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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by Denise190466 on May 27, 2007, at 14:56:53
Are scientists yet able to see from brain scans what is happening to the brain when somebody responds positively to an antidepressant compared to when they don't respond well? i.e what is happening to receptors and in what parts of the brain.
I'd love to know why my brain used to respond so well to them and yet now doesn't.
Denise
Posted by Racer on May 27, 2007, at 15:34:15
In reply to Brain scans and antidepressants, posted by Denise190466 on May 27, 2007, at 14:56:53
Yes, and no. That sort of study requires more than just giving a drug and doing a scan. It has been done more often, as far as I know, in anti-psychotics than anti-depressants, but I'm sure someone out there has tried it with ADs.
There are a few pdocs out there who are using scans to predict responses to various ADs, but I'm not sure it's worth the cost. They're basing it on correlations -- "Out of 8000 scans I've seen, the ones which most closely resemble yours have belonged to people who responded well to Drug X, therefore I'll give you Drug X." There are, as yet, no studies showing anything more concrete.
Sad to say, there's not much out there beyond trial and error. As for why something used to work better than it does now, there are a lot of other factors that could be looked into:
1. Age related biochemical changes. Especially in women entering middle age, those would be pretty influential. (I say that as a woman firmly into her middle years.)
2. Weight changes. As most of us are aware, many drugs out there affect weight. If you've gained weight, your body's chemistry is changing a bit, AND many drugs do have a mg/kg ratio they like to stay in. Additionally, metabolic changes associated with weight fluctuations can affect the way your body processes a medication.
3. Life changes. It's easy to overlook this part, but basic life changes make a difference, too. When I was in my 20s, ADs made a hell of a difference for me -- I felt as though they opened up a lot of hope that hadn't been there. Now, though, a lot of that hope is just plain gone. I no longer have unlimited potential -- I'm a middle aged woman, and there's not a lot that I can do to affect meaningful changes to my life. (I'm not saying I can't take steps to improve my life. I'm only saying that I don't have all the options I had in my 20s.) That change alone is enough to dampen my subjective response to ADs.
Those are just what came to mind off hand. I'm sure there are more that I didn't think of.
Hope that helps.
Posted by Phillipa on May 27, 2007, at 19:03:22
In reply to Re: Brain scans and antidepressants » Denise190466, posted by Racer on May 27, 2007, at 15:34:15
Add getting old older than middle age and no future to look forward too a bleaker picture. But I didn't know the amount of fat influenced it. Thanks Racer. Love Phillipa
Posted by linkadge on May 27, 2007, at 19:37:51
In reply to Re: Brain scans and antidepressants » Denise190466, posted by Racer on May 27, 2007, at 15:34:15
I think that tollerance to AD's is probably cellular. I mean, theres only so much cellular energy.
AD's just overchanrge the existing circutry.
Depression is probably not due to low neurotransmitter as much as it is subsensitivity to existing neurotransmitter.
AD's do not fix the circutry, and probably worsen the functionality of the existing cicutry over time.
Linkadge
Posted by deniseuk190466 on May 28, 2007, at 12:30:46
In reply to Re: Brain scans and antidepressants » Denise190466, posted by Racer on May 27, 2007, at 15:34:15
Racer,
Thanks, I was wondering if scans can actually show the neurons in the brain or do you have to actually take slices of the brain to actually see the cells? I was wondering if when they say that antidepressants increase neurogenesis, or when they say they downregulate other receptors, if they could actually see that happening.
As far as the other things you mentioned, I'm 41 now so not really in middleage, my weight has not changed since my 20s, although I have lost a lot of weight over the past 8 months due to this depression and anxiety, coming off Seroxat and switching to Remeron and then to Lexapro.
I don't feel different about life than I did in my 20s, at least I don't think I do. My circumstances are no worse or better than they were, infact when this depression and anxiety started again my circumstances were better. So it bemuses me. Well I guess I will never know.
Thanks....Denise
Posted by deniseuk190466 on May 28, 2007, at 12:33:09
In reply to Re: Brain scans and antidepressants, posted by linkadge on May 27, 2007, at 19:37:51
Linkadge,
When you say Depression is probably not due to low neurotransmitter as much as it is subsensitivity to existing neurotransmitter. Do you mean the sensitivity of the receptors receiving the transmitter?
