Conclusion That Egg Consumption Reduces Alzheimer's Disease Not Very Significant

A study in the peer reviewed Journal of Nutrition claiming a 47% reduction in clinical diagnosis of Alzheimer's during life due to eating at least one egg a week, is much weaker than it appears at face value. 

The results (based upon a clinical diagnosis during life) were consistent with benefits as low as 17% within the margin of error.

 

And, the clinical diagnosis rates weren't very accurate. Post-mortem examination of the brains of more than half of the sample (578 cases) found a 56% false negative rate for clinical diagnosis during life and an 18% false positive rate for clinical diagnosis during life. This casts doubt on whether the lifetime clinical diagnosis data is meaningful at all, given its immense inaccuracy. 

The results when based on autopsies were consistent with benefits as low as 10% for two or more eggs a week.

Both these results are only modestly better than the p=0.05 statistical significance threshold, and the fact that the cases where Alzheimer's disease was accurately diagnosed showed less of a benefit, also casts doubt on the significance of this study. None of the evidence supporting the author's hypothesis that dietary choline intake was the protective factor was statistically significant, and none of the results were significant at anything close to the p=0.01 level. This significance, moreover, is overstated, because the study fails to adjust for the inaccuracy of the clinical diagnosis process or for the uncertainty in the result caused by self-reporting of what people ate. 

Dietary self-reporting is particularly problematic in a population where a large percentage of the reporters will ultimately be diagnosed with Alzheimer's disease in less than ten years. It could be that many people who don't report weekly egg consumption did so because their memory was not good enough to remember everything that they ate in the last month due to having undiagnosed or subclinical levels of Alzheimer's disease, rather than being due to actually eating fewer eggs.

The sample size is small, so the statistical significance of the result is modest. The total sample was 1024 people, and only 370 of them did not eat at least one egg a week.

Also casting doubt on the result is the fact that there was no dose-response effect (i.e. eating more than one egg a week is no better than eating one egg a week, and eating no eggs is not significantly different from eating 1-3 eggs a month) and indeed, eating more than one egg a week reduced the benefit in individuals who had post-mortem exams done, relative to those who had one egg a week.

The average diagnosis at 6.7 ± 4.8 years from the start of the study is also soon enough after the study began, that given strong evidence in the literature (which is not mentioned in the literature review in the study) that Alzheimer's disease starts at sub-clinical levels decades before it is diagnosed in many cases. So, the diet of the people in the study during the study period probably didn't influence the outcomes.

Finally, while the study controls for 13 potential confounding factors (of which some, like education, didn't vary significantly between the subgroups), it could easily have omitted an important factor. And, it doesn't prove cause and effect either. For example, it could be that having undiagnosed Alzheimer's disease influences your body in a way that you don't like eating eggs as much.

Thus, while the study might justify further research, its conclusion the weekly egg consumption greatly reduces Alzheimer's disease onset risk is too weak to make a life choice based upon, or to recommend clinically, despite the fact that their best fit benefit purports to be as much as a 47% reduction in the risk of getting Alzheimers. Indeed, if anything, the details of the data tend to favor some uncontrolled for confounding factor that is merely mildly correlated with egg consumption.

The failure of the study to engage with many of these issues in a forthright manner also casts doubt on the quality of the peer review at the Journal of Nutrition for this study.

The study and its abstract are as follows:

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with increasing prevalence due to population aging. Eggs provide many nutrients important for brain health, including choline, omega-3 fatty acids, and lutein. Emerging evidence suggests that frequent egg consumption may improve cognitive performance on verbal tests, but whether consumption influences the risk of Alzheimer’s dementia and AD is unknown.

Objectives: To examine the association of egg consumption with Alzheimer’s dementia risk among the Rush Memory and Aging Project cohort.

Methods: Dietary assessment was collected using a modified Harvard semiquantitative food frequency questionnaire. Participants’ first food frequency questionnaire was used as the baseline measure of egg consumption. Multivariable adjusted Cox proportional hazards regression models were used to investigate the associations of baseline egg consumption amount with Alzheimer’s dementia risk, adjusting for potential confounding factors. Subgroup analyses using Cox and logistic regression models were performed to investigate the associations with AD pathology in the brain. Mediation analysis was conducted to examine the mediation effect of dietary choline in the relationship between egg intake and incident Alzheimer’s dementia.

Results: This study included 1024 older adults {mean [±standard deviation (SD)] age = 81.38 ± 7.20 y}. Over a mean (±SD) follow-up of 6.7 ± 4.8 y, 280 participants (27.3%) were clinically diagnosed with Alzheimer’s dementia. Weekly consumption of >1 egg/wk (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.34, 0.83) and ≥2 eggs/wk (HR: 0.53; 95% CI: 0.35, 0.81) was associated with a decreased risk of Alzheimer’s dementia. Subgroup analysis of brain autopsies from 578 deceased participants showed that intakes of >1 egg/wk (HR: 0.51; 95% CI: 0.35, 0.76) and ≥2 eggs/wk (HR: 0.62; 95% CI: 0.44, 0.90) were associated with a lower risk of AD pathology in the brain. Mediation analysis showed that 39% of the total effect of egg intake on incident Alzheimer’s dementia was mediated through dietary choline.

Conclusions: These findings suggest that frequent egg consumption is associated with a lower risk of Alzheimer’s dementia and AD pathology, and the association with Alzheimer’s dementia is partially mediated through dietary choline.

Yongyi Pan, et al., "Association of Egg Intake With Alzheimer’s Dementia Risk in Older Adults: The Rush Memory and Aging Project" 154(7) The Journal of Nutrition 2236-2243 (2024). https://doi.org/10.1016/j.tjnut.2024.05.012.

The Shooting In Washington Park

The Shooting

The description of the events in this section is compiled mostly from multiple news reports at the Denver Post (including this one), the Denver Gazette, and three TV news channel websites (7 News including this one, 9 News, and Fox 31 News).

My previous post on middle class crime, was motivated by, and a prelude to, this post about the February 2, 2025 shooting in Washington Park, in Denver, Colorado, about three blocks from my home, that took place around 2:30-2:40 p.m. on a sunny warm day in broad daylight, just minutes after my wife decided to take another route home from the Washington Park Recreation Center than she had been planning to take. 

The shooting took place roughly Downing and Kentucky streets near a major west entrance to the park (it may have taken place a block further south at Downing and Tennessee, there are conflicting reports and there is a park bench there that could have been the one central to this story).

Twenty-eight year old Ryan Martin Egelston is suspected of having gotten into an argument with another man over a park bench at this location. 

As a Denver Post story explains:

Egelston got into a fight with another man in the park around 2 p.m. Sunday after the man asked if he could share a park bench with Egelston, according to an arrest affidavit released by the Denver Police Department.

Witnesses told investigators that Egelston spat on the man, pushed him in the chest and punched him in the lower back, according to the affidavit.

The man was walking away with his bike when Egelston allegedly pulled out a gun and shot at him. Egelston didn’t hit the man, but police said the bullet punctured one of the bike’s tires.

