Posted by Uppendown on March 21, 2002, at 17:15:04
Hi Ya'll,
I was reading further up the page where somebody was asking about the different types of depression... and, of course, the ongoing questions about what works, and what doesn't... In the spirit od "support and education" that this site is here for, I thought I'd add this...
Hope it helps ...
Best Wishes,
U&D
DIAGNOSIS DETAILS
Types of depression
* What kinds of depression are there?
* What types don?t get better?
* What if anxiety is the main problem?
* Types of anxiety
* Generalized anxiety disorder (GAD)
* GAD or Bipolar II?
* Can kids have bipolar disorder? What does that look like?
* Are my kids going to get it?Bipolar variations
* Are we stretching the diagnosis too far? Is this a bipolar "bandwagon"?
* Normal? mentally ill? Where?s the line between them?
* What's the difference between bipolar and "borderline personality disorder"?Why does this happen?
* What about hormonal effects on mood? (revised Apr 2000)
* What?s the latest theory about what causes bipolar disorder? (revised Feb 2002)What kinds of depression are there?
You will run into many adjectives describing depression. Here are some of the most common variations:
* acute or chronic
* situational or unprovoked
* ("exogenous" or "endogenous")
* prolonged grief
* due to medical condition
* atypical"Acute" means severe, and generally also means sudden, implying that prior to this severe depression the person was much less depressed, perhaps not at all. The opposite is "chronic", meaning the person has had this for years. The usual DSM term for this is "dysthymia" (technically, depressed more days than not, for more than two years).
Situational depressions have clear causes (or at least people think there is such a connection). Unprovoked, or "endogenous" depressions come "out of the blue": no clear event is associated with the start. Some people will call this "chemical" depression, meaning there was an internal cause, not an external one.
Most people experience sadness when they lose something to which they were emotionally attached. When the loss is great, such as the death of a family member, people can experience a deep grief. In many respects this looks like "depression", but most people will feel themselves gradually coming out of it, starting within a few days or sometimes a week or two. Grief that continues beyond about 1 month is generally considered "prolonged" and may need some help to resolve.
Depression can be associated with medical conditions. Strokes and Parkinson?s disease are among the most common such causes, but several common medications, and many other diseases (problems with the immune system , heart, and especially hormones such as thyroid) can be associated with depression. The list is so long that "ruling out" all these other diseases is very impractical. You can end up with a lot of tests that are painful and even carry some risk, such as a heart catheterization or using a scope to examine your stomach or intestines. After a blood test looking at least at thyroid function, it is not routine to go looking for potential medical causes for depression. Rather, the doctor looks for signs and symptoms of these illnesses to see if they might be the cause. Without such signs and symptoms, it is very unlikely that there is some "medical" basis for your depression.
Finally, in this brief survey, there is "atypical depression". Technically this refers to a group of patients who have depressive symptoms but also have other features: "mood reactivity" (intense emotional reactions), and sleeping too much and/or eating too much, thus gaining weight. This symptom complex has been shown to identify a group of people who respond better to an MAOI (monoamine oxidase inhibitor) than to imipramine, another older antidepressant. Other symptoms associated with the "atypical" label include "leaden paralysis" (extreme lack of energy), and "rejection sensitivity" (over-sensitive to perceived slights), although these were recently shown not to predict imipramine non-response as well.Sotsky All these symptoms have tremendous overlap with bipolar symptoms. In fact, interpersonal sensitivity is specifically associated with bipolar II.Benazzi Moreover, bipolar disorder tends not to respond well to the older antidepressants, and may respond best to the MAOI?s. Are these really different diseases, or just different aspects of a complex syndrome? If a person does well on an MAOI, great. If the response is not enough, or fades away, consider bipolar disorder as an alternative explanation for this symptom pattern.
What types don?t get better?
