![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 18 of 18. This is the beginning of the thread.
Posted by jrbecker on August 1, 2003, at 12:05:46
Antidepressants Give Extra Protection
Medications shield hippocampus in brains of depressed womenFRIDAY, Aug. 1 (HealthDayNews) -- Antidepressants seem to protect an important brain structure that's often damaged by depression.
That claim comes from a Washington University School of Medicine study in the August issue of the American Journal of Psychiatry.
The researchers studied an area of the brain called the hippocampus in 38 women who had experienced an average of five episodes of major depression in their lifetimes. Only some of those episodes of depression had been treated with antidepressants.
The hippocampus is involved in memory and learning. Previous research found the hippocampus is smaller in people who have been clinically depressed than in people who have never suffered depression.
In this new study, the researchers used high-resolution magnetic resonance imaging (MRI) to measure hippocampal volumes in the 38 women. The women were also interviewed to determine how long each of their depressions lasted and their use of antidepressants.
The study found that, on average, hippocampal volume was smaller than normal in depressed women and that the less time a women had spent taking antidepressants, the smaller her hippocampus.
The amount of lost hippocampus volume was predictable based on the number of days of depression versus the time spent on antidepressants, the study says.
"Our results suggest that if a woman takes antidepressants whenever she is depressed, depression would have less effect on the volume of her hippocampus. It is the untreated days that seem to affect hippocampal volumes," lead author Dr. Yvette I. Sheline, associate professor of psychiatry, radiology and neurology, says in a news release.
http://www.healthday.com/view.cfm?id=514421
>>>a similar article...
>>>
Public release date: 1-Aug-2003
Contact: Nicole Vines
vinesn@msnotes.wustl.edu
314-286-0105
Washington University School of MedicineAntidepressant drugs may protect brain from damage due to depression
St. Louis, Aug. 1, 2003 –- Studying women with histories of clinical depression, investigators at Washington University School of Medicine in St. Louis found that the use of antidepressant drugs appears to protect a key brain structure often damaged by depression.
Previous research has shown that a region of the brain involved in learning and memory, called the hippocampus, is smaller in people who have been clinically depressed than in those who never have suffered a depressive episode. Now, researchers have found that this region is not quite as small in depressed patients who have taken antidepressant drugs.
The study, led by Yvette I. Sheline, M.D., associate professor of psychiatry, radiology and neurology, appears in the August issue of the American Journal of Psychiatry. The hippocampus is a part of the brain's limbic system, a group of structures important to emotion and motivation. Using high-resolution magnetic resonance imaging (MRI), Sheline's team measured hippocampal volumes in 38 women who had experienced an average of five episodes of major depression in their lifetimes. Only some of those episodes had been treated with antidepressant drugs.
"In addition to their brain scans, each woman was interviewed on two occasions by independent interviewers to determine how long each depressive episode lasted and how much, if any, of that episode was treated with antidepressants," Sheline says.
The team compared hippocampal volumes to the number of days on or off treatment. They found that on average, hippocampal volume was smaller than normal in depressed women, and that the less time a woman had spent taking antidepressants, the smaller her hippocampus. The amount of volume loss was predictable, based on the number of days depressed versus the number of days on antidepressant treatment.
"Our results suggest that if a woman takes antidepressants whenever she is depressed, depression would have less effect on the volume of her hippocampus," Sheline says. "It is the untreated days that seem to affect hippocampal volumes."
Animal studies also have demonstrated that antidepressant drugs can protect against stress-induced decreases in hippocampal volumes. Why the hippocampus shrinks is not clear. It may be that brain chemicals released during depression, such as cortisol, damage brain cells. Or it could be that depression damages the connections between nerve cells, resulting in a smaller volume. But however the damage is done, Sheline says it is clear from this study that antidepressant drugs can limit volume loss.
"We've shown in other studies that people with hippocampal damage also have problems with certain memory tests," she says. "And large epidemiology studies have shown that major depression is a risk factor for the later development of Alzheimer's disease. So it seems clear that volume loss in the hippocampus can have very negative effects, not to mention the devastating problems caused by depression itself."
Sheline and colleagues did not look at specific antidepressants to compare whether one was better than another at preserving hippocampal volumes, but any antidepressant seems to protect the brain better than no treatment.
Sheline says because volume loss in the hippocampus appears to be cumulative -- that is, the more episodes of depression, the more volume loss -- it is important to recognize and treat depression right away to prevent damage. It also may be worthwhile for patients to continue taking antidepressants between episodes of depression.
"Many psychiatrists already recommend that some patients who are prone to depression remain on antidepressants permanently to protect against depression," Sheline explains. "These apparent neuroprotective effects provide a further argument for at least strongly considering remaining on antidepressants."