And what do you mean when you talk about circuits? Do you mean how different neurons interact with each other?
Thanks....Denise
Posted by linkadge on May 28, 2007, at 14:20:56
In reply to To linkadge, posted by deniseuk190466 on May 28, 2007, at 12:33:09
Well, to think of depression as simply a imbalence of chemicals may be simplistic. There are real structural differences about the brains of depressed people.
It may be that the longer one remains depressed, the more pathological the disease becomes. It is clear that the brain you are working with now is not the same one as when AD's worked.
People with panic disorder, for instance, have far fewer 5-ht1a receptors as normal individuals. SSRI's may work by stimulating those remaining receptors, but they are not fixing the problem.
Perhaps the problem continues to get worse (ie more 5-ht1a receptors loss) in spite of proper treatment.It could be neurodegenerative. Perhaps its like parkinsons, where dopaminergic cell loss continues dispite treatment with dopaminergic agents.
There are even some studies that suggest treatment with antidepressants worsens the long term outcome for depressive illness. Just like how l-dopa may actually speed the advancement of parkinsons.
Sometimes with these things, hindsight is 20-20. Ie somebody discovers a drug that helps people, and then "oh ya ya, clearly the drug is helping people by affecing chemical x"
Linkadge
Posted by Phillipa on May 28, 2007, at 19:49:37
In reply to Re: To linkadge, posted by linkadge on May 28, 2007, at 14:20:56
Link so I am dying as nothing works for me may as well get it out of the way why wait til it's worse? Love Phillipa
Posted by linkadge on May 29, 2007, at 6:42:58
In reply to Re: To linkadge » linkadge, posted by Phillipa on May 28, 2007, at 19:49:37
Well, theres always hope. Hopefully somebody smart will come up with something.
Linkadge
Posted by Racer on May 29, 2007, at 13:49:48
In reply to To Racer, posted by deniseuk190466 on May 28, 2007, at 12:30:46
>
> Thanks, I was wondering if scans can actually show the neurons in the brain or do you have to actually take slices of the brain to actually see the cells? I was wondering if when they say that antidepressants increase neurogenesis, or when they say they downregulate other receptors, if they could actually see that happening.
>As I understand it, some studies use radioactive markers to record binding at various receptors, so in that sense they can see some of that happens in the brain. Obviously, those are heavy duty studies, and are not just standard operating procedure. I believe there's something similar going on in the studies showing neurogenesis, but I'm not quite sure what the mechanism is.
A lot of the studies, though, extrapolate from animal studies. They record blood flow patterns in the brains of mice or rats, then sacrifice them to see what's actually happened. Then they extrapolate that to humans with similar blood flow patterns.
Posted by Larry Hoover on May 29, 2007, at 17:40:43
In reply to Brain scans and antidepressants, posted by Denise190466 on May 27, 2007, at 14:56:53
> Are scientists yet able to see from brain scans what is happening to the brain when somebody responds positively to an antidepressant compared to when they don't respond well? i.e what is happening to receptors and in what parts of the brain.
>
> I'd love to know why my brain used to respond so well to them and yet now doesn't.
>
> DeniseThere are a number of studies which show metabolic abnormalities in depressed, and in depressed-but-in-remission brains. They can see changes that occur in response to treatment. Somewhat similar changes occur in both drug-treated subjects and those receiving cognitive-behavioural therapy....if the treatment is successful. Non-responders tend to continue to resemble untreated depressed subjects' brains.
The studies I'm referring to demonstrate regional brain activity, by measuring glucose consumption. The resulting image, a PET scan, shows brighter regions where glucose metabolism is high. In depressed brains, some regions that would be active in a healthy brain are not active, whereas other regions are much more active when compared to healthy subjects. Successful treatments do normalize some of these disturbances, but others remain abnormal.
The take home message is that antidepressant treatment is, at best, an incomplete treatment for depression. Same goes for therapy. Whatever the pathophysiology of depression really is, it likely continues to change the brain, despite treatment.
Here are some references....
