyboards, notes, etc. and feels he must continually wash his hands until they are red and carry antimicrobial hand cleanser with him and use it ceaselessly in order to calm the anxiety that attends him constantly. When we both become curious about his past and present important relationships, what seems focal is his relationship with his mother, who is quite controlling, manipulative, and guilt-inducing. One might see his fear of contamination as a concretization of this relational problem, and an attempt to solve it through concrete action - i.e., His mother is, psychologically, 'toxic', and that relationship the underpinning of a world-view and experience in which the entire world is a dangerous, 'toxic' place in which one must constantly guard oneself against being 'infected' and harmed by others.

Now, I do not take the 'classically' analytic viewpoint that if the nature of the real (relational, external and internal) problem is elucidated and comprehended by the patient, the problematic symptoms automatically disappear. Life, and therapy, should only be so simple. One may divide logic that people run on into two types: Rational, which we are most familiar with and are taught is how people 'really' operate, and what I call Emotional Logic, which has its own reasoning and 'grammar', if you will, and which I think trumps 'rational logic' about 95% of the time in determining our behaviors. If a patient can 'catch on' and become familiar with 'emotional logic' and how it operates in them, a good many things that seem to make no sense on the surface (e.g., handwashing in order to prevent fatal contamination) begin to make sense as emotional phenomenon (having the experience of being 'infected' by a parent's controlling 'agenda' for oneself, one might naturally wish to be free of such a toxic relationship. - The wish and struggle for such freedom makes sense to me - and I think would to most people, if it is visible and comprehended.)

But as said, insight itself does not resolve a problem. I would propose that what is therapeutic (at least to my experience) is a mutually-reactive combination of insight *and* action. On the 'relational side' of the problem, understanding its nature might allow the patient more 'freedom' with which to experiment taking a more autonomous stance in relation to the problematic parent. Experiencing the results of what happens from such 'experimentation', how and the degree to which one can engage in it, and seeing how it differs from one's assumptions about outcomes, hopefully adds to insight, which in turn in the best of circumstances adds to additional 'freedom' to experiment, and try out and establish new patterns of relationship.

Similarly, to the extent and degree which the patient can muster at any time, insight into the relational dilemma which underlies the immediately observable symptoms, may allow the patient more 'freedom' to 'experiment' with doing something *other* than what his anxiety dictates, and if they can observe the results, compare them to what they were 'sure' would happen, the degree of freedom from the 'slavery' of ritual which they have felt was imperative to perform may be increased.





jkoretz
jkoretz

@MelBaum ,

Thanks for asking that question - it's more complex than it looks on the surface, given that 1. Suffering itself is not only problematic but respectable; and 2. One would assume that if you can pin down the cause of such suffering (which in this syndrome is undeniable), you can specify how to treat it and thus reduce such suffering. My take on it is that the relationship between determining cause and treatment is more complex than one might think. But I would like to respond to your very pertinent question and attempt to answer it. It may take me a day or two to get the time to do that, but I promise you I will return and do so as soon as I can clear up the time to compose that response. Thanks for your patience

VasuMurti
VasuMurti

John Stuart Mill observed, "The reason for legal intervention in favor of children apply not less strongly to the case of those unfortunate slaves — the animals." 

People for the Ethical Treatment of Animals

501 Front StreetNorfolk, VA  23510

(757) 622-PETA (7382)(757) 622-0457 (fax)

In Defense of Animals

3010 Kerner Blvd.San Rafael, CA  94901

(415) 448-0048

(415) 454-1031 (fax)

Compassion Over Killing

PO Box 9773Washington, DC  20016

(301) 891-2458

info@cok.net

Physicians Committee for Responsible Medicine

5100 Wisconsin Avenue, NW

Suite 400

Washington, DC  20016

(202) 686-2210

pcrm@pcrm.org

jkoretz
jkoretz

@MelBaum 

MelBaum,

I'm glad if it was of some help. On your personal experience, that there is no apparent tie to any environmental (including relational) experience, it's intriguing: On the one hand, one has to respect an other's personal experience. No one knows what your experience is like better than you. On the other, I've found that oftentimes 'links' between behavior and experience are so well disguised, (the 'wallpaper' of everyday life I wrote of), that there are connections to be discovered, they just aren't apparent or considered yet. In any case, I wish you peace and wellness in your journey.