Currently, Sheline's team is looking at whether antidepressant drugs prevent damage to hippocampal neurons or whether they may potentially restore previously lost volume. It is unclear whether drugs can restore volume that was lost, but she says this research demonstrates that without treatment, hippocampal volume loss in depressed patients was more extensive than it was in those who took antidepressant drugs.
###
Sheline YI, Gado MH, Kraemer HC. Untreated depression and hippocampal volume loss. The American Journal of Psychiatry, vol. 160:6, pp. 1516-1518, Aug. 1, 2003.This research was supported by grants from the National Institute of Mental Health and the Division of Research Resources of the National Institutes of Health.
(sorry, no direct link)
Posted by SLS on August 1, 2003, at 12:27:01
In reply to just more evidence...ADs protect the brain, posted by jrbecker on August 1, 2003, at 12:05:46
Hi JRB.
Do you personally feel that hippocampal volume can be regenerated once remission is achieved?
I hope so. Mine must be the size of a pea.
- Scott
Posted by joebob on August 1, 2003, at 12:57:05
In reply to Re: just more evidence...ADs protect the brain, posted by SLS on August 1, 2003, at 12:27:01
Posted by linkadge on August 1, 2003, at 15:22:25
In reply to could phos serine and efa help restore hippocampus (nm), posted by joebob on August 1, 2003, at 12:57:05
Clinical remission is often accompanied by restoration of near/full volume of the hippocampus. Lithium has been shown to increase brain volume in some of these critical areas. AD's are less studied but beleived to exert similar effects. Keep stress to a minimum, excercise aerobically, take your medication, and the the brain cells will grow.
Linkadge
Posted by linkadge on August 1, 2003, at 15:28:56
In reply to could phos serine and efa help restore hippocampus (nm), posted by joebob on August 1, 2003, at 12:57:05
I'm sure that keeping all the brains required lipids at plentiful levels would positivly protect agains neurodegeneration.
EFA's like omega 3's are the backbone of the myelin sheath, which protects nerve fibers from starvation and various insults. They protect nerve survival and provide neuronal integrity / plactivity.
I would be under the impression that any drug that can create a sustainable improvement in mood
would be effective against the physical ravages
of mood disorders.I beleive uncontrolled anxiety is the real cause of problems.
Linkadge
Posted by jrbecker on August 1, 2003, at 17:32:24
In reply to Re: just more evidence...ADs protect the brain, posted by SLS on August 1, 2003, at 12:27:01
> Hi JRB.
>
> Do you personally feel that hippocampal volume can be regenerated once remission is achieved?
>
> I hope so. Mine must be the size of a pea.
>
>
> - Scottthat's a good question, Scott, and I don't think the research has answered that yet. There are so many classes of drugs that are neuroprotective, including mood stabilizers and ADs, which are not only neuroprotective, but also promotes regeneration. Dr. Manji of UCLA/NIMH has done a great job summmarizing this research, perhaps you can explore more on this from his studies.
Can total replacement of reduced volume be achieved from ADs and mood stabilizers? From what I've read, not likely. Or is it also a factor that we have smaller hippocampi to begin with? Anyways, Manji and others have offered a plethora of other chemical mechanisms to research that would expand on the neuroprotection seen in ADs and mood stabilizers. Coincidentally, this was somewhat the topic of an above thread. Start at the beginning of the thread to read the NYTimes article that spurs the discussion. Then read some of the links provided in one of my follow-up threads.
http://www.dr-bob.org/babble/20030728/msgs/246746.html
Only thing I would add is that although hippocampal dysfunction is definitely apparent, it's not the whole picture in terms of the etiology, since a lot of the research points to cortical areas of dysfunction as well. But as you'll read, the research is very much underway to get further "upstream" in the etiology of depression to see where the real problems are beginning (they obviously don't end just with the neurotransmitters).
Posted by Zenclearer on August 2, 2003, at 10:13:26
In reply to Re: just more evidence...ADs protect the brain » SLS, posted by jrbecker on August 1, 2003, at 17:32:24
Does anyone have any information (or know anything about) neuroprotective potential of Wellbutrin (vs the ssris)?
Most of what I've read regarding BDNF has been associated with the ssri's and some of the cholinergics.
Also, regarding amphetamines (dexadrine, not meth), does anyone have any information about any relations (positive or negative) with BDNF or other neuroprotective properties? I know about neurodegenerative effects (at high doses).
And I am famililar with potentiated neuro-platisticity under learning conditions (very short-term experiments; see recent piece in Science, about working with elderly and potentiating tactile sensitivity, although learning was not retained after stims discontinued).
Essentially, I am somewhat concerned about long-term use of low-does amphetamines. Instinctively, I have some feeling that rebound phenomena activates some inflammatory cascades, etc, and we know that's not good for the Ms. Brain. So I suppose I am more concerned about protential rebound reactions, and the effect on the brain over time.
