Prozac Disrupts Behavior/Cortisol Over Generations

[aguilaroja]

Dr. Peat has mentioned environmental and nutrient issues that affect multiple generations, illustrating problems with genetic dogma. Biologist used new terms like epigenetics and trans-generational to explain non-dogmatic events.
Estrogen, memory and heredity: Imprinting and the stress response

It is not surprising that a substance impairing metabolism has multi-generation effects. In this recent publication, when zebrafish embryos were exposed to Prozac, there were disruptions of behavior and cortisol response for two generations. [Zebrafish are commonly used to model neuro-behavioural changes in labs.]

A separate study out of Qingdao, China showed that Bisphenol S (BPS) has thyroid disrupting action in mother zebrafish which was passed to the non-exposed offspring generation. The study did not mention looking beyond one generation of effect.
Bisphenol S is used in epoxies and found, though in small amounts, in a wide variety of paper products, including tickets, banknotes, mailing envelopes, airplane boarding passes, and airplane luggage tags.

Parents Might Pass the Effects of Prozac on to Future Generations
"And that’s exactly what Vera-Chang saw—at least, in the fish that had spent their early development Prozac-free. Those who had been exposed to fluoxetine, on the other hand, remained stalwart bottom-dwellers. “It’s like they didn’t have energy to keep exploring,” Vera-Chang explains, “as if they were experiencing burnout.”

Effects of Antidepressants Span Three Generations in Fish
"Examining several generations of the fish, the scientists revealed that the cortisol effects persisted through the exposed animals’ offspring, grand-offspring, and great-grand-offspring—but the behavioral disruptions only continued across two."

Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio. - PubMed - NCBI
Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio
"early FLX exposure significantly modified numerous pathways closely associated with cortisol synthesis in the male adults from the F0 and F3 generations. We also show that the low cortisol levels are linked to significantly reduced exploratory behaviors in adult males from the F0 to F2 FLX lineages. This may be a cause for concern given the high prescription rates of FLX to pregnant women and the potential long-term negative impacts on humans exposed to these therapeutic drugs."

Transgenerational thyroid endocrine disruption induced by bisphenol S affects the early development of zebrafish offspring. - PubMed - NCBI
"Plasma levels of thyroxine (T4) were significantly decreased in F0 females while 3,5,3'-triiodothyronine (T3) plasma levels were significantly increased in F0 females and males; moreover, TH content in eggs (F1) spawned by exposed F0 generation exhibited similar changes as the F0 females, with significant decreases in T4 and increases in T3, demonstrating BPS-induced maternal transfer of thyroid endocrine disruption. Further, excessive levels of maternal T3 in the offspring resulted in delayed embryonic development and hatching, swim bladder inflation defect, reduction in motility, developmental neurotoxicity, and lateral stripe hypopigmentation in non-exposed F1 embryos and larvae."

 

[Makrosky]

Holy ***t. @haidut don't miss this.

 

[haidut]

Holy ***t. @haidut don't miss this.

Yes, truly amazing! Thanks @aguilaroja ! He already posted these in the other thread on Prozac causing male aggression towards females.
So much for non-irritability of acquired traits. Lamarck must be clapping in his grave.

 

[Makrosky]

Yes, truly amazing! Thanks @aguilaroja ! He already posted these in the other thread on Prozac causing male aggression towards females.
So much for non-irritability of acquired traits. Lamarck must be clapping in his grave.

Now I wonder if this is something strictly specific to SSRI drugs or it happens on other drug families like PPI inhibitors, statins, painkillers, birth control pills, blood pressure, asthma, etc...

 

[haidut]

Now I wonder if this is something strictly specific to SSRI drugs or it happens on other drug families like PPI inhibitors, statins, painkillers, birth control pills, blood pressure, asthma, etc...

What does your instinct tell you? I think you already know the answer
Acquired traits, be it from drugs or life experiences, ARE heritable. Anything that causes harm will likely affect your children as well. You can mitigate the damage by keeping metabolism high but ultimately the best approach would be to avoid exposure to those poisons.