MelBaum
MelBaum

Dr Koretz,
Than you for your detailed and informative response. While I do agree with you that many OCD cases may have external environmental causes, my personal experience has been that this does not account for all OCD situations.The treatment approach that you proposed based on a combination of insight and experience certainly seems to have the potential to alleviate the anguish felt by OCD sufferers. Your elaboration of the notion of how experience initiates thoughts and behaviors is very enlightening.

jkoretz
jkoretz

@MelBaum

Part 2

I would say two additional things, which are my opinion, and to which I claim no scientifically 'provable truths': 1. Experience is always the teacher for all of us. (Emotion is the signifier that one has had a 'real', impactful experience.) Experience 'makes' behavior - including compulsions, in this instance. And it is not a singular experience, a unitary 'traumatic incident' in almost all cases that produces behavior, but repetitive experience, over a long period of time, such that such experience becomes the 'wallpaper' of everyday life, so 'regular' a part of our environment that it can go unnoticed. It is the repetitive nature of experience that makes problematic behaviors so recalcitrant. It also means that finding 'new' behaviors, which implies 'disbelieving' in old experience, must also be repetitive in order to have beneficial effects. Simply put, one doesn't abandon one's obsessive rituals because of one instance in which the feared harm did not appear, but over time, repeated experience with such anticipated harm not appearing as feared has an erosive effect on the 'old belief' system, as such it increasingly cannot be supported, even with 'emotional logic' in the face of repetitive, contradictory experience.

I take issue with Cognitive Behavioral Therapy (CBT - which Kluger identifies as being 'very successful' in the treatment of OCD - the currently fashionable 'paradigms' such as 'evidence based therapy' and the like are as much nonsense of his 'scientific' attributions of causes to 'proven' malfunctions in specific areas of the brain.)  CBT is deficient in that it posits that  initial 'causes' in one's relationship or experience need never be bothered with. Indeed, the idea that we have a 'psychological interior' and an 'internal' life and world-concept have no place in CBT. All that exists are symptoms, and the goal of treatment is symptom reduction. Causes, if they exist, are irrelevant. Or so they say. So, if you are anxious, let us teach you 'techniques' to reduce stress (Never mind the origin of the stress - irrelevant.) Or let us expose the patient to the feared stimulus and let the patient see that his fears are unrealistic, and thus they are cured of such irrational notions. (A patient I saw who was afraid, among other things, about outside spaces was taken on an 'experiential walk' into the parking lot outside the therapy room by his CBT therapist - intending to show the patient that his fears were groundless, and thus break the pattern of obsessive worry. What the therapist obviously didn't count on was the patient becoming 'psychotically unglued' and having an emotional meltdown in that parking lot under the emotional pressure that such a 'therapeutic' measure put him. If the therapist had a better sense of the root 'cause' of the patient's fears, perhaps he would've been more aware of issues of the patient's character structure, emotional resiliency or brittleness, and the critical issues of timing and nature of interventions.) However, insurance companies love CBT's idea of only treating symptoms, having symptom relief as the measure and goal of therapy, and the idea that this is 'scientific' because it is somehow 'evidence based' (relegating 'experience-based' to the realm of fiction?)  In any case, it costs less than most any other form of treatment (except medication), and you might well wonder if there is a cause-effect relationship between the ascendancy of such paradigms and what insurance is willing to pay for these days, e.g., short-term, symptom reduction oriented therapy. 'Scientifically based', of course ;-)

By the same token, I think 'classical' analytic therapy, while closer to my own viewpoint, is rather 'light' on the 'doing' side of what one may call the 'therapeutic equation': One gains insight into their behavior, but as I've stated above, insight alone is not enough. If 'old experience' constructed pathological thoughts and behaviors, change must be instigated by having 'new experiences', that are contrary to, and  'constructively destructive' of old, pathological experiences and patterns of behavior. Some forms of analytic therapy account for the 'experiential' side of the equation by saying that 'experience' comes in the form of the relationship between the patient and the therapist. This is certainly true, I believe. But I also think 'experience' might play a broader part than most schools of analytic therapeutic thought give it.

The one thing I do not do is claim that the knowledge I have of this is scientific, or that it can be demonstrated through scientific means. I think such claims in general are faulty, but the full reasons for that are another discussion entirely. Let me leave it at this: One may think of psychotherapy as more art than science. In the same manner that one cannot hope to judge what is 'good' or 'true' art by scientific means, a full, meaningful, and useful description of the complexity of human beings, and how they may change, is something that science has not, and probably will not, be able to capture in its fullest sense, one that does it proper justice.

I hope my response has been useful in answering your question.

jkoretz
jkoretz

@MelBaum 

Did not see this new comment by you until after I posted a response to your initial inquiry. I think you've got something there, in terms of brain studies that show differential patterns between subjects diagnosed with a symptom or syndrome and those of 'control' subjects' brains: There is no indicator of whether this is, as you point out, 'cause', or 'effect', much less what such patterns are specifically significant of.

MelBaum
MelBaum

Dr Koretz,

I am looking forward to your response. I have read several books and reports that reference brain imaging studies performed on OCD sufferers. The researchers highlight areas of the brain that are overactive when compared to normal controls with the implication that those unhealthy brain circuits are the cause of the OCD. However, my intuition has been that while these studies demonstrate the consequences of OCD on the brain - they by no means establish the cause of OCD as faulty brain circuitry.