Posted by Shawn. T. on August 2, 2003, at 11:50:00
In reply to Other brain questions, posted by Zenclearer on August 2, 2003, at 10:13:26
Zenclearer: Amphetamine has been shown to increase BDNF in the rat amygdala, piriform cortex and hypothalamus (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12213320&dopt=Abstract ); I'm not sure about how it affects the hippocampus with regards to BDNF expression. I don't know how Wellbutrin affects BDNF; however, I would *assume* that it increases BDNF levels. Most antidepressants have been shown to increase BDNF expression.
Switching gears, I believe that cortisol plays a key role in the hippocampal neurodegenerative effects of depression. Cortisol probably augments the neurotoxic effects of glutamate released in the hippocampus during stress; cortisol may also play a role in increasing extracellular hippocampal glutamate levels. In addition, cortisol is likely to decrease BDNF levels in the hippocampus. This is significant because BDNF is probably responsible for basal neurogenesis in the hippocampus. CREB is also an important factor in neurogenesis; however, I'm not aware of how cortisol might affect CREB. Some evidence suggests that CREB is essential for BDNF upregulation, but I'd like to see more research to support that conclusion.
So antidepressants influence the hippocampus in two key ways: counteracting neurotoxicity and increasing neurogenesis via key factors such as BDNF and CREB. SSRI's probably affect the size of the hippocampus by reducing the effect of cortisol and possibly by desensitizing/downregulating 5-HT2A receptors; 5-HT2A receptor activation has been associated with decreased BDNF expression in the hippocampus. I believe that it is possible that norepinephrine reuptake inhibitors could increase BDNF expression by downregulating beta-adrenoceptors; however, I lack the evidence to state that with any assuredness. Furthermore, the normalizing effects of SNRI's on the HPA axis suggests that these drugs may influence the damaging effects of cortisol. I believe that the effects of antidepressants on BDNF and cortisol definitely provides evidence that suggests that they can increase the size of the hippocampus after successful treatment; the degree to which this occurs would probably depend on the individual, the antidepressant, and environmental stressors.
For anyone really interested in learning more about this topic, here's a bibliography:
Cortisol, glutamate, and the hippocampus:
Corticosterone peak is responsible for stress-induced elevation of glutamate in the hippocampus.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9787265&dopt=AbstractThe exacerbation of hippocampal excitotoxicity by glucocorticoids is not mediated by apoptosis.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12624538&dopt=AbstractStress and depression: possible links to neuron death in the hippocampus.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12071509&dopt=Abstract3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063975&dopt=AbstractProtective and Damaging Effects of Stress Mediators
http://content.nejm.org/cgi/content/full/338/3/171?ijkey=2ayL2HP0PzdXQDetrimental effects of chronic hypothalamic-pituitary-adrenal axis activation. From obesity to memory deficits.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9824846&dopt=AbstractBDNF:
How antidepressants work
New perspectives on the pathophysiology of depressive disorder
http://bjp.rcpsych.org/cgi/content/full/178/4/299Stress, metaplasticity, and antidepressants.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12420802&dopt=AbstractEvidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12420802&dopt=AbstractCorticosterone effects on BDNF expression in the hippocampus. Implications for memory formation.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10938581&dopt=AbstractCorticosterone inhibits generation of long-term potentiation in rat hippocampal slice: involvement of brain-derived neurotrophic factor.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11102572&dopt=AbstractIncreased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11522260&dopt=AbstractAlterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12842310&dopt=AbstractDecreased serum brain-derived neurotrophic factor levels in major depressed patients.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11927139&dopt=AbstractAntidepressants and neuroplasticity.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12180273&dopt=Abstract5-HT2A Receptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex
http://www.jneurosci.org/cgi/content/full/17/8/2785Role of 5-HT2A receptors in the stress-induced down-regulation of brain-derived neurotrophic factor expression in rat hippocampus.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10076858&dopt=AbstractDifferential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12393228&dopt=AbstractCREB:
Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8601816&dopt=AbstractAbnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12622660&dopt=AbstractChanges in CREB-phosphorylation during recovery from major depression.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12393305&dopt=AbstractAbnormalities in the cAMP signaling pathway in post-mortem brain tissue from the Stanley Neuropathology Consortium.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11576759&dopt=AbstractcAMP response element-binding protein is essential for the upregulation of brain-derived neurotrophic factor transcription, but not the behavioral or endocrine responses to antidepressant drugs.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11943827&dopt=AbstractShawn
Posted by zinya on August 2, 2003, at 13:16:26
In reply to Re: just more evidence...ADs protect the brain » SLS, posted by jrbecker on August 1, 2003, at 17:32:24
JRB,
greetings ... I've just stumbled on this thread and went to the link you gave here to the prior thread as well - I'm double-posting this in both threads to hope to catch you.
I'm wondering if the experience I've been recounting to doctors who give me only glazed looks for the past 15 years could begin to be explained if I understand correctly the line of interconnection you seem to be outlining here between neural and (adrenal? and) depression-triggering 'damages'.
