The Clinical Practitioner

NAPPP

The Clinical Practitioner

© 2021 National Association of Professional Psychological Providers TCP Online ISSN 2373-July 2021 Volume 16 No. 7

Mysterious Brain Disorder Spreading In America

By John Caccavale, Ph.D. ABMP

A mysterious brain disorder has been working its way through a significant portion of the population. Although dispersed across the country and can be found in every state, there are regions where this disorder is more highly concentrated. The disorder is afflicting people without regard to gender, age, and ethnicity although there is a clear racial demarcation preset as Caucasians appear to be experiencing the disorder at significantly higher rates than other racial groups. Some surveys estimate that that, overall, about 30% of the adult population may afflicted with this disorder.

At first it was thought that the disorder might have been related to COVID-19, however, there are reports that symptoms have been appearing all over the country since at least 2015. What’s concerning about this disorder is that many experts believe that there is no cure on the horizon. In fact, the spread might become more of a health problem than COVID or any of the other debilitating health problems that have been seen over the past 60 years. For psychologists and first mental health responders, this is particularly worrisome because, if the experts and functional MRIs are correct, there may be no interventions that can successfully address this spreading epidemic. So, what are the symptoms of this disease and what is it called? This appears to be the $64 dollar questions.

Common Symptoms of Those Afflicted With Morologus Es

Although experts have not settled on a particular name for this mysterious disorder, most refer to it by its Latin name - its meaning will become clearer. Even as the precise origin of the disorder is not completely known, symptoms, which include both auditory and visual hallucinations, lack of reality testing, rage, paranoia, inability to make decisions based on facts, and a host of other important functions related to cognitive functioning, have been located in a major part of the brain.

The Clinical Practitioner

July 2021 Vol. 16 No. 7

Contents:

Mysterious brain disorder

by John Caccavale Pg. 1 FDA News Pg. 4 FDA News Pg. 6 Drug News Pg. 9 Alternative Approaches Pg. 10 Behavioral News by Levon Margolin Pg. 13 CE questions By Gary Traub Pg. 17 Free CE Course List Pg. 18

Editor-In-Chief David Reinhardt Ph.D. Editors Sharna Wood, Ph.D. Gary Traub, Ph.D. Levon Margolin, Ph.D. Past Issues http://na ppp.org/backissues.html Submissions Editor.TheClinicalPractitioner@gmail. com

NAPPP on the Web

www.NAPPP.org

NAPPP Executive Board John Caccavale, Ph.D.

Jerry Morris, Psy.D. David Reinhardt, Ph.D.

Sharna Wood Ph.D. Cheri Surloff Ph.D. Keith Petrosky, Ph.D NAPPP Advisory Board

Ward Lawson, Ph.D.

To get a clearer picture of the range of the debilitating symptoms of this mysterious disorder, real life examples of how these symptoms are impacting the daily lives of those afflicted, and those who come in contact with them, will demonstrate the importance to professional psychologists. Medical experts have given up on trying to find a cure or something that could halt the progression of the disorder, however, as of yet, there are no medications that have proved effective. Ordinary psychotropic medications have failed and at least one surgical procedure has been outlawed. Electro-shock therapy would likely fail because the number of machines just aren’t available and it’s also unlikely that people afflicted with the disorder would agree to be treated. This is why it will fall to psychology practitioners to try to find some intervention, if not for the afflicted but for those affected by them.

The Shared Hallucinations of Those Afflicted With Morologus Es

While there are many forms of the hallucinations those afflicted with Morologus Es seem to believe in, the most disturbing aspect of the disorder is that these hallucinations are not contained only to specific individuals. They are shared hallucinations that are consistent and pronounced by the afflicted word for word. For example, the following is only a short list of the more disturbing shared hallucinations. The list is short because almost daily new ones seem to appear and added to the list. Some hallucinations also are transformed into extended versions of previous ones.

1. There is a pizza parlor in Brooklyn, New York where Hilary Clinton is holding kidnapped children where they are subsequently defiled by pedophiles and then eaten to get rid of the evidence. An extended version of this hallucination is that the children are subjected to fear to raise their epinephrine levels to be collected and used to make the pedophiles, who are all Democrats, strong and powerful. In essence, Democrats are a cabal of Satanic, cannibalistic pedophiles, who run a global child sex trafficking ring, and

conspired against former President Donald Trump throughout his presidency.

2. Vaccinations to protect against COVID-19, and perhaps all vaccines, contain microchips so that the government can track individual movements and change people’s brains. An extended version of this hallucination is that the vaccine contains particles that magnetizes the recipient of the vaccine. (This is different from those who object to vaccines on religious grounds or other health reason.)

The Crisis in Clinical Psychopharmacology II

researchers. One common missive that the afflicted believe in is that Princess Diana was murdered after trying to stop the September 11 attacks.

4. The 2020 national election was stolen from Donald Trump. This hallucination has many extensions. Italian hackers used satellites to then hack into voting machines and changed votes from Trump to Biden. The Chinese, late at night and under cover of dark, dumped hundreds of thousands of votes in key cities for Biden. The proof is that there are bamboo fibers in the illegal mail ballots. In August 2021, Trump will be reinstated as president. 5. There are no mass shootings and murders. It’s all a hoax by the government to take away guns from patriots.

6. Donald Trump is the most honest and moral president ever and sent from God to restore the rightful to their rightful place. Guess who are the rightful.

Now The Serious Part

I think that these limited examples provide a glimpse into the extent of the problem.

As a psychologist, people demonstrating beliefs in these ridiculous whatevers worry me. A good number have demonstrated a tendency for violence and rage. As a citizen, I am more than concerned. As a human being, I try to have empathy but find that there appears to be no workable solution to address many of these people. Clearly, simply being ignorant and believing in crazy stuff is not alarming, nor does it mean that everyone who believes in such banter is abnormal. Or, at least, should not be. However, as these shared hallucinations grow, become extended, and enabled by those who hate, manipulate, and capitalize on the most afflicted among them, we should all be concerned.