 

[aguilaroja]

He... posted these in the other thread on Prozac causing male aggression towards females.
...Lamarck must be clapping in his grave.

As clarification, while pre-natal exposure studies were cited in the other post, the study here by Vera-Chang & Trudeau is a different item, mentioned specifically to highlight the multi-generational effects. There could be an entire research line re-do the hundreds of pre-natal exposure studies and look across multiple generations. Usual commerce does not incentivize this. It probably did not occur even to exceptional researchers like Theo Colborn in a previous generation.

 

[aguilaroja]

Now I wonder if this is something strictly specific to SSRI drugs or it happens on other drug families like PPI inhibitors, statins, painkillers, birth control pills, blood pressure, asthma, etc...

Some studies have already been done. Perhaps a review article is underway somewhere, but it is not known to me. Recall, again, an academic researcher is likely to have a hundred times better funding support for finding a possible slight benefit of a commercial drug than for finding potential hazards.
Props to Dr. Peat for raising the issue decades ago. Numerous studies have only been published in the last year or two.

Trans-generational studies also have a longer time frame. It is more work to do them, but long lasting effects are more significant.

Transgenerational blunting of morphine-induced corticosterone secretion is associated with dysregulated gene expression in male offspring. - PubMed - NCBI
"...sex-specific alterations in opioid-mediated regulation of the HPA axis are transgenerationally transmitted for at least two generations following female adolescent morphine exposure. These effects may play a role in the previously observed changes in morphine analgesia and reward-related behaviors observed in this phenotype"

Transgenerational effects of diesel particulate matter on Caenorhabditis elegans through maternal and multigenerational exposure. - PubMed - NCBI
"Continuous exposure to DPM at 0.1 and 1.0 µg/mL impaired the brood size in F2 to F5 generations. "

Maternal care modulates transgenerational effects of endocrine-disrupting chemicals on offspring pup vocalizations and adult behaviors. - PubMed - NCBI
"Maternal care of F2 dams towards their F3 offspring was altered in a lineage-dependent manner, particularly in PCB paternal-lineage animals. When F3 pups were recorded for ultrasonic vocalizations (USVs) following separation from the mother, the rate of neonatal USVs in F3 offspring were decreased in PCB paternal-lineage pups."

 

[Wagner83]

So prozac causes hypocortisolism and increases t3 levels over many generations, I wonder what Ray Peat would say about that.

 

[haidut]

So prozac causes hypocortisolism and increases t3 levels over many generations, I wonder what Ray Peat would say about that.

The abstracts are misleading, the effects is not positive. Prozac blunted the cortisol response to a cortisol stimulate (ACTH). That is a VERY bad effect. The healthy response would be a robust cortisol increase so that CRH and ACTH can be suppressed. When cortisol does not rise robustly enough, CRH and ACTH stay elevated and both are highly detrimental to health. You want short term cortisol responses to be HIGH, so that the cortisol stimulants CRH/ACTH can be suppressed and thus chronic cortisol levels to stay relatively low.
Corticotropin-releasing hormone - Wikipedia
"...In the short term, CRH can suppress appetite, increase subjective feelings of anxiety, and perform other functions like boosting attention. Although the distal action of CRH is immunosuppression via the action of cortisol, CRH itself can actually heighten inflammation, a process being investigated in multiple sclerosis research.[8]"

From the study on cortisol.
"...The decreased basal and stress-induced cortisol production in FLX-exposed male ZF led us to predict a reduced responsiveness of the steroidogenic interrenal cells (equivalent to the cortical cells in the mammalian adrenal). We therefore administered adrenocorticotropic hormone (ACTH) to determine its impact on basal and stimulated cortisol production in the F0 and F3 generations. To control for handling/injection stress, we included both noninjected and saline-injected control groups. A two-way ANOVA was performed to assess the effects of the injection and the FLX concentrations on cortisol levels. The expected increase in total cortisol levels across the injected groups (noninjected, saline and ACTH groups) was observed in both the F0 [F(2,96) = 157.436, P < 0.001] and F3 [F(2,91) = 154.809, P < 0.001]. However, the interrenal cells of the males from the FLX lineages had a significantly attenuated response in each injection group compared with the CTR lineage in the F0 [F(2,96) = 28.441, P < 0.001] and F3 [F(2,91) = 22.345, P < 0.001] generations (Fig. 1B)."