As saw in the last section, there is a group of patients with depression who do not get better with standard treatment, and so are called "treatment resistant". Some of these people have depression that may eventually respond to the right combination of psychotherapy and medications, and actually have difficult versions of "unipolar depression". Could you be one of those? How long should you go on trying antidepressants and/or therapy?
There is no standard answer to this question. The simple answer is: read this site and if you think "bipolar" might explain your history, consider trying mood stabilizers. If you already have tried them, and didn?t improve, were you taking an antidepressant at the time? Antidepressants can make bipolar disorder worse and keep mood stabilizers from being effective ? my opinion. You should read the appendix "Do I really have to stop my antidepressant?".
But what if you?ve tried 3 or more antidepressants and several therapists? And you don?t drink alcohol, which you may have already learned to avoid. If you have a mood disorder this complex ? what then? You could have something more like Borderline Personality Disorder.Goldberg(a)
There are surely other reasons to have a treatment resistant depression, which hopefully we will understand further soon. This includes influences of other illnesses such as stroke or Parkinson?s disease; immune disorders such as lupus erythematosus; cardiac problems like congestive heart failure, and so forth. There is growing research on the effect of reproductive hormones on mood, that may explain some women?s mood experience.
However, at present, eventually "treatment resistance" boils down to these two options:
1. more antidepressant trials
2. reconsider psychotherapy (some, more, different type)Recent research in psychotherapy has shown that two types of psychotherapy -- interpersonal and cognitive/behavioral therapy ? work as well as medications in mild to moderate depression, possibly with greater long term effectiveness.Frank and Thase. But eventually, after multiple trials of medications and therapy, what then? Long before then, one should apply an old rule of medicine: if the patient does not respond to a routine treatment, always reconsider the diagnosis. Has something previously been ruled out that now needs to be reconsidered? Has something been omitted previously that should now be included?
People with treatment resistant depression may get better with mood stabilizers (discussed in detail below). Mood stabilizers may also be useful in multiple other conditions related to mood disorders, including: impulse control disorders, borderline personality disorder, premenstrual syndrome, irritable bowel syndrome, migraine, dissociative disorder, and as add-on medication in unipolar depression. Getting better on one of these medications doesn?t mean you have bipolar disorder, but by then the label doesn?t matter as much.
This kind of thinking leads to an argument that mood stabilizers are being used too widely, or that the bipolar concept is being stretched too far.Sobo The best response to this concern is simply to read the main references on this issue by mood specialistsFreeman; McElroy; Perugi; Angst; Akiskal ; Akiskal and Pinto; Goodwin; Fawcett; Jamison For my personal response to this concern, read the appendix "Stretching the Diagnosis Too Far"? a Bipolar "Bandwagon"?
What if anxiety is the main problem?
Types of anxiety
First, you must recognize the distinct types of anxiety that have highly effective treatments:
* panic disorder
* obsessive compulsive disorder
* social phobiaEach can have up to an 80% response to treatment, without medications! For panic disorder, David Barlow and colleagues developed a cognitive-behavioral therapy that has the best track record, better than medications. Several current self-help books capture much of this approach, though perhaps not enough. Barlow?s 12-session (or less) method is still the "gold standard" of this technique. I have used his treatment manual with over 50 patients with results similar to his research ? and it?s actually rather fun! To access Barlow?s approach, call all the psychologists in your area and ask if they are using cognitive behavioral therapy for treatment of panic disorder. If they actually use Barlow?s manual (Mastery of Your Anxiety and Panic: MAP; not available in bookstores, as the creators intended it for use with a therapist), all the better.
For obsessive-compulsive disorder, several research teams have defined a cognitive-behavioral therapy that can also work as well or better than medication. An easily read summary is Brain Lock, by the head of the UCLA treatment program. Lee Baer and Edna Foa are other major contributors to this field who each have their own paperbacks. To access this treatment in your area, use the same "call ?em all" method and ask if the therapist is doing "exposure and response prevention", or "cognitive-behavioral therapy", for OCD.
