Overview | p53 | p63 | ACE-2 | Prokineticin | Kisspeptin | VEGF | Epigenetics | Neuropathy | Studies
Introduction
A number of treatments that inhibit serotonin reuptake – antidepressants, antibiotics, antihistamines and analgesics – along with retinoids used for skin and other problems, and finasteride and related drugs for hair loss, can cause enduring sexual dysfunctions.
These conditions include post-SSRI sexual dysfunction (PSSD), post-retinoid sexual dysfunction (PRSD), also called post-Accutane syndrome (PAS), post-finasteride syndrome (PFS) and persistent genital arousal disorder (PGAD). Once triggered they can persist for years or decades after stopping treatment.
There are thousands of recorded cases, almost certainly tens of thousands of people affected, and in all probability hundreds of thousands affected. At least 15% of the 1 billion people living in the ‘West’ (150 million) are on drugs known to cause the problem, most of whom expect that everything will revert to normal when their current treatment stops, but for many it won’t.
These devastating conditions, lack of hope for an imminent cure or even understanding of the problem, and in some cases the failure of doctors to recognize these disorders, lead people to take their own lives.
Many doctors, PhDs and others suffering these conditions have engaged in forums and other settings and done a lot of work to track down a cause and possible remedy – at present to no avail. Efforts to date have focused on the brain and obvious targets like serotonin, dopamine systems and the effects of neurosteroids.
Novel perspectives
This Research Forum hopes to open novel perspectives on the problems and perhaps on ways to do clinical research.
Over the last decade, RxISK has made it very clear that people affected by treatment induced alcoholism, suicide or sexual dysfunction have a motivation to solve problems that is often worth more than any academic expertise. Motivated folk with no background in the issues can sift through and master astonishing amounts of complex information. We want to mobilize a collective effort to turn up new leads on PSSD and related conditions and to draw the conditions to the attention of researchers.
The focus in this forum is on the body not the brain, and on proteins, especially regulatory proteins, and enzymes rather than on amines like serotonin. The enduring sexual dysfunctions don’t just involve an action of drugs on sexual function but what looks more like the flipping of a switch so that a particular effect stays locked in place. This is more likely to involve a protein than an amine.
At the core of these syndromes are changes in genital skin sensation. We usually say genitals become numb, but it is likely more complex than this with affective touch being lost. And genitals can also become irritable as in PGAD. So it makes sense to look at things like skin and even hair.
Finasteride restores hair, while SSRIs, isotretinoin and Covid cause hair problems, and all four act on skin and cause sexual dysfunction.
Researchers are more likely to engage if the research holds out a prospect of future cures for other conditions rather than shedding more light on sexual function alone.
SSRIs, isotretinoin and other retinoids appear useful in Covid and other viral infections. In addition to preventing infection, retinoids can reverse the anosmia that Covid causes. Besides Covid, all of these drugs also look like they have an anti-cancer effect.
Added to these findings, it appears thalidomide can treat Covid. Thalidomide also causes sexual dysfunction, and like SSRIs and retinoids it can be helpful for cancer. It is most famous for causing birth defects, which SSRI and isotretinoin also cause.
In the case of birth defects, many seem linked to switches being flipped at the wrong time. In the case of cancer, the treatments seem to flip a switch at the right time. It also appears that thalidomide and related drugs can treat some cancers.
Solving what causes an alteration in genital sensation to endure is likely to shed a great deal of light also on what causes suicide on a range of drugs, both through akathisia which is like PGAD, or emotional numbness which is like genital numbness.
It will also shed light on what causes dependence on many drugs, as the enduring sexual dysfunctions typically show up in withdrawal states.
In addition, this research seems likely to open up a potential for new antiviral and anti-cancer agents.
It is important for any letters sent to researchers to emphasize possible breakthroughs in treating viruses like Covid or cancers as it is to focus on solving a treatment induced problem.
How can you contribute?
Hunting
Just googling some of the details listed here will throw up some fascinating nuggets of information. There is a lot to unearth simply by looking for links between serotonin and ACE-2 receptors, or links between retinoids and finasteride on the one side with skin keratin on the other (keratin is an extraordinary molecule) or linking any of these drugs to promising proteins listed here like kisspeptin, prokineticin and others.
We invite you to play around with things. Almost all of the interesting target proteins we know about to date have come from people like you – not from experts.
There is a set of links at the top of this page which take you to other pages for each of the target proteins. They contain lists of articles that can be explored, and you can add comments at the bottom. We will add further pages as more targets and information becomes available.