The first one is pretty much right on the subject you enquired about, IMHO. Immediately below the abstract is a link to the full-text, for those interested. Next, below that, is a nice summary of the various theories of depression (excellent graphics). The last two are a couple of full-text imaging studies. They're quite large .pdf files, because they contain images.
Lar
Eur Neuropsychopharmacol. 2002 Dec;12(6):527-44.
Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism.
Drevets WC, Bogers W, Raichle ME.
Neuroimaging in Mood and Anxiety Disorders Section, National Institutes of Health, NIMH/MIB, Bethesda, MD 20892, USA. drevetsw@intra.nih.govNeurophysiological studies of major depression performed using PET imaging have shown abnormalities of regional cerebral blood flow (CBF) and glucose metabolism in multiple prefrontal cortical and limbic structures that have been more generally implicated in emotional processing. The current study investigated the effects of antidepressant drug treatment in these regions using PET measures of glucose metabolism. Subjects with primary MDD (n=27) were imaged while unmedicated and depressed, and, of these, 20 were rescanned following chronic antidepressant drug treatment. Regional metabolism was compared between unmedicated depressives and controls and between the pre- and post-treatment conditions in regions-of-interest (ROI) where metabolism or flow had previously been shown to be abnormal in unmedicated depressives. At baseline, the mean metabolism was increased in the left and right lateral orbital cortex/ventrolateral prefrontal cortex (PFC), left amygdala, and posterior cingulate cortex, and decreased in the subgenual ACC and dorsal medial/dorsal anterolateral PFC in the unmedicated depressives relative to controls, consistent with the results of previous studies. Following treatment, metabolism significantly decreased in the left amygdala and left subgenual ACC, and corresponding changes in the orbital and posterior cingulate cortices approached significance. The metabolic reduction in the amygdala and right subgenual ACC appeared largely limited to those subjects who both responded to treatment and remained well at 6 months follow-up, in whom the reduction in amygdala metabolism tightly correlated with the reduction in HDRS scores. The magnitude of the treatment-associated, metabolic change in the amygdala also correlated positively with the change in the stressed plasma cortisol levels measured during scanning. These data converge with those from other PET studies to indicate that primary MDD is associated with abnormal metabolism in limbic and paralimbic structures of the mesiotemporal and prefrontal cortices. Chronic antidepressant drug treatment reduces metabolism in the amygdala and ventral ACC in subjects showing a persistent, positive treatment response. In contrast, the persistence of the abnormal metabolic deficits in the dorsomedial/dorsal anterolateral PFC in MDD during treatment may conceivably relate to the histopathological changes reported in these regions in post mortem studies of MDD.
http://www.nature.com/nrn/journal/v6/n3/full/nrn1629.html
Posted by deniseuk190466 on May 31, 2007, at 4:09:40
In reply to Re: Brain scans and antidepressants » Denise190466, posted by Larry Hoover on May 29, 2007, at 17:40:43
Larry,
Thanks for this information, I have seen some of these studies before and I will try and read/digest all of what you have sent me, it's difficult for me to take things in at the best of times.
I guess they can see activity then but not what that activity relates to in relation to receptors, whether certain types of receptors are increasing or decreasing, that sort of thing. All they can see is activity but not what it actually signifies as far as neurons go.
Denise
Posted by Larry Hoover on May 31, 2007, at 9:11:47
In reply to To Larry Hoover, posted by deniseuk190466 on May 31, 2007, at 4:09:40
> Larry,
>
> Thanks for this information, I have seen some of these studies before and I will try and read/digest all of what you have sent me, it's difficult for me to take things in at the best of times.
>
> I guess they can see activity then but not what that activity relates to in relation to receptors, whether certain types of receptors are increasing or decreasing, that sort of thing. All they can see is activity but not what it actually signifies as far as neurons go.
>
>
> DeniseAs far as I know, receptor densities can only be measured using tissue samples, something we don't do to living humans. There are some post-mortem studies, though, comparing treated and untreated depressives.
Neurogenesis is implied from animal studies, again, as far as I know.
Lar
Posted by deniseuk190466 on June 1, 2007, at 14:50:41
In reply to Re: To Larry Hoover » deniseuk190466, posted by Larry Hoover on May 31, 2007, at 9:11:47
.
This is the end of the thread.
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