People with social phobia experience intense anxiety, very similar to or including panic attacks, but only in social situations. When they are by themselves, they do not feel anxious. They can go to a mall if they don?t have to interact with anyone (as opposed to panic disorder patients, who tend to fear the enclosed, "can?t escape" feeling of a crowded public place). Social phobia ranges from very mild performance anxiety to an inability to handle interactions with any but the most familiar people, and can be extremely debilitating. You will hear about Paxil for social phobia as its manufacturer was the first to jump through the hoops to gain FDA approval for this indication, but other SSRI?s may be equally effective. Moreover, there is a cognitive/behavioral therapy similar to that for panic disorder that has efficacy equal to medications and may have better long term results.Liebowitz If you think you might have something like social phobia also (very common in bipolar disorder) then do have a look at this fine website on that subject, including their emphasis on cognitive behavioral approaches. If you wish, read some theorizing about the evolutionary basis of social phobia, and how it might be, in some ways, the "opposite" of gregarious hypomania.
Post-traumatic stress disorder can be much harder to treat. Similar cognitive methods can help some, and several classes of medications also may help (antidepressants, antipsychotics, and mood stabilizers), but many symptoms can remain.
Generalized Anxiety Disorder
Lastly among the long-lasting anxiety diagnoses there is "Generalized Anxiety Disorder" (GAD). Here are the symptoms:
Generalized Anxiety Disorder
Disorder (DSM-IV)
Cognitive* worry
* difficulty concentratingEnergy
* keyed up, on edge
* restlessness, tension
* easily fatigued
* difficulty falling/staying asleepMood
* irritability
There is no treatment with response rates comparable to the treatments for panic, OCD, or social phobia. Several groups have tried to adapt cognitive therapy to this condition, with limited success. Medication treatment is even more disappointing. Benzodiazepines (Valium, Librium, Klonopin, Ativan, Restoril, Xanax) usually help a lot, almost perfectly, for a short while. But they lose their effect in most patients, and the dose must be increased to get symptom control again. Then the pattern repeats, the dose growing steadily higher. In some patients some benefit is maintained at the higher doses, but many physicians are uncomfortable with long term use of these drugs. Eventually some doctor will simply refuse to continue them, and then the person is exposed to her/his anxiety again. If the medication is stopped quickly, she/he has "withdrawal" anxiety (or even more serious physical withdrawal symptoms, which can be life-threatening) in addition to the original symptoms.
Buspirone (U.S.: Buspar) is similar to benzodiazepines but without the dose increase/withdrawal risk. It generally has has little or no effect, in my experience. Certainly if there were patients who did very well with it, I wouldn?t see them! But usually the good news filters to me eventually, and currently there is very limited enthusiasm for this medication, based on what I hear from colleagues.
Antidepressants can provide substantial relief of symptoms. Recently venlafaxine (U.S.:Effexor) has been approved by the FDA as having effectiveness, as other antidepressants have shown before.Feighner The problem with this approach is that it clearly does not help enough people, as most patients who reach me have already had trials of multiple antidepressants with limited improvement.
GAD or BPII?
In my experience it is very clear that some people who are experiencing anxiety, who often have been diagnosed with GAD, respond to the mood stabilizer approaches described below. Could they have had a form of bipolar disorder?
Sometimes the answer to the question doesn't matter as much as just trying to identify people who would respond well to mood stabilizer medications. Two symptoms that seem to best identify people who are going to respond to these medications, are, in my experience:
* profound insomnia; and
* difficulty concentrating.These are two of the GAD symptoms; I?ve put them in brackets in the right column below. Add the symptoms of bipolar II (using the broad criteria of the head of the mood disorders clinic at UC San Diego, Dr. Akiskal), and you?ll see we have basically duplicated the DSM rules for GAD:
Generalized Anxiety Disorder (DSM-IV)
Bipolar II (Akiskal + Phelps)
Cognitive* worry
* difficulty concentratingEnergy
* keyed up, on edge
* restlessness, tension
* easily fatigued
* difficulty falling/staying asleepMood
* irritability
Cognitive
* free floating anxiety
* [difficulty concentrating]Energy
* motor agitation
* restlessness
* extreme fatigue
* [profound insomnia]Mood
* dysphoria, irritability
When you look at these virtually identical lists, I hope it makes sense to you than anyone with GAD symptoms who has not responded well to antidepressants should consider a trial of mood stabilizers. Remember, not everyone will respond. Raised hopes carry risk of dashed hopes later, so be cautious and wait for the "proof in the pudding".