It would be great if any of you who find interesting articles can write a short set of notes as to why this article might offer ways forward.
If you have suggestions for new targets, please leave a comment with details of how you think it might fit in and what to say about it.
Contacting
If finding and reading articles is not for you, the articles that will hopefully accumulate on these pages always have at least one email address – sometimes emails for all authors.
Someone needs to draw the attention of these researchers to PSSD, PFS, PRSD and PGAD, to the terrible toll of suffering these conditions cause, and how a breakthrough might dramatically shift the way we view ourselves, as well as lead to possible cancer and Covid treatments.
The researchers also need to hear about the RxISK Prize. This $100,000 Prize for someone who makes a truly significant contribution toward solving these problems shows researchers that people with these conditions are serious and want someone to find answers.
The hope is that some researchers are already working on something that could provide an answer. The Prize offers them an incentive to consider whether they might have the answer to our problem and didn’t realise it because they hadn’t heard of it.
There are template emails below which you can use or adapt.
Please leave a comment afterwards about anything useful that came from any contact you have managed to make.
Expert input
As material on the forum builds up, hopefully researchers will come to visit the site to get articles from us, to contribute more articles, and to engage further.
In your email/letter, especially if there is some interest, it would be wonderful if you could invite a member of the prokineticin or p73 or other research teams to write a short piece about their protein/target to tell all of us about their area of research and any possibilities they can envisage for how some aspect of what they are doing might help.
If we get discussions going between those affected and researchers working on possibly related areas we may end up creating a new way to do research.
Template email
Subject: Possible role of [insert here] in enduring sexual dysfunctions
Dear Dr X,
I am writing with regard to your recent work on [insert here]. Your work opens up the possibility that you have an answer to a problem you didn’t know existed.
A number of treatments that inhibit serotonin reuptake – antidepressants, antibiotics, antihistamines and analgesics – along with retinoids used for skin and other problems, and finasteride and related drugs used for hair loss, can cause enduring sexual dysfunctions.
These conditions include post-SSRI sexual dysfunction (PSSD), post-retinoid sexual dysfunction (PRSD), also called post-Accutane syndrome (PAS), post-finasteride syndrome (PFS) and persistent genital arousal disorder (PGAD). Once triggered they can persist for years or decades after stopping treatment. See the articles:
- Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin
- Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases
There are thousands of recorded cases, almost certainly tens of thousands of people affected, and in all probability hundreds of thousands affected. At least 15% of the 1 billion people living in the ‘West’ (150 million) are on drugs known to cause the problem, most of whom expect that everything will revert to normal when their current treatment stops, but for many it won’t.
These devastating conditions, lack of hope for an imminent cure or even understanding of the problem, and in some cases the failure of doctors to recognize these disorders, lead to people taking their own lives.
For over a decade, doctors and PhDs among other people with the condition have focused on brain research and serotonin, dopamine systems or neurosteroids, but these drugs affect the body from skin and hair to blood and guts more than the brain.
You work opens up new perspectives. I am inviting you to explore these conditions and would like to make you aware there is prize of $100,000 for anyone who establishes what is happening and what might be done to remedy the problem – see RxISK Prize.
In addition to this, recent work on thalidomide, SSRIs, and isotretinoin points to both anti-cancer and anti-Covid effects for all these treatments.
If there are any ways in which your research might map onto some aspect of these problems, please let me know. If there are any articles you think might be helpful for me or others to read, it would be good to get these references. Similarly, if you have any colleagues working on this or in related areas, I’d appreciate getting their contact details.
Template email to epigeneticists
[Very few people are called epigeneticists. Googling though does throw up research groups in which epigeneticists play a part. Departments of Genetics may be able to offer leads and it may also be worth emailing folk who give their background as Genomics.]
Dear Dr X,
Given your background as having worked on epigenetics, I am writing to draw your attention to recent epigenetic studies on finasteride, two on Citalopram an SSRI – Cit A and Cit B, and two linked to isotretinoin – Iso A and Iso B.
These studies were undertaken because a number of treatments that inhibit serotonin reuptake – antidepressants, antibiotics, antihistamines and analgesics – along with retinoids used for skin and other problems and finasteride and related drugs used for hair loss can cause enduring sexual dysfunctions.