A brief history, as I know no other way to present my 'case study'. I lived 34 years with energy for anything I wanted, never knew what pain was really, not chronic pain. In 1981, after a serious roller skating accident which left me with a compression fracture between my 4th and 5th lumbars, i discovered a congenital anomaly (quite a unique one according to my chiropracter) involving an extra half a lumbar fused to my sacrum which has from birth presumably meant a pull on my right hip that creates something of an angle. Perhaps some childhood accidents like crashing on my coccix had some impact, but never chronic pain until that 1981 accident. It started first to manifest in sciatic pain for some years. Then a chronic viral infection beginning in 1985 entered the picture. By 1987, i crashed (compounded by the stress and grief of my father's death) into a 'black curtain' of zero energy and only at that point did the doctors look back and realize i'd been running with the chronic viral infection for 2 years, having gone in for sheer exhaustion, had blood tests but no one told me of the infection, figuring it would pass.
For two years from 87 to 89, recovery was elusive. Every time i would try to resume normal activity, which had included swimming between one and two miles a day prior to '87, i recrashed into zero energy even though i resumed with very gradual steps (like 1/4 mile only). Walking became a re-injuring activity. I was referred to various specialists who diagnosed Epstein-Barr, then Chronic Fatigue, also fibromyalgia, miofascial pain syndrome... I tried all kinds of traditional and nontraditional (eg acupuncture) methods.
I was given Prozac first in 89, later lithium (because of merely a one-day-ever manic episode and because i tend to do "fast talk" when i'm with a doctor trying to cram a lot into a visit and some then think i'm hyper but i'm not. What i've eventually come to realize is that my adrenal system, shown in blood work in 2000 to be depleted, is erratic but almost entirely on the no-adrenalin, no-energy side of the pendulum.
Okay, with that as some peripheral but converging background:
I've been telling my doctors for all these years that, in my lay terms, "My back goes out on me and then i just cascade downwards into no energy and feeling depressed." By which i mean that the nerve damage (pinched nerve) in my sacroiliac area -- or then also after getting hit in 1990 by a red-light-runner and suffering additional neck nerve damage from a concussion into my driver's window -- also enough nerve damage that i can no longer applaud as that hand clapping triggers nerve damage that also cycles into body-wide energy flagging and other downturns.
Doctors have been hard pressed to see how or why a reinjury to lower back nerve pain should be related to body-wide energy levels and depressive states. They seem to distrust me that i'm accurately assessing that i'm fine until a reinjury of my back and that that then alone launches a downcycle impacting depression.
Would an upshot of this research you have presented suggest that in fact there would be a plausible cause-effect linkage?
And, to get to remedies, as I'm now on Effexor (month 2 at 150 mg) after having tried without success Prozac, lithium, depakote, zoloft, paxil and celexa at various crisis moments over the past 15 years, usually having to quit due to side effects but sometimes because of no positive effect.
I have begun to wonder (since the Effexor I'd been led to hope would start to work on my adrenal system and show energy benefits by 150 mg levels but so far after 2 weeks at this level has shown none -- and i have had two back reinjuries -- rotated lumbar -- during this time period):
Would I perhaps be better off treating back injuries with stronger painkillers (I tend to try to get by with just 1/2 a vicodin which often is enough to be satisfactory but i've also learned that a full vicodin not only masks the pain but gives me actual energy restoration -- yet i am reluctant to take a full vicodin on a regular basis for fear of addiction), that perhaps if i did let myself take a full vicodin more immediately more regularly at the first sign of back pain, would i perhaps "envelop" the pain that perhaps then would not deplete (?) the adrenal system which then might not -- along the lines of what i gather from the research you cite -- trigger the depressive cycles??
I realize this can at best be answered on a theroretical level here based on a streamlined (!! believe me, you got the short version!) case study and no physical examination plus you are a researcher not a doctor. However, if you have any thoughts on the "logic" of the kind of connection I have long sensed intuitively lies at the root of this past 15 years of debilitation which has impacted my career and my ability to travel as i used to, etc. It's this lay sense that "my back (nerve damage in lumbar/sacrum) that goes out and then i cascade into depression that takes longer to recover from than the back pain itself."
Any thoughts? And apologies if this feels like an imposition in terms of being something out of your bailiwick.
thanks,
zinya
Posted by Zenclearer on August 2, 2003, at 15:33:51
In reply to Neurobiological Mechanisms Involved, posted by Shawn. T. on August 2, 2003, at 11:50:00
Thank you Shawn. I will enjoy your reading list.
My concerns are amphetamines are my concerns that they may tamper with cortisol levels.
Any knowledge of that?