A recent email that I received from someone who was sent a post from our listserv stated: “Oh, and yes, we will take our country back by any means necessary.”

For example, I don’t think that the things I write

about in the TCP are extreme or particularly outrageous. Yet, I continue to get the vilest and threatening emails from people who do not like some the subjects I write about. This article is not likely to be a favorite. This has prompted me to believe that the threatening emails I keep getting from people, who are sent posts and articles from the TCP by psychologists on our listserv, are more a function of their clinical presentation than their politics. Their politics appears to be a convenient way to socially rationalize their disorder. I also do not think that I am the only psychologist or citizen to be concerned about people who rely on anything told to them or comes into their head and then acts on lies and deceptions. It is the potential for violence that concerns me most, and unfortunately, there are people who believe that vast numbers of us should be eliminated by any means necessary. Where have we heard and seen this before?

Biden urged not to give top FDA job to official over her role in opioid crisis

Groups fighting the US opioid epidemic have called on Joe Biden to appoint a new head of the Food and Drug Administration (FDA) after describing the acting commissioner as unfit for the post because of her part in the mass prescribing of painkillers that have caused hundreds of thousands of deaths.

In a letter to the administration, 28 groups accused Dr Janet Woodcock of presiding over “one of the worst regulatory agency failures in US history” as head of the FDA department responsible for approving new prescription opioids, the Center for Drug Evaluation and Research (CDER).

Drug makers conspired to worsen the opioid crisis. They have blood on their hands.

Woodcock was named acting FDA commissioner by the new administration on the day Biden took office. The letter urged the president not to nominate her to permanently head the agency.

“In its opioid decision-making, Dr Woodcock, and the division she supervised, consistently put the interests of opioid manufacturers ahead of public health, often overruling its own scientific advisors and ignoring the pleas of public health groups, state Attorneys General, and outraged victims of the opioid crisis,” the letter said.

The signatories of the letter include the medical group Physicians for Responsible Opioid Prescribing, the consumer advocacy organisation Public Citizen, and campaign groups representing families harmed by opioids such as Fed Up!.

The letter accused Woodcock of “dereliction of duty” for allowing opioid manufacturers to spend years disseminating false claims that narcotic painkillers were less addictive and more effective than they really were, contributing to the rise of mass opioid prescribing and spread of an epidemic that has claimed more than 500,000 lives.

“Recent reports that the pharmaceutical industry enthusiastically supports Dr Woodcock’s candidacy for FDA Commissioner do not surprise us,” the letter said. “We strongly urge that her position as Acting

Commissioner be a very short transition prior to

President Joe Biden nominating a Commissioner who has a track record focused on public health.”

Two US senators who have previously criticised the FDA’s handling of opioids, Ed Markey and Maggie Hassan, backed the call for a different person to head the agency.

“The FDA’s decision-making processes for the approval and labelling of opioid drugs going back decades remain of serious concern, and it’s important that the next FDA Commissioner is someone who has demonstrated that they have learned from the FDA’s past mistakes – not someone who has been involved in repeating them,” they said in a joint statement.

It is not clear whether Biden intends to nominate Woodcock to head the FDA permanently.

The criticism comes at a sensitive time for the FDA after its credibility was shaken by political interference by Donald Trump over coronavirus. But the agency was already facing accusations that it was less interested in regulating opioid manufacturers than protecting their financial interests.

The FDA helped unleash the epidemic two decades ago when it approved the sale of a high-strength narcotic pill, OxyContin, as safer and more effective than other painkillers based on the false claims of the manufacturer, Purdue Pharma. Since then the agency has approved other opioids for wide prescribing even as the evidence mounted that the drugs were addictive, open to abuse and often not effective for long-term use. The FDA was also embarrassed by revelations that officials responsible for opioid approvals were taking part in “pay to play” schemes where manufacturers paid tens of thousands of dollars to attend meetings to draw up the criteria for approving prescription narcotics.

In 2017, President Trump’s opioid commission identified the failure of the FDA and other federal institutions to properly regulate opioids as an important factor in the rise of the epidemic. The letter noted that Woodcock was instrumental in the approval of a powerful opioid, Zohydro, even though the FDA’s own scientific advisory committee voted 11-2 to keep the drug off the market because it was unsafe. The FDA leadership has the authority to

override the decisions of its advisory committees. Dr Raeford Brown, a former chair of the FDA’s opioid advisory committee, described Woodcock as a very able administrator who played an important role in maintaining continuity at the agency when commissioners changed with each new administration. But he said the part she played in unleashing

prescription opioids into America without sufficient controls or oversight made her “unfit” to head the FDA. “The way the whole issue of opioids played out, and the development of policy in CDER, was clearly a cause of the opioid crisis because there was a wilful blindness. “They didn’t want to see that the things they were doing were causing the problem. She was in charge of that. She more than anybody should be held accountable. I’m shocked she hasn’t been held accountable,” said Brown.

“She chose to support the pharmaceutical industry and neglect the public health issues.”

https://www.theguardian.com/us-news/2021/jan/28/ fda-janet-woodcock-opioids-biden

FDA Leader Explains Rationale Leading to Controversial Alzheimer’s Drug Approval The US Food and Drug Administration (FDA) has provided a detailed and documented account of how it arrived at its decision to approve the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen/ Eisai), including the release of several internal

documents...Since the drug was approved, three of the advisory committee’s members resigned in protest. In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the US Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD. In its letter, the group noted that the FDA’s decision “showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

In today’s letter, the CDER director noted, “this was

one of the most complex applications in recent history” and admitted that deliberations were lengthy and difficult.

“It’s also not surprising, in fact it was to be expected, that there would be different viewpoints about the data, including dissenting opinions about the approval decision,” Cavazzoni wrote.

However, this “is what scientific debate is all about; and while difficult at times, it should be celebrated,” she added. “Please know that every opinion was heard, and the approval is a direct reflection of this open and robust scientific and regulatory debate.”