These conditions include post-SSRI sexual dysfunction (PSSD), post-retinoid sexual dysfunction (PRSD), also called post-Accutane syndrome (PAS), post-finasteride syndrome (PFS) and persistent genital arousal disorder (PGAD). Once triggered they can persist for years or decades after stopping treatment. See the articles:
- Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin
- Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases
There are thousands of recorded cases, almost certainly tens of thousands of people affected, and in all probability hundreds of thousands affected. At least 15% of the 1 billion people living in the ‘West’ (150 million) are on drugs known to cause the problem, most of whom expect that everything will revert to normal when their current treatment stops, but for many it won’t.
These devastating conditions, lack of hope for an imminent cure or even understanding of the problem, and in some cases the failure of doctors to recognize these disorders, lead to people taking their own lives.
For over a decade people with the condition have focused on brain research. Researchers have focused on predetermined changes – for instance linked to neurosteroids on which finasteride unquestionably works, or systems linked to depression on which SSRIs work. But these drugs affect the body from skin and hair to blood and guts more than the brain.
There has been a more recent epigenetic turn to the research as well as a switch to looking at regulatory proteins like p63 and related proteins, and proteins like prokineticin and kisspeptin in functions like affective touch.
To the untrained eye the biggest effects in these epigenetic studies appear to be on things related to skin and proteins that are not usually linked to the clinical actions of finasteride, SSRIs or isotretinoin.
Along with colleagues, none of whom have any knowledge of epigenetics, I was wondering how these studies might look to an epigeneticist who has no preconceived ideas about how these drugs must be working.
What might be of even greater importance than skin or sex might be some evidence of an effect on something that could have a switch function – something that might lead to a function like sex or touch being shut down rather than just influenced.
Another angle is that all the treatments that cause these problems seem to be beneficial in the treatment of Covid and cancer, and the key events may lie in this area also.
I am inviting you to explore these conditions and would like to make you aware there is prize of $100,000 for anyone who establishes what is happening and what might be done to remedy the problem – see RxISK Prize.
If there are any ways in which your research might map onto some aspect of these problems, please let me know. If there are any articles you think might be helpful for me or others to read, it would be good to get these references. Similarly, if you have any colleagues working in the epigenetic area who might be interested, I’d appreciate getting their contact details.
Dear Dr. Healy,
Thank you for this great initiative. We all hope that this research forum will lead to some interesting leads.
Here I present a potential mechanism of PFS/PSSD/PRSD involving an RFRP3 protein (in humans) (I will abbreviate RFRP). I also present a study protocol to demonstrate this theory.
INTRODUCTION
Here we present two studies of RFRP3 that will help us establish a potential theory about the possible mechanism of these syndromes. Based on these two studies, we will establish a potential etiology for this syndrome and provide an experimental protocol to demonstrate it.
STUDY 1: Hypothalamic RFRP3 knockdown prevents chronic stress-induced infertility and embryonic resorption (http://dx.doi.org/10.7554/eLife.04316.001)
Study Summary:
Female rats exposed to a stressor for a period of 18-days followed by a 4-day recovery period without a stressor were compared to a control group without a stressor. The mating frequency of the stressor-exposed rats was compared to that of a control group. As expected, the stressor-exposed group had a statistically significant decrease in mating frequency compared to the control group.
The level of RFRP mRNA and RFPR receptors (indicator of gene expression) in the hypothalamus and the level of corticosterone (indicator of stress) in venous blood were assessed during both the stress and recovery periods of the brain. As expected, the stress hormone (corticosterone) increased during the stress period and returned to normal during the recovery period. RFRP mRNA and RFRP receptor levels increased compared to control during the stress period and, interestingly, remained elevated even after recovery compared to control.
The study authors hypothesized that this persistent increase in RFRP and RFRP receptor gene expression plays a causal role in lingering sexual behavior. To prove this hypothesis, they used a viral vector containing an shDNA plasmid. The shDNA plasmid was composed of a shRNAmir gene and a promoter region, called TetOFF, controlling the initiation of shRNAmir transcription. The presence of doxicycline prevented the TetOFF promoter region from initiating transcription. Therefore, transcription of shDNA was prevented by the presence of doxicycline. In other words, doxicycline acts as a switch for shDNAmir transcription. The shDNA is transcribed into shRNA, which will be processed by a protein called Dicer and will yield a small interfering RNA (siRNA). These siRNAs will interfere with the mRNA of the targeted gene (here RFRP) and prevent its translation. This is a well known technique to silence a target gene in vivo using the RNA interference machinery. This process is briefly described here: https://en.wikipedia.org/wiki/Short_hairpin_RNA#/media/File:ShRNA_Lentivirus.svg.
