HoldsUp

Huberman Lab · 2026-02-09 · Andrew Huberman (host), Kathryn Paige Harden

How Genes Shape Your Risk Taking & Morals | Dr. Kathryn Paige Harden

47 research-tied claims examined: 4 contradicted 3 overstated 5 context 28 supported 7 unverified

4 Contradicted by research
0:58:26Kathryn Paige Hardencontradictedmoderate

Childhood-onset antisocial behavior shows a male-to-female sex ratio between 2:1 and 4:1.

"The sex ratio varies, but sometimes it's two to one, sometimes it's as high as four to one." (said at 0:58:26)

The speaker claimed that the male-to-female sex ratio for childhood-onset antisocial behavior varies between 2:1 and 'as high as four to one'. However, published developmental psychopathology literature and longitudinal research show that childhood-onset (life-course persistent) antisocial behavior exhibits a much larger male preponderance, often reported between 4:1 and up to 10:1. In contrast, the narrower sex ratio cited by the speaker (~1.5:1 to 2:1) is characteristic of adolescent-onset antisocial behavior.

1:08:00Kathryn Paige Hardencontradictedlow

A subsequent study identified rare MAOA mutations in several other impulsively aggressive boys referred to a hospital.

"And later there was another group that found this ostensibly rare mutation in several other impulsively aggressive boys that had been referred to their hospital." (said at 1:08:00)

The claim that a subsequent hospital-based cohort study identified the rare Brunner syndrome MAOA point mutation (or novel functional MAOA deficiency mutations) across several other impulsively aggressive boys is contradicted by replication studies. Following the initial 1993 description by Brunner et al. in a single Dutch kindred, subsequent screening studies of aggressive, impulsive, and institutionalized males (such as 54 aggressive males in secure facilities screened by Craddock et al., 2001) failed to identify MAOA-deficiency mutations in psychiatric/hospital referrals. Complete loss-of-function MAOA mutations (Brunner syndrome) remain exceptionally rare, with only isolated kindreds/individual cases identified globally rather than a series of cases among hospital referrals.

1:38:50Kathryn Paige Hardencontradictedlow

A study on marital conflict found that after an argument, men's cortisol levels spiked and quickly returned to baseline, whereas wives' cortisol levels remained elevated for approximately 24 hours.

"And they looked at how long did men's cortisol remain elevated after an argument compared to the wives' cortisol. And it was basically like they had the fight, his spiked up and then it went down like classic Trier curve, and hers was elevated for like 24 hours afterwards." (said at 1:38:50)

Studies of marital conflict and endocrine responses (notably the classic laboratory conflict paradigms by Kiecolt-Glaser and colleagues) have found that wives often exhibit greater or more persistent neuroendocrine reactivity (such as cortisol and catecholamines) in response to negative marital interactions or spousal withdrawal compared to husbands. However, acute cortisol responses to an argument follow standard physiological recovery kinetics over hours rather than remaining elevated for 24 hours. In these studies, cortisol was typically measured over a 30-minute conflict discussion, short recovery periods (e.g., 15-60 minutes), or pooled across daytime hours (8:00 a.m. to 10:00 p.m.), not showing a continuous 24-hour post-conflict elevation in wives.

2:34:14Kathryn Paige Hardencontradictedmoderate

The heritability of personality traits continues to increase with age until around age 30.

"Heritability of personality continues to increase until around age 30." (said at 2:34:14)

The claim confuses personality traits with general cognitive ability (intelligence). In behavioral genetics, the heritability of intelligence is well-documented to increase from childhood through young adulthood (reaching ~70–80% around age 30, known as the Wilson effect). In contrast, twin and lifespan studies of personality traits show that personality heritability remains roughly stable (~40–50%) or decreases across adulthood, as environmental and life experiences account for an increasing proportion of variance across the lifespan.

3 Overstated
0:56:50Kathryn Paige Hardenoverstatedlow

Between 50% and 75% of children with conduct disorder onset before age 10 and callous-unemotional traits develop an adult substance use disorder.