About 90 seconds later, Egelston shot at a second, unrelated victim from behind, striking him near the jaw, according to the affidavit. Witnesses told the Denver Post on Sunday that the bullet entered the man’s neck and went out his face.

“At no point did the second victim and (Egelston) appear to have any sort of disagreement or altercation prior to the shooting,” Denver police officials said in the arrest affidavit.

Chaos erupted in the crowed park in response. A medical doctor who was in the park nearby provided first aid to the man who was shot until an ambulance arrived and took him to a hospital. The man who was shot is expected to survive despite these serious injuries.

UPDATE: February 14, 2025:

A silver lining to the fateful day was the presence of Lakshmi Karra, Denver Health family medicine doctor, who was also at the park. She rushed to help Ben without hesitating. "I noticed that there was what looked like a gunshot wound on his neck," she said. "I took his picnic blanket out of his bag and I held pressure on his wound." Karra called 911 after which the Denver Health Paramedics rushed Ben to the hospital.

From 9 News.  

Egelston was muttering and cursing to himself and displayed his handgun to two women nearby telling them not to photograph him. He then tried to flee in his red Hyundai sedan.  

The 7 News story adds some details from the arrest affdavit and criminal case:

Moments after the second shooting, Egelston was seen walking southbound on S. Downing St. from E. Kentucky Ave. before he got inside a red Hyundai Sudan with Colorado license plate CIS-K97.

Denver Police officers who responded to the scene chased the vehicle with their sirens blaring before they rammed the car at E. Kentucky Ave. just west of S. Downing St. “due to the active threat to the public and in an attempt to limit a high-speed chase,” according to the affidavit.

At least two Denver police patrol cars surrounded the vehicle and took Engelson into custody. A black Glock handgun was then recovered from the passenger seat of the vehicle, according to investigators.

Egelston was taken to Denver Police Department headquarters where he was interviewed by police about two hours later following the shootings, though it’s not clear why Egelston got into an argument with the first victim and why he reportedly shot the two men, as the affidavit obtained by Denver7 Monday is heavily redacted.

The suspect is currently being held for investigation of attempted first-degree murder on a $1 million cash-only bond.

He was also carrying a concealed weapon in a Denver park, which is itself illegal.

UPDATE (February 10, 2024) from the Denver Post:

Ryan Martin Egelston has been charged with four counts of first-degree attempted murder, one count of assault and one count of vehicular eluding, all felonies, according to court records. He is also charged with six sentence-enhancing charges related to violent crimes and weapons.

Egelston told police he didn’t intend to shoot anyone, that he thought the two victims were involved in psyops and he was previously hospitalized for mental health concerns.

A GoFundMe has been established for the shooting victim Ben Varga, who is 23 years old, by his family. As I write this, it has raised $34,935 towards a $40,000 goal from 530 donors. Varga was taken to Denver Health, a level one trauma center. The GoFundMe page explains that:

On February 2nd, 2025, our friend, brother, and son, Ben Varga, was the victim of a shooting in Wash Park, Denver. Ben was shot from behind while waiting to meet up with friends. The bullet traveled through the back of his neck and straight through his jaw and chin. We are incredibly grateful that he survived. In what can only be described as a miracle, the bullet narrowly missed critical structures like his trachea and spine, preventing even more devastating consequences. The visible impact on his face is minimal, given that the bullet traveled in a way that left his facial structure largely intact on the surface. Since the incident, Ben has been in the Surgical Intensive Care Unit (SICU) at Denver Health, undergoing multiple surgeries and receiving round-the-clock care. His recovery will be long, but we remain hopeful. . . . 

Ben, a lifelong Coloradan, has always had a deep love for his home state and the community around him. He graduated from CU Boulder's Leeds School of Business last May, is a dedicated Buffs fan, and recently moved to downtown Denver to start a new job. Ben is also a big fan of all Colorado sports, including the Broncos, Avalanche, and Nuggets. When he's not cheering for local teams, he loves skiing, playing pickleball, trying new restaurants, and traveling the world. As a triplet, he shares a special bond with his brother, sister, and family. His love extends deeply to his friends and his dogs, Tatum and Bernie.

Ben's picture appears on his "recovery" blog: 

About Shooting Suspect Ryan Egelston

The suspect in this case is not much of a fit to stereotypes about random shootings in big cities.

Egelston attended the University of Dayton, in Ohio, from 2015-2019 where he got decent enough grades, after graduating from Buffalo Grove High School in Buffalo Grove, Illinois (a Chicago suburb) on schedule, starting in August of 2011. He was born sometime in 1996. While he was in college, in the summer of 2018, he was an intern with Respire Ministries, helping to teach English to Haitian immigrants (probably the ones made famous in the 2024 Presidential race).

After he graduated with a bachelor's degree in accounting and finance he became a CPA for the Big Four accounting firm of Deloitte, which he rose to the position of senior auditor over a period of two years and four months. He moved to Denver in 2021 to work as a senior associate for a financial consulting firm involving "interim financial assistance primarily to Fortune 1000 companies during critical times of need" performing accounting, auditing and compliance functions for a year until November of 2022, and was admitted as a licensed CPA in Colorado by reciprocity.

Before moving to Denver and until shortly after he moved to Denver, he was a treasurer and trustee on the board of the mother church, called "Destiny Church" and an "inherited church" called "Risen Church" and was a youth ministry leader at Destiny Church that served more than 100 members. At these meetings he "casted vision." He also worked in their addiction ministries.

Then, his ordinary and highly successful career path shifted. He took what he described as a "gap year" and "career break" for nineteen months, until May of 2024, during which he "authored over 4 unpublished books and numerous business consulting articles and thought leadership." Over the last nine months he has been working remotely providing accounting and finance consulting services for "One10" which I suspect, but don't know, is the entity in which he engaged in self-employment.

He describes himself as revivalist preacher and a Revelations 11 witness, maintained a blog until September of 2023, and made a dozen or two TikTok posts. The blog posts were pretty out there from the perspective of the uninitiated. For example, his September 25, 2023 blog post (the last one on his site) he said: 

Moore’s Law is the prophetic fulfillment of Daniel 12:4, which is prophecy on the end time’s that detail that knowledge shall increase stating, “Many shall run to and fro, and knowledge shall increase.”

The pictures and videos on his website and TikTok posts depict a clean cut, fit, white young man, who is almost frenetic with impatient energy.

The "about me" section on his webpage says (fancy formatting in the original not fully preserved):

Passionate About Revival, Writing Books, Teaching the Word of God,

Empowerment, Leadership Development,

Business Development/Consulting Services, and Public Speaking

I am a small business owner who is 'sold out' with a deep passion to preach and teach the Word of God with all my chips on the table, and I offer speaking arrangements where I hope to be the spiritual thermostat for you, your business, or your church! When not speaking or writing books, I love to consult with companies and would love the opportunity to help take your business to the next level and be a sounding board of wisdom in your room, a voice of reason, a voice that you can trust that will come in looking out for your best intentions with the utmost excellence. Business is my passion, people are my concentration, and the Word of God is what I belt out and yearn to live out with the very actions of my life. I choose to live 'under the Word,' apply it in every area of my life, and yearn to see an on-fire and burning church ready with oil for the return of Christ.