In the presence of doxicycline (the RFRP gene is expressed), rats exposed to stress have a reduced mating rate. Without doxicycline (the RFRP gene is not expressed), the stress-exposed rats had a normal mating rate. This is well summarized in figure 4 of the study. From these observations, we can assume that high RFRP gene expression plays a causal role in the persistence of abnormal sexual behavior after stress exposure.
Why is this study interesting?
In terms of PFS/PSSD/PRSD, this study is of great interest because it demonstrates the role of a protein in an induced persistent sexual dysfunction. But it is of even greater interest in light of another study (see Study 2 below).
STUDY 2: Citalopram (antidepressant) administration causes sexual dysfunction in male mice via RF-amide-related peptide in the dorsomedial hypothalamus (doi:10.1016/j.neuropharm.2010.03.018)
Summary of study:
Mice chronically treated with citalopram (5 mg/kg/BW) for 4 weeks were compared with a control group. As expected, altered sexual behavior of male mice was observed compared to the control group. Cell number, fiber number, and mRNA expression of GnRH, kisspeptin, RFRP, and RFRP receptor were assessed in the following brain regions: POA, AVPV, ARC, and DMH.
The study found no relevant results (cell number, mRNA) for Kisspeptin or GnRH compared to control. However, they did find some interesting results regarding RFRP: increased neurons in DMH, increased RFRP-immunoreactive fiber density in POA, increased RFRP receptor mRNA levels in POA (by “increased,” I mean statistically significant; p<0.05). However, no statistically significant change was observed in RFRP mRNA levels in the POA, an increase was observed but did not reach statistical significance (control: 0.63 +/- 0.25 citalopram: 0.79 +/- 0.26; p=unknown).
Based on the change observed following chronic citalopram treatment, we can speculate that RFRP plays a role in the observed sexual dysfunction during SSRI intake.
Why is this study interesting?
This study highlights the potential role of RFRP and its receptor in SSRI-induced sexual dysfunction. This is in agreement with the previous study showing that modulated expression of the RFRP receptor gene causes altered sexual behavior in female rats. Interestingly, the part of the POA brain that showed increased RFRP receptor gene expression is known to be involved in sexual behavior. In fact, lesions in these areas are linked to loss or abnormality of sexual function: Impairment of mating behavior in male rats following lesions in the preoptic-anterior hypothalamic continuum (https://doi.org/10.1016/0006-8993(67)90076-5).
Given that RFRP plays a causal role in the persistent stress-induced sexual dysfunction observed in female rats and given the increase in RFRP receptor gene expression following chronic SSRI treatment, we can assume that SSRI-induced sexual dysfunction involves RFRP.
BUT HOW DO WE PROVE SUCH A HYPOTHESIS?
Here is the interesting part. We can easily propose a study to demonstrate whether RFRP plays a causal role in SSRI-induced sexual dysfunction. The first study we presented uses a viral vector to inject a DNA plasmid into the host genome. The DNA plasmid acts as a gene expression switch for the RFRP gene. The same viral vector and DNA plasmid can be used to demonstrate whether or not RFRP plays a causal role in SSRI-induced sexual dysfunction. Simply replace the stress sessions with chronic SSRI treatment and maintain them on drug (no recovery period i.e test the hypothesis while mices are on the drug). If, by deactivating the expression of the RFRP gene, sexual dysfunction is alleviated, we can infer that RFRP plays a causal role.
Further studies can be conducted to strengthen this theory. Gene expression of RFRP and RFRP receptor can be assessed in the hypothalamus or POA of mice on 5-alpha reductase or isotretinoin. If the expression of RFRP and RFRP receptor genes is increased in the evaluated regions compared to a control group, this would confirm the involvement of RFRP as a common potential cause of PFS/PSSD/PRSD.
Furthermore, if this theory proves to be true, it is very likely that the same mechanism is involved in patient with sexual dysfunction when taking SSRIs, finasteride, or isotretinoin.
CAN A CASE CONTROL STUDY BE PERFORMED TO DEMONSTRATE THIS IN HUMANS?
