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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by SLS on November 2, 2000, at 23:52:02
Bipolar Disorder: 30% higher density of synapses in specific brain structures.
Study size: 16 patients
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Dr. Koop: Full articlehttp://www.drkoop.com/news/stories/october/hs/mood_swings.html
----------------------------------------------Introduction:
Too Many Brain Cells Mean Mood Disorder
Mood Swings Linked to OverstimulationOct. 3, 2000
Julia McNamee Neenan
HealthSCOUTIf you've got a severe mood swing disorder, your brain is not only physically overpacked with cells, but they may be firing so much that the brain can't filter out all the stimulation, says a new study.
In those with bipolar disorder, two major areas of the brain contain 30 percent more cells that send signals to other brain cells, says a report in today's American Journal of Psychiatry. The extra signal-sending cells may lead to a kind of overstimulation, which makes sense considering the symptoms of bipolar disorder, says the study's lead author, Dr. Jon-Kar Zubieta. He is an assistant professor of psychiatry and nuclear medicine at the University of Michigan at Ann Arbor.
Posted by judy1 on November 3, 2000, at 0:26:33
In reply to Bipolar Disorder - 30% more neuronal synapses ?, posted by SLS on November 2, 2000, at 23:52:02
I rather like the idea of having too many brain cells, too bad they're not more constructive things. Hope you have been well, Judy
Posted by tenuous on November 3, 2000, at 5:32:35
In reply to Bipolar Disorder - 30% more neuronal synapses ?, posted by SLS on November 2, 2000, at 23:52:02
> In those with bipolar disorder, two major areas of the brain contain 30 percent more cells that send signals to other brain cells
Seems to indicate that they should be able to diagnose bipolar by scanning these two areas of the brain.
Posted by danf on November 3, 2000, at 9:06:24
In reply to Bipolar Disorder - 30% more neuronal synapses ?, posted by SLS on November 2, 2000, at 23:52:02
Data & conclusions, tsk tsk.....
bipolar women were no different than normal women.
The men were different.
were the bipolar folks treated ? Does this pattern change with adequate treatment ?
PET scan was used ( which does not have a fine resolution ). No cells were counted, in any way, Yet someone jumped to the conclusion that there were different neural cell numbers.
The technique used shows metabolic activity of a certain type. This metabolic activity may correlate with Bipolar. The findings in women certainly make the base theory a bit suspect, at this point.
This paper neither proves nor disproves anything.
were the bipolar folks in hospital ? maybe they all had grapefruit juice in the hospital & the normals had orange juice at home??? were they on meds ?
One must be very careful in evaluating studies of this type. The information should be critically compared with other known reliable data. May be it is valid & adds a small amount of information ?
The conclusions should not be blindly accepted as either truth or fact.
Posted by SLS on November 3, 2000, at 14:38:03
In reply to Re: Bipolar Disorder - 30% more neuronal synapses ?, posted by danf on November 3, 2000, at 9:06:24
> The conclusions should not be blindly accepted as either truth or fact.I agree.
I hope the "?" in my subject line helped to convey this.
> Does this pattern change with adequate treatment?
I believe this observation was trait-specific rather than state-specific.
Where do you get your information regarding the resolutions of PET and MRI?Not that I know any different, but are you assuming that the equipment used in ultra-high-tech research facilities is the same as those used clinically in hospitals? Are you aware of the technique of superimposing PET upon MRI?
- Scott
Posted by danf on November 3, 2000, at 16:18:02
In reply to Re: Bipolar Disorder - 30% more neuronal synapses ?, posted by SLS on November 3, 2000, at 14:38:03
Scott,
thanks for the citations & the discussion.
PET resolution.. seems to be a few mm. much larger than the micron size of neurons. PET imaging is based on metabolic markers & not on physical things like walls of nerves, etc
Resolution, kind of does not matter as PET resolution is about 6 orders of mangitude less than the size of nerve fibers in the brain. a few mm vrs a few microns.
MRI also is based on things like water content & other elemental content of tissue, not on an exact physical characteristic like the color of the tissue. MRI is similar. a few mm resolution.
There is nothing bad about this, just the limitations present.
So PET scanning gives an index of metabolic activity of the nerve tissue. an increased index means more vesicle activity /presence, not necessarily more nerves. Because this is a metabolic measurement & not a physical one, things in the diet, like alcohol, sugar, chemicals & drugs & maybe grapefruit may have an effect.
in calculating grey brain tissue volume, multiple 2 dimensional cuts are taken & measured & a 3 dimensional volume calculated. There are always problems with quantative calibration of the machines from day to day. Supply voltages vary slighty from day to day. The detectors gradually become less sensitive over time. None of these things are major. They do make it difficult to measure with a high degree of precision, changes of a few percent. There is always the error of measurement of some thing which is a few mm thick, as in... is it 10 mm thick or 11mm thick ( a 10% difference ), etc
Both of these testing devices are used more for qualitative ( is something present & what does it look like ) imaging than for quantatitive imaging ( how much is there ).
For the brain grey matter volume study, it does not really matter. If we accept the 3% as real, what does this mean ? does it mean that there are more nerves or does it mean the nerve cells are 3% larger ?
The testing method does not tell us so we have to guess which is more likely... Since we know Li affects membrane permeability, it is a reasonable hypothesis that the cells get slightly larger.
These are just the normal kinds of questions, one asks ones self when reading a published report.
Posted by SLS on November 3, 2000, at 20:27:33
In reply to Re: Bipolar Disorder - 30% more neuronal synapses ?, posted by danf on November 3, 2000, at 16:18:02
Hi Dan.