Posted by Shawn. T. on August 3, 2003, at 14:15:18
In reply to Re: Neurobiological Mechanisms Involved » Shawn. T., posted by Zenclearer on August 2, 2003, at 15:33:51
I was able to find one study involving humans; 20mg of dextroamphetamine has been shown to increase cortisol levels in male subjects (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2501383&dopt=Abstract ). I couldn't find any research involving the relationship between chronic amphetamine use and cortisol levels in humans, but I would assume that the effect remains. Chronic administration of amphetamine to rats has been shown to increase corticosterone (the equivalent of cortisol in rats) levels (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8886751&dopt=Abstract and http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9352323&dopt=Abstract ). In children with ADHD, stimulants like amphetamine and methylphenidate (Ritalin) seem to normalize their cortisol levels which is interesting.
I'm not sure how amphetamine- mediated cortisol release might affect the hippocampus. I do know that corticosterone plays a role in the development of MDMA (ecstacy) induced serotonin terminal degeneration in the hippocampus of rats (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2470597&dopt=Abstract ). However, I don't think that that information is applicable to amphetamine. Personally, I don't believe that anyone should take amphetamines without also taking antioxidants; the monoamine nerve terminal damage associated with amphetamines can be prevented by antioxidants. It would be prudent for researchers to look into the problems that might be associated with amphetamine- induced cortisol release in patients without ADHD (and adults with ADHD).
Shawn
Posted by Zenclearer on August 3, 2003, at 17:11:50
In reply to Re: Neurobiological Mechanisms Involved » Zenclearer, posted by Shawn. T. on August 3, 2003, at 14:15:18
Many thanks again. I should have bothered to do the Pubmed search myself, and thank you for that work. :)
Hm. My concerns are somewhat validated, although I do realize the situation is complex, especially with ADHD.
But my concerns have been building regarding use in adults (with less resiliant brains than children), even if the adults do have ADHD.
Posted by SLS on August 3, 2003, at 19:40:18
In reply to Other brain questions, posted by Zenclearer on August 2, 2003, at 10:13:26
From Medscape:
Antidepressants May Protect Against Hippocampal Volume Loss
Laurie Barclay, MD
Aug. 1, 2003 — Antidepressants may protect against hippocampal volume loss associated with depression, according to the results of a small trial published in the August issue of the American Journal of Psychiatry. The amount of volume loss was predictable from the number of days depressed versus the number of days receiving antidepressant treatment."Our results suggest that if a woman takes antidepressants whenever she is depressed, depression would have less effect on the volume of her hippocampus," lead author Yvette I. Sheline, MD, from Washington University School of Medicine in St. Louis, Missouri, says in a news release. "It is the untreated days that seem to affect hippocampal volumes."
Using high-resolution magnetic resonance imaging (MRI), the investigators measured hippocampal volume in 38 female outpatients with major depression and in 38 controls matched for age, education, and height. On average, the depressed women had a previous history of five depressive episodes, only some of which were treated with antidepressant drugs. Each woman was interviewed by two independent interviewers to determine the duration of each depressive episode and of antidepressant treatment.
Hippocampal volume was smaller in depressed women than in controls. Longer episodes during which depression was untreated with antidepressants was directly correlated with decreases in hippocampal volume.
"We've shown in other studies that people with hippocampal damage also have problems with certain memory tests," Dr. Sheline says. "Large epidemiology studies have shown that major depression is a risk factor for the later development of Alzheimer's disease. So it seems clear that volume loss in the hippocampus can have very negative effects, not to mention the devastating problems caused by depression itself."
The mechanism of hippocampal atrophy is not clear, but it may involve cortisol or other neurotransmitters released during depression damaging neurons or synapses. Animal models also suggest that antidepressant drugs may protect against stress-induced hippocampal volume loss. This study did not distinguish the effects of specific antidepressants.
According to the investigators, cumulative hippocampal volume loss with repeated depressive episodes mandates early recognition and treatment.
"Many psychiatrists already recommend that some patients who are prone to depression remain on antidepressants permanently to protect against depression," Dr. Sheline says. "These apparent neuroprotective effects provide a further argument for at least strongly considering remaining on antidepressants."
The National Institute of Mental Health and the Division of Research Resources of the National Institutes of Health supported this research through grants.
Am J Psychiatry. 2003;160(6):1516-1518
Reviewed by Gary D. Vogin, MD
Posted by jrbecker on August 4, 2003, at 11:31:14
In reply to Re: just more evidence...ADs protect the brain » jrbecker, posted by zinya on August 2, 2003, at 13:16:26
> JRB,
>
> greetings ... I've just stumbled on this thread and went to the link you gave here to the prior thread as well - I'm double-posting this in both threads to hope to catch you.
>
> I'm wondering if the experience I've been recounting to doctors who give me only glazed looks for the past 15 years could begin to be explained if I understand correctly the line of interconnection you seem to be outlining here between neural and (adrenal? and) depression-triggering 'damages'.