Currently, I am writing books believing God to impact thousands of people in whatever manner possible and dream of speaking all around the world. I am deeply passionate about client service and love adding value in the consulting sphere solving complex problems and being the sounding board for decision makers like you! Moreover, I'd love to come speak at your church or organization and inspire and build up one anothers' faith, usher in a spirit of revival, and preach LIGHTS out. If you think I'd be a great fit to speak, please do not hesitate to reach out!

A Reddit thread provides some more insights about him. One comment states:

Went to college with this guy. He became super religious after moving to Colorado and started going a little nutty. We always knew he was a little off, this is taking it to the next level.

Another comment in the thread states:

I'm almost certain I saw this dude tweaking around 1st and Emerson like two weeks ago. Same red hyundai parked in the alley, same build/look. He was trying to get into the abandoned homes on that block. I remember it now because the dude looked really wound up and had something he kept pocketing/holding. i got the fuck away ASAP. It confirms my initial suspicions that it was a gun. freaky shit.

A third comment in the thread states: 

OMG this dude came through the gas station one night and was having some kind of schizophrenic episode. He did the gesture of a rifle in his arms and I asked him if he was doing alright. He like snapped out of it said he’s going great and then went back to his episode.

Analysis

Looking at all of the facts and circumstances, including his own statement to police, I have to concur with the final Reddit comment quoted above that this shooting is probably a result of Ryan Egelston developing schizophrenia symptoms (or if not that, some other form of psychosis).

His life apparently started to go off track sometime between late 2021 when he left his job at Deloitte and November of 2022 when he left the position that he took in Denver after only a year to take a "gap year." He would have been 25-26 years old at the time, which is a very typical time for men with schizophrenia and other forms of psychosis (whose brains develop at a somewhat later age than women) to have their symptoms reach a point where they become unmanageable. These symptoms probably presented themselves at a more manageable level, perhaps even at such a slight level that one could doubt that they were real, several years earlier.

Inability to function in a highly structured conventional business setting like an accounting firm, paranoia and overreaction to unaggressive conduct from others, claims to see "visions", and making seemingly bizarre connections between ideas that other would see as unrelated, are all classic symptoms of schizophrenia.

He probably didn't self-diagnose his situation as a mental health issue (although his claim that he was previously hospitalized suggests otherwise), and his religious peers probably didn't either, as it seemed to be consistent with his self-image as a religious prophet or witness. 

His behavior as reported at Reddit and his lack of work history according to LinkedIn, also suggests that he may have been nearing the end of his rope financially, after being on the top of the world financially briefly after college as an accountant at a big national accounting firm, and then apparently exhausting his savings. This may have further fueled his paranoia and desperation.

From the perspective of criminal law, his behavior seems to belie the state of mind (typically associated with severe schizophrenia) that is necessary for him to present an insanity defense to his charges, although his lawyers, once hired or appointed, will probably have no choice but to present this defense in the criminal prosecution arising from this incident. The statement he made to police after the shooting might support this defense.

If he is not found to be incompetent and involuntarily committed as a threat to himself and others, he will probably plea bargain down from attempted murder to aggregated assault and received a fairly lengthy prison sentence in connection with that charge.

As a result of the quick response of the police to the incident, the numerous witnesses, and the ample physical evidence, a defense strategy claiming that he wasn't the shooter, or that he had a legal justification for the shooting, such as self-defense, would almost surely be futile. 

It is also plausible that an investigation will link him to other crimes for which he may face additional charges for which an insanity defense is not available (such as burglary, or carrying a concealed weapon in a Denver city park).

Middle Class Crime

Middle Class Prison Inmates Are Rare

There is a lot of data on the characteristics of offenders and nature of the offenses committed overall, and there is significant data on sentencing for felonies (sentencing data for misdemeanors and ordinance violations is much harder to come by).

One of the things that we know from that data is that having any college education, even attending a single semester at community college and then dropping out, profoundly reduces you odds of being a prison inmate relative to have no college education at all. Your odds of being a prison inmate are 40-fold or more lower.

Clearly, this is mostly a sorting effect. 

Your likelihood of being a prison inmate is highest if you don't graduate from high school and also don't earn a GED. 

The next highest likelihood of being a prison inmate is earning a GED (even though it takes a higher IQ to do so than it does to graduate from high school in the ordinary course), rather than graduating from high school and then not receiving any further higher education. This reflects the fact that people, especially men, drop out of high school not just because they are low in IQ and not succeeding in school for that reason. They also drop out because they have trouble behaving appropriately in a high school setting, which is highly connected to their likelihood of committing crimes and going to prison.

Graduating from high school in the ordinary course rather than earning a GED, and then not receiving any further higher education is the next highest likelihood of being a prison inmate, and is still quite high.

But, some college or more dramatically reduces your likelihood of being a prison inmate, and the number of prison inmates who are in that category is so small that the statistics often aren't broken down further into people who have only some college, people who have associate's degrees, people who have four year degrees, and people who have graduate or professional degrees beyond a four year undergraduate degree.

By comparison, in the general population:

In 2022, the highest level of education of the population age 25 and older in the United States ranged from less than high school to advanced degrees beyond a bachelor’s degree.

9% had less than a high school diploma or equivalent.

28% had high school as their highest level of school completed.

15% had completed some college but not a degree.

10% had an associate degree as their highest level of school completed.

23% had a bachelor’s degree as their highest degree.

14% had completed advanced education such as a master’s degree, professional degree or doctorate. . . . 

In 2022, 30.1% of men age 25 and older had completed a high school diploma or GED as their highest level of educational attainment, compared with 27.0% of women age 25 and older.

In 2022, 39.0% of women age 25 and older, and 36.2% of men in the same age range, had completed a bachelor’s degree or more as their highest level of educational attainment. 

About 16% of adults have passed a GED exam. About half of people who pass the GED exam go on to have at least some college. So, about 8% of adults have a GED as their highest educational credential (roughly the same as the percentage of high school dropouts who haven't passed a GED exam). 

Both high school dropouts and people who have a GED exam as their highest educational credential are disproportionately men. In the case of the GED, this is, in part, because a large share of GED exams are taken high school dropouts who are in prison, and prison inmates are disproportionately men.

So, about 36% of men have at least a four year degree, 24% of men have some college but no degree or an associate's degree, about 20% of men graduated from high school in the ordinary course, 10% have a GED rather than a high school diploma and no college, and about 10% of men are high school dropouts who have not earned a GED.

The roughly 60% of men with at least some college have a dramatically reduced likelihood of going to prison. The 20% of men who are high school dropouts or only have a GED have a highly elevated likelihood of going to prison, and the 20% of men who graduate from high school but have no further high education have an intermediate likelihood of going to prison. On average, these men are in the bottom quarter of high school graduates academically (although a variety of other factors influence a decision not to pursue any higher education after graduating from high school).