"So of those kids who have conduct disorder, especially before the age of 10 with these callous-unemotional features, we would expect that 50 to 75% of them will have a substance use disorder in adulthood." (said at 0:56:50)

Although childhood conduct disorder and conduct problems are recognized risk factors for later substance use problems, the specific assertion that 50% to 75% of children with early-onset conduct disorder (before age 10) and callous-unemotional (CU) traits develop an adult substance use disorder is an overstatement not supported by the literature. Meta-analyses demonstrate only modest associations (θ ≈ 0.15-0.17) between CU traits and youth substance use, and prospective longitudinal cohorts (such as Fast Track and the Child Development Project) indicate that CU traits generally fail to provide substantial incremental predictive validity for adult substance use disorders once general conduct problems are accounted for.

1:06:10Kathryn Paige Hardenoverstatedvery low

An autopsy following Charles Whitman's mass shooting at UT Austin found that he had a tumor in his amygdala.

"When after he died, the state of Texas ordered an autopsy, and they found that he had this tumor... He got a tumor in his amygdala, and he wouldn't have done it if he hadn't had this tumor." (said at 1:06:10)

Following the 1966 University of Texas tower shooting, an autopsy and subsequent medical review by the Governor-appointed Connally Commission did find a glioblastoma (astrocytoma) in the temporal lobe compressing the amygdala and adjacent limbic structures. However, asserting that 'he wouldn't have done it if he hadn't had this tumor' is an overstatement. Forensic neuropathologists and historical expert panels concluded that while the tumor may have contributed to his impulse dysregulation and mood changes, definitive causation cannot be established, particularly given other contributing factors including amphetamine abuse, severe emotional stressors, and potential traumatic brain injury.

1:46:47Kathryn Paige Hardenoverstatedvery low

In animal experiments where rats are shocked while pressing a bar for alcohol, some rats cease pressing the bar while others paradoxically increase their rate of pressing.

"If you give a rat alcohol every time it presses a bar, and then you stop mid-experiment and you start shocking it, some rats will stop pressing the bar, and other rats will actually increase their rate of behavior." (said at 1:46:47)

In rodent operant conditioning models of compulsive alcohol use, introducing footshock punishment reveals a bimodal distribution: punishment-sensitive rats suppress or cease lever pressing, whereas punishment-resistant (compulsive) rats continue to press and seek alcohol despite the shock. However, published literature characterizes this compulsive phenotype as persistent, aversion-resistant responding (resistance to suppression), rather than a paradoxical increase above baseline response rates.

5 Needs context
0:00:00Kathryn Paige Hardenneeds contextmoderate

Observing someone receive an electric shock typically activates the anterior insula, but if the person is portrayed as violating a moral or social norm, the brain shows a reward response involving dopamine instead.

"There is a reward that we can see in the brains of people when they see someone suffer if that person is first portrayed as a wrongdoer. So ordinarily if you see someone be shocked, you have anterior insula. It's like you're being shocked, too. Unless that person is first portrayed as violating some moral or social norm, in which case dopamine, you get a reward out of seeing that person punished." (said at 0:00:00)

The speaker accurately describes the findings of landmark neuroimaging research by Singer et al. (2006). In that study, observing a fair player receive electric shocks activated empathy- and pain-related areas, including the fronto-insular / anterior insula cortex. However, when observing an unfair player (a norm violator) receive pain, empathy responses were significantly reduced and reward-related brain circuitry was activated instead. Context is warranted because this reward activation was prominently observed in male participants (female participants still showed empathic insula activation toward unfair players), and fMRI measures blood-oxygen-level-dependent (BOLD) activation in dopaminergic reward areas (such as the nucleus accumbens) rather than direct dopamine neurotransmission.

0:13:18Kathryn Paige Hardenneeds contextlow

Executive cognitive functions such as attention shifting and updating are more strongly related to chronological age, whereas risk sensitivity, peer-oriented learning, and certain emotional responses are more strongly tied to pubertal development.

"So, it does seem like there are some cognitive functions, like if you're thinking about executive function ability, your ability to shift attention or update, the things that are tested by a standard IQ test, those seem to be much more age-related, whereas your ability to learn from peers versus your parents, your sensitivity to risk and certain types of emotions, that seems to be more tied to pubertal development than with age." (said at 0:13:18)

The speaker's distinction aligns with prominent theoretical neurodevelopmental frameworks (such as dual-systems models of adolescence), which propose that 'cool' executive cognitive functions (e.g., working memory updating, set-shifting) track linear chronological age and prefrontal cortical maturation, whereas 'hot' socioemotional processing, risk sensitivity, and peer orientation are driven primarily by gonadal hormones and pubertal maturation. However, empirical studies attempting to statistically disentangle chronological age from pubertal status have yielded mixed results. Recent systematic reviews note that while many 'cool' executive functions are primarily age-dependent, evidence regarding the independent contribution of pubertal status versus age remains inconclusive and heterogeneous across sexes and task domains.