Obviously, the mRNA level of RFRP3 in the hypothalamus can only be assessed by a biopsy of the hypothalamus. This requires the subject to be anesthetized and undergo surgery. Such a biopsy can also induce lesions that can have devastating consequences. Therefore, evaluation in the hypothalamus cannot be performed for obvious ethical reasons. However, RFPR3 and its receptor are present in several tissues including the testis: Immunolocalization of RFamide-related peptide 3 in a desert rodent Gerbillus tarabuli during seminiferous epithelium cycle (doi: https://doi.org/10.1016/j.tice.2018.09.005). According to this study, RFPR3 also plays a role in spermatogenesis which appears to be impaired in PFS/PSSD/PRSD. Therefore, biopsy in the peripheral zone can potentially help us explore the role of RFRP in PFS/PSSD/PRSD sufferers.
CONCLUSION
We have presented here, a potential mechanism of PFS/PSSD/PRSD involving RFRP3 and its receptor. A study protocol has been presented to prove this causal mechanism. Thanks for reading, let me know what you think.
Sincerely
Serguei Novitchok
Dear Dr.Healy & Co,
I am writing to introduce a potential study to assess autoantibodies in people with PSSD using protein arrays. This technique allows us to assess the autoantibody profile of people with the disease. I also explain why the discovery of a “PSSD’s autoantibody fingerprint” would provide us with a potential diagnostic tool and aid in our future research.
INTRODUCTION
Autoantibodies are a hallmark of pathologies involving the humoral branch of the immune system. Autoantibodies play a causal role in several autoimmune conditions such as Hashimoto’s disease (anti TSH receptor autoantibodies), some forms of Addison’s disease (anti 21-Hydroxylase autoantibodies) or Graves’ disease (anti-thyroid-stimulating immunoglobulin (TSI) autoantibodies). Autoantibody testing is therefore a useful tool for diagnosing certain autoimmune diseases. However, limiting autoantibody testing to the diagnosis of autoimmune diseases is a misconception. Autoantibodies are present in many diseases even if their role in these diseases is not elucidated or if their role is not causal. Therefore, autoantibody profiling is even discussed as a diagnostic tool for diseases that are not directly related to immune system dysfunction.
Some example :
-A Protein Microarray Signature of Autoantibody Biomarkers for the Early Detection of Breast Cancer (https://doi.org/10.1021/pr100686b) : “From these, 119 antigens had a partial area under the ROC curve (p 91% specificity. Twenty-eight of these antigens were confirmed using an independent serum cohort (n = 51 cases/38 controls, p < 0.05). Using all 28 AAb, a classifier was identified with a sensitivity of 80.8% and a specificity of 61.6% (AUC = 0.756)."
-Using protein microarray to identify and evaluate autoantibodies to tumor-associated antigens in ovarian cancer (https://doi.org/10.1111/cas.14732) : "An optimized panel of three anti-TAA (GNAS, p53, and NPM1) autoantibodies was identified to have relatively high sensitivity (51.2%), specificity (86.0%), and accuracy (68.6%), respectively. This panel can identify 51% of OC patients with CA125 negative. This study supports our assumption that anti-TAA autoantibodies can be considered as potential diagnostic biomarkers for detection of OC"
-Exploring autoantibody signatures in brain tissue from patients with severe mental illness (https://doi.org/10.1038/s41398-020-01079-8 ) : "Among the detected autoantigens, higher IgG reactivity in subjects with schizophrenia, as compared to psychiatrically healthy subjects, was found against the glutamate ionotropic receptor NMDA type subunit 2D (anti-GluN2D)."
– A very interesting study regarding small fiber neuropathy (SFN). In this study they isolated some potential auto antibodies that could serve as a potential biomarker for SFN. Novel Autoantibodies in Idiopathic Small Fiber Neuropathy (https://doi.org/10.1002%2Fana.26268) : "Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC = 2.99 and 3.07, respectively, p = 0.003, q = 0.076), DBNL (FC = 2.11 and 2.16, respectively, p = 0.009, q < 0.003), and KRT8 (FC = 1.65 and 1.70, respectively, p = 0.043, q < 0.003). "
(caveat: some diagnostic tools, even if they have high specificity, may lead to overdiagnosis. If a large population is screened with a diagnostic tool that has low specificity, it will yield many false positives. This leads to overdiagnosis and therefore overtreatment. All touted diagnostic tools or biomarkers must be carefully considered and the benefit/risk ratio carefully assessed. Screening is not harmless. The pharmaceutical industry is known to push screening. The above study should be read in the light of this warning).
