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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by NKP on December 3, 2022, at 4:39:47
Numerous studies seem to indicate that antipsychotic use results in a reduction in brain volume. I'm not sure what to make of this.
I saw a study that found a small but significant reduction in brain volume within hours of taking a once-off dose of haloperidol, with brain volume later returning to baseline. I suspect that this short-term reduction in brain volume is due to a reduction in blood flow to the brain, rather than a loss of neurons.
The concern is what happens if you take antipsychotics long term. Could chronically reduced blood flow result in permanent atrophy in the long run? Does this impact intelligence?
Apparently loss of brain volume in schizophrenics who do *not* take antipsychotic medication, is greater than in schizophrenics who *do* take antipsychotic medication. If antipsychotics are neurotoxic, as some claim, then they seem not to do a very good job of being neurotoxic in schizophremics at least.
Questions:
(i) What are your thought on the matter of brain volume loss caused by antipsychotics?
(ii) Is this also an issue with low dose antipsychotics as used to treat depression?
(iii) What about drugs like flupentixol and aripiprazole? As I understand it, these increase dopaminergic signalling at low doses, doing roughly the opposite of an antipsychotic. Would this also result in a reduction of brain volume?
Posted by linkadge on December 3, 2022, at 12:11:02
In reply to Antipsychotics and brain volume, posted by NKP on December 3, 2022, at 4:39:47
Antipsychotics do have an impact on brain volume. For instance, animals chronically given antipsychotics show reductions in brain volume. The typical antipsychotics are probably worse in this regard than atypicals (possibly due to higher D2 binding and less binding to other protective receptors - like 5-ht1a). The newer partial agonist drugs may also have advantages in that they seem to do more to stabilize dopamine firing rather than strict blockade. Although, some of the newer ones can dysregulate glucose, which probably isn't great for the brain either.
Dose is likely a factor. Nutrition, exercise and lifestyle are also likely factors. Some of the animal models suggest that antioxidants (vitamin C and E) were protective against antipsychotic induced atrophy. Lithium too, in general has been shown to improve brain structure and grey matter volume in bipolar patients. It also seems to reduce dopamine supersensitivity and offset some of the alterations resulting from other psychiatric drug use.
As you mention too, psychotic (and manic) episodes are linked to a progressive loss of grey matter, so keeping stable is also important for protecting the brain. So, it's not a simple equation.
There are complimentary treatments for schizohprenia, which, by themselves, are generally not effective, but have been shown to augment the effects of antipsychotics.
For example, one study showed that 1/2 dose risperidone + vitamin C was as effective as full dose risperidone. Some studies show that melatonin can enhance the effect of antipsychotics. Melatonin tends to be anti-dopaminergic and also sensitizes the 5-ht1a receptor, which may make 5-ht1a active drugs more effective (i.e. abilify, seroquel, rexulti, etc). You might also talk to your doctor about a low dose of lithium (especially if schizoaffective is present). It tends to stabilize the dopamine system (via inhibition of GSK3). In some patients it has antipsychotic effects in its own right.
If psychotic depression is present, then adding some fluvoxamine may be beneficial. It is an SSRI with potent sigma-1 receptor agonist properties. This action may be responsible for its increased effectiveness in psychotic depression and may produce pro-cognitive effects.
If metabolic effects are at all present, then speak to your doctor about metformin. This has neuroprotective properties and can offset brain insulin resistance.
A recent study suggested too that multivitamin supplementation preserved brain volume (in older age individuals) compared to a cocoa supplement.
Linkadge
Posted by SLS on December 3, 2022, at 13:16:14
In reply to Antipsychotics and brain volume, posted by NKP on December 3, 2022, at 4:39:47
I dont know the biology behind the alterations in tissue activity produced by antipsychotics, but it might have to do with D2 dopamine receptor blockade reducing neurotransmission regionally.
Less DA activity = less glucose needed to be metabolized for energy.
PET = Positron Emission Tomography
Regional brain activity can be measured by using PET scans. My brain was one of the first to be imaged at the NIH. I had been an inpatient research subject. To accomplish this, PET scans use Start Trek technology <grin>. Really. Scientists measure the rate at which glucose is consumed as a measure of regional neural activity. This trick uses fluorodexyglucose as a substitute for glucose. Cells dont recognize the difference. Nevertheless, fluorodeoxyglucose provides energy to the cell in exactly the same way as normal glucose. This is where things get pretty cool. When the fluorodeoxyglucose is consumed for energy, electrons (matter) and positrons (antimatter) are liberated. When these particles collide, both disappear. They are annihilated. This annihilation event converts matter into energy in the form of gamma rays. The gamma rays liberated are detected by sensors along the inner surface of a tube, much like a MRI. Matter-Antimatter. Long live Scotty and the U.S.S. Enterprise warp engines.
