Kaufman, 2003 Selective serotonin reuptake inhibitor discontinuation syndrome is associated with a rostral anterior cingulate choline metabolite decrease: a proton magnetic...

[Altostrata]

Biol Psychiatry. 2003 Sep 1;54(5):534-9.
Selective serotonin reuptake inhibitor discontinuation syndrome is associated with a rostral anterior cingulate choline metabolite decrease: a proton magnetic resonance spectroscopic imaging study.
Kaufman MJ¹, Henry ME, Frederick Bd, Hennen J, Villafuerte RA, Stoddard EP, Schmidt ME, Cohen BM, Renshaw PF.

Abstract at http://www.ncbi.nlm.nih.gov/pubmed/12946882

The selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome (DS) is an important potential complication of treatment for major depression. We hypothesized that SSRI treatment discontinuation, resulting in change in clinical state, would be associated with reduced rostral anterior cingulate choline (Cho) metabolite ratios. Individuals with a DSM-III-R diagnosis of unipolar major depression who had been stabilized on paroxetine (n = 13) or fluoxetine (n = 13) were study subjects. They were monitored for change in clinical state (mood ratings, discontinuation symptoms) and underwent proton magnetic resonance spectroscopic imaging of the rostral anterior cingulate 3 days after medication substitution with active SSRI and placebo.Placebo-day Cho/Cre (choline/total creatine) metabolite ratios were decreased in four paroxetine and two fluoxetine subjects meeting DS criteria, as compared with asymptomatic subjects (Mann-Whitney z = -2.31, p =.021). Discontinuation syndrome is associated with a rostral anterior cingulate Cho/Cre metabolite ratio decrease that may reflect dynamics of rostral anterior cingulate function.

[oskcajga]

File attached.

 

Hmm, apparently I can't attach the PDF?

 

 

Here's really all that I gained from reading this article, other than the fact that it's one of many articles and lines of scientific research that thinks they can apply a reductionist approach to understanding the brain:

 

We propose that astrocytes contribute to Cho metabolite
changes based on several lines of evidence. The 1HMRS
Cho content of cultured rodent brain astrocytes is more
than double that detected in cultured neuronal cells (Urenjak
et al 1993), and astrocytes are the most abundant cell
type in the brain, accounting for more than half of its total
cellular content (Fillenz et al 1999). Thus, mass balance
arguments suggest that brain Cho metabolite changes
likely reflect events in astrocytes. Astrocytes contain
serotonin receptors (Cohen et al 1999; Hirst et al 1998a;
Whitaker-Azmitia et al 1993) and transporters (Hirst et al
1998b) and thus are sensitive to synaptic serotonin levels.

Additionally, stress-related hormones, which are elevated
in DS (Michelson et al 2000a), inhibit astrocyte proliferation
(Crossin et al 1997) and could alter membrane
turnover. Moreover, astrocytes are the primary site of
glucose uptake into the brain (Fillenz et al 1999) and thus
may be involved in glucose uptake changes observed in
depressed subjects (Brody et al 1999; Buchsbaum et al
1997; Kennedy et al 2001; Mayberg et al 1997, 2000; Wu
et al 1999).

 

So the SSRI's, as I suspected, change fundamental features of crucial cell types in the brain and their metabolites - this is a change in gene expression leading to altered levels of metabolites (any change in metabolites is a gene level response).  Discontinuation syndrome also leads to increased levels of stress hormones.

[westcoast]

Great find. I think a reductionist approach is appropriate when you're trying to figure out what drugs did to the brain. (Although this study can't rule out the possibility that pre-existing differences led to the DS and the DS-related findings.

I've noticed that NCBI tends to get the the heart of things I am interested in; it must be entirely free of psychiatric influence. I keep seeing it in the urls I end up clicking in pubmed.

I recently read and forgot 90% of an article about astrocytes, saying they're more important than we were told in the past. This sure makes t sound like that.

 

Downside: Small number of patients, and they don't say how many were symptomatic in each group, or at least it's unclear. "four paroxetine and two fluoxetine subjects meeting DS criteria" could be the only four and the only two who met DS criteria, or they could be  subset of the afflicted.

Now, off to see what Michelson 2000a was all about.

[Altostrata]

pdfs are a permitted file type. Please try to add it again as an attachment to a post, osk.