As we have seen, autoantibodies may represent a fingerprint of a specific disease. Therefore, it would be interesting to assess the "autoantibody fingerprint" of PSSD. Assessing the autoantibody fingerprint of PSSD may have several advantages: First, it could provide us with a potential biomarker (thus a diagnostic tool). Second, it could be useful to guide us in further research, as a specific set of autoantibodies may suggest some type of dysfunction.
WHAT ARE THE TECHNIQUES FOR SCREENING FOR AUTOANTIBODIES?
There are several techniques to evaluate the existence of antibodies against a specific antigen:
– ELISA: A specific antigen is coated on a well and probed with serum. By using a labeled antibody specific to the idiotypic determinant of human antibodies, it can be verified whether or not antibodies have bound to the self-antigen being evaluated.
– Western blot: A mixture of self-antigens is separated by electrophoresis. The separated bands of known antigens are then probed with the sample suspected to contain specific antibodies for one or more of these antigens. The reaction of radiolabeled antibodies specific for the human idiotypic antigen determinant is detected.
– Bead-based assay: The antigens of interest are bound to beads. The beads are probed with sera. A secondary antibody (antibody specific for the human idiotypic determinant of human antibodies) is used.
Other techniques also exist. However, none of these techniques can screen the entire human proteome. To overcome this problem, a protein microarray composed of the entire human proteome can be used. The Baylor study used DNA microarrays to assess gene expression relative to a control. The same can be done using a protein microarray, except that the wells of the microarray are made up of proteins and serum antibodies are probed, not labeled cDNA from patient RNA. This will allow for the screening of a wide range of potential autoantigens. Depending on the microarray used, it may cover the entire human proteome.
A STUDY TO ASSESS THE AUTOANTIBODY PROFILE USING A PROTEIN ARRAY
A case-control study can be performed. A group of people with PSSD can be compared to a group of healthy volunteers. Serum from each participant will be collected. The serum will be added to all microarray wells (each well contains a specific protein). We wash the microarray plate to remove antibodies that did not bind to the proteins. Using a radiolabeled secondary antibody specific to human antibodies, we detect the autoantibodies that have reacted with the proteins in the well. We compare the result of the case group to the control group. The size of the cohort must be carefully considered in order to achieve statistical significance.
THE STRENGTH OF THIS STUDY
As mentioned above, such a study can provide us with a biomarker for PSSD and thus a diagnostic tool. Depending on the autoantigen and autoantibodies found, it could guide future research because a specific set of autoantibodies or autoantigens could be specific for a certain type of dysfunction. In addition, if relevant autoantibodies are found, they could be evaluated in another study among people with PFS or PRSD (using ELISA or western blot because protein arrays are very expensive). This would provide further evidence that PSSD, PFS, and PRSD are the same disease, even if accordding to the symptoms it seem obvious.
The Baylor study also had a drawback, their biopsy was very localized in one specific area. They did a scrotal biopsy. Gene expression is of course very dependent on the tissue being evaluated. This is less the case if we collect serum. Also, it is much easier to collect a blood sample than to do a biopsy. This represent an other advantage of this study.
THE LIMITATIONS OF THIS STUDY
One limitation of this study is its cost. I have not made a thorough estimate of the cost of such a protocol, but some of the materials needed may be expensive. A protein microarray plate costs about $1500. Suppose we recruit 60 patients (30 with PSSD, 30 healthy volunteers), it would cost about $90,000 just to obtain the microarray plate. Serum collection is actually very cheap. Other equipment would be needed. So we can estimate that such a study would cost about $110,000. We also need to find a research team that can conduct a protein microassay experiment and is willing to perform such a study.
We also need to consider the sensitivity and specificity of a diagnostic tool that looks for autoantibodies. If the specificity is low (e.g., 96%), it cannot be used as a diagnostic tool because it would produce many false positives.
CONCLUSION
Finding a "PSSD autoantibody fingerprint" may represent a great achievement. It could provide us with a diagnostic tool and guide us to interesting new leads. Thank you for reading, let me know what you think.
Sincerely
Serguei Novitchok
Part of the issue comes down to lack of sensitivity, and likely involvement of dopamine for reward and pleasure.
Just to explain the reason why I find this interesting:
“DEPTOR inhibits cell proliferation and confers sensitivity to dopamine agonist in pituitary adenoma”
https://pubmed.ncbi.nlm.nih.gov/31176743/
Obviously this is about cancer and not our issue. But the mechanism still counts. If someone said there is a lack of pituitary sensitivity to dopamine in PSSD, I’d say that makes sense. And that lack of sensivity might be the same in other parts.