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

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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.


This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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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.

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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.


2009: Cancer hospital said I had adjustment disorder because I thought they were doing it wrong. Their headshrinker prescribed Effexor, and my life set on a new course. I didn't know what was ahead, like a passenger on Disneyland's Matterhorn, smiling and waving as it climbs...clink, clink, clink.

2010: Post surgical accidental Effexor discontinuation by nurses, masked by intravenous Dilaudid. (The car is balanced at the top of the track.) I get home, pop a Vicodin, and ...

Whooosh...down, down, down, down, down...goes the trajectory of my life, up goes my mood and tendency to think everything is a good idea.
2012: After the bipolar jig was up, now a walking bag of unrelated symptoms, I went crazy on Daytrana (the Ritalin skin patch by Noven), because ADHD was a perfect fit for a bag of unrelated symptoms. I was prescribed Effexor for the nervousness of it, and things got neurological. An EEG showed enough activity to warrant an epilepsy diagnosis rather than non-epileptic ("psychogenic") seizures.

:o 2013-2014: Quit everything and got worse. I probably went through DAWS: dopamine agonist withdrawal syndrome. I drank to not feel, but I felt a lot: dread, fear, regret, grief: an utter sense of total loss of everything worth breathing about, for almost two years.

I was not suicidal but I wanted to be dead, at least dead to the experience of my own brain and body.

2015: I  began to recover after adding virgin coconut oil and organic grass-fed fed butter to a cup of instant coffee in the morning.

I did it hoping for mental acuity and better memory. After ten days of that, I was much better, mood-wise. Approximately neutral.

And, I experienced drowsiness. I could sleep. Not exactly happy, I did 30 days on Wellbutrin, because it had done me no harm in the past. 

I don't have the DAWS mood or state of mind. It never feel like doing anything if it means standing up.

In fact, I don't especially like moving. I'm a brain with a beanbag body.   :unsure:

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Altostrata

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


This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

All postings © copyrighted.

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