,,,and Einstein. Matter / antimatter is converted into pure energy in the form of gamma rays. E=MC(2).
I dont have copies of the results of my PET scan, but they looked very much like this:
Scary.
It just so happens that the higher the rate of energy production within a brain structure, the higher the rate at which oxygen is consumed there. This is supported only by an increase in blood flow and the resulting increase in the volume of brain tissue. If, however, the activity of neurons in reduced, so is blood flow, and the resulting volume of brain structures are reduced. Therefore, it is not necessary for a reduction in the size of brain structures to be an index of the numbers of functional neurons.
I would venture to guess that the reduction in the volume of brain structures seen immediately upon the introduction of a AP - as you described - is the result of a reduction in neural activity, as dopamine postsynaptic receptors are blocked. Less neural activity = a reduced need for oxygen, yielding a compensatory reduction of blood flow / tissue volume.
I have no idea what happens after this. Any ideas?
- Scott
Posted by SLS on December 3, 2022, at 17:27:15
In reply to Re: Antipsychotics and brain volume, posted by linkadge on December 3, 2022, at 12:11:02
Linkage -
Not to blow smoke up your butt, but this is exactly the type of information I rely on you for.
Your posts are invaluable to me. This is a wonderful piece of writing.
Thank you.
- - Scott
Posted by NKP on December 4, 2022, at 6:28:14
In reply to Re: Antipsychotics and brain volume » linkadge, posted by SLS on December 3, 2022, at 17:27:15
This study appears to show that antipsychotics reduce brain inflammation:
https://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2013.11.3.144
If so, might that account for the reduction in brain volume brought about by antipsychotic use?
Posted by SLS on December 4, 2022, at 7:51:20
In reply to Re: Antipsychotics and brain volume, posted by NKP on December 4, 2022, at 6:28:14
Hi, NKP.
How do interpret the results of this study as it relates to brain volume?
Isn't brain inflammation common in depression? I never looked into the effects of antidepressants on brain inflammation. It may be that the association of depression and inflammation is not so easily explained. Which came first, the inflammation or the depressive state? After the induction of a mood illness, does a primary disease pathology and a pro-inflammatory reaction to it become self-reinforcing? Perhaps a positive-feedback loop accelerates the development of symptoms or makes the depression more robust and less likely to remit spontaneously.
- Scott
Posted by Jay2112 on December 4, 2022, at 11:13:05
In reply to Re: Antipsychotics and brain volume, posted by SLS on December 4, 2022, at 7:51:20
> Hi, NKP.
>
> How do interpret the results of this study as it relates to brain volume?
>
> Isn't brain inflammation common in depression? I never looked into the effects of antidepressants on brain inflammation. It may be that the association of depression and inflammation is not so easily explained. Which came first, the inflammation or the depressive state? After the induction of a mood illness, does a primary disease pathology and a pro-inflammatory reaction to it become self-reinforcing? Perhaps a positive-feedback loop accelerates the development of symptoms or makes the depression more robust and less likely to remit spontaneously.
>
>
> - ScottInteresting, that sertraline was one the only one of all the antidepressants to be shown to be pro-inflammatory. Sertraline actually reminds me more of a cross between amphetamine and an antipsychotic. It does have stronger than most SSRI Dopamine reuptake properties, but the SRI part of the drug may counter-act? I dunno...
Jay
Posted by NKP on December 4, 2022, at 13:51:07
In reply to Re: Antipsychotics and brain volume, posted by Jay2112 on December 4, 2022, at 11:13:05
This is a study on brain volume change during flupentixol use:
Antipsychotic naive patients having their first schizophrenic episode were given flupentixol for one year. A control group consisting of non-schizophrenic subjects who were not given an antipsychotic, was included.
There are a few points in the study that I find curious:
(i) The schizophrenia group actually started with *higher* average grey matter volume than the control group (449 949 mm^3 vs 445 567 mm^3). I don't know if this difference is statistically significant though.
(ii) Both the schizophrenia group *and the control group* had a reduction in grey matter volume over the course of the twelve months (4.6 % vs 1.12 %). Again I don't know if the loss of grey matter volume in the control group is statistically significant.
(iii) The white matter volume of *both* groups increased: 2.5 % for the schizophrenia group, and 1.4 % for the control group.
(iv) The subcortical grey matter volume of *both* groups increased: 0.5 % for the schizophrenia group, and 1.5 % for the control group. I don't know if this increase in the schizophrenia group is statistically significant.
These figures are only averages taken across the groups. For example, the change in grey matter volume mentioned in point (ii) above, varied from around -2 % to as much as around -8 % for the schizophrenia group, and from around 0 % to around -2 % for the control group.
This is the end of the thread.
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