1:12:30Andrew Huberman (host)needs contextlow

Rabies is a neural virus that infects the amygdala and causes individuals to become very aggressive.

"Like we can make the connection very easily, but that's a neural virus that hits the amygdala among other things and causes people to get very aggressive." (said at 1:12:30)

Rabies is a classic neurotropic virus that ascends through the central nervous system, affecting the brainstem and limbic system (which includes the amygdala). In the encephalitic ('furious') form of rabies, limbic and central involvement commonly produces severe agitation, hyperactivity, and behavioural changes. However, while aggression and biting are characteristic behavioural features in animal hosts, humans typically present with severe agitated delirium, hydrophobia, aerophobia, and autonomic dysfunction rather than directed aggressive biting, and pathology involves widespread neuronal dysfunction across multiple central and limbic structures rather than an isolated lesion to the amygdala.

1:37:25Kathryn Paige Hardenneeds contextmoderate

Research shows that the same genes predisposing boys to physical aggression also predict relational aggression in girls.

"And so what we see in research is that the same genes that predict physical aggression in boys predict relational aggression in girls." (said at 1:37:25)

Behavioral genetic and twin studies confirm that physical aggression and relational (social) aggression share substantial underlying genetic etiology (with bivariate twin models estimating that a major portion of genetic influences on physical aggression also influence social/relational aggression). However, quantitative twin modeling indicates that these shared genetic and environmental factors operate similarly across both boys and girls, rather than functioning as a sex-divergent genetic switch where genes selectively manifest as physical aggression exclusively in boys and relational aggression exclusively in girls.

2:33:43Kathryn Paige Hardenneeds contextmoderate

The heritability of cognitive ability and intelligence test scores increases with age until approximately age 12.

"So the heritability of cognition, intelligence test scores goes up until around age 12, in which case it stays pretty heritable from then." (said at 2:33:43)

The speaker correctly describes the phenomenon known as the 'Wilson Effect'—that the heritability of cognitive ability and IQ increases during development and remains high thereafter. However, large twin cohorts show that the increase in heritability does not plateau at age 12; rather, it continues to rise linearly through adolescence (from ~41% at age 9 to ~55% at age 12 and ~66% at age 17), reaching an asymptote of approximately 80% in young adulthood (around 18–20 years of age).

28 Supported by research
0:04:17Kathryn Paige Hardensupportedhigh

A person's first psychotic episode typically occurs in late adolescence or early adulthood.

"If you're going to have a first psychotic episode, that's going to be in late adolescence, early adulthood." (said at 0:04:17)

Large-scale epidemiological studies and meta-analyses consistently demonstrate that the onset of primary psychotic disorders typically occurs during late adolescence and early adulthood. A major meta-analysis of 192 epidemiological studies (Solmi et al., 2022) found that the peak age of onset for schizophrenia-spectrum disorders and primary psychotic states is 20.5 years (median 25 years, interquartile range 20–34 years).

0:08:07Kathryn Paige Hardensupportedmoderate

For girls, earlier onset of puberty predicts increased risk for mental health issues, physical health problems, earlier menopause, and a shorter lifespan.

"For girls, early pubertal timing seems to be the best predictor of risk for mental health problems, physical health problems, earlier menopause, shorter lifespan." (said at 0:08:07)

Large-scale epidemiological studies, systematic reviews, and meta-analyses consistently support the association between early pubertal timing (early menarche) in girls and increased risk across all four stated domains: mental health problems (e.g., elevated risk of depression), physical health disorders (including obesity, type 2 diabetes, metabolic syndrome, and reproductive cancers), earlier/premature menopause, and reduced lifespan (higher all-cause mortality).

0:08:55Kathryn Paige Hardensupportedmoderate

Boys' emotional development is more heavily affected by the pace or tempo of puberty than by the age at which puberty starts.