One expects that among the 20% of men who graduate from high school but have no further education, men who are at the top of that group academically and behaviorally but didn't go to college because they had decent job prospects or went into the military or couldn't afford to go to college, probably have a likelihood of going to prison similar to that of people who drop out of college soon after starting college. But men who are the the bottom of that group academically and behaviorally probably have a likelihood of going to prison similar to but somewhat lower men who drop out of high school and then earn a GED but don't pursue further education. They are able to behave marginally well enough to meet the minimum requirements to graduate, and are not totally stupid.

So, the likelihood of going to prison is probably most elevated among men in the bottom 30% to 1/3rd of success in the formal education system, and are profoundly reduced among men who are more successful in the formal education system.

Operationally, however, since there is almost no data sorting high achieving and well-behaved high school graduates with no college, from low achieving and poorly behaved high school graduates with no college, we can define "middle class" inmates as inmates who have some college or more.

Questions That Are Hard To Answer

1. Some of the reason that middle class inmates are so rare is that middle class criminal defendants tend to have only minimal prior criminal records and are seen as having good prospects of rehabilitation. They also tend to have been legal representation in the court system, make good choices about when to accept plea bargains, take actions that judges view as mitigating circumstances, and behave in the way that sentencing judges want them to in the court process, relative to non-middle class criminal defendants. 

So, a middle class criminal defendant who commits the same crime as a non-middle class criminal defendant is more likely to receive probation, a fine, community service, time in a half-way house, or a jail sentence, than an ordinary prison sentence, especially for less severe crimes. Likewise, even if they receive a prison sentence, it is likely to be shorter than the sentence that a typical non-middle class criminal defendant would receive for the same crime.

2. Middle class criminal defendants probably tend to commit less serious crimes, when they are convicted of crimes. They tend not to commit "blue collar" property crimes that can send you to prison like car theft, burglary, or grand larceny of tangible personal property (as opposed to fraud or theft of intangible assets). They also probably tend to commit the same sorts of crimes that are disproportionately committed by women.

3. I suspect that middle class criminal defendant who actually go to prison have mostly either committed high dollar/drug volume non-violent crimes like fraud or drug dealing, or have committed serious violent crimes for which a prison sentence is really the only plausible sentence. But, I don't know that for a fact and I haven't seen good data on that point.

4. I don't know and would be interested to know how educational attainment beyond high school influences one's likelihood of being a prison inmate. I would suspect that the risk is reduced with greater educational attainment, but the data isn't there to show how significantly protective education beyond "some college" is in terms of likelihood of being a prison inmate.

4. The trio of serious substance abuse issues, serious mental health issues, and traumatic brain injury are pervasive in a huge share of all prison inmates. Middle class prison inmates are probably no exception. Indeed, these issues probably make up a bigger share of middle class prison inmates, since economic pressures on these inmates are usually more mild.

But notably, the protective effect of even some college is huge, despite the fact that the rates of serious substance abuse and serious mental health problems is very significant even among college educated people. Most likely, people with at least some college (overall, not just prison inmates) both have mental health and substance abuse problems that are sufficiently moderate that they can function well enough to finish high school and spend some time in college, and they are better at coming up with mental health treatment, substance abuse rehabilitation, and self-help programs to manage to live an at least moderately normal life despite these challenges, while the most severely impaired people have behavioral problems early enough that they can't finish high school and some college, and/or they can't figure out a self-help regime or access the mental health care system resources that they need.

Also, some mental health and substance abuse problems have a relatively late onset. 

Susceptibility to substance abuse has a very strong genetic component. But people who grew up in strict families, or avoided substances after seeing how it affected other family members, may not have had access to substances that they can abuse, or strictly avoided substances that they can abuse, until they are in or have graduated from college.

Most mental health conditions are genetic or congenital. And, most of them, like ADHD, autism spectrum disorders, psychopathy, anxiety disorders, and OCD typically manifest before you finish high school, so people with particularly severe cases of these conditions that aren't treated adequately either don't graduate from high school for behavioral reasons or just barely scrape by at that time. Most of them, except clinical levels of autism spectrum disorder and psychopathy are quite common. Substance abuse, ADHD (as a result of high levels of impulsivity and impairments to working and being a student at regular jobs), and psychopathy seem to have the strongest association with criminal conduct that can send you to prison. Other mental health conditions, while also common, seem much less likely to be associated with criminal activity.

But psychosis (i.e. manic-depression and schizophrenia) tends to manifest in late adolescence or in one's 20s as your neural connections thin out in the brain transition from childhood to adulthood. It tends to emerge a little later in men than in women because their brains mature a little bit later than women. Psychosis is rare but devastating in its effect on your ability to function. Psychoses are also among the most heavily genetic mental health conditions.  Even if early mild symptoms of psychosis manifest in late high school or college, these way be manageable until a few years later. (As an aside, one thing that is almost a litmus test for schizophrenia is heavy nicotine use, which despite its other harmful health effects, provides some limited relief from schizophrenia symptoms. A very large percentage of schizophrenics who have access to nicotine, legally or illicitly, use it.) 

M.S. typically manifests at ages similar to psychosis but has a viral cause, and its neurodegenerative symptoms can mirror major mental health issues and gets worse over time since it is degenerative. Further, traumatic brain injury, major depression (apart from manic depression) and PTSD are predominantly not genetic or congenital and can manifest at any age. Finally, some forms of dementia, whose symptoms are often only unmistakable in late life, and stokes (including TIAs) can also give rise to symptoms similar to major mental health issues.

These mental and cognitive health conditions that manifest after one typically starts college probably disproportionately impact middle class inmates, since these impairments do not interfere with behavior until these key educational landmarks are reached. 

Autism and ADHD Incidence

About 1 in 25 American boys ages 5 to 17 have a diagnosis of autism. Boys are four times more likely than girls to be diagnosed with the condition. Diagnoses of attention-deficit/hyperactivity disorder: 14.5 percent of American boys, 8 percent of girls. The likelihood of an ADHD diagnosis decreases as family income increases.

From the Washington Post. 

Beyond The Adversarial Models For Mental Health And Incapacity

I'm litigating an adult guardianship case. It isn't the first time I've done one. As a general rule, there is, at least, a lawyer for the person asking for a guardianship, a court appointed visitor (social work who sees what's going on), a court appointed lawyer for the person upon whom a guardian is to be imposed, and a court appointed guardian ad litem for the person to have a guardian impose, in addition to a judge and a judge's division clerk involved. A physician's letter from none of those people is preferred. There is an emergency guardianship option, but the usual process takes about two months. Sometimes more lawyers are involved if there are disputes over who should be appointed. Sometimes, adult protective services is involved.