“The remaining scientific review documents in the Aduhelm action package are not yet available, but will be made available to the public as soon as the internal process of review and redaction is complete,” the FDA noted on its site.

In the document, FDA’s Decision to Approve New Treatment for Alzheimer’s Disease, Cavazzoni noted that the “highly complex” data included in the submission package for the drug “left residual uncertainties regarding clinical benefit.”

However, after listening to the patient community and reviewing all the data, the FDA chose to use the Accelerated Approval pathway, deciding that the potential benefit to patients outweighed the drug’s risks.

Of two phase 3 trials, only one met its primary endpoint. However, in all trials, including earlier studies, “Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion,” Cavazzoni wrote. “It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” she added. Medscape June 23, 2021

Dr. Reinhardt: Several trials of other chemicals that dissolve plaques have been conducted. All resulted in a worsening if dementia symptoms. That science is dead end. Even though all members of the advisory commttee voted it down, the decision to approve was based on the volume of the “paient community.” This same reasoning has been used in the past to promote a flat earth, the sun revolving about the earth,

using ace water baths for schizophrenia and drilling holes in the skull to release evil spirits. Apparently psychiatric science has not reached the age of reason. Commenting on medscape’s report, Dante Marciani summarized the science: “The problem is not with the amyloid-beta, but how scientists interpret it. Amyloid is a normal protein with unique roles, but amyloid can suffer structural changes to form aberrant toxic oligomers which trigger damages in neural cells, leading to their death. This was shown over 20 years ago. Plaque is actually a protection mechanism, that by trapping and immobilizing the toxic amyloid oligomers, protects against them. Indeed, autopsies of cognitively normal people over 70 years old, shows that many of them have plaque with no mental problems. It also has been shown that antibodies against plaque, good or bad, solubilize plaque, i.e., reduces it by freeing toxic oligomers. The results are increasing cell death. That antibodies against the toxic oligomeric amyloid protects against neural degeneration, has been shown using animal models, where those antibodies isolated from human IVIG preparations. Also, that transfer of those oligomers to brains of normal nonhuman primates result in the neurodegeneration, shows that they are the causative agents for Alzheimer’s disease. Also, it is well known that families with specific mutations in amyloid, develop the disease at a very early age. The problem is that practically all of the past failed studies focused on either the normal amyloid or the plaques, ignoring the actual pathological agents: the amyloid beta oligomers. Thus, in my opinion the problem is not with the science behind amyloid, but with the scientists working in this disease. Looking for other alternatives, reminds me of Aesop gable, about the fox and the grapes.

Shawn OBrian found, “It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” The amyloid hypothesis is, so far, based solely on correlation. That correlation seems to be less strong than previously thought, now that we’re studying the brains of cognitively intact older people that have amyloid plaques. My money, for what it’s worth, is that amyloid is not the ultimate cause of Alzheimer’s, and drugs such as this are likely to do more harm than good. Maybe it’s actually good that its price tag is far out of reach for most people. In place of the fruitless amyloid hypothesis, I think more research money should be spent in two other

areas: 1) Infection, trauma and pollution - beta amyloid deposition is“downstream” in terms of causation; a wide range of insults lead to neuronal cell death and amyloid deposition is a consequence of cell death, not its cause. (1st link) 2) Cerebral insulin resistance and mitochondrial dysfunction are important contributors to pathogenesis and support the hypothesis that cerebral fructose metabolism is a key initiating pathway for Alzheimer’s disease. (2nd link) Ultimately there may be numerous initiators of the Alzheimer’s process if the “downstream” theory of amyloid deposition is accurate, and it’s a result of cell injury, and not the cause. It’s time to listen to Einstein (do something different if you want to avoid getting the same ineffective results).”

Rob Jacobs asked, “What needs to be redacted from a scientific review document?”

Why indeed?

Dementia News

Lipophilic statin use linked to increased risk of dementia

In patients with mild cognitive impairment, taking lipophilic statins more than doubles their risk of developing dementia compared to those who do not take statins. According to research presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting, positron emission tomography (PET) scans of lipophilic statin users revealed a highly significant decline in metabolism in the area of the brain that is first impacted by Alzheimer’s disease. Statins are medications used to lower cholesterol and reduce the risk of heart attack or stroke. They are the most commonly used drugs in the developed world, and nearly 50 percent of Americans over age 75 use a statin. Different types of statins are available based on a patient’s health needs, including hydrophilic statins that focus on the liver and lipophilic statins that are distributed to tissues throughout the body.

Abstract 102. “Lipophilic Statins in Subjects with Early Mild Cognitive Impairment: Associations with Conversion to Dementia and Decline in

Posterior Cingulate Brain Metabolism in a Long-term Prospective Longitudinal Multi-Center Study,” Prasanna Padmanabham, Stephen Liu and Daniel Silverman, University of California, Los Angeles, Los Angeles, California. Reported in medicalXpress 6/15/21

Dr. Reinhardt: Lipophilic statins include atorvastatin, simvastatin, lovastatin, fluvastatin, cerivastatin and pitavastatin, while hydrophilic statins include rosuvastatin and pravastatin. Clinical benefits of statins have so far proven elusive.

Better alternatives to aducanumab

A recent medscape/Google poll of physicians’ views on the fake drug aducanumab garnered some interesting comments on known substances that are bebneficial in dementia.

In regards to Dr. Charmichael’s comment “Baicalein has already been shown to have these properties and has been / is being used successfully to recover memory and cognition.” Baicalein, In traditional Chinese medicine this herb (known as Ban Zhi Lian, Scutellaria baicalensis, or Baikal skullcap), no human trials have been published, other than case studies and many rat studies but with multiple millenia of experiential evidence. “Studies showed that baicalein possesses a range of key pharmacological properties, such as reducing oxidative stress, anti-inflammatory properties, inhibiting aggregation of

disease-specific amyloid proteins, inhibiting excitotoxicity, stimulating neurogenesis and differentiation action, and anti-apoptosis effects. Based on these properties, baicalein shows therapeutic potential for Alzheimer’s disease and Parkinson’s disease.” (CNS Drugs. 2017 Aug;31(8):639-652. doi: 10.1007/s40263-017-0451-y. Dr. Reinhardt: Mild side effects (which can be

therapeutically useful versus pharmaceutical

treatments) include lowering of blood sugar, lowering of blood pressure, and slowing of blood clotting. Monitor and reduce dependence on destructive pharmaceutics as appropriate.