Can kids have bipolar disorder? What does that look like?
We know this is a genetic disorder. So anyone who has this illness is going to wonder if their kids (born or yet to be created) could get it. If the current view that early treatment can decrease an entire lifetime of symptoms holds up, detecting early signs of the illness will be crucial. So this question of how bipolar disorders show up in kids is crucial too.
Unfortunately, the "diagnosis" puzzle is even harder in kids than it is in adults. But, as one researcher put it, the most important step in diagnosing bipolar disorder is to suspect it in the first place. The worst error is not to consider it. Even if the diagnosis is held until fairly certain, that's better than missing it entirely, which is the case all too often.
Fortunately, though, there is a wonderful website to help parents with their worries as they watch their children grow up and wonder about whether they might have bipolar disorder. It's run by the Child & Adolescent Bipolar Foundation. It has the full text of an expert summary from 1997 about how to diagnose and treat kids. See their "About Early Onset Bipolar Disorder" in the Learning Center as a start, but go back for their Reference Center as well. It includes full text of a wonderful collection of articles, many pretty technical, but very well selected. This site is a real gift to parents.
Are my kids going to get it? (added Jan. '01)
Yes, it's genetic. For more on that, see the section below on "what causes bipolar disorder?" and especially the page about genetics. Ok, if it's genetic, how likely are your kids to get it?
The answer used to be "roughly 20% chance if 1 parent has it, 50-70% chance if both do". Those figures apply to Bipolar I data; there has not been separate work on Bipolar II families, though the picture looks roughly the same so far.
However, thanks to a fine article by Duffy and colleaguesDuffy, there's more to say than that now. Their article is very technical, so the following is a "translation" into plain english; any errors in translation are mine.
Here's how that math works, in case you were wondering: "20%" means that if you had 5 kids, statistically one would have a mood disorder. If you only had two kids, there would be a bit more than 50% chance that neither of them would be affected, versus a bit less than 50% chance that one would be affected.
Dr. Duffy and her colleagues emphasize that "20%" is just an average risk, if one parent has bipolar disorder. From there, you need to take into account how many affected relatives you have. If there are a lot, the risk to your children is higher; if there aren't very many, then the risk is lower than 20%.
If you want more details, read the special section on genetics and risk.
Are we stretching the diagnosis too far? Is this a bipolar "bandwagon"?
Even some psychiatrists think this bipolar way of thinking has gone too far.Sobo They are concerned that excitement about this diagnosis and the treatment options it opens has become a "bandwagon". Yet, how can we tell the difference between a useful new way of thinking and a bandwagon? Won?t they look similar, perhaps identical, at first? Surely we already know the answer to this puzzle: "the proof is in the pudding"! Patient outcomes will tell us how valuable a new approach really is.
Granted there will be some placebo value initially for almost any "new" treatment that comes along. That?s why data from "open trials" of a new medication (no control group, no blinding of patients or providers) almost always overrate effectiveness. Only later when the controlled trials are done do we get a clearer sense of what the medication offers relative to placebo. Gabapentin (U.S. Neurontin) is a good example of this, now shown to be no better than placebo despite great initial interest and positive results.
Bandwagons aside, if a patient with depression happens also to have irritability, or insomnia, or anxiety - is he/she "bipolar", or is that stretching the diagnosis too far?