The effects on T3 is also misleading if you judge by the abstract only. Increased T3 but lower T4 is not necessarily a good result. Furthermore, the effects of BPS were due to increased CRH and TSH which is hardly a good sign. It's like saying that higher T due to excessively high LH/FSH is good. It is not, and it called "compensated hypogonadism". BPA and BPS are thyroid antagonists and this is another reason thyroid hormone levels may be elevated - i.e. antagonists typically raise the levels of the hormone whose receptor they antagonize. But the elevations are of little use if the "receptor" is being blocked by the antagonist.
"...Upon BPS exposure, the up-regulated expression of crh and 307 tshβ in F0 females may cause an over-stimulation of the thyroid follicles. Consistent 308 with this, hypertrophy and hyperplasia of the follicular epithelium and colloid 309 depletion were also observed in F0 females (Fig. S1C, Supporting Information), 310 indicating enhanced activity of the thyroid follicles (Chen et al., 2016)."

 

[Wagner83]

Thanks!

 

[Astolfo]

What can be done to reverse these changes?

@haidut

 

[Momado965]

The abstracts are misleading, the effects is not positive. Prozac blunted the cortisol response to a cortisol stimulate (ACTH). That is a VERY bad effect. The healthy response would be a robust cortisol increase so that CRH and ACTH can be suppressed. When cortisol does not rise robustly enough, CRH and ACTH stay elevated and both are highly detrimental to health. You want short term cortisol responses to be HIGH, so that the cortisol stimulants CRH/ACTH can be suppressed and thus chronic cortisol levels to stay relatively low.
Corticotropin-releasing hormone - Wikipedia
"...In the short term, CRH can suppress appetite, increase subjective feelings of anxiety, and perform other functions like boosting attention. Although the distal action of CRH is immunosuppression via the action of cortisol, CRH itself can actually heighten inflammation, a process being investigated in multiple sclerosis research.[8]"

From the study on cortisol.
"...The decreased basal and stress-induced cortisol production in FLX-exposed male ZF led us to predict a reduced responsiveness of the steroidogenic interrenal cells (equivalent to the cortical cells in the mammalian adrenal). We therefore administered adrenocorticotropic hormone (ACTH) to determine its impact on basal and stimulated cortisol production in the F0 and F3 generations. To control for handling/injection stress, we included both noninjected and saline-injected control groups. A two-way ANOVA was performed to assess the effects of the injection and the FLX concentrations on cortisol levels. The expected increase in total cortisol levels across the injected groups (noninjected, saline and ACTH groups) was observed in both the F0 [F(2,96) = 157.436, P < 0.001] and F3 [F(2,91) = 154.809, P < 0.001]. However, the interrenal cells of the males from the FLX lineages had a significantly attenuated response in each injection group compared with the CTR lineage in the F0 [F(2,96) = 28.441, P < 0.001] and F3 [F(2,91) = 22.345, P < 0.001] generations (Fig. 1B)."

The effects on T3 is also misleading if you judge by the abstract only. Increased T3 but lower T4 is not necessarily a good result. Furthermore, the effects of BPS were due to increased CRH and TSH which is hardly a good sign. It's like saying that higher T due to excessively high LH/FSH is good. It is not, and it called "compensated hypogonadism". BPA and BPS are thyroid antagonists and this is another reason thyroid hormone levels may be elevated - i.e. antagonists typically raise the levels of the hormone whose receptor they antagonize. But the elevations are of little use if the "receptor" is being blocked by the antagonist.
"...Upon BPS exposure, the up-regulated expression of crh and 307 tshβ in F0 females may cause an over-stimulation of the thyroid follicles. Consistent 308 with this, hypertrophy and hyperplasia of the follicular epithelium and colloid 309 depletion were also observed in F0 females (Fig. S1C, Supporting Information), 310 indicating enhanced activity of the thyroid follicles (Chen et al., 2016)."