This herb is widely used in non-US healthcare. It is inexpensive (about $10 per month) and very safe.

Several commenters suggested low dose lithium treatment. Lithium has been shown in multiple studies to reduce incidence of dementia in bipolar patients. Low dose lithium in drinking water has been shown to be effective as well. “ Results from animal and human studies suggest that lithium in therapeutic doses may improve learning and memory and modify the risk of developing dementia. Additional preliminary studies suggest that subtherapeutic levels, including microlevels of lithium, may influence human cognition.” (JAMA Psychiatry . 2017 Oct 1;74(10):1005-1010. doi: 10.1001/jamapsychiatry.2017.2362.) The study had 74K dementia subjects and 734K controls, and found that those with lower lithium levels had higher incidence of dementia (p=.001)

Lithium is a naturally occurring element with

overwhelming evidence that it is essential for health. Few studies have been published on microlevels, and none have been published comparing the effectiveness of a 5 mg dose of lithium versus the potentially deadly 600-1200 mg doses used by “modern” medicine. I believe several studies have been conducted but the results not published as they would not support the pharmaceutical, lab testing and psychiatric visits that are required with today’s use. Low dose lithium has been used for over 2 centuries in the US for symptoms including depression, schizophrenia, ADHD, dementia, migraines and cluster headaches, insomnia, stress and pain. 5 mg lithium orotate or aspartate is adverse side effect free and inexpensive- less than $7.00 per month.

Large-scale plasma proteomic profiling

identifies a high-performance biomarker panel for Alzheimer’s disease screening and staging Blood proteins are emerging as candidate biomarkers for Alzheimer’s disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD.

We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of

AD.

We identified 429 proteins that were dysregulated in AD plasma. We selected 19 “hub proteins”

representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690– 0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages.

This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging.

Alzheimer’s & Dementia, 2021; DOI: 10.1002/ alz.12369

Dr. Reinhardt: This testing development may help cognitively impaired people plan their futures,

although it may be of little clinical usefulness. It seems to correctly identify the protein fragments that are associated with Alzheimers, similar to finding burned wood after a fire does little to help determine the cause of that fire. There are several known causes of dementia, including iron overload, zinc deficiency, glycine deficiency, folate deficiency and B12 deficiency, as well as blood vessel leakage in the brain. We

already have tests for these issues although they are seldom used. Still, if chemical research could find its way past trying to block natural processes such as the sequestering of nerve damaging substances by dissolving plaques, we might be able to find the actual causes of dementias through an additive approach, supporting the immune system.

Read on:

High cerebrospinal amyloid-ß 42 is associated with normal cognition in individuals with brain amyloidosis

The UC-led study, conducted in collaboration with the Karolinska Institute in Sweden, claims that the treatment of Alzheimer’s disease might lie in normalizing the levels of a specific brain protein called amyloid-beta peptide. This protein is needed in its original, soluble form to keep the brain healthy, but

sometimes it hardens into “brain stones” or clumps, called amyloid plaques.

“It’s not the plaques that are causing impaired cognition,’’ says Alberto Espay, the new study’s senior author and professor of neurology at UC. “Amyloid plaques are a consequence, not a cause,” of Alzheimer’s disease, says Espay, who is also a member of the UC Gardner Neuroscience Institute.

Espay says that scientists have focused on treatments to eliminate the plaques. But the UC team, he says, saw it differently: Cognitive impairment could be due to a decline in soluble amyloid-beta peptide instead of the corresponding accumulation of amyloid plaques. To test their hypothesis, they analyzed the brain scans and spinal fluid from 600 individuals enrolled in the Alzheimer’s Disease Neuroimaging Initiative study, who all had amyloid plaques. From there, they compared the amount of plaques and levels of the peptide in the individuals with normal cognition to those with cognitive impairment. They found that, regardless of the amount of plaques in the brain, the individuals with high levels of the peptide were cognitively normal.

They also found that higher levels of soluble amyloid-beta peptide were associated with a larger hippocampus, the area of the brain most important for memory.

According to the authors, as we age most people develop amyloid plaques, but few people develop dementia. In fact, by the age of 85, 60% of people will have these plaques, but only 10% develop dementia, they say.The most relevant future therapeutic approach for the Alzheimer’s program will be replenishing these brain soluble proteins to their normal levels, says Espay.

Brain amyloidosis does not invariably predict dementia. We hypothesized that high soluble 42-amino acid ß amyloid (Aß42) peptide levels are associated with normal cognition and hippocampal volume despite increasing brain amyloidosis. Higher soluble Aß42 levels were observed in NC ( amyloid-positive normal cognition) (864.00 pg/ml) than in MCI mild cognitive impairment) ( (768.60 pg/ml) or AD (617.46 pg/ml), with the relationship between NC, MCI, and AD maintained across all amyloid tertiles. In adjusted analysis, there was a

larger absolute effect size of soluble Aß42 than SUVR for NC (0.82 vs. 0.40) and MCI (0.60 vs. 0.26) versus AD. Each standard deviation increase in Aß42 was associated with greater odds of NC than AD (adjusted odds ratio, 6.26; p < 0.001) or MCI (1.42; p = 0.006). Higher soluble Aß42 levels were also associated with better neuropsychological function and larger hippocampal volume.

Conclusions: Normal cognition and hippocampal volume are associated with preservation of high soluble Aß42 levels despite increasing brain amyloidosis. The Lancet EClinicalMedicine Published:June 28, 2021DOI:https://doi.org/10.1016/j.

eclinm.2021.100988

Drug News

Anticholinergic Medication Burden–Associated Cognitive Impairment in Schizophrenia

Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients.