First, remember the new "spectrum" way of thinking about this. We should not be asking a black-and-white "bipolar or not?" question. Rather, ask "how much of this bipolar-like trait might be present?"
Secondly, we should think of "diagnosis" in these cases as a heuristic process. I love this term. It describes exactly where we are in this dilemma. Per Webster?s dictionary, heuristic means "valuable for research but unproved or incapable of proof". We let go of the need for certainty in favor of assessing usefulness.
A heuristic approach to this problem asks not "do I really have bipolar disorder?" but rather: "If I try mood stabilizers, what is the likelihood of benefit? What is the likelihood of risk? How effective are the alternatives, and what is the risk they pose?"
A brief trial of valproate presents low risk in people who have normal liver tests. Long-term treatment is different. Weight gain is very common and must be managed cautiously, as there are numerous health risks associated with obesity, and possibly some risk of changes in reproductive hormones in women.
If weight gain is not going to be a problem because we are going to replace the medication if appetite increase occurs, the remaining risks of valproate are viewed as quite minor by most people (see my Depakote handout). Thus even if their symptoms are not severe, people often still conclude that at least a test of the medication will bother them less than continuing their symptoms.
Even if the risks were greater, such as with carbamazepine, many people still conclude the risk is justified because they have reached a stage where "no treatment", or continued trials of antidepressants, or even quality psychotherapy, is far less preferable.
For a similar but more historical and elegant discussion of this "bandwagon" issue, see this essay by Dr. Ghaemi, a research psychiatrist in the Psychopharmacology Program at Cambridge Hospital, and an instructor in psychiatry at Harvard Medical School.
Normal? mentally ill? Where?s the line between them?
In general, people who ask this question are really worried about their own sanity, or about how they will be perceived by others, especially if they are labeled as "bipolar". However, the question should be resisted, in favor of a new "model" of the illness. Again, think in terms of a spectrum, or continuous line. You will remember the "mood spectrum":
plain depression --------------------------------- manic-depressive
("unipolar") (bipolar I)
A similar spectrum exists, from completely mentally healthy, to severely impaired by mental symptoms. As stated in the milestone document "Mental Health: Report of the Surgeon General" (1999), mental health and mental illness are merely extremes on a continuum:
Mental Health ----------------------------------- Mental Illness
"Ill" or "healthy" sets up a yes-or-no, black-or-white distinction that is really a problem in bipolar disorder, where people can have long phases with no symptoms. Do they still have a mental illness? Imagine a man who has had a heart attack. Perhaps he has worked hard at physical activity after his attack and no longer has any limitations. Does he have a cardiac illness? What if he instead has no limitations because his medications work very well? Does he still have a cardiac illness? (Perhaps even more to the point, have you ever heard anyone ask those kinds of questions!?) Our society?s tendency to think in black-or-white terms creates this labeling problem.
For example, consider the following headline: "Kinkel unlike the other shooters: mental illness set Springfield teen apart from other youths who terrorized schoolmates". Kip Kinkel killed multiple classmates in a Springfield, Oregon high school. He was later said to have an "urge to kill". This was regarded as evidence of a mental illness, and somehow different from the presumed motives of the several other gun-wielding adolescents who killed their classmates in other schools. These other youths were completely "normal"?
Or as a less extreme example, consider one of my patients with bipolar disorder, a college professor. When she applied for a new drivers? license, there was the question: "Do you have a mental illness?" What?s she supposed to say, when her symptoms have been 80% controlled for several years, and she has Bipolar II anyway, which has not been recognized as impairing driving safety? The question reflects the expectation: yes, or no? Do you, or do you not? The professor was very uncomfortable with being forced into this black-or-white position.
