Do delusions have therapeutic value?

This 2019 UK review discussed delusions, aka false beliefs about reality:

“Delusions are characterized by their behavioral manifestations and defined as irrational beliefs that compromise good functioning. In this overview paper, we ask whether delusions can be adaptive notwithstanding their negative features.

We consider different types of delusions and different ways in which they can be considered as adaptive: psychologically (e.g., by increasing wellbeing, purpose in life, intrapsychic coherence, or good functioning) and biologically (e.g., by enhancing genetic fitness).”


1) Although the review section 4 heading was Biological Adaptiveness of Delusions, the reviewers never got around to discussing the evolved roles of brain areas. One mention of evolutionary biology was:

“Delusions are biologically adaptive if, as a response to a crisis of some sort (anomalous perception or overwhelming distress), they enhance a person’s chances of reproductive success and survival by conferring systematic biological benefits.”

2) Although section 5’s heading was Psychological Adaptiveness of Delusions, the reviewers didn’t connect feelings and survival sensations as origins of beliefs (delusions) and behaviors. They had a few examples of feelings:

“Delusions of reference and delusions of grandeur can make the person feel important and worthy of admiration.”

and occasionally sniffed a clue:

“Some delusions (especially so‐called motivated delusions) play a defensive function, representing the world as the person would like it to be.”

where “motivated delusions” were later deemed in the Conclusion section to be a:

“Response to negative emotions that could otherwise become overwhelming.”

3) Feelings weren’t extensively discussed until section 6 Delusions in OCD and MDD, which gave readers the impression that feelings were best associated with those diseases.

4) In the Introduction, sections 4, 5, and 7 How Do We Establish and Measure Adaptiveness, the reviewers discussed feeling meaning in life, but without understanding:

  1. Feelings = meaning in life, as I quoted Dr. Arthur Janov in The pain societies instill into children:

    “Without feeling, life becomes empty and sterile. It, above all, loses its meaning.

  2. Beliefs (delusions) defend against feelings.
  3. Consequentially, the stronger and more numerous beliefs (delusions) a person has, the less they feel meaning in life.

5) Where, when, why, and how do beliefs (delusions) arise? Where, when, why, and how does a person sense and feel, and what are the connections with beliefs (delusions)?

The word “sense” was used 29 times in contexts such as “make sense” and “sense of [anxiety, coherence, control, meaning, purpose, rational agency, reality, self, uncertainty]” but no framework connected biological sensing to delusions. Papers from other fields have detailed cause-and-effect explanations and diagrams for every step of precursor-successor processes.


Regarding the therapeutic value of someone else’s opinion of a patient’s delusions – I’ll reuse this quotation from the Scientific evidence page of Dr. Janov’s 2011 book “Life Before Birth: The Hidden Script that Rules Our Lives” p.166:

“Primal Therapy differs from other forms of treatment in that the patient is himself a therapist of sorts. Equipped with the insights of his history, he learns how to access himself and how to feel.

The therapist does not heal him; the therapist is only the catalyst allowing the healing forces to take place. The patient has the power to heal himself.

Another way Dr. Janov wrote this was on p.58 of his 2016 book Beyond Belief as quoted in Beyond Belief: The impact of merciless beatings on beliefs:

No one has the answer to life’s questions but you. How you should lead your life depends on you, not outside counsel.

We do not direct patients, nor dispense wisdom upon them. We have only to put them in touch with themselves; the rest is up to them.

Everything the patient has to learn already resides inside. The patient can make herself conscious. No one else can.”

https://onlinelibrary.wiley.com/doi/full/10.1002/wcs.1502 “Are clinical delusions adaptive?”

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Non-emotional memories

This 2019 US review covered memory mechanisms:

“With memory encoding reliant on persistent changes in the properties of synapses, a key question is how can memories be maintained from days to months or a lifetime given molecular turnover? It is likely that positive feedback loops are necessary to persistently maintain the strength of synapses that participate in encoding.

These levels are not isolated, but linked by shared components of feedback loops.”


Despite the review’s exhaustive discussion, the reviewers never came to the point. The word cloud I made of the review’s most frequent thirty words had little to do with why memory occurs.

Why do some stimuli evoke a memory in response? Why are almost all of the stimuli an organism receives not remembered?

Much of the discussion was baseless because it excluded emotion. Many of the citations’ memory findings relied on emotion, though. For example, in the subsection Roles of persistent epigenetic modifications for maintaining LTF [long-term facilitation], LTP [long-term potentiation], and LTM [long-term memory]:

  • Histone acetylation is increased after fear conditioning in the hippocampus and amygdala.
  • Correspondingly, inhibition of histone deacetylase enhances fear conditioning and LTP.
  • Following fear conditioning, histone phosphorylation is also increased.
  • DNA methylation is also up-regulated in the hippocampus and amygdala after fear conditioning, and inhibition of DNA methylation blocks fear LTM.”

http://learnmem.cshlp.org/content/26/5/133.full “How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory”

Our brains are shaped by our early environments

This 2019 McGill paper reviewed human and animal studies on brain-shaping influences from the fetal period through childhood:

“In neonates, regions of the methylome that are highly variable across individuals are explained by the genotype alone in 25 percent of cases. The best explanation for 75 percent of variably methylated regions is the interaction of genotype with different in utero environments.