"We did a study many years ago where we found that boys were less affected by when it started but more affected, at least for their emotional development, by how quickly it happened, with boys where they changed overnight having the hardest time sort of assimilating all these changes that are happening" (said at 0:08:55)

The speaker accurately describes their 2010 longitudinal study (Mendle, Harden, Brooks-Gunn, & Graber), which followed 128 boys and 138 girls over 4 years to examine pubertal timing versus pubertal tempo. The authors found that while pubertal timing was the primary predictor of depressive symptoms in girls, for boys, pubertal tempo (the rate of physical change) was a stronger predictor of depressive symptoms than the age at which puberty began.

0:09:50Kathryn Paige Hardensupportedmoderate

Faster biological aging as measured by DNA methylation epigenetic clocks predicts shorter lifespan, worse health, and earlier mortality.

"So there's great work in aging that shows that the epigenetic clock measured by DNA methylation starts ticking in infancy, and faster biological aging as measured by the epigenome predicts shorter lifespan, worse health, earlier mortality." (said at 0:09:50)

Extensive meta-analyses of prospective cohort studies confirm that accelerated biological aging, measured via DNA methylation epigenetic clocks (such as Horvath and Hannum clocks), independently predicts all-cause mortality, shorter lifespan, and adverse health outcomes even after adjusting for chronological age and established lifestyle and cardiovascular risk factors.

0:10:15Kathryn Paige Hardensupportedmoderate

An epigenetic clock trained on physical pubertal maturation correlates with chronological aging clocks and relates to more rapid aging later in life.

"What we looked at is, well, instead of training an epigenetic clock on age, can we train it on pubertal development? So, how physically mature you are? And what we found is you can. So, the clock is ticking as you get older, but there's another clock that's also ticking as you become more physically mature. And those two things are correlated. So the epigenetic changes that we see as you go through puberty faster do seem to be related to aging more rapidly even in older life." (said at 0:10:15)

Evidence supports the speaker's claim. Researchers have developed DNA methylation (epigenetic) clocks trained specifically on physical pubertal development and pubertal age rather than chronological age alone. These pubertal epigenetic markers correlate with biological aging signatures across species and earlier pubertal timing/tempo is linked to accelerated biological aging clocks (e.g., DunedinPACE, GrimAge) and elevated epigenetic mortality risk later in life.

0:16:53Kathryn Paige Hardensupportedmoderate

Girls raised with a non-biological father tend on average to reach puberty earlier than girls raised with their biological father.

"It is true that girls, human girls who are raised with a non-biological father do, on average, tend to go through puberty earlier." (said at 0:16:53)

A substantial body of literature, including meta-analyses and longitudinal cohort studies, supports the claim that the absence of a biological father and the presence of non-biological male figures (stepfathers/half-brothers) in the household are associated on average with earlier pubertal timing (earlier menarche and earlier breast development) in girls.

0:18:35Kathryn Paige Hardensupportedmoderate

The average age of puberty onset has been continuously falling with every successive historical cohort.

"And that's part of why we're seeing that the age of puberty keeps going down with every successive cohort. I mean, it's been falling for basically as long as we've been keeping data, people have been going through puberty earlier." (said at 0:18:35)

Extensive epidemiological data and systematic reviews demonstrate a long-term historical secular trend toward earlier pubertal onset (e.g., thelarche) and menarche across successive birth cohorts. A 2020 systematic review and meta-analysis of worldwide data found that the average age of pubertal onset in girls (assessed by thelarche) decreased by approximately 0.24 years (nearly 3 months) per decade between 1977 and 2013. Large cohort analyses and meta-analyses spanning over a century (e.g., in Europe and Asia) similarly show continuous historical declines in pubertal timing across successive birth cohorts dating back to the 19th century, although the rate of decline has varied by region, socioeconomic conditions, and time period.

0:28:20Kathryn Paige Hardensupportedmoderate

Scandinavian adoption and pedigree studies show that having a biological parent with alcohol addiction increases an offspring's likelihood of having multiple sexual partners, conduct disorder, or violent crime arrests, even when reared apart.