On one hand, the concern that the process not put an adult in a subordinated position with reduced autonomy rights without adequate due process is legitimate. On the other hand, the process puts a lot of barriers in the way of getting help and intervention to people who, by definition, aren't able to reasonably manage their own affairs and are highly vulnerable to manipulation in any formal process. We put a lot of highly paid professionals in place to check and balance each other, instead of placing greater trust into fewer people at a lower cost. I have to think that this isn't the optimal system. We should have a system that is more pro-active and doesn't pose quite such high barriers to intervention, perhaps with more pro-active follow up and supervision of fiduciaries that extends beyond a paper record.

The thing is that, whether or not they get it, lots of people, maybe half or more, are going to spend some time in their lives when they need, or would benefit from, transitioning to having someone who can make decisions for them. An adversarial model for securing this situation, and a placing a premium on autonomy, which makes sense for most of one's adult life, even in times of physical illness, isn't optimal for lots of people at the end of their lives.

Mental health care, likewise, really ought to be more pro-active. And, the assumptions of the physical health care system, which is oriented towards a "cure" of temporary illnesses and injuries, really isn't appropriate for a large share of mental health care conditions which are congenital or at least permanent. Symptom management is the concern, not a "cure". The push for mental and physical health care parity may have been a good transitional way to leverage more insurance coverage and access to mental health care, but the truth is that they are fairly disjoint and efficiently providing each involves different professionals. The privacy concerns are different. The kind of treatment setting that is needed is different. We should have systems in place to pro-actively intervene in the face of predictable crisis situations. 

Addiction Is Genetic Predisposition Plus

Most people who try drugs don’t get addicted, even to opioids or methamphetamine, which suggests that ‌factors other than simply being exposed to a drug can contribute to addiction. ‌The majority of people who do get hooked have other psychiatric disorders, traumatic childhoods or both — only ‌7 percent report no history of mental illness. ‌‌Nearly 75 percent of women with heroin addiction‌‌ were sexually abused as children — and most people with any type of addiction have suffered at least one and often many forms of childhood trauma‌‌.

Chandra Sripada, professor of psychiatry and philosophy at the University of Michigan, argues that distorted thinking is more important in addictive behavior than overwhelming desire, leading to what he calls “unreliable” control over use. . . .  During addiction . . . despairing thoughts about oneself and the future — not just thoughts about how good the drug is — predominate. At the same time, thoughts about negative consequences of use are minimized, as are those about alternative ways of coping. Drugs are overvalued as a way to mitigate distress; everything else is undervalued. The result is an unstable balance, which, more often than not, tips toward getting high.

This theory ‌is helpful for explaining who is most likely to get addicted and what is most likely to generate recovery. Risk factors like poverty, a traumatic childhood and mental illness generate excess stress while tending to produce negative thoughts about oneself. In my case, I was depressed and isolated because of what I later learned was undiagnosed autism spectrum disorder — and hated myself for my inability to connect. The result was a mental climate conducive to relying on drugs, even when they no longer ‌provided relief.

Factors linked to recovery — like social support and employment — can offset distorted thoughts and inflated valuation of drug use. Essentially, people make better choices when they recognize and have access to better options‌. If you are locked in a room with an escape route unknown to you hidden under the carpet, you are just as trapped as if that exit didn’t exist. My recovery began when I saw that there was a bearable way out.

This is why punitive approaches so often backfire: Causing more pain to people who view drugs as their only way to cope drives desire to use even more. Punishment doesn’t teach new skills that can allow better decisions.

From the New York Times. 

The story has many other worthwhile insights, for example, on how addition is neither a total absence of free will nor a totally unfettered free choice.

The Genetics Of Autism and ADHD

A new study compared the genetic profiles of people diagnosed with an autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and people diagnosed with both disorders. Both conditions are highly heritable. 

The study used large data set with 23,583 subjects (with ADHD and/or one of four subtypes of autism spectrum disorder) and 42,201 controls, apparently mostly from the national health records of Denmark and possibly also from 23andMe data. The study excluded individuals with a moderate to severe mental retardation from both its subjects and its controls.

The study finds seven genes that are associated with both disorders, and five genes that distinguish between the disorders which are also associated with educational attainment, neuroticism and regional brain volume. 

The Paper And Its Abstract

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. 

We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. 

Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. 

These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.

Manuel Mattheisen, et al., "Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups" Nat Genet (September 26, 2022). https://doi.org/10.1038/s41588-022-01171-3 (closed access).

The Data Set

The data set was apparently a national health care record system for Denmark in which there were 2,304 cases with both ADHD ad an autism spectrum disorder, 11,964 ADHD cases without an autism spectrum disorder, and 9,315 cases with an autism spectrum disorder without ADHD, although some of the data may also have been from the 23andme consumer genetic profiling company (a data set that would include me, my family, and a number of my extended family members). Also:

Controls were randomly selected from the full control cohort to roughly match a 1:4 ratio in cases and controls. . . . we excluded individuals with a moderate to severe mental retardation (ICD10: F71-F79) from both the case and control cohort.

Autism spectrum disorder cases were further categoried into four subtypes: childhood autism (cha, ICD10 F84.0); atypical autism (ata, ICD10 F84.1); Asperger’s syndrome (asp, ICD10 F84.5); and pervasive disorders, unspecified and others (pdm, ICD10 F84.8+9). 

It appears that ADHD cases were not subtyped, which is something of a shame. There is good reasons to think that the genetic basis of ADHD predominantly inattentive type (i.e. without hyperactivity), has a different genetic basis than ADHD combined type (and ADHD predominately hyperactive which probably overlaps heavily with the combined type). This level of information ought to have been available although empirically efforts to further subtype ADHD probably wouldn't have been available in the data. See, e.g, prior posts at this blog from September 8, 2012, April 3, 2012, and October 18, 2017 (Genetics of ADHD hyperactivity/impulsivity and inattention dimensions are quite different),

A Key Figure From The Paper

A figure from the closed access paper:

Fig. 2: Comparison of PRS profiles across ADHD and ASD subtypes for 15 traits and/or phenotypes that have shown significant genetic correlations with ADHD and ASD in the past.

Peer Review

The relatively new practice of disclosing comments from the peer review of the paper, provides some interesting insights although it is rather technical and difficult to evaluate without an open access manuscript to reference it to for the most part. Some notable comment state:

A serious limitation of this study is that the design relies on the common psychiatric nosology that in particular for ASD and ADHD has been problematic, surely in the past when only one of both diagnosis was allowed. Given the high comorbidity between ADHD and ASD, and among other psychiatric disorders in general, plus the fact that recent research shows that ‘genes do not respect diagnostic classifications’ (see CDG publications) I would rather see a focus on the shared genetic findings for ADHD and ASD, in aiming to find general genetic/biological vulnerabilities for trans diagnostic neurodevelopmental problems, instead of relying on a classification system that has surely proven its value in clinical practice but does not seem to guide biological underpinnings of those disorders.

and

Concerning the used sample, I would appreciate getting some more details on the assessment of comorbid ASD and ADHD in the respective cohort. While some of the individuals might have been diagnosed under DSM-IV, which did not allow a comorbid diagnosis of ADHD, I wonder if and how this was accounted for in the datasets. In light of the cited Meta-study 25-32% of ASD individuals do fulfill the criteria for ADHD. In this study, the comorbid cohort accounts for 10% of the sample (assuming they were from both the ASD and the ADHD cohorts).

