On Thu, 22 Aug 2002, "John H." <johnhkm at overhere.com.au> wrote:
>>No, recent fMRI studies in Toronto demonstrated that the efficacy of the
>SSRIs may well be mediated by their ability to reduce hippocampal activation
>and stimulate neurogenesis in the dentate gyrus. Cortisol reduces
>neurogenesis, probably via the mutual antagonism of GR occupation and nfkb
>transcription; nfkb being essential not only for LTP but also neurogenesis
>or probably just any any-cell-genesis. In short, the drugs, while having
>their problems (I have bad reactions to SSRIs), can work remarkably well in
>some people by encouraging hippocampal rehabilitation and facilitating
>reactivation of the frontal cortices which tend to be quieter in depression.
IAN: Hi John! It's true that Prozac (fluoxetine) appears to
induce hippocampal neurogenesis (pubmed.com, enter 11961119).
However, Paxil (paroxetine) -- which like Prozac is a member
of the SSRI family of antidepressants -- has been shown to
cause thalamus atrophy in children treated with Paxil for
obsessive-compulsive disorder. The thalamus is of course
an important brain center. It's not clear at this time if
this is an SSRI-wide effect that might occur in all people,
but it seems reasonable to cautiously speculate that thalamic
atrophy might be an effect of SSRIs per se occurring in anyone.
About the abstracts included below....
[1] is the first study to find thalamic atrophy -- or as they
say, "decrease in thalamic volumes" -- in children on Paxil.
[2] is a follow-up that tested the hypothesis that thalamic
atrophy was a feature of OCD treatment per se, ie, perhaps
successful cognitive therapy also causes thalamic atrophy.
The results of this relatively small study indicate that
"reduction in thalamic volume after paroxetine therapy may
be specific to paroxetine treatment." With these results in
mind, I'd surely prefer a method of treatment that could be
successful and not cause atrophy of any region of the brain.
[3] is an email reply to me from one of the researchers in 1.
*****************************************************************
[1] Arch Gen Psychiatry 2000 May;57(5):449-56
Decrease in thalamic volumes of pediatric patients with obsessive-
compulsive disorder who are taking paroxetine.
Gilbert AR, Moore GJ, Keshavan MS, Paulson LA, Narula V, Mac
Master FP, Stewart CM, Rosenberg DR.
Department of Psychiatry, Wayne State University School of
Medicine, Detroit, Mich, USA.
BACKGROUND: Thalamic dysfunction has been implicated in obsessive-
compulsive disorder (OCD). While OCD frequently has its onset
during childhood, to our knowledge, no prior study has measured
neuroanatomical changes in the thalamus of patients with OCD near
the onset of illness, and before and after treatment. METHODS:
Volumetric magnetic resonance imaging studies were conducted in 21
psychotropic drug-naive children, aged 8 to 17 years, with OCD and
21 case-matched healthy comparison subjects. Magnetic resonance
imaging studies were also conducted in 10 of the 21 patients with
OCD after 12 weeks of monotherapy with the selective serotonin
reuptake inhibitor, paroxetine hydrochloride. RESULTS: Thalamic
volumes were significantly greater in treatment-naive patients
with OCD than in controls but declined significantly after
paroxetine monotherapy to levels comparable with those of
controls. Decrease in thalamic volume in patients with OCD was
associated with reduction in OCD symptom severity. CONCLUSIONS:
Our findings provide new evidence of thalamic abnormalities in
pediatric OCD and further suggest that paroxetine treatment may
be paralleled by a reduction in thalamic volume. These reductions
may, however, not be specific to paroxetine treatment and could
be due to a more general treatment response, and/or spontaneous
improvement in symptoms. Our findings are preliminary given the
small sample size and our inability to measure discrete thalamic
nuclei.
Publication Types:
Clinical Trial
PMID: 10807485 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10807485&dopt=Abstract
****************************************************************
[2] Biol Psychiatry 2000 Aug 15;48(4):294-300
Thalamic volume in pediatric obsessive-compulsive disorder
patients before and after cognitive behavioral therapy.
Rosenberg DR, Benazon NR, Gilbert A, Sullivan A, Moore GJ.
Department of Psychiatry & Behavioral Neurosciences, Wayne State
University School of Medicine, Detroit, Michigan 48201, USA.
BACKGROUND: Neurobiologic abnormalities in the thalamus have
been implicated in the pathophysiology of obsessive-compulsive
disorder. We recently reported increased thalamic volume in
treatment-naive pediatric obsessive-compulsive disorder patients
versus case-matched healthy comparison subjects that decreased
to levels comparable to control subjects after effective
paroxetine therapy. To our knowledge, no prior study has measured
neuroanatomic changes in the thalamus of obsessive-compulsive
disorder patients near illness onset before and after cognitive
behavioral therapy. METHODS: Volumetric magnetic resonance imaging
studies were conducted in 11 psychotropic drug-naive 8-17-year-old
children with obsessive-compulsive disorder before and after 12
weeks of effective cognitive behavioral therapy monotherapy (> or
=30% reduction in obsessive-compulsive disorder symptom severity).
RESULTS: No significant change in thalamic volume was observed in
obsessive-compulsive disorder patients before and after cognitive
behavioral therapy. CONCLUSIONS: Our findings suggest that
reduction in thalamic volume after paroxetine therapy may be
specific to paroxetine treatment and not the result of a general
treatment response or spontaneous improvement. These results are
preliminary in view of the small sample studied.
PMID: 10960160 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10960160&dopt=Abstract
****************************************************************
[3]
Date: Mon, 08 May 2000 23:57:13 -0400
To: Ian Goddard <xxx>
From: "Dr. Rosenberg" <xxx>
Subject: Re: Your Study
At this point it's not clear although we have several hypotheses. We
saw a differential maturation of thalamic volume in OCD patients and
controls that might reflect a neural network dysplasia with a possible
reduction in synaptic pruning in OCD pts vs controls (the normal
pruning of neural elements during peripubertal period). Cell death or
loss of cell mass is one possibility, probably best looked at in
post-mortem studies. We recently published a priority communication in
biological psychiatry (february 2000) showing decreased NAA/Cho +Cr
levels suggestive of possible neuronal dysfunction (NAA is thought to
be a marker of neuronal viability); however, more recent analysis also
suggests potential choline abnormalities. Finally, the thalamus is a
densely serotonergic region and possible aberrations in development
could lead to altered volume. This was a surprising finding, clearly
requires replication with larger samples; also, our inability to
measure subdivisions of the thalamus: we are working on a new program
that allows us to do this and we hope to delineate whether medial
regions (which we would hypothesize) would be more affected)
At 05:07 PM 5/8/00 -0400, you wrote:
>Hello Doctor Rosenberg,
>>I just read your study in the May issue if the Archives
>of Clinical Psychiatry. I think it could prove to be a
>real breakthrough. The question I have is what's the
>cause of the observed reduction of thalamus volume?
>Could it be a result of cell death or the loss of
>cell mass? If not that, than what other cause?
>>Thank you for your time and attention.
>>-- Ian Goddard
>>http://IanGoddard.net
"To lengthen thy life, lessen thy meals." Benjamin Franklin
Caloric Restriction: http://users.erols.com/igoddard/cr.htm
Ongoing CR-monkey-study update: "In the monkeys...those on
reduced feeding since the study started are dying at a rate
that is about half that of the monkeys receiving a full food
ration." Associated Press: Eating less may extend human life.
August 1, 2002 : http://www.msnbc.com/news/788746.asp?0si=-