"So these big data registries, you get them in Sweden, you get them in the Scandinavian countries that keep track of every single one of their citizens. And what you see is that the seven deadly sins run in families. So if you have a biological parent who's addicted to alcohol, you are more likely to have many sexual partners. And you're also more likely to be diagnosed with conduct disorder or be arrested for a violent crime, even if you were never raised by that parent." (said at 0:28:20)

Scandinavian national registry adoption studies (notably Swedish cohorts analyzed by Bohman, Cloninger, Kendler, and colleagues) demonstrate significant cross-trait genetic transmission within the externalizing spectrum. Having a biological parent with alcohol use disorder or externalizing problems increases the adopted-away offspring's risk of criminal convictions (including violent crime), conduct disorder, and related externalizing behaviors, even when reared in an adoptive environment without that biological parent.

0:29:13Kathryn Paige Hardensupportedmoderate

The polygenic variants associated cross-cuttingly with impulsivity, substance use, and aggressive behaviors are most actively expressed during cortical development in the second and third trimesters in utero.

"So what we found is that there's many, many, many genes that affect all of these behaviors. It's massively what we call polygenic. So it's not just one thing in one part of your genome. It's distributed throughout your genome, and that those genes are most expressed in neurodevelopment in utero in second and third trimester. So if you look at genes that are associated with all of these things and you see, okay, when in the human lifespan are they most active? They're active during cortical development in the second and third trimester." (said at 0:29:13)

In a massive multivariate genome-wide association study (GWAS) of approximately 1.5 million individuals investigating cross-cutting genetic liability across externalizing spectrum phenotypes (impulsivity, substance use disorders, ADHD, and antisocial behavior), researchers identified hundreds of loci distributed across the genome. Bioinformatic gene-property and spatiotemporal developmental enrichment analyses (using resources such as BrainSpan) revealed that genes tagged by these polygenic variants are heavily enriched for neurodevelopmental processes and show peak expression during prenatal neurodevelopment, specifically during second- and third-trimester cortical neurogenesis and differentiation.

0:30:56Kathryn Paige Hardensupportedmoderate

Genes associated with substance use disorders and conduct disorder affect early life brain development and the balance between inhibition and excitation.

"Because if you look at the genes that are causing them, they seem to be affecting this pattern of brain development very, very early in life and this balance between the brain's inhibition and excitation." (said at 0:30:56)

Large-scale multivariate genome-wide association studies (GWAS) analyzing millions of individuals across externalizing disorders (including substance use disorders, conduct disorder, and ADHD) demonstrate that shared genetic risk variants are significantly enriched for genes involved in early neurodevelopment, synaptic function, and the balance between inhibitory (GABAergic) and excitatory (glutamatergic) neurotransmission.

0:34:00Kathryn Paige Hardensupportedmoderate

Chronic engagement in maladaptive behaviors such as drug use, aggression, and risky sexual behavior typically involves three personality dimensions: sensation-seeking, disinhibition, and antagonism or callousness.

"usually when we think of people who are chronically engaging in some behavior despite it having negative consequences for themselves and other people—so this could be drug use, this could be aggression, this could be risky sexual behavior—we can typically think of three dimensions of sort of personality and temperament that are often at play. And one of them is this sensation-seeking drive for intensity... And then one is this disinhibition, failure of self-control... And then another, which I think is less well-studied, is what people call antagonism or callousness" (said at 0:34:00)

Extensive empirical research in personality psychopathology—including the Hierarchical Taxonomy of Psychopathology (HiTOP), the DSM-5 Alternative Model for Personality Disorders, and the Triarchic Model—demonstrates that chronic externalizing and maladaptive behaviors (such as substance use, aggressive behaviors, and high-risk behaviors) map directly onto core personality dimensions including disinhibition (impulsivity/lack of self-control), sensation-seeking/boldness (drive for excitement/intensity), and antagonism/callousness (meanness/low agreeableness).

0:41:50Kathryn Paige Hardensupportedmoderate

A psychological study conducted after the fall of the Berlin Wall found significant individual differences in deliberate ignorance regarding whether former East German citizens chose to view their Stasi surveillance files.