Mental events of other kinds can also be spread on a spectrum from completely unremarkable ("normal") to very unusual. Fanaticism, for example, demonstrates a continuous spectrum. It extends from people with no particular intense interests; to strongly held beliefs; to extreme beliefs as manifest in some members of Greenpeace or the NRA; to complete loss of perspective as in followers of suicidal religious cults, or Timothy McVeigh (bomber of the U.S. Federal Building in Oklahoma City) ; to overt paranoia such as seems common in the statements of Militant Federalist members (mysterious black helicopters, elaborate conspiracy theories) or the Y2K fearful (no need to stock up on supplies, as the world is coming to an end); and finally to clearly delusional beliefs such as those in the "Unabomber" Manifesto, or Kip Kinkel?s "need to kill".
But a "fanatacism spectrum" makes sane/insane questions much more difficult. Our legal system is predicated upon "black-or-white" distinctions: right/wrong, impulsive/premeditated, sane/insane. Society can handle black and white, but struggles with continuous spectrums.
Yet in the process it leaves patients with bipolar disorder in yes/no dilemmas that have no answer as such. Part of "destigmatizing" mental illness will eventually require recognizing "shades of gray" of mental dysfunction (and their probable genetic basis). We should all resist the question "mentally ill?", as such. It is just another limitation set upon people with mental health symptoms.
What's the difference between bipolar and "borderline personality disorder"?
If you haven't heard about "borderline", you can skip this section. This ends up being a rather long story, so I've moved it to it's own page. For a discussion on how thinking about "diagnosis" is shifting away from labels like this, toward a concept of symptom "spectrum, read this brief essay.
What about hormonal effects on mood?
When the DSM included premenstrual syndrome ("PMS") as a psychiatric disorder, there were protests in the streets of San Francisco (at the American Psychiatric Association meeting) by women?s groups opposed to making an "illness" out of women?s mood experiences. This point is well taken, and at the same time raises the question again regarding the term "mental illness" (as opposed to "normal"). Meanwhile, growing evidence suggests a need to critically evaluate the role of steroid hormones on mood, as follows.
Research doctors have reported several patients whose anxiety was successfully treated with medications altering steroids.Jacobs, Herzog(a) DSM "mixed states" and "rapid cycling" are widely recognized as occurring far more often in women than in men.Kilzieh Women with bipolar disorder have a 50% risk of depression after childbirth.Leibenluft Newer antidepressants affect the production of a key progesterone metabolite.Griffin And steroid medications are recognized as capable of precipitating manic symptoms in both Bipolar I and IIBrown and Suppes.
Andrew Herzog, chief of neuroendocrinology at Harvard, has performed or reviewed much research which indicates that reproductive hormones powerfully modulate mood and anxiety.Herzog(b) Estrogen increases the action of an "excitatory" neurotransmitter called glutamate, which is so powerful it can damage cells with its excitation effects if not properly balanced. The "yin" to glutamate?s "yang" is GABA, an "inhibitory" neurotransmitter, the activity of which is increased by progesteroneGriffin. Estrogen acts like an antidepressant, and progesterone roughly like Valium or Xanax. But too much estrogen can cause anxiety (just like antidepressants do in bipolar disorder), and too much progesterone can leave a woman sedated and low-energy. There is a complex balance between these hormones, and that balance varies throughout the menstrual cycle.
Recently an excellent summary of what Psychiatry currently knows about hormones and mood was published by Deborah Sichel, M.D. and Jeanne Watson Driscoll, M.S., R.N., called Women's Moods (ISBN 0-688-14898-0). They review what is known about premenstrual symptoms, pregnancy, postpartum (just after childbirth) changes, and menopause -- examining how mood is affected by the hormonal changes of each phase. Although this website will continue to collect and present further advances in our understanding of these mood changes -- for a single reference source, easily read, in the most understanding and supportive language you could ask for, Dr. Sichel and Ms. Driscoll's book is the place to go.
In the meantime, as I have begun to recognize the importance of these hormonal influences, I have been asking about menstrual function in all women with mood symptomsPiontek and Wisner. I am astounded at the frequency of abnormalities. As found recently in a small study on this subjectRasgon, almost every woman has something amiss. If cycling, they are irregular; and a surprising number have had uterine or ovarian surgery. Bad experiences on birth control pills are often common, but dramatic improvements in mood with estrogen have also been seen. There is much for us to learn about this.