>
> A brief history, as I know no other way to present my 'case study'. I lived 34 years with energy for anything I wanted, never knew what pain was really, not chronic pain. In 1981, after a serious roller skating accident which left me with a compression fracture between my 4th and 5th lumbars, i discovered a congenital anomaly (quite a unique one according to my chiropracter) involving an extra half a lumbar fused to my sacrum which has from birth presumably meant a pull on my right hip that creates something of an angle. Perhaps some childhood accidents like crashing on my coccix had some impact, but never chronic pain until that 1981 accident. It started first to manifest in sciatic pain for some years. Then a chronic viral infection beginning in 1985 entered the picture. By 1987, i crashed (compounded by the stress and grief of my father's death) into a 'black curtain' of zero energy and only at that point did the doctors look back and realize i'd been running with the chronic viral infection for 2 years, having gone in for sheer exhaustion, had blood tests but no one told me of the infection, figuring it would pass.
>
> For two years from 87 to 89, recovery was elusive. Every time i would try to resume normal activity, which had included swimming between one and two miles a day prior to '87, i recrashed into zero energy even though i resumed with very gradual steps (like 1/4 mile only). Walking became a re-injuring activity. I was referred to various specialists who diagnosed Epstein-Barr, then Chronic Fatigue, also fibromyalgia, miofascial pain syndrome... I tried all kinds of traditional and nontraditional (eg acupuncture) methods.
>
> I was given Prozac first in 89, later lithium (because of merely a one-day-ever manic episode and because i tend to do "fast talk" when i'm with a doctor trying to cram a lot into a visit and some then think i'm hyper but i'm not. What i've eventually come to realize is that my adrenal system, shown in blood work in 2000 to be depleted, is erratic but almost entirely on the no-adrenalin, no-energy side of the pendulum.
>
> Okay, with that as some peripheral but converging background:
>
> I've been telling my doctors for all these years that, in my lay terms, "My back goes out on me and then i just cascade downwards into no energy and feeling depressed." By which i mean that the nerve damage (pinched nerve) in my sacroiliac area -- or then also after getting hit in 1990 by a red-light-runner and suffering additional neck nerve damage from a concussion into my driver's window -- also enough nerve damage that i can no longer applaud as that hand clapping triggers nerve damage that also cycles into body-wide energy flagging and other downturns.
>
> Doctors have been hard pressed to see how or why a reinjury to lower back nerve pain should be related to body-wide energy levels and depressive states. They seem to distrust me that i'm accurately assessing that i'm fine until a reinjury of my back and that that then alone launches a downcycle impacting depression.
>
> Would an upshot of this research you have presented suggest that in fact there would be a plausible cause-effect linkage?
>
> And, to get to remedies, as I'm now on Effexor (month 2 at 150 mg) after having tried without success Prozac, lithium, depakote, zoloft, paxil and celexa at various crisis moments over the past 15 years, usually having to quit due to side effects but sometimes because of no positive effect.
>
> I have begun to wonder (since the Effexor I'd been led to hope would start to work on my adrenal system and show energy benefits by 150 mg levels but so far after 2 weeks at this level has shown none -- and i have had two back reinjuries -- rotated lumbar -- during this time period):
>
> Would I perhaps be better off treating back injuries with stronger painkillers (I tend to try to get by with just 1/2 a vicodin which often is enough to be satisfactory but i've also learned that a full vicodin not only masks the pain but gives me actual energy restoration -- yet i am reluctant to take a full vicodin on a regular basis for fear of addiction), that perhaps if i did let myself take a full vicodin more immediately more regularly at the first sign of back pain, would i perhaps "envelop" the pain that perhaps then would not deplete (?) the adrenal system which then might not -- along the lines of what i gather from the research you cite -- trigger the depressive cycles??
>
> I realize this can at best be answered on a theroretical level here based on a streamlined (!! believe me, you got the short version!) case study and no physical examination plus you are a researcher not a doctor. However, if you have any thoughts on the "logic" of the kind of connection I have long sensed intuitively lies at the root of this past 15 years of debilitation which has impacted my career and my ability to travel as i used to, etc. It's this lay sense that "my back (nerve damage in lumbar/sacrum) that goes out and then i cascade into depression that takes longer to recover from than the back pain itself."
>
> Any thoughts? And apologies if this feels like an imposition in terms of being something out of your bailiwick.
>
> thanks,
> zinya
Zinya,
That's quite a history.Do you mind if I ask some questions...
What is your diagnosis, currently? Talk more to the bipolar piece that your docs have suspected.
What is the current cocktail? You mentioned Effexor @ 150mg, but are you still on the Lithium?
Rate your symptoms on a 1-10 scale.
How do you like your current pdoc? How open is he/she to your input? Do you feel he is doing a fair job?