"there was a great study after the wall came down in Berlin that was conducted on whether or not people want to know the contents of their files, like who was reporting on them. And some people were like, "Of course I want to know. Of course I want to know who was saying what about me." And other people were saying, "No, I don't. Ignorance is bliss. Deliberate ignorance is what I want."" (said at 0:41:50)

A study investigating deliberate ignorance regarding the opening of the East German Stasi archives after 1991 found that many citizens actively chose not to view their files. Combining psychological survey methods and historiographical analysis, the researchers identified distinct individual motivations for choosing deliberate ignorance (or wanting to know), such as emotion regulation, avoiding interpersonal conflict, skepticism of the recorded information, and prioritizing personal harmony over institutional transparency.

  • supports: Why people choose deliberate ignorance in times of societal transformation. (Cognition 2022)
    "The opening of East Germany's Stasi archives in 1991 has often been lauded as a model of transparency in a transformative period. Yet many citizens have rejected the opportunity to read their files. To examine the reasons people invoke for this deliberate ignorance, we combined survey methods from psychology with historiographical methodologies. Our findings reveal a diverse range of reasons for deliberate ignorance, including regulation of negative emotions, avoidance of personal conflict, scepticism about the information compiled, and rejection of the victorious political system's authority over the files." (abstract, passage verified)
    pubmedfull study (doi)
0:55:56Kathryn Paige Hardensupportedmoderate

Onset of antisocial behavior before the age of 10 is one of the strongest prognosticators for a life-course-persistent pattern of antisocial offending.

"And that's one of the biggest predictors of what people have called a life-course-persistent pattern of antisocial offending, which is onset before the age of 10." (said at 0:55:56)

Terrie Moffitt's developmental taxonomy and extensive prospective longitudinal data (such as from the Dunedin Multidisciplinary Health and Development Study) establish childhood-onset antisocial behavior (conventionally defined in DSM criteria as onset prior to age 10) as the primary distinguishing predictor of a life-course-persistent trajectory of antisocial behavior and offending, compared to adolescence-limited antisocial behavior.

0:59:10Kathryn Paige Hardensupportedvery low

Male guinea pigs are significantly more vulnerable to the adverse effects of preterm birth than female guinea pigs.

"we also see this in animals, that male guinea pigs are much more vulnerable to the effects of preterm birth than female guinea pigs." (said at 0:59:10)

Preclinical studies using the guinea pig model of preterm birth demonstrate distinct sex-dependent vulnerabilities, with males exhibiting more pronounced adverse neurodevelopmental, neurochemical, and behavioral alterations (such as persistent reductions in frontal cortical dopaminergic pathway expression, decreased subcortical myelination, hyperactivity, and elevated stress responses) compared to females. Because this evidence is derived entirely from animal models, the GRADE certainty is rated as very low.

0:59:18Kathryn Paige Hardensupportedmoderate

Preterm birth disrupts the GABA-to-glutamate excitatory-inhibitory balance in neural development.

"Again, preterm birth disrupts that same kind of GABA to glutamate excitatory-inhibitory balance that um we're also seeing popping up in the genetic research." (said at 0:59:18)

Preterm birth disrupts the neurochemical excitation/inhibition (E/I) balance between GABAergic inhibition and glutamatergic excitation during neural development. In normal development, the fetal brain is maintained in an inhibitory-dominant state facilitated by placental neurosteroids acting on GABA-A receptors. Preterm delivery prematurely removes these maternal/placental trophic factors, diminishing GABAergic tone, while neonatal complications (such as hypoxia and excess glucocorticoids) elevate glutamatergic signaling, leading to a pathological shift toward excessive excitation.

0:58:58Kathryn Paige Hardensupportedhigh

Most genetic studies focus exclusively on the autosomes and exclude the sex chromosomes from analysis.

"most genetic studies just focus on the autosomes. So, just focus on, you know, the non-sex chromosomes." (said at 0:58:58)

Surveys of published genome-wide association studies (GWAS) confirm that the vast majority of genetic association analyses exclude the sex chromosomes (X and Y) and focus exclusively on the autosomes. A 2023 analysis of summary statistics in the NHGRI-EBI GWAS Catalog found that only 25% of studies reported results for the X chromosome and only 3% reported on the Y chromosome, while 0% of sampled polygenic scores contained weights for sex-chromosomal variants.

1:06:50Kathryn Paige Hardensupportedvery low

In a studied Dutch family with high rates of male aggression and criminal offenses, affected men inherited a rare mutation in the MAOA gene on the X chromosome.