What?s the latest on what causes bipolar disorder? (updated Feb 2002)
Despite great research effort, there is still no certain gene, nor even a certainly linked chromosome, for any form of bipolar disorder. Several chromosomes keep coming up, but none has been fully confirmed. (However, these seems likely to change very soon: see below). Nearly all researchers seem to have concluded this is a multi-gene condition. The mixture of so many bipolar variations may be one of the biggest obstacles in this search: it is difficult to consistently compare "apples with apples", when so many different variations exist.
However, the genetic basis of the disorder seems unquestioned now. For example, identical twins are highly likely both to be affected: about 80% in bipolar disorder. Cardno Another disease called "Huntington?s Disease" is caused by repeated "triplets" in the DNA string (three basic DNA building blocks occurring over and over again in a row, where they shouldn?t be). Studies of triplet repeats have been mixed in bipolar disorder: 4 studies found abnormal repeats and 4 did not.Margolis In addition, non-genetic influences have also been studied, particularly birth trauma, which was shown in a recent study to be significantly associated with bipolar disorder. Kinney
NEW NEWS (Nov. 2000): A research group at the University of California, San Diego, under the direction of Dr. John Kelsoe, has begun to report some solid results identifying at least one of the genes which may participate in causing bipolar disorder. If you'd like to see what they're thinking, translated into plain English (all mistakes in translation are mine), click here. You may be able to actually participate in this genetic research if you have a brother or sister who also has symptoms. Go to the UCSD Genetics Research website to learn more and sign up.
Researchers still have not been able to show what the basic problem of bipolar disorder is. We still don?t know exactly what structures in the brain are involved, or what has happened to the cells in that area, or what?s different about the molecules within those cells. However, we know it has something to do with your biological clock -- to see some amazing patient experience that demonstrates the role of the clock, click here.
And, some of the molecular changes that medications cause are beginning to be understood. These changes give us a small window into areas that might be "abnormal" in bipolar disorder. Here are a few of the changes that lithium produces. This might sound like a foreign language to you, but it will give you an idea of how complicated this all is -- and also how much we've learned already: Saldubina
* Lithium affects inositol levels, fairly directly; it's not clear how inositol fits into all this, but some people think inositol itself may have some treatment value. (The risks and benefits of such an approach are basically completely unknown).
* Lithium affects serotonin metabolism through an "autoreceptor" pathway that regulates serotonin release. This may relate to its antidepressant effects.
* Lithium affects the brain's own growing-and-pruning system, where it may have protective effects against the effects of stress hormones. This is one of the most studied effects, and most exciting.
* Lithium inhibits glycogen synthase kinase-3 (GSK-3), which is involved in a wide range of signal transduction pathways -- these are the pathways down which a message travels from the cell surface to the nucleus. However, this lithium effect occurs at high concentrations and may be more relevant for its toxic effect.
* Lithium increases glutamate reuptake and thus decreases glutamate availability in synapses. Glutamate is an excitatory neurotransmitter and its reduction could exert an antimanic effect. Glutamate has also been associated with causing cell death when its levels are high, again suggesting a protective effect of lithium.I hope you can see from this that there is a lot of research going on. This is just what we need to understand more about the cause of bipolar disorder, just where in the brain the problem originates and how that eventually shows up in people's symptoms.
An example of why this research could be so useful: an NIMH teamDetera-Wadleigh is studying what lithium does to genes, as it does indeed appear to lead to changes in DNA activity. If we can learn which genes, and what gene products are involved, this might allow things like:
a simple blood test for bipolar disorder (at least some forms of it);
a test that would show whether someone will respond to lithium;
designing treatments based on the most fundamental "abnormality" of bipolar disorder, namely the DNA and the protein products that come from it.
On to Treatment -->
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