To answer your more general question, there's no doubt a connection between your physical ailment (back issues) and your depression -- I'm assuming your question was somewhat rhetorical though. The anguish you're going through everytime you re-injure your back is probably putting your mood into a tailspin. That's our kryptonite -- a vulnerability to stressors, as minor as they come. The biological science behind why this occurs has been the details of this thread. For a more simplified summary of this topic, go to:
http://www.mcmanweb.com/article-44.htm
The reaction to chronic stress is quite different across individuals. Some react by sleeping very little, poor appetite, fearing overly anxious all the time. While others exhibit the opposite symptoms of poor energy, sleeping all the time, ravenous appetite, and no motivation. Most are a mix of these symptoms. Atypical depression, has a lot in common with both CFS, FMS, and other physiological ailments in terms of poor energy. But for more on the diff's b/t the two types of depression, as well as atypical depression's overlap with CFS, see:
http://www.mcmanweb.com/article-200.htm
http://www.dr-bob.org/babble/20030407/msgs/217313.html
http://www.cfids-cab.org/cfs-inform/Cfsdepression/vanhoof.etal03.pdf
Despite being very similar CFS/FMS and atypical depression are still viewed as different diagnostically. One, because the pain element seems to be only apparent in FMS and sometimes CFS. But more importantly, in terms of looking at it causationally in terms of the mood aspect, all physical ailments can bring on depression only as a direct result of dealing with the stress of a dabilitating condition. However, with atypical depression, low mood seems to be the core of the illness to begin with, and is intimately linked with the physical symptoms of low energy and sluggishness. In general of course, all illnesses, to varying degrees are brought on by interaction with the environment. And perhaps, your depression would have never come out (at least to this severity) if you hadn't injured your back. But that can be said about pretty every one of us, to varying degrees, since depression is thought to be only a biological ~predisposition~ to illness -- but actual day-to-day life is the acid test to see if we can the withstand stress. No one can live in a bubble though.
PS -- Apologies if this is repetitive to some of the info you already know, but I'm ignorant to what knowledge you retain already on the subject.
Posted by zinya on August 5, 2003, at 0:28:30
In reply to Re: just more evidence...ADs protect the brain » zinya, posted by jrbecker on August 4, 2003, at 11:31:14
hi JRB,
gosh, thanks for your responsiveness. I will follow the links you provided, which i very much appreciate, but for now to answer your Qs:
>
> What is your diagnosis, currently? Talk more to the bipolar piece that your docs have suspected.Well, I would say that most diagnoses are a bit up in the air at the moment. The fibromyalgia and myofascial pain syndrome still apply. Depression is a supposition and i'm trying Effexor now as my 6th or so attempt at seeing if there is a biochemical basis and answer for it. I'm sorry if i didn't make clear that all the other a-d's i indicated i'd tried were only tried temporarily. Each one caused side effects i couldn't tolerate or in one or two cases, did no apparent good. The last a-d i'd taken before Effexor, which i started in late May, was in Dec. 2000, first Celexa and then Paxil, with bad side effects from both and quit.
The sciatica and pelvic pain problems are congenital but then triggered by accidental injury, as explained in earlier post.
I gave up tracking the CFIDS cuz it just didn't seem like there was a treatment. I have had a couple of periods of pursuit of new doctors etc. but that gets old very fast when the result is ineffectual. It's been a while.
There were only two mds, one in about 1990, one in 1993 who thought bipolar was possible and put me on lithium and depakote, respectively. I was willing to give it a try but i never thought that sounded right. I had a couple of very brief manic episodes in a whole lifetime against chronic depressive episodes. I tend to have a 'beat the clock' instinct when under time constraints (like doctors' appts) and i do what they call 'fast talk' which makes some doctors mistake it for manic behavior but it's limited to md. visits -- which they tend not to believe when i tell them not to judge by that.
>
> What is the current cocktail? You mentioned Effexor @ 150mg, but are you still on the Lithium?Only the Effexor, @150 level for 2 wks. now
> How do you like your current pdoc? How open is he/she to your input? Do you feel he is doing a fair job?
I'm currently being prescribed by an internist who's known me for 5 years and previously helped me enough to know my history but he's not a pdoc. I would consider changing both to find a p-doc and someone closer to me, but I'm in a gap without insurance, needing to get blue shield but that is symptomatic of the kind of task that requires a kind of energy i don't have. This doctor used to be great but now his practice has quadrupled and he's constantly hassled so that's part of my wish to change at some point too. (I've had four different extended therapy phases over past 20 years at various times for various durations. I do have a bereavement counselor at present who has been great.)
thanks again for your interest and your info which i will pursue...
zinya
Posted by jrbecker on August 6, 2003, at 13:38:11
In reply to Re: just more evidence...ADs protect the brain » jrbecker, posted by zinya on August 5, 2003, at 0:28:30
sounds like you're on the upswing a little bit.