> PET resolution.. seems to be a few mm. much larger than the micron size of neurons. PET imaging is based on metabolic markers & not on physical things like walls of nerves, etc
No, this is not necessarily true. One type of imaging does involve glucose utilization - an indicator of brain activity. It is accomplished by using a tagged form of glucose called flourodeoxyglucose.
Other uses of PET imaging include tagged ligands for receptors or specific proteins. I think this is what was used for this study. The proteins targeted were the monoamine transporter receptors, the ligand being dihydrotetrabenazine. Results yielded a measurment of the *density* of synapses, not the volume of tissue.
> Resolution, kind of does not matter as PET resolution is about 6 orders of mangitude less than the size of nerve fibers in the brain. a few mm vrs a few microns.
Again, the density of anhilation events serves well to assay for the density of synapses in a particular brain region. There is no need to look at one neuron at a time.
> MRI also is based on things like water content & other elemental content of tissue, not on an exact physical characteristic like the color of the tissue. MRI is similar. a few mm resolution.
Who needs to know the color? Imaging the morphology of tissues is what this test is designed to accomplish.
> There is nothing bad about this, just the limitations present.
I don't know what the current state of the art is.
> So PET scanning gives an index of metabolic activity of the nerve tissue. an increased index means more vesicle activity /presence, not necessarily more nerves. Because this is a metabolic measurement & not a physical one, things in the diet, like alcohol, sugar, chemicals & drugs & maybe grapefruit may have an effect.
Again, it is not a measurement of glucose utilization that was performed, but rather, the increase in the number of synapses in a given volume of brain tissue as determined by the density of transporter proteins.
> in calculating grey brain tissue volume, multiple 2 dimensional cuts are taken & measured & a 3 dimensional volume calculated. There are always problems with quantative calibration of the machines from day to day. Supply voltages vary slighty from day to day. The detectors gradually become less sensitive over time. None of these things are major. They do make it difficult to measure with a high degree of precision, changes of a few percent.
30%
> Both of these testing devices are used more for qualitative ( is something present & what does it look like ) imaging than for quantatitive imaging ( how much is there ).
PET = quantitative
> For the brain grey matter volume study, it does not really matter. If we accept the 3% as real, what does this mean ? does it mean that there are more nerves or does it mean the nerve cells are 3% larger ?I keep getting mixed up myself. I think you may be confusing this study with that of the earlier thread ivolving a lithium-induced 3% increase in cortical volume.
> The testing method does not tell us so we have to guess which is more likely... Since we know Li affects membrane permeability, it is a reasonable hypothesis that the cells get slightly larger.I didn't know that lithium affected membrane permeability. I'll have to review this stuff.
> These are just the normal kinds of questions, one asks ones self when reading a published report.
Yup. I think most of your questions are answered in the abstract.
In addition, sex-specific differences are not unexpected. There are differences in the frequency of different presentations of bipolar disorder between the sexes. For instance, rapid-cyclicity is seen more frequently in women than in men.
Your Devil's advocate,
Scott-------------------------------------------------------------
Too Many Brain Cells Mean Mood Disorder
Mood Swings Linked to OverstimulationOct. 3, 2000
Julia McNamee Neenan
HealthSCOUTIf you've got a severe mood swing disorder, your brain is not only physically overpacked with cells, but they may be firing so much that the brain can't filter out all the stimulation, says a new study.
In those with bipolar disorder, two major areas of the brain contain 30 percent more cells that send signals to other brain cells, says a report in today's American Journal of Psychiatry. The extra signal-sending cells may lead to a kind of overstimulation, which makes sense considering the symptoms of bipolar disorder, says the study's lead author, Dr. Jon-Kar Zubieta. He is an assistant professor of psychiatry and nuclear medicine at the University of Michigan at Ann Arbor.
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Am J Psychiatry 2000 Oct;157(10):1619-28 Related Articles, Books, LinkOut
High vesicular monoamine transporter binding in asymptomatic bipolar I disorder: sex differences and cognitive correlates.Zubieta JK, Huguelet P, Ohl LE, Koeppe RA, Kilbourn MR, Carr JM, Giordani BJ, Frey KA
[Medline record in process]
OBJECTIVE: It has been hypothesized that anomalies in monoaminergic function underlie some of the manifestations of bipolar disorder. In this study the authors examined the possibility that trait-related abnormalities in the concentration of monoaminergic synaptic terminals may be present in patients with asymptomatic bipolar disorder type I. METHOD: The concentration of a stable presynaptic marker, the vesicular monoamine transporter protein (VMAT2), was quantified with (+)[(11)C]dihydrotetrabenazine (DTBZ) and positron emission tomography. Sixteen asymptomatic patients with bipolar I disorder who had a prior history of mania with psychosis (nine men and seven women) and individually matched healthy subjects were studied. Correlational analyses were conducted to examine the relationship between regional VMAT2 binding, cognitive function, and clinical variables. RESULTS: VMAT2 binding in the thalamus and ventral brainstem of the bipolar patients was higher than that in the comparison subjects. VMAT2 concentrations in these regions correlated with performance on measures of frontal, executive function. In addition, sex differences in VMAT2 binding were detected in the thalamus of the bipolar patients; the male patients had higher binding than the women. No sex differences in binding were observed in the healthy comparison group. CONCLUSIONS: These initial results suggest that higher than normal VMAT2 expression and, by extension, concentration of monoaminergic synaptic terminals, may represent a trait-related abnormality in patients with bipolar I disorder and that male and female patients show different patterns. Also, VMAT2 concentrations may be associated with some of the cognitive deficits encountered in euthymic bipolar disorder.
PMID: 11007716, UI: 20464850
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