Cross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB). ACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling

for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage. Conclusions: Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes—including psychotropics used in usual care— should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.

American Journal of psychiatry Published

Online:14 May 2021 https://doi.org/10.1176/appi. ajp.2020.20081212

Dr. Reinhardt: The adverse effects for these drugs have been well documented, as have their lack of efficacy. Cochrane found only 9% of recipients had moderate or better improvement in delusions. FDA Okays New Drug Option for

Schizophrenia, Bipolar I Disorder

The US Food and Drug Administration (FDA) has approved a once-daily oral medication, which is a combination of olanzapine and samidorphan (Lybalvi, Alkermes), for the treatment of schizophrenia and bipolar I disorder.

The drug is approved for the treatment of adults with schizophrenia and for adults with bipolar I disorder, as a maintenance monotherapy or to treat acute manic or mixed episodes, as either monotherapy or an adjunct to lithium or valproate.

Medscape Medical News https://www.medscape. com/viewarticle/952177?src=WNL_mdpls_210604_ mscpedit_psych&uac=19361SY&spon=12&impID=342 0817&faf=1

Dr. Reinhardt: Samidorphan (SAM), a µ-opioid receptor antagonist, is structurally related to the mixed-opioid-receptor antagonist naltrexone. Combining the 2 chemicals may breath new life to olanzapine, now patent expired but reemerging as Lybalvi. It should be an easy sell given how poorly other antipsychotics fare in a cost/benefit analysis.

Association of Depressive Symptoms with Rapid Kidney Function Decline in Adults with Normal Kidney Function

Previous research has found a link between depressive symptoms and rapid kidney function decline in

patients with chronic kidney disease. We aimed to evaluate the prospective association between depressive symptoms and rapid decline in kidney function in Chinese adults with normal kidney function. A total of 4763 participants with eGFR=60 ml/min per 1.73 m2 at baseline were enrolled. Baseline depressive symptoms were determined using a ten-item Center for Epidemiologic Studies Depression scale with a cutoff score of greater than or equal to ten to define high depressive symptoms. The GFR was estimated by a combination of serum creatinine and cystatin C. The primary outcome was rapid decline in kidney function, defined as an annualized decline in eGFR of =5 ml/min per 1.73 m2. Secondary outcome was defined as an annualized decline in eGFR of =5 ml/min per 1.73 m2 and to a level of <60 ml/min per 1.73 m2 at the exit visit.

During a median follow-up of 4 year 260 participants developed rapid decline in kidney function. Overall, there was a significant positive association between baseline depressive symptoms and rapid decline in kidney function. Consistently, compared with participants with low depressive symptoms a significantly higher risk of rapid decline in kidney function was found among those with high depressive symptoms.

Conclusions: High depressive symptoms were significantly associated with a higher risk of rapid kidney function decline among Chinese adults with normal kidney function

“While our study does not show causality, it demonstrated that high depressive symptoms were significantly associated with rapid decline in kidney function among Chinese adults with normal kidney function. If further confirmed, our data provide some evidence for depressive symptom screening and effective psychosocial interventions to improve the prevention of CKD.”

At baseline, information on age, sex, smoking and drinking status (no or yes), living residence (rural or others), marital status, and educational level were

obtained from the questionnaires. Educational level was classified as illiteracy, literate, primary school, and middle school or above. Health-related factors included self-reported smoking and drinking status, self-reported physician-diagnosed diabetes and heart disease, and use of medications for diabetes

CJASN May 2021, CJN.18441120; DOI: https://doi. org/10.2215/CJN.18441120

Dr. Reinhardt: The researchers no doubt had good intentions, and revealed no link to chemical companies. However, this study continues the practice of trying to prove that various physical ailments are CAUSED by “Depression”.

Although supplemental material was not available for review, the authors state they excluded participants with a “psychiatric condition”: “ However, excluding participants with emotional, nervous, or psychiatric problems or use of related medications at baseline did not substantially change our findings.”Apparently depression was not considered to be one of these factors, or there would have been no participants. By extension, “anti”depressants for such depression would not be excluded. “... only four symptoms: bothered by things; had trouble concentrating; felt everything was an effort; and felt lonely were significantly associated with rapid kidney function decline.”

Is it possible that reduced kidney function results in irritability, brain fog, and fatigue? Ask any dialysis patient about this! Were those with severe depression on “anti”depressants excluded, which seems unlikely, and could these chemicals? Studies have found that ‘anti”depressants have no positive effect on

depression in non-dialysis kidney patients. Prescribing information for various “anti”depressants never mention effect on kidney function, and it is possible this has been under the radar in such studies.

Prenatal exposure to paracetamol associated with ADHD and autism symptoms in childhood An epidemiological study of more than 70,000

children in six European cohorts has linked symptoms of attention-deficit/hyperactivity disorder (ADHD) and

autism spectrum conditions (ASC) to the mothers’ use of paracetamol (acetaminophen) during pregnancy. The study, published in the European Journal of Epidemiology, was led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the “la Caixa” Foundation.

In total, the researchers analysed 73,881 children for whom data were available on prenatal or postnatal exposure to paracetamol, at least one symptom of ASC or ADHD, and main covariates. Depending on the cohort, 14% to 56% of the mothers reported taking paracetamol while pregnant.

The study found that children exposed to paracetamol before birth were 19% more likely to develop ASC symptoms and 21% more likely to develop ADHD symptoms than children who were not exposed.

“Our findings are consistent with previous research,” explained ISGlobal researcher Sílvia Alemany, lead author of the study. “We also found that prenatal exposure to paracetamol affects boys and girls in a similar way, as we observed practically no differences.” Alemany S, Avella-García C, Liew Z, García-Esteban R, Inoue K, Cadman T, López-Vicente M, González L, Riaño Galán I, Andiarena A, Casas M, Margetaki K, Strandberg-Larsen K, Lawlor DA, El-Marroun H, Tiemeier H, Iñiguez C, Tardón A, Santa-Marina L, Júlvez J, Porta D, Chatzi L, Sunyer J. Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and

hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts.

