Depression Traced to Overactive Brain Circuit

Neither a placebo procedure in patients nor tryptophan depletion in healthy volunteers triggered the mood and brain activity changes. Brain scans revealed that a key emotion-processing circuit was overactive only in patients in remission — whether or not they had re-experienced symptoms — and not in controls. Since the abnormal activity did not reflect mood state, the finding suggests that tryptophan depletion unmasks an inborn trait associated with depression.

Alexander Neumeister, M.D., Dennis Charney, M.D., Wayne Drevets, M.D., NIMH Mood and Anxiety Disorders Program, and colleagues, report on their positron emission tomography (PET) scan study in the August 2004 Archives of General Psychiatry.

The NIMH researchers and others had previously shown that omitting tryptophan from a cocktail of several other essential amino acids washes out the precursor chemical from the blood and brain, depleting serotonin and often triggering symptoms in people with a history of depression — and even in healthy people from depression-prone families. This added to evidence that a genetic predisposition that renders some people vulnerable to inadequate serotonin activity may be at the root of the mood disorder.

The researchers scanned subjects after their blood tryptophan levels were reduced by about three-fourths, using a radioactive tracer (a form of glucose, the brain’s fuel), which reveals where the brain is active during a particular experimental condition.

They randomly gave 27 unmedicated depressed patients-in-remission and 19 controls either pills containing seven essential amino acids, such as lysine and valine, or identical-looking placebo pills. Subjects received either the active pills or placebos in repeated trials over several days in a blind, crossover design.

Sixteen (59 percent) of the patients experienced a transient return of symptoms under tryptophan depletion; their mood lifted to normal by the next day. Compared to controls, the patients showed increased brain activity in a circuit coursing through the front and center of the brain (orbitofrontal cortex, thalamus, anterior cingulate, and ventral striatum) — areas involved in regulating emotions and motivation that have been implicated in previous studies of depression. Whereas previous studies interpreted the circuit activation as a transient, mood-dependent phenomenon, the new evidence suggests that circuit over-activation is likely an underlying vulnerability trait, say the researchers.

Because of its ability to unmask what appears to be a trait marker for major depressive disorder, the researchers suggest that tryptophan depletion may be a useful tool for studying the genetic basis of depression.

“Since brain function appears to be disregulated even when patients are in remission, they need to continue long-term treatment beyond the symptomatic phase of their illness,” noted Neumeister, who recently moved to the Yale University psychiatry department. Also participating in the research were: Drs. Allison Nugent, Tracy Waldeck, Omer Bonne, Earl Bain and Marilla Geraci, David Luckenbaugh, NIMH; Dr. Markus Schwarz, Munich University Hospital of Psychiatry, Dr. Peter Herscovitch, NIH Clinical Center PET Department.

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An interesting diagram of the human brain and the affected areas described here is on the press release link.

12 thoughts on “Depression Traced to Overactive Brain Circuit”

  1. .
    …the limits of cause and effect. The link you’ve given, while very interesting and rather extensive, lists “Heavy Metal Toxicity” as a “Weak or unproven link” to depression. Following the link on to depression, I could spend the next year trying to determine all the things that could be affecting me.

    I understand that you’re opposed to medicinal treatment of depression — in fact, if I could find anything else that works I would prefer that to pills. BUT, I either have to trust the doctors and psychiatrists and professionals who prescibe meds and work with me or I will fall into the stupid trap of self-medicating. Among veterans, it’s common to see dosages adjusted, meds not being taken, or instructions simply ignored. It’s a lesson in what not to do.

    So I have to once again state that when you’re suffering from depression, you’ll do damn near anything to climb out of it. Thanks for giving me a couple of things to check out.

    jon

  2. The site also covered the role of amino acids, if you were able to get that far.  

    Once again, I have not suggested that the short term use of such devices is unnecessary.  I am merely convinced that there is a better way.  One that is better for one’s mind, soul and body.  As the site indicates, there are issues of damage to organs, especially to the heart and liver which are not halted by the artificial aversion of symptoms and have played a role in leading the body and mind into a worse state of ‘depression’.

    Above all of this, I disapprove of the majority of psychologists and psychiatry itself.   I sincerely feel that MOST have no intention of legitimately fixing the problem, but instead of keeping a person only feeling good enough to think the Dr. is effective, but not good enough to be independent from him.  You may have thought that in all this that I am against you.  But in this particular case, if I win, you win.  

  3. .
    I read the whole thing and several of the links as well. Let’s not muddy up the issue by pointing at amino acids now — or at any of the other possible factors in depression referenced by the link you specified. You distincly pointed toward “heavy metal toxicity”, which probably leads to physical symptoms that exacerbate depression.

    You may be convinced there’s a “better way”, but who’s to judge if that “better way”, for that person and THEIR depression, doesn’t include the things you don’t like or agree with? The “better way” is probably several things at the same time (things that will probably change over time). To me, the whole point of these discussions (in BOTH of the depression polls) seem to be treating, improving or eliminating the depression. And that means doing whatever you think it takes to lift yourself out of the depression.