The sensitivity to the SSRIs was always a problem for me as well. Effexor was always more tolerable, at least in terms of the sedation. I'm sure everyone else has given you this pep talk, but I just want to resonate that effexor was the one that I really did see gradual improvement on every week throughout the first 2-3 months. Not only will the mood effect improve, but more importantly, the side effects will diminish little by little. This being said, I'm surprised you started at 150 instead of a lower dose. Is this so you get more of a noradrenergic effect for the management of the pain? I only mention all this b/c you said you quit meds in the past due to sensitivity. So if anything, consider lowering the dose if you just can't tolerate it. As for the noradrenergic effect, the belief that there is no NE effect at lower levels is unfounded, there is less activity, but there is still some going on. If the high dose is more about treating the pain, or your doc recommends the high dose for any other reason, then please disregard my above comments -- they were only meant to address my fear of you disconintuing due to the side effects.
As for the doc, if you feel he has a unique advantage by knowing your history and is generally good to work with, then stick with him. But if you feel that by being just an internist might be a barrier to knowing further treatment options, than by all means, explore pdoc options. Once again, this is said more for precaution rather than needed advice.
sounds like progress on your part lately. And given your pain symptomology, you seem to be a great candidate for duloxetine when it arrives. take care
JB
Posted by jrbecker on August 6, 2003, at 15:08:13
In reply to Re: Effexor.... » zinya, posted by jrbecker on August 6, 2003, at 13:38:11
whoops, "upswing" could be ambiguous. I just meant by that, "feeling better."
> sounds like you're on the upswing a little bit.
>
> The sensitivity to the SSRIs was always a problem for me as well. Effexor was always more tolerable, at least in terms of the sedation. I'm sure everyone else has given you this pep talk, but I just want to resonate that effexor was the one that I really did see gradual improvement on every week throughout the first 2-3 months. Not only will the mood effect improve, but more importantly, the side effects will diminish little by little. This being said, I'm surprised you started at 150 instead of a lower dose. Is this so you get more of a noradrenergic effect for the management of the pain? I only mention all this b/c you said you quit meds in the past due to sensitivity. So if anything, consider lowering the dose if you just can't tolerate it. As for the noradrenergic effect, the belief that there is no NE effect at lower levels is unfounded, there is less activity, but there is still some going on. If the high dose is more about treating the pain, or your doc recommends the high dose for any other reason, then please disregard my above comments -- they were only meant to address my fear of you disconintuing due to the side effects.
>
> As for the doc, if you feel he has a unique advantage by knowing your history and is generally good to work with, then stick with him. But if you feel that by being just an internist might be a barrier to knowing further treatment options, than by all means, explore pdoc options. Once again, this is said more for precaution rather than needed advice.
>
> sounds like progress on your part lately. And given your pain symptomology, you seem to be a great candidate for duloxetine when it arrives. take care
>
> JB
Posted by zinya on August 9, 2003, at 20:32:07
In reply to Re: Effexor.... » zinya, posted by jrbecker on August 6, 2003, at 13:38:11
JRB
thanks again... And you're quite sensitive to realize the value of modifying even "upswing" :)) .. yes, I guess that sounds like it's cuz i gather here that you're a "user" as well as researcher... and had your own experience on Effexor. indeed, i've had a couple of floundering days since last writing, seemingly again triggered mostly by the back pains...
which sounds like that's relevant to your mention of "duloxetine" - Should i know what that is? have you mentioned it previously already? if so, forgive me... You can redirect me if you have. If not, i take it this is some new kind of pain med? is it also combined with something else (as Effexor combines two functions?)
I don't recall without looking back exactly what i said but clearly there was a miscommunication about my dosages on Effexor. To the contrary, i was sooo cautious about side effects given previous drugs, what i tried or thought i'd indicated was that i started even lower than the lowest dose. I split 37.5's in half and went twice as long as lesser doses at each stage, from 18.75 to 37.5 to 56 to 75 to 100 ... over a two-month period before i ever got to 150 which will be 3 wks ago this tuesday...
I'm thinking of staying at 150 for another month though to see if that slight 'uptick' i reported last time might return and sustain at 150 level. I don't want to take a higher "therapeutic" level than necessary - always cautious too about how much prescription drug my liver is having to process ...
Plus i got a rash on back and then chest this week and it was a few days before i began to realize that maybe it's from the Effexor so i want to see if that passes... The sweating is still a hassle, but even falling asleep prematurely one night and only waking 7 hrs late for taking my dose didn't screw me up TOO badly, although the worst was the 2nd day after i'd tried to get somewhat back to schedule but that meant having an overlap of 5 hrs with two 150's in my system at once and i guess that caused the nausea and sleep problems, but that was 2 days ago and it feels sort of back to normal now...
I take it you no longer take Effexor?? Is there a reason you quit you might share?
thanks again (also for clarifying that the 150 isn't a magic norep. point ... I guess then it's just a matter of reaching more of a critical mass of dosage that begins to provide a norep. component adequate to a given body's adrenal threshold to start making a difference? and so it would then vary by indiv when it would start being noticeable?)
again, thanks,
zinya
This is the end of the thread.
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