The responses gave rise to a table regarding the shared risk genes:

The Genetics Of Schizophrenia

We've known that schizophrenia, and schizophrenia subtypes have a strong genetic component for a long time. 

We are far from having a comprehensive genetic level understanding of the condition, but we have identified particular genes that play a major part in about half of the most severe and treatment resistant cases. 

Of course, even if we did have a comprehensive genetic understanding, that wouldn't itself, give us a cure or even a better treatment for it. But ultimately a better understanding of the condition and the various causes of this syndrome is worthwhile and is likely to lead to actionable knowledge in individual cases.

Extreme phenotype sequencing has led to the identification of high-impact rare genetic variants for many complex disorders but has not been applied to studies of severe schizophrenia. We sequenced 112 individuals with severe, extremely treatment-resistant schizophrenia, 218 individuals with typical schizophrenia, and 4,929 controls. 

We compared the burden of rare, damaging missense and loss-of-function variants between severe, extremely treatment-resistant schizophrenia, typical schizophrenia, and controls across mutation intolerant genes. Individuals with severe, extremely treatment-resistant schizophrenia had a high burden of rare loss-of-function (odds ratio, 1.91; 95% CI, 1.39 to 2.63; P = 7.8 × 10^−5) and damaging missense variants in intolerant genes (odds ratio, 2.90; 95% CI, 2.02 to 4.15; P = 3.2 × 10^−9). 

A total of 48.2% of individuals with severe, extremely treatment-resistant schizophrenia carried at least one rare, damaging missense or loss-of-function variant in intolerant genes compared to 29.8% of typical schizophrenia individuals (odds ratio, 2.18; 95% CI, 1.33 to 3.60; P = 1.6 × 10^−3) and 25.4% of controls (odds ratio, 2.74; 95% CI, 1.85 to 4.06; P = 2.9 × 10^−7). 

Restricting to genes previously associated with schizophrenia risk strengthened the enrichment with 8.9% of individuals with severe, extremely treatment-resistant schizophrenia carrying a damaging missense or loss-of-function variant compared to 2.3% of typical schizophrenia (odds ratio, 5.48; 95% CI, 1.52 to 19.74; P = 0.02) and 1.6% of controls (odds ratio, 5.82; 95% CI, 3.00 to 11.28; P = 2.6 × 10^−8). 

These results demonstrate the power of extreme phenotype case selection in psychiatric genetics and an approach to augment schizophrenia gene discovery efforts.

Anthony W. Zoghbi, , et al., "High-impact rare genetic variants in severe schizophrenia"118 (51) PNAS e2112560118 (December 21, 2021). 

https://doi.org/10.1073/pnas.2112560118

Brain Scans Lend Insight Into Six Common Psychiatric Conditions

We are starting to figure out how psychiatric disorders previously classified solely by symptoms are related to each other (and different from each other) at a biological level in the brain. 

"We found that 4 major psychiatric disorders -- major depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder -- show a surprisingly high level of similarity in their brain structural abnormalities," said Dr. Opel. The shared brain areas showing structural aberrations were mainly in cortical areas associated with cognitive processing, memory and self-awareness. 

On the flipside, Dr. Opel added, "we were able to identify regional abnormalities with high specificity for certain disorders." Interestingly, these distinct structural differences sometimes appeared in the same area for two disorders, but in opposite directions from the norm. 

In contrast, attention-deficit/hyperactivity disorder and autism spectrum disorder did not share brain structural signatures with any other disorders. That may be because those disorders are considered developmental diseases with a distinct etiology from the other psychiatric conditions, which have more in common. 

The researchers do not yet understand the mechanisms behind the shared structural elements, but a growing body of evidence shows that these psychiatric disorders also share common genetic as well as environmental influences, which might underlie the current findings.

From Science Daily. The paper and its abstract are as follows:

Background 

Neuroimaging studies have consistently reported similar brain structural abnormalities across different psychiatric disorders. Yet, the extent and regional distribution of shared morphometric abnormalities between disorders remains unknown. 

Methods 

Here, we conducted a cross-disorder analysis of brain structural abnormalities in 6 psychiatric disorders based on effect size estimates for cortical thickness and subcortical volume differences between healthy control subjects and psychiatric patients from 11 mega- and meta-analyses from the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta Analysis) consortium. Correlational and exploratory factor analyses were used to quantify the relative overlap in brain structural effect sizes between disorders and to identify brain regions with disorder-specific abnormalities. 

Results 

Brain structural abnormalities in major depressive disorder, bipolar disorder, schizophrenia, and obsessive-compulsive disorder were highly correlated ( r = .443 to r = .782), and one shared latent underlying factor explained between 42.3% and 88.7% of the brain structural variance of each disorder. The observed shared morphometric signature of these disorders showed little similarity with brain structural patterns related to physiological aging. In contrast, patterns of brain structural abnormalities independent of all other disorders were observed in both attention-deficit/hyperactivity disorder and autism spectrum disorder. Brain regions showing high proportions of independent variance were identified for each disorder to locate disorder-specific morphometric abnormalities. 

Conclusions 

Taken together, these results offer novel insights into transdiagnostic as well as disorder-specific brain structural abnormalities across 6 major psychiatric disorders. Limitations comprise the uncertain contribution of risk factors, comorbidities, and medication effects to the observed pattern of results that should be clarified by future research.

Nils Opel, et al., "Cross-Disorder Analysis of Brain Structural Abnormalities in Six Major Psychiatric Disorders: A Secondary Analysis of Mega- and Meta-analytical Findings From the ENIGMA Consortium." Biological Psychiatry, 2020; DOI: 10.1016/j.biopsych.2020.04.027

Against Trans-Substantive Health Care Policy

I understand the impulse, particularly in the area of mental health care and reproductive health care for these red haired children of the main allopathic medical system's institutions and health care coverage.

But, I am not convinced that this is a good approach, not withstanding the undeniable existence of strong mind-body connections in certain kinds of conditions.

From an economic perspective, reproductive health care "naturally" is tied to the entire life cycle. Pregnancies in modern civilization are a few times a lifetime thing, at most, so an annual expenditure oriented health care lan isn't a good way to spread the economic burdens associated with them.

Also, reproductive health care happens to be the focal point of intense, intransigent and enduring political conflicts in our society, while making up only a tiny percentage of total health care costs. 

Insulating this controversial but not very expensive part of the health care system from the ordinary uncontroversial heartland of allopathic medical treatments for predominantly physical conditions, which are exceedingly expensive in the United States, and vice versa, makes sense. A lack of controversy, comparatively, is a good step towards securing widespread public support for the expensive ordinary health care portion which it needs.