    I’m reminded of the joke about the blon…er, woman facing financial problems who asks God to let her win the lottery. But come the next drawing, she doesn’t win and loses her car. So she pleads harder, but once again she doesn’t win and loses her house. Desparate, she describes to God how financial ruin has crippled her career, made her kids go hungry, and battered her self esteem. “Could I please win the lottery?” she asks again. Suddenly, a Voice from above answers, “Look, work with Me on this. Go buy a ticket!” In other words, ya gotta do whatever it takes…

    I tend to agree with you that psychologists and psychiatrists (and yes, many other professions) have a vested interest in keeping a patient as a paying customer. However, since most VA services are free and there is a large demand on their time, I tend to think VA professionals would rather get rid of me by treating me successfully.

    No, I don’t think you’re against me and I think Frued was obsessed with sex. I also think most mental health professionals don’t know from personal experience what depression is, which to me hampers their effectiveness. I’m just trying to do whatever (meds, therapy, education, attitude adjustments, etc.) it takes to get out of this rut.

    jon

  4. and I’ve received it in MANY forwards, being blonde and all.  Okay, these days, I take advantage of the wonders of modern chemicals for that “just been out in the sun” (and the Clairol factory) look, but the joke does make a pertinent point, no matter what shade one’s hair color.

    Your best argument is that VA physicians would surely like to see you on your way and perking along again.  They have nothing to gain by hooking you on meds to keep you coming back.  I have a feeling they’ll have their hands full with returning troops from the Iraqi war.

    I DO feel, though, that some counselors HAVE suffered from depression and perhaps other traumatic events.  I believe one reason some mental health professionals go into the field is to help those who are suffering, to participate in the process of lifting others out of the quicksand  where they themselves were trapped at one time.

    As you pointed out, in EVERY profession are the charlatans, out for their own gain at the expense of others.

  5. .
    Fact is, there was an increase in patients at the VA from Desert Storm. For years the VA has been beset with WWII vets, Korean vets, and Vietnam vets (not to mention Grenada, Somalia, etc.). Still, most of the vets are grey-haired. Once the Iraq and Afghanistan troops start coming home, it’s not going to be pretty. Not only is this a fairly unpopular “war”, but the conditions are terrible, the time spent overseas has been extended, the battle conditions are simlilar to the guerilla tactics experienced in Vietnam, and too many lives have been lost (no politics, merely facts). I hope the medical and mental health professions have learned something from Vietnam — they’re going to need it.

    As for the VA and meds, in an appointment yesterday I was asked again, “What do you want to do?” In other words, what drugs to take, what therapy to pursue, etc. My answer was a simple, “You’re the professional, what do you think I should do?” For some vets, it’s amazing the narcotics they ask for and get.

    If there are counselors of any ilk that have suffered from depression, I’ve never met one. Perhaps my ten or twenty contacts have been unusual. I do know of many in various specialties — like asthma, child abuse, drug or alcohol abuse, STDs, or weight loss — because of their own problems. Overall, though, I think many get into various professions because of some fascination with the specialty (gynecology comes to mind…).

    jon

  6. I wasn’t thinking specifically about depression, but when my daughter had panic attacks at age 16, I took her to a psychiatrist who described IN DETAIL what my adolescent daughter was feeling because she (the dr.) had experienced panic attacks in medical school.  I cannot TELL you how that helped my child feel that she wasn’t losing her mind.  (My daughter has a pronounced mitral valve prolapse, which can be a factor leading to panic attacks — so much for the “It’s all in your head” theory.)

    I also know that many times social workers and counselors are those who were traumatized as children and want to do whatever they can to prevent the same in another child’s life.   I was thinking more along those lines rather than actual depression.

    I have a good friend who is a counselor and did have a turbulent period of depression in his life several years ago.   He confided in me that he’d love to be in counseling himself, but he was fearful that it would ruin his career.

    I think I’m conceding that you may be right about professionals and their knowing firsthand about depression.

    The VA docs?   SURELY they wouldn’t ask a returning 21 year-old, fresh from the desert, “What do you want?”   Surely they simply know by now that you are informed and have your stuff together enough to suggest what to try. Asking that question to shell-shocked young vets is like offering them a land mine park for R&R.

  7. .
    …do INDEED ask “What do you want?” Not only in the mental health branch (where 95% of the vets abuse[d] drug or alcohol) but in the physical health branch. Perhaps the couple hundred examples I’ve seen is a small sampling, but that’s the way I (and most others I’ve talked to) have seen it. Meds are less expensive than a doctor’s time.

    While the VA did learn a lot from the Vietnam vets and medical science has progressed over the years, a patient’s treatment is still influenced by the patient. One saving grace may be that the VA has a $25,000 income cap for non-senior citizens or the
    non-disabled (as far as I know).

    As for me being informed, I think I am — but I’m no professional with the power or desire to self-medicate. My last visit I suggested dropping one med, but instead had the dosage increased. Argh…! I’ll see what happens.

    This is one of my pet peeves about the professionals I get to see: most haven’t experienced what I have, physically or mentally or treatment-wise. Your daughter was very fortunate.

    jon

  8. The VA is re-evaluating the Vets here, too.   My husband spent several years in Italy while in the military (no serious combat tho) and was recently informed that he would need to reapply for medical services.  According to one of our friends, who is retired military and about 70 years old, the new reapplication process means that all these guys are going to be placed at a much lower level of services than they had before.  In other words, one would have to be literally on his death bed before he could be seen by VA doctors here.

    does the funding issue that you’re referring to vary from state to state?  

  9.  No kidding.  

    And I always thought that the brits were so “progressive”.   What happened there?

    I guess `progressive’, in this case, must merely mean that one has more awareness of the world at large, with no adequate means to cope with what he’s become aware of.  

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