"I write in my book this story of this Dutch family where basically all the women in the family were functioning okay, but half the men in the family were—one raped his sister, one stabbed his boss with a pitchfork, multiple—one committed arson, multiple of the men were in prison... And what they found is that on the X chromosome, they had inherited a rare mutation in the MAOA gene." (said at 1:06:50)

The claim accurately describes the classic pedigree study of a Dutch kindred (known as Brunner syndrome). Brunner and colleagues (1993) identified a large Dutch family where several affected males exhibited borderline intellectual disability and prominent impulsive aggressive behaviors, including arson, attempted rape, and physical violence. Genetic linkage and sequencing localized the condition to the X chromosome (Xp11.23-11.4) and identified a specific nonsense point mutation in exon 8 of the structural gene for monoamine oxidase A (MAOA), resulting in complete enzymatic deficiency. Because this evidence originates from a single kindred genetic pedigree/case-series design, the certainty of evidence is graded as very low according to standard criteria.

1:07:28Kathryn Paige Hardensupportedhigh

MAOA is an enzyme that degrades monoamines which regulate neuronal communication.

"So MAOA is an enzyme that degrades monoamines that regulate how your neurons are talking to one another." (said at 1:07:28)

The statement accurately reflects standard neurobiology and biochemistry. Monoamine oxidase A (MAOA) is an enzyme located on the outer mitochondrial membrane that oxidatively deaminates and degrades monoamine neurotransmitters (including serotonin, norepinephrine, and dopamine), which mediate chemical neurotransmission and communication between neurons.

1:18:31Kathryn Paige Hardensupportedmoderate

Bacterial colonies contain mechanisms of enforcement where bacteria send out signals to harm individual bacteria that consume excessive shared resources like iron.

"If you have bacteria, colonies of bacteria, and one bacterium starts to soak up too much of the iron or some mineral in the environment that they all need, the others will send out signals to try to hurt that one. And they're like, stop doing that. Stop freeloading. Stop taking too much." (said at 1:18:31)

The speaker's colloquial description accurately captures the microbial sociobiology concepts of 'policing' and 'sanctioning' against social cheating in bacteria. In bacterial populations, individuals share costly public goods (such as iron-scavenging siderophores or extracellular enzymes). When 'cheater' or 'freeloader' mutants stop contributing to public goods production while continuing to consume them, cooperative bacteria can deploy quorum-sensing-regulated chemical sanctions (such as toxic cyanide or pyocyanin in Pseudomonas aeruginosa) that selectively inhibit or kill the cheater strains, thereby maintaining cooperation.

  • supports: Quorum sensing and policing of Pseudomonas aeruginosa social cheaters. (Proceedings of the National Academy of Sciences of the United States of America 2015)
    "A possible way to restrict cheater emergence is by policing where cooperators produce costly goods to sanction or punish cheats... By using RhlR quorum sensing mutants and cyanide synthesis mutants, we show that cyanide production is costly and cyanide-producing cooperators use cyanide to punish LasR-null social cheaters. Cooperators are less susceptible to cyanide than are LasR mutants. These experiments demonstrate policing in P. aeruginosa, provide a mechanistic understanding of policing, and show policing involves the cascade organization of the two quorum sensing systems in this bacterium." (abstract, results)
    pubmedfull study (doi)
  • supports: Pyocyanin Restricts Social Cheating in Pseudomonas aeruginosa . (Frontiers in microbiology 2018)
    "Quorum sensing (QS) in Pseudomonas aeruginosa coordinates the expression of virulence factors, such as exoproteases and siderophores, that are public goods utilized by the whole population of bacteria, regardless of whether they invested or not in their production. These public goods can be used by QS defective mutants for growth, and since these mutants do not contribute to public goods production, they are considered social cheaters... Here, we demonstrate, using competition experiments and mathematical models, that, indeed, pyocyanin increases the fitness of the cooperative QS-proficient individuals and restricts the appearance of social cheaters." (abstract, results, passage verified)
    pubmedfull study (doi)
1:25:35Andrew Huberman (host)supportedmoderate

PFAS forever chemicals have been linked to hormone disruption, gut microbiome disruption, and fertility issues.

"As I've discussed before on this podcast, these PFAS or forever chemicals like Teflon have been linked to major health issues such as hormone disruption, gut microbiome disruption, fertility issues, and many