A meta-analysis including 45,821 individuals with attention-deficit/hyperactivity disorder and 9,207,363 controls suggests that conditions such as preeclampsia, Apgar score lower than 7 at 5 minutes, breech/transverse presentations, and prolapsed/nuchal cord – all of which involve some sort of poor oxygenation during delivery – are significantly associated with attention-deficit/hyperactivity disorder. The dopaminergic system seems to be one of the brain systems most affected by perinatal hypoxia-ischemia.

Exposure to childhood trauma activates the stress response systems and dysregulates serotonin transmission that can adversely impact brain development. Smaller cerebral, cerebellar, prefrontal cortex, and corpus callosum volumes were reported in maltreated young people as well as reduced hippocampal activity.

Environmental enrichment has a series of beneficial effects associated with neuroplasticity mechanisms, increasing hippocampal volume, and enhancing dorsal dentate gyrus-specific differences in gene expression. Environmental enrichment after prenatal stress decreases depressive-like behaviors and fear, and improves cognitive deficits.”


The reviewers presented strong evidence until the Possible Factors for Reversibility section, which ended with the assertion:

“All these positive environmental experiences mentioned in this section could counterbalance the detrimental effects of early life adversities, making individuals resilient to brain alterations and development of later psychopathology.”

The review’s penultimate sentence recognized that research is seldom done on direct treatments of causes:

“The cross-sectional nature of most epigenetic studies and the tissue specificity of the epigenetic changes are still challenges.”

Cross-sectional studies won’t provide definitive data on cause-and-effect relationships.

The question that remains to be examined is: How can humans best address these early-life causes to ameliorate their lifelong effects?

https://onlinelibrary.wiley.com/doi/full/10.1111/dmcn.14182 “Early environmental influences on the development of children’s brain structure and function” (not freely available)

A therapy to reverse cognitive decline

This 2018 human study presented the results of 100 patients’ personalized therapies for cognitive decline:

“The first examples of reversal of cognitive decline in Alzheimer’s disease and the pre-Alzheimer’s disease conditions MCI (Mild Cognitive Impairment) and SCI (Subjective Cognitive Impairment) have recently been published..showing sustained subjective and objective improvement in cognition, using a comprehensive, precision medicine approach that involves determining the potential contributors to the cognitive decline (e.g., activation of the innate immune system by pathogens or intestinal permeability, reduction in trophic or hormonal support, specific toxin exposure, or other contributors), using a computer-based algorithm to determine subtype and then addressing each contributor using a personalized, targeted, multi-factorial approach dubbed ReCODE for reversal of cognitive decline.

An obvious criticism of the initial studies is the small number of patients reported. Therefore, we report here 100 patients, treated by several different physicians, with documented improvement in cognition, in some cases with documentation of improvement in electrophysiology or imaging, as well.”

https://www.omicsonline.org/open-access/reversal-of-cognitive-decline-100-patients-2161-0460-1000450-105387.html “Reversal of Cognitive Decline: 100 Patients”


The lead author commented on Josh Mitteldorf’s informative post A cure for Alzheimer’s? Yes, a cure for Alzheimer’s!:

  1. “We have a paper in press, due to appear 10.22.18 (open access, JADP, I’ll send a copy as soon as available), showing 100 patients with documented improvement – some with MRI volumetrics improved, others with quantitative EEG improvements, others with evoked response improvements, and all with quantitative cognitive assessment improvement. Some are very striking – 12 point improvements in MoCA, for example – others less so, but all also have subjective improvement. Hopefully this will address some of the criticisms that we haven’t documented improvement in enough people.
  2. We were just turned down again for a randomized, controlled clinical trial, so on the one hand, we are told repeatedly that no one will believe that this approach works until we publish a randomized, controlled study, and on the other hand, we’ve been turned down (first in 2011/12, and now in 2018), with the complaint that we are trying to address more than one variable in the trial (as if AD is a single-variable disease!). Something of a catch-22. We are now resubmitting (unfortunately, the IRBs are not populated by functional medicine physicians, so they are used to seeing old-fashioned drug studies), and we’ll see what happens.
  3. I’ve been extending the studies to other neurodegenerative diseases, and it has been impressive how much of a programmatic response there seems to be in these “diseases.”
  4. I agree with you that there are many features in common with aging itself.
  5. You made a good point that APP is a dependence receptor, and in fact it functions as an integrating dependence receptor, responding to numerous inputs (Kurakin and Bredesen, 2015).
  6. In the book and the publications, we don’t claim it is a “cure” since we don’t have pathological evidence that the disease process is gone. What we claim is “reversal of cognitive decline” since that is what we document.
  7. As I mentioned in the book, AD is turning out to be a protective response to multiple insults, and this fits well with the finding that Abeta has an antimicrobial effect (Moir and Tanzi’s work). It is a network-downsizing, protective response, which is quite effective – some people live with the ongoing degenerative process for decades.
  8. We have seen several cases now in which a clinical trial of an anti-amyloid antibody made the person much worse in a time-dependent manner (each time there was an injection, the person would get much worse for 5-10 days, then begin to improve back toward where he/she was, but over time, marked decline occurred), and this makes sense for the idea that the amyloid is actually protecting against pathogens or toxins or some other insult.
  9. It is important to note that we’ve never claimed that all people get better – this is not what we’ve seen. People very late in the process, or who don’t follow the protocol, or who don’t address the various insults, do not improve. It is also turning out to be practitioner dependent – some are getting the vast majority of people to improve, others very few, so this is more like surgery than old-fashioned prescriptive medicine – you have to do a somewhat complicated therapeutic algorithm and get it right for best results.
  10. I’m very interested in what is needed to take the next step in people who have shown improvement but who started late in the course. For example, we have people now who have increased MoCA from 0 to 9 (or 0 to 3, etc.), with marked subjective improvement but plateauing at less than normal. These people had extensive synaptic and cellular loss prior to the program. So what do we need to raise the plateau? Stem cells? Intranasal trophic support? Something else?
  11. I haven’t yet seen a mono-etiologic theory of AD or a mono-therapeutic approach that has repeatedly positive results, so although I understand that there are many theories and treatments, there doesn’t seem to be one etiology to the disease, nor does there seem to be one simple treatment that works for most. It is much more like a network failure.”

At a specific level:

  • “There doesn’t seem to be one etiology to the disease,
  • nor does there seem to be one simple treatment that works for most.
  • We don’t have pathological evidence that the disease process is gone.”

For general concepts, however:

  • “AD is turning out to be a protective response to multiple insults,
  • It is a network-downsizing, protective response, which is quite effective.
  • The amyloid is actually protecting against pathogens or toxins or some other insult.”

For a framework of an AD cure to be valid, each source of each insult that evoked each “protective response” should be traced.

Longitudinal studies would be preferred inside this framework. These study designs would investigate evidence of each insult’s potential modifying effect on each “protective response” that could affect the cumulative disease trajectory of each individual.

In many cases, existing study designs would be adequate if they extended their periods to the end of the subjects’ natural lifetimes. One AD-relevant example would be extending the prenatally-restraint-stressed model used in:

The framework would also encourage extending studies to at least three generations to investigate evidence for transgenerational effects, as were found in:

An hour of the epigenetic clock

This 2018 presentation by the founder of the epigenetic clock method described the state of the art up through July 2018. The webinar was given on the release day of The epigenetic clock now includes skin study.


Segments before the half-hour mark provide an introduction to the method and several details about the concurrently-released study. The Q&A section starts a little before the hour mark.

Fear of feeling?

Here’s a 2018 article from two researchers involved in the Dunedin (New Zealand) Longitudinal Study. They coauthored many studies, including People had the same personalities at age 26 that they had at age 3.

The paper’s grand hypothesis was:

“A single dimension is able to measure a person’s liability to mental disorder, comorbidity among disorders, persistence of disorders over time, and severity of symptoms.”

The coauthors partially based this on:

“Repeated diagnostic interviews carried out over 25 years, when the research participants were 11, 13, 15, 18, 21, 26, 32, and 38 years old, and include information about seven diagnostic groups: anxiety, depression, attention deficit hyperactivity disorder, conduct disorder, substance dependence, bipolar disorder, and schizophrenia.”


https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2018.17121383 “All for One and One for All: Mental Disorders in One Dimension” (not freely available)


More about the coauthors:

Two psychologists followed 1000 New Zealanders for decades. Here’s what they found about how childhood shapes later life

“Dunedin and other studies show that most people have at least one episode of mental illness during their lifetime.”


What compels people to manufacture “universal” truths? Is this a poor substitute for feeling and understanding historical, factual, personal truths?

What if the price we pay for avoiding and pressuring down our feelings is: A wasted life?

What if the grand hypothesis worth proving is: For one’s life to have meaning, each individual has to regain their feelings?

Fitting data

Let’s start out the new year with a repost of a cautionary reminder:

“Both “predict and “explain” imply that investigators have uncovered a reliable structure to phenomena, the latter involving hypotheses describing unseen mechanisms, leading to a new ability to control events and produce formerly unpredicted/unpredictable outcomes. This is clearly not a fair description of post hoc correlation-fishing.

The current publication system almost forces authors to make causal statements using filler verbs (e.g. to drive, alter, promote) as a form of storytelling (Gomez-Marin, 2017); without such a statement they are often accused of just collecting meaningless facts.”

https://mythsofvisionscience.wordpress.com/2018/12/30/neuroscience-newspeak-or-how-to-publish-meaningless-facts/ “Neuroscience Newspeak, Or How to Publish Meaningless Facts”