Prenatal and infant paracetamol exposure and development of asthma: the Norwegian Mother and Child Cohort Study

Paracetamol exposure has been positively associated with asthma development. We examined the

association of prenatal and infant (first 6 months) paracetamol exposure with asthma development while addressing confounding by indication.

There were independent modest associations

between asthma at 3 years with prenatal paracetamol

exposure (adj. RR 1.13; 95% CI: 1.02-1.25) and use of paracetamol during infancy (adj. RR 1.29; 95% CI: 1.16-1.45). The results were consistent for asthma at 7 years. The associations with prenatal paracetamol exposure were seen for different indications (pain, respiratory tract infections/influenza and fever). Maternal pain during pregnancy was the only indication that showed an association both with and without paracetamol use. Maternal paracetamol use outside pregnancy and paternal paracetamol use were not associated with asthma development. In a secondary analysis, prenatal ibuprofen exposure was positively associated with asthma at 3 years but not asthma at 7 years.

Conclusions: This study provides evidence that prenatal and infant paracetamol exposure have independent associations with asthma development. Magnus MC, Karlstad Ø, Håberg SE, Nafstad P, Davey Smith G, Nystad W. Prenatal and infant paracetamol exposure and development of asthma: the Norwegian Mother and Child Cohort Study. Int J Epidemiol. 2016 Apr;45(2):512-22. doi: 10.1093/ije/dyv366. Epub 2016 Feb 9. PMID: 26861478; PMCID: PMC5841883.

California considers declaring common pain killer carcinogen

State regulators have reviewed 133 studies about acetaminophen, all of which were published in peer-reviewed journals. Some studies reported an increased risk of some types of cancers, while others did not. Overall, the review noted acetaminophen has been difficult to examine because it is hard to isolate it from other variables that could contribute to cancer, such as smoking.

Acetaminophen/paracetamol: A history of errors, failures and false decisions

Acetaminophen/paracetamol is the most widely used drug of the world. At the same time, it is probably one of the most dangerous compounds in medical use, causing hundreds of deaths in all industrialized countries due to acute liver failure (ALF). The

history of the discovery of paracetamol starts with an

Alternative Approaches

error (active against worms), continues with a false assumption (paracetamol is safer than phenacetin), describes the first side-effect ‘epidemy’ (phenacetin nephropathy, drug-induced interstitial nephritis) and ends with the discovery of second-generation problems due to the unavoidable production of a highly toxic metabolite of paracetamol N-acetyl-p-benzoquinone imine (NAPQI) that may cause not only ALF and kidney damage but also impaired development of the fetus and the newborn child.

Dr. Reinhardt: Yet ads continue to tell us “4 out of 5 doctors recommend Tylonol”.

A drug from resin to combat epileptic seizures Synthetic resin acid derivatives selectively open the hKV7.2/7.3 channel and prevent epileptic seizures New molecules, developed by researchers at Linköping University, Sweden, have promising properties as possible drugs against epilepsy. A study published in the journal Epilepsia shows that several of the molecules have antiseizure effects.

Previous work by the research group at Linköping University has shown that resin acids, which are found in the resin from pine and spruce trees, can affect certain types of ion channel. The scientists used these natural resin acids as a starting point to develop new, similar molecules. The long-term goal is to create drugs that prevent epileptic seizures.

Epilepsia First published: 04 June 2021 https://doi.org/10.1111/epi.16932

Dr. Reinhardt: Once perfected and marketed, it will be one more example of a patentable chemical that was created from nature, in this case pine resin. “Modern” medicine seems to be a couple of millenia behind. Pine is used for upper and lower respiratory tract swelling (inflammation), stuffy nose, hoarseness, common cold, cough or bronchitis, fevers, tendency towards infection, and blood pressure problems. Some people apply pine directly to the skin for mild muscle pain and nerve pain. Early research suggests that taking vitamin C along with a specific product containing pine extract (Enzogenol) for 5 weeks improves thinking and

memory in middle-aged and older men.

Pine is used in Traditional Chinese Medicine ( He shou wu) to promote healthy aging and treat a variety of conditions, including diabetes, cancer, and heart disease.

Design of a Stable Cyclic Peptide Analgesic Derived from Sunflower Seeds that Targets the Opioid Receptor for the Treatment of Chronic Abdominal Pain

The rising opioid crisis has become a worldwide societal and public health burden, resulting from the abuse of prescription opioids. Targeting the opioid receptor (KOR) in the periphery has emerged as a powerful approach to develop novel pain medications without central side effects. Inspired by the traditional use of sunflower (Helianthus annuus) preparations for analgesic purposes, we developed novel stabilized KOR ligands (termed as helianorphins) by incorporating different dynorphin A sequence fragments into a cyclic sunflower peptide scaffold. As a result, helianorphin-19 selectively bound to and fully activated the KOR with nanomolar potency. Importantly, helianorphin-19 exhibited strong KOR-specific peripheral analgesic activity in a mouse model of chronic visceral pain, without inducing unwanted central effects on motor coordination/sedation. Our study provides a proof of principle that cyclic peptides from plants may be used as templates to develop potent and stable peptide analgesics applicable via enteric administration by targeting the peripheral KOR for the treatment of chronic abdominal pain.