Meanwhile, mental health care has very modest functional overlap between the personnel who deal with one and those who deal with physical health. One can be a competent mental health practitioner without having a full fledged medical doctor's education the way that a psychiatrist does, and MD's are an extremely high cost way to provide mental health services that less expensive specialist practitioners could provide just as well.

Also, physical health care institutions, for the most part, are designed, perhaps poorly, for patients with mostly episodic acute afflictions for which the normative treatment is a cure or one time recovery, who can effectively advocate for themselves in a large bureaucratic system or have someone to do so on their behalf.

But, a good mental health care system, almost by definition, needs to meet the needs of patients who often by virtue of the condition that they seek to treat are ill equipped to advocate for themselves in a large bureaucratic system, and are paradigmatically chronic, incurable conditions that are part of who someone is as a person, that need to be managed for a lifetime.

Further, some kinds of care like dentistry, hearing and vision care, while superficially like other kinds of allopathic physical health care, seem to work well with different business models based upon narrow specialization among health care practitioners, relatively non-urgent timing needs for care in most cases, and a focus on continuing maintenance and management of symptoms as much as cures, that make conventional capitalist consumer goods and services business models work better for them than for other parts of health care.

Why take sub-industries of the health care system in the U.S. like dentistry and vision care that aren't deeply broken and try to fold them into the rest of the health care system in the United States which is deeply broken? 

The Genetics Of Mental Health

A major new genome wide association study published in the journal Science has significant new findings related to mental health. The core finding of the study is as follows:

The final results indicated widespread genetic overlap across different types of psychiatric disorders, particularly between attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder, and schizophrenia. The data also indicated strong overlap between anorexia nervosa and obsessive-compulsive disorder (OCD), as well as between OCD and Tourette syndrome. 

In contrast, neurological disorders such as Parkinson's and multiple sclerosis appeared more distinct from one another and from the psychiatric disorders -- except for migraine, which was genetically correlated to ADHD, major depressive disorder, and Tourette syndrome.

From here.

A full set of abstracts from the article appear below the fold.

An Obamacare Critic's Concerns Considered

A friend of mine reports this exchange on the Facebook page of her Congressman (emphasis mine):

So today, as I often do, I posted a pointed but respectful critical comment on my Rep. (Dave Brat)'s Facebook page, in response to him voting yes on the "healthcare" bill today. Below is one of the responses to my comment. 

"Fine with me. I am sick of paying premiums 5 times higher to cover deadbeats with issues from obesity, smoking, drugs, maternity, PMs, meds and sports injuries. Stick it to them ...they stuck it to us."

My friend was somewhat shocked by the response, basically because it was so heartless.

I think it is fair to assume that this particular response is a sincere, heartfelt statement about why this particular constituent doesn't like the current Obamacare system, and that lots of other people hold the same view.

Essentially, this constituent frames this as a moral issue and believes that a lot of her health insurance premiums (it could be a he or a she, I don't actually know), are due to bad choices deliberately made by others that she shouldn't have economic responsibility for subsidizing.

Also, ultimately, her grievance is that her health insurance premiums are too high, and she really just wants to solve the problem that these premiums impose on her household budget and doesn't really much care what the consequences of a solution to that problem might be.

The premiums she pays for the conditions she claims run up premiums five fold, actually account for closer to 45% of her premiums, with smoking and obesity being the primary sources of those costs which account for 32% of her premiums (v. 13% for the other complained of charges). But, this is still significant and the premium surcharges allowed by Obamacare for smokers, in practice, account for only about 2% of increased health care expenses associated with smoking. But, about 24% of American adults are obese, about 17% smoke, and about 6% are both obese and smoke, so the surcharges she proposes would affect about 41% of people with health insurance.

It would take a $315 per month smoking surcharge to prevent smokers from being subsidized by non-smokers (the current average is $70), and given that Obamacare allows up to a 50% premium increase for smokers and that the average monthly premium for a family of four is $833, a significant share of that subsidy could be reduced by increasing the surcharge for smokers. Thus, a non-smoking family of four with pay about $661 per month for health insurance, while a family of four with one smoker would pay $976 per month for health insurance, and if there were two smokers they would pay $1,291 per month.

To prevent subsidies for obese people, there would have to be a $214 per month premium increase for them per year relative to the status quo, while non-obese people would see a $92 per month premium decrease. Thus, a family of four with no obese people would pay $741 a month for health insurance, while a family of four with one obese person would pay $955 a month, and a family of four with four obese people would pay $1,597 a month.

If both of these factors were combined a family of four with no smokers and no one who was obese would pay about $570 a month for health insurance, while a family of four with four obese people and two smokers would pay $2,055 a month for health insurance.

On one hand, smoking and obesity combined with mandatory health insurance does impose a substantial ($266 a month) take on families with no smokers who have no one who is obese.

On the other hand, these are very common conditions which are very difficult to change even in the face of large monetary incentives, and forcing individuals to bear their individualized share of a global expenditure defeats the purpose of health insurance to a great extent, and the practical effect of increased premiums for smokers and the obese which are sufficient to fully ameliorate the subsidy would prevent many smokers and obese people from obtaining any coverage.

But, speaking with an economist's "third hand", it is also possible to reduce the amount of the subsidy cause by the health insurance premium setting process, without eliminating it entirely, splitting the difference between the approaches. One can have some surcharges that don't fully capture the additional costs of including someone with certain

For example, one could reduce the monthly premium for health insurance from $833 per month to $758 per month, if the smoking surcharge was $158 per month per smoker, and the obesity surcharge was $107 per month per obese person. This would push the premium for a family of four with two smokers and four obese people to $1,502 per month. It would push the premium for a family of four with no smokers put four obese people to $1,186 per month, and for a family of four with no smokers and two obese people to $972 per month. So, premium surcharges for some high cost conditions that a significant economic incentive might reduce the incidence of might be justified in a health care policy.

On the other hand, there are other conditions like maternity coverage, sports injuries, prescription medicine coverage, and mental health care, where the premium reduction benefits of excluding coverage would be modest, but the impact in individuals with these needs would be high. And, in the case of prescription medicine coverage and mental health care, there is very little that a prudent person could do to avoid having these conditions.

A fair decision to consider certain risks in setting premiums involves a mix of the amount of subsidy involved, on average, with allowing people with those above average risks to have an unsurcharged premium, and the extent to which the condition is avoidable.

The analysis that leads to these conclusion are below.

ASGH 2017 Abstracts

The abstracts of the conference presentations at the American Society of Human Genetics Conference in Orlando, Florida for 2017 which is currently in progress is available here. It sorts by first digit of the paper number so, for example, 2, 20, 201 and 2001 are all adjacent to each other. Plenary and platform talks have numbers up to 372. Higher numbers are poster-presentations.

General observation. Lots of studies looked at whether disease predictive tools like risk scores work across ancestry lines. Generally they do, but often they omit additional ancestry specific genes with similar phenotypic consequences.