Wouldnt cypro reverse that?

 

[Astolfo]

Wouldnt cypro reverse that?

Cypro made me way worse while taking it. It has cortisol blocking effects afaik.

 

[Momado965]

Cypro made me way worse while taking it. It has cortisol blocking effects afaik.

What were the effects of lowered cortisol, did you experience?

 

[Astolfo]

What were the effects of lowered cortisol, did you experience?

Heart palpitaions
Skin numbness
Dizziness
Visual disturbances
Cognitive impairment

I opened a topic about that. People said that these were possible because the anticortisol and hypoglycemic effects of cypro.

I didn’t see any improvement from that med.

 

[ShotTrue]

I believe this is the book I read that discussed that prozac was basically made by Eli Lilly, who knew it was a poison but still wanted money from it. It describes how ADHD and SSRI's came about and what some of the effects are:
https://www.amazon.com/Anatomy-Epidemic-Bullets-Psychiatric-Astonishing-ebook/dp/B0036S4EGE

A very peaty book on mental illness medications @haidut

 

[Astolfo]

I believe this is the book I read that discussed that prozac was basically made by Eli Lilly, who knew it was a poison but still wanted money from it. It describes how ADHD and SSRI's came about and what some of the effects are:
https://www.amazon.com/Anatomy-Epidemic-Bullets-Psychiatric-Astonishing-ebook/dp/B0036S4EGE

A very peaty book on mental illness medications @haidut

Are all antidepressants like a posion? I’m asking it in wrong place, I know, but I need something to ease me right now.

I have already serious neurological side effects from 20 days fluoxetine usage, but I’m not sure if all the antidepressants will make me even worse.

 

[johnwester130]

Dr. Peat has mentioned environmental and nutrient issues that affect multiple generations, illustrating problems with genetic dogma. Biologist used new terms like epigenetics and trans-generational to explain non-dogmatic events.
Estrogen, memory and heredity: Imprinting and the stress response

It is not surprising that a substance impairing metabolism has multi-generation effects. In this recent publication, when zebrafish embryos were exposed to Prozac, there were disruptions of behavior and cortisol response for two generations. [Zebrafish are commonly used to model neuro-behavioural changes in labs.]

A separate study out of Qingdao, China showed that Bisphenol S (BPS) has thyroid disrupting action in mother zebrafish which was passed to the non-exposed offspring generation. The study did not mention looking beyond one generation of effect.
Bisphenol S is used in epoxies and found, though in small amounts, in a wide variety of paper products, including tickets, banknotes, mailing envelopes, airplane boarding passes, and airplane luggage tags.

Parents Might Pass the Effects of Prozac on to Future Generations
"And that’s exactly what Vera-Chang saw—at least, in the fish that had spent their early development Prozac-free. Those who had been exposed to fluoxetine, on the other hand, remained stalwart bottom-dwellers. “It’s like they didn’t have energy to keep exploring,” Vera-Chang explains, “as if they were experiencing burnout.”

Effects of Antidepressants Span Three Generations in Fish
"Examining several generations of the fish, the scientists revealed that the cortisol effects persisted through the exposed animals’ offspring, grand-offspring, and great-grand-offspring—but the behavioral disruptions only continued across two."

Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio. - PubMed - NCBI
Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio
"early FLX exposure significantly modified numerous pathways closely associated with cortisol synthesis in the male adults from the F0 and F3 generations. We also show that the low cortisol levels are linked to significantly reduced exploratory behaviors in adult males from the F0 to F2 FLX lineages. This may be a cause for concern given the high prescription rates of FLX to pregnant women and the potential long-term negative impacts on humans exposed to these therapeutic drugs."

Transgenerational thyroid endocrine disruption induced by bisphenol S affects the early development of zebrafish offspring. - PubMed - NCBI
"Plasma levels of thyroxine (T4) were significantly decreased in F0 females while 3,5,3'-triiodothyronine (T3) plasma levels were significantly increased in F0 females and males; moreover, TH content in eggs (F1) spawned by exposed F0 generation exhibited similar changes as the F0 females, with significant decreases in T4 and increases in T3, demonstrating BPS-induced maternal transfer of thyroid endocrine disruption. Further, excessive levels of maternal T3 in the offspring resulted in delayed embryonic development and hatching, swim bladder inflation defect, reduction in motility, developmental neurotoxicity, and lateral stripe hypopigmentation in non-exposed F1 embryos and larvae."

prozac increases progesterone and allopregnanolone though

 

[johnwester130]

Dr. Peat has mentioned environmental and nutrient issues that affect multiple generations, illustrating problems with genetic dogma. Biologist used new terms like epigenetics and trans-generational to explain non-dogmatic events.
Estrogen, memory and heredity: Imprinting and the stress response

It is not surprising that a substance impairing metabolism has multi-generation effects. In this recent publication, when zebrafish embryos were exposed to Prozac, there were disruptions of behavior and cortisol response for two generations. [Zebrafish are commonly used to model neuro-behavioural changes in labs.]

A separate study out of Qingdao, China showed that Bisphenol S (BPS) has thyroid disrupting action in mother zebrafish which was passed to the non-exposed offspring generation. The study did not mention looking beyond one generation of effect.
Bisphenol S is used in epoxies and found, though in small amounts, in a wide variety of paper products, including tickets, banknotes, mailing envelopes, airplane boarding passes, and airplane luggage tags.

Parents Might Pass the Effects of Prozac on to Future Generations
"And that’s exactly what Vera-Chang saw—at least, in the fish that had spent their early development Prozac-free. Those who had been exposed to fluoxetine, on the other hand, remained stalwart bottom-dwellers. “It’s like they didn’t have energy to keep exploring,” Vera-Chang explains, “as if they were experiencing burnout.”

Effects of Antidepressants Span Three Generations in Fish
"Examining several generations of the fish, the scientists revealed that the cortisol effects persisted through the exposed animals’ offspring, grand-offspring, and great-grand-offspring—but the behavioral disruptions only continued across two."

Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio. - PubMed - NCBI
Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio
"early FLX exposure significantly modified numerous pathways closely associated with cortisol synthesis in the male adults from the F0 and F3 generations. We also show that the low cortisol levels are linked to significantly reduced exploratory behaviors in adult males from the F0 to F2 FLX lineages. This may be a cause for concern given the high prescription rates of FLX to pregnant women and the potential long-term negative impacts on humans exposed to these therapeutic drugs."

Transgenerational thyroid endocrine disruption induced by bisphenol S affects the early development of zebrafish offspring. - PubMed - NCBI
"Plasma levels of thyroxine (T4) were significantly decreased in F0 females while 3,5,3'-triiodothyronine (T3) plasma levels were significantly increased in F0 females and males; moreover, TH content in eggs (F1) spawned by exposed F0 generation exhibited similar changes as the F0 females, with significant decreases in T4 and increases in T3, demonstrating BPS-induced maternal transfer of thyroid endocrine disruption. Further, excessive levels of maternal T3 in the offspring resulted in delayed embryonic development and hatching, swim bladder inflation defect, reduction in motility, developmental neurotoxicity, and lateral stripe hypopigmentation in non-exposed F1 embryos and larvae."

prozac increases progesterone and allopregnanolone

 

[ShotTrue]

Are all antidepressants like a posion? I’m asking it in wrong place, I know, but I need something to ease me right now.

I have already serious neurological side effects from 20 days fluoxetine usage, but I’m not sure if all the antidepressants will make me even worse.

Too big of a question for me to answer, but ssri's seem that way. Upping natural dopamine may be a better way of feeling better