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Here’s a sample of news stories from this past month:

Scientists discover a new class of memory cells in the brain @Medical_Xpress, Rockefeller University

Scientists have long searched in vain for a class of brain cells that could explain the visceral flash of recognition

that we feel when we see a very familiar face, like that of our grandmothers. But the proposed "grandmother

neuron"—a single cell at the crossroads of sensory perception and memory, capable of prioritizing an

important face over the rabble—remained elusive. Now, new research reveals a class of neurons in the brain's

temporal pole region that links face perception to long-term memory. It's not quite the apocryphal

grandmother neuron—rather than a single cell, it's a population of cells that collectively remembers

grandma's face. The findings, published in Science, are the first to explain how our brains inculcate the faces of

those we hold dear. "When I was coming up in neuroscience, if you wanted to ridicule someone's argument

you would dismiss it as 'just another grandmother neuron'—a hypothetical that could not exist," says Winrich

Freiwald, professor of neurosciences and behavior at The Rockefeller University. "Now, in an obscure and

understudied corner of the brain, we have found the closest thing to a grandmother neuron: cells capable of

linking face perception to memory." The idea of a grandmother neuron first showed up in the 1960s as a

theoretical brain cell that would code for a specific, complex concept, all by itself. One neuron for the memory

of one's grandmother, another to recall one's mother, and so on. At its heart, the notion of a one-to-one ratio

between brain cells and objects or concepts was an attempt to tackle the mystery of how the brain combines

what we see with our long-term memories. Scientists have since discovered plenty of sensory neurons that

specialize in processing facial information, and as many memory cells dedicated to storing data from personal

encounters. But a grandmother neuron—or even a hybrid cell capable of linking vision to memory—never

emerged. "The expectation is that we would have had this down by now," Freiwald says. "Far from it! We had

no clear knowledge of where and how the brain processes familiar faces."

Researchers identify brain circuit for spirituality @Medical_Xpress, Brigham and Women's Hospital

@BehavioralNews

the Brigham's Center for Brain Circuit Therapeutics. "We were astonished to find that this brain circuit for

spirituality is centered in one of the most evolutionarily preserved structures in the brain." To conduct their

study, Ferguson and colleagues used a technique called lesion network mapping that allows investigators to

map complex human behaviors to specific brain circuits based on the locations of brain lesions in patients. The

team leveraged a previously published dataset that included 88 neurosurgical patients who were undergoing

surgery to remove a brain tumor. Lesion locations were distributed throughout the brain. Patients completed

a survey that included questions about spiritual acceptance before and after surgery. The team validated their

results using a second dataset made up of more than 100 patients with lesions caused by penetrating head

trauma from combat during the Vietnam War. These participants also completed questionnaires that included

questions about religiosity, such as, "Do you consider yourself a religious person? Yes or No?" Of the 88

neurosurgical patients, 30 showed a decrease in self-reported spiritual belief before and after neurosurgical

brain tumor resection, 29 showed an increase, and 29 showed no change. Using lesion network mapping, the

team found that self-reported spirituality mapped to a specific brain circuit centered on the PAG. The circuit

included positive nodes and negative nodes—lesions that disrupted these respective nodes either decreased

or increased self-reported spiritual beliefs. Results on religiosity from the second dataset aligned with these

findings. In addition, in a review of the literature, the researchers found several case reports of patients who

became hyper-religious after experiencing brain lesions that affected the negative nodes of the circuit. Lesion

locations associated with other neurological and psychiatric symptoms also intersected with the spirituality

circuit. Specifically, lesions causing Parkinsonism intersected positive areas of the circuit, as did lesions

associated with decreased spirituality. Lesions causing delusions and alien limb syndrome intersected with

negative regions, associated with increased spirituality and religiosity. "It's important to note that these

overlaps may be helpful for understanding shared features and associations, but these results should not be

over-interpreted," said Ferguson. "For example, our results do not imply that religion is a delusion, that

historical religious figures suffered from alien limb syndrome, or that Parkinson's disease arises due to a lack

of religious faith. Instead, our results point to the deep roots of spiritual beliefs in a part of our brain that's

been implicated in many important functions." The authors note that the datasets they used do not provide

rich information about the patient's upbringing, which can have an influence over spiritual beliefs, and that

patients in both datasets were from predominantly Christian cultures. To understand the generalizability of

their results, they would need to replicate their study across many backgrounds. The team is also interested in

untangling religiosity and spirituality to understand brain circuits that may be driving differences. Additionally,

Ferguson would like to pursue clinical and translational applications for the findings, including understanding

the role that spirituality and compassion may have in clinical treatment.

Autistic individuals more likely to use recreational drugs to self-medicate @Medical_Xpress, University of Cambridge

@BehavioralNews

drinking compared to 8% of non-autistic adults. There were also some sex differences in patterns of substance

use: autistic males were less likely than non-autistic males to report ever having smoked or used drugs. In

contrast, the team did not find differences in the patterns of frequency of smoking or drug use between

autistic and non-autistic females. However, despite lower rates of substance use overall, the qualitative

findings of the study provide a much less hopeful picture: autistic adults were nearly nine times more likely

than non-autistic peers to report using recreational drugs (such as marijuana, cocaine and amphetamines) to

manage unwanted symptoms, including autism-related symptoms. Drugs were used to reduce sensory

overload, help with mental focus, and provide routine, among other reasons. Several autistic participants also

indirectly referenced using substances to mask their autism. Past research has shown that this behavioural

management (also known as 'camouflaging' or 'compensating') has been linked to emotional exhaustion,

worse mental health, and even increased risk of suicide among autistic adults. Autistic adolescents and adults

were also over three times more likely than others to report using substances to manage mental health

symptoms, including anxiety, depression, and suicidal thoughts. Several participants specifically noted that

they used drugs for self-medication. However, this self-medication was not always viewed as negative by

participants, and several noted that using recreational drugs allowed them to reduce the doses of prescribed

medications for mental health conditions, which was a welcome change due to the sometimes significant side

effects from their prescribed medications.

Regular physical activity linked to more 'fit' preteen brains @Medical_Xpress, Children's Hospital Boston

We know exercise has many health benefits. A new study from Boston Children's Hospital adds another

benefit: Physical activity appears to help organize children's developing brains. The study, led by Dr. Caterina

Stamoulis, analyzed brain imaging data from nearly 6,000 9- and 10-year-olds. It found that physical activity

was associated with more efficiently organized, robust, and flexible brain networks. The more physical activity,

the more "fit" the brain. "It didn't matter what kind of physical activity children were involved in," says Dr.