14 Sperm have more de novo mutations than other kinds of cells

Various sporadic human diseases, ranging from autism spectrum disorders to congenital heart disease and muscular dystrophies, are caused by de novo mutations. In a classical model, these are assumed to occur at a low rate in the parental germ cells (10-4-10-8). Consequently, de novo mutations identified by genetic testing are often assigned a low risk of recurrence in siblings. This idea is increasingly challenged by the detection of mosaicism in the parents. However, previous studies were largely restricted to the analysis of somatic tissues, whose genetic information is, by definition, not transmitted to the next generation. Here, we directly assessed the presence of inherited “de novo” mutations in paternal sperm and discovered abundant, germline restricted mosaicism. These samples were collected from a panel of fourteen families with a proband presenting with autism spectrum disorder. For all of these a candidate de novomutation had been identified in our ongoing genetic studies of this disorder. Employing digital droplet PCR, the causative variants were detectable in 4 sperm samples, but virtually absent or drastically reduced in the somatic tissue for 3. The latter mutations were present a high allelic fractions (AF), comprising SNVs in NR2F1 (AF=8%) and GRIN2A (AF=15%), as well as a large deletion of CACNG2 (AF=10%). As a consequence, the GRIN2A variant, despite being undetectable in the father by classical genetic testing, was inherited by three siblings presenting with phenotypes consistent with this mutation.

We next used deep whole genome sequencing (90x) of matched sperm and blood samples of four fathers to test for germline mosaicism of all de novo variants present in the offspring. 5-10% of these mutations were detectable in the paternal sperm, half of which were absent or at very low levels (<2%) in the matched blood. These data, together with an unbiased analysis employing mosaic variant detection algorithms, suggest that germline-specific or germline-enriched mosaicism is currently underestimated. This information has important potential implications for clinical practice. Based on our results, genetic analysis of sperm has the potential to quantify individualized recurrence risks for affected families, but could also have predictive value for prospective fathers.

18 Alternative splicing of brain-expressed transcripts distinguishes major adult psychiatric disorders

19 Sexually dimorphic DNA methylation in human brain and relevance to psychiatric disorders

134 Gene x environment links between obesity and depression

204 Migraine risk inheritance patterns in Finland

216 Genome testing is very useful in treating NICU patients

1033 Genetics of child onset psychosis

1038 Gene associated with intellectual disability with severe self-harm

1048 DNA testing determines cause of 30% of intellectual disability cases not otherwise determinable

1287 Estimating contamination in DNA samples without doing comparisons

1314 Estimating genetic condition frequency with a combination of determination of frequency in people with monogenetic cause disease and review of population sample of genomes

1461 Infant development is affected by their microbiomes.

1596 Large, long term study evaluates stroke risk

1611 Search for opiod addiction gene in white women

1612 New markers for schizophrenia severity (about 80% hereditary)

1700 Genes involved in disorders of sex development (e.g. hemaphrodites)

2059 FASD (Fetal Alcoholism Spectrum Disorder) is indistinguishable from ADHD and has genetic origins rather that prenatal alcohol exposure origins; FAS (Fetal Alcohol Syndrome) has an environmental cause and is very distinct from FASD and ADHD.

2099 Some ADHD genes found in African-Americans are not found in other populations. A stable 6%-7% of kids are diagnosed with ADHD which is 75% to 90% genetic. (One of the other studies notes an 80% persistence from childhood to adulthood.)

2144 Genetics of ADHD hyperactivity/impulsivity and inattention dimensions are quite different

2199 Most lifespan benefits of education are mediated through smoking or not

2468 DNA studies of kids with ADHD are worth it 8%-13% of the time.

2523 Discusses mosaicism and chimerism in humans

2579 Aging as measured by telomeres in preschoolers already differs based on sex and race in New Zealand children

2767 BMI is 48%-60% hereditary

2842 Alcoholism is 50%-65% hereditary

Child Psychopathy Can Be Managed With Cutting Edge Treatment

It has been known for a while now that a significant share of individuals who as adults would be classified as pyschopaths have had that traits since at least age 3-4 and probably congenitally (the etiology of psychopathy is unknown but is believed to involve the limbic system in general and the amygdala, in particular).

A story in The Atlantic magazine discusses two programs that have been successful in helping kids with this condition manage it. It doesn't cure the condition, although there is some hope that childhood treatment may alter its progression. But, it does use psychological hacks flowing from an understanding of how psychopathy changes a person behaviorally to tame a child's destructive and dangerous tendencies, and to channel the child into more pro-social behavior.

The article is rich, credible, consistent with other writing on the topic and worth time to read, even though it is lengthy.

Until now, no really proven treatment programs existed. The condition is present in about 1% of kids, comparable in frequency to schizophrenia, bipolar personality and autism spectrum conditions. But, because its connotations are (rightfully) so horrible, there hasn't been a social movement to help those who suffer from it in the same way that there has for those other conditions. For the most part, the existing default approach has been to address this conditions through the ordinary criminal justice system, both for juveniles and adults, by imposing long periods of incarceration or capital punishment.

The Genetics of PTSD

The Study and Its Raw Results

A new genetic study is casting light on post-traumatic stress disorder, which shows much different hereditary patterns in men than in women. (Hat tip to Razib Khan's twitter feed.)

Half of the 20,000+ study subjects were European-American and half were African-American, which is atypical for a large scale GWAS study like this one.  Typically, for GWAS studies, almost all of the risk factor genes were individually rare and small in effect. The genetics of PTSD risk in women appears to be massively polygenetic in a manner that could not entirely inaccurately be summarized as a risk based upon cumulative genetic load.

About 29% of PTSD risk in women is heritable (at the low end of what is typical for many personality traits and much lower, for example, than IQ or schizophrenia or alcoholism). In men, the heritable component of PTSD risk is not significantly different from zero.

The genetic component of the PTSD risk in women overlaps significantly with schizophrenia risk, and more modestly with bipolar disorder and unipolar depression (unsurprisingly since these conditions have similar genetic overlap with schizophrenia in general).

Analysis

The abstract doesn't provide raw PTSD rates, but my intuition is that most PTSD in men is almost exclusively environmental in cause, while women experience environmental events that trigger PTSD in people who aren't especially susceptible to PTSD at much lower rates. Therefore, PTSD associated with high vulnerability to events that might not cause PTSD in the average person is statistically discernible in women, but vanishes into the statistical noise in men, even though excessive vulnerability to marginally PTSD inducing events in men may actually be present at similar rates in men as in women.

This suggests that the genes associated with PTSD risk in women are probably, in some broad sense, basically genes associated with resilience or lack thereof in the face of stressors such as those posed by a less extreme PTSD triggering event. 

On the other hand, the particular association with schizophrenia, which makes some sense given that PTSD is typically defined as experiencing trauma-like reactions in circumstances where the trauma causing event is no longer present, may alternatively suggest that these genes reflect how "grounded in sensory experience" as opposed to being vulnerable to having internal neurological processes overwhelm one's senses a person's nervous system is.