Stamoulis, who directs the Computational Neuroscience Laboratory at Boston Children's. "It only mattered

that they were active." Dr. Stamoulis and her trainees, Skylar Brooks and Sean Parks, tapped brain imaging

data from the Adolescent Brain Cognitive Development (ABCD) study, a long-running study sponsored by the

National Institutes of Health. They used functional magnetic resonance imaging (fMRI) data to estimate the

strength and organizational properties of the children's brain circuits. These measures determine how

efficiently the brain functions and how readily it can adapt to changes in the environment. "The preteen years

are a very important time in brain development," notes Dr. Stamoulis. "They are associated with a lot of

changes in the brain's functional circuits, particularly those supporting higher-level thought processes.

Unhealthy changes in these areas can lead to risky behaviors and long-lasting deficits in the skills needed for

learning and reasoning." The team combined these data with information on the children's physical activity

and sports involvement, supplied by the families, as well as body mass index (BMI). Finally, they adjusted the

data for other factors that might affect brain development, such as being born before 40 weeks of gestation,

puberty status, sex, and family income. Being active multiple times per week for at least 60 minutes had a

widespread positive effect on brain circuitry. Children who engaged in high levels of physical activity showed

beneficial effects on brain circuits in multiple areas essential to learning and reasoning. These included

@BehavioralNews

Study finds time-restricted eating may reduce diabetes-related hypertension @Medical_Xpress, Elizabeth Chapin,

University of Kentucky

A new University of Kentucky College of Medicine study suggests that time-restricted eating may be able to

help people with Type 2 diabetes reduce nocturnal hypertension, which is characterized by elevated blood

pressure at night. The study published in PNAS June 22 found that time-restricted eating, a routine in which

eating is restricted to a specific window of time during each day, helped prevent and improve diabetes-related

nocturnal hypertension in mice. Study authors Ming Gong, Ph.D., M.D., professor in the Department of

Physiology, and Zhenheng Guo, Ph.D., professor in the Department of Pharmacology and Nutritional Sciences,

are hopeful their findings will mean time-restricted eating could offer similar benefits for people. "We are

excited about these findings and the implications they could have in future clinical studies," said Guo. "In

addition to lifestyle changes like diet and exercise, time-restricted eating could have a healthy impact on

people with Type 2 diabetes." Normally, blood pressure falls at night and increases upon awakening, in line

with the body's circadian rhythm. In some hypertensive patients, the typical nighttime decrease does not

occur. This "nondipping" blood pressure is prevalent in patients with Type 2 diabetes and is associated with

increased events of cardiovascular disease. The study found that imposing time-restricted feeding prevented

diabetic mice from developing nondipping blood pressure. The practice also effectively restored the disrupted

blood pressure circadian rhythm in mice that already had nondipping blood pressure. Researchers restricted

the mice's access to food to eight hours during their typical active awake times every day. When food

availability was increased to 12 hours, the practice was still effective in preventing and treating nondipping

blood pressure. Guo says this is evidence that the effects were caused by the timing of feeding and not calorie

restriction.

Research pinpoints role of dopamine in songbird's brain plasticity @Medical_Xpress, Patty Shillington, University of

Massachusetts Amherst

Neuroscientists at the University of Massachusetts Amherst have demonstrated in new research that

dopamine plays a key role in how songbirds learn complex new sounds. Published in the Journal of

Neuroscience, the finding that dopamine drives plasticity in the auditory pallium of zebra finches lays new

groundwork for advancing the understanding of the functions of this neurotransmitter in an area of the brain

that encodes complex stimuli. "People associate dopamine with reward and pleasure," says lead author

Matheus Macedo-Lima, who performed the research in the lab of senior author Luke Remage-Healey as a

Ph.D. student in UMass Amherst's Neuroscience and Behavior graduate program. "It's a very well-known

concept that dopamine is involved in learning. But the knowledge about dopamine in areas related to sensory

processing in the brain is limited. We wanted to understand whether dopamine was playing a role in how this

brain region learns new sounds or changes with sounds." Studying vocal learning in songbirds provides insight

into how spoken language is learned, adds behavioral neuroscientist Remage-Healey, professor of

Continuing Education Credit

By Gary Traub, Ph.D.

TCP and completing the following questions. E-mail your answers to Dr. John Caccavale, NAPPP, at [email protected]

1. In the opening article, Dr. Caccavale de-scribes a “mysterious brain disorder spreading in America”, which he calls _______________________

2. The pizza parlor where Hilary Clinton is alleg-edly holding kidnapped children where they are defiled by pedophiles is said to be located where?

3. Dr. Caccavale asserts that 99% of those who believe in the tenets of Q-anon are mentally ill. True/False

4. Groups fighting the US opioid epidemic have accused what doctor of presiding over one of the worst regulatory agency failures in US history?

5. What high-strength opioid was touted as as safer and more effective than other pain killers based on false claims of that drug’s manufac-turer?

6. Which pharmaceutical company created the drug referred to in the previous question? 7. What is the name of the controversial new

Alzheimer’s drug that upon approval, led to 3 members of the advisory committee resigning in protest?

8. Dr. Reinhardt points out that several stud-ies of chemicals that dissolve plaques have reported a worsening of dementia symptoms. True/False

9. In the section “More on Dementia”, it was mentioned that consumption of what class of drugs more than doubles the risk of demen-tia?

10. What traditional Chinese medicine herb has been shown to reduce oxidative stress, and has anti-inflammatory properties?

11. In the same article, Dr. Reinhardt mentions what naturally occurring element that can

reduce incidence of dementia in bipolar pa-tients?

12. B12 deficiency was mentioned as a potential cause of dementia. True/False

13. By the ago of 65, ____% of people will develop amyloid plaques, but only ____% develop dementia.

14. Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties. True/False

15. The chemical name for SAM is __________________.

16. High depressive symptoms were significantly associated with a higher risk of rapid kidney function decline among Chinese adults, but generally more among those with impaired kidney function. True/False

17. Several articles mentioned that the use of what commonly used drug has been associ-ated with ADHD, autism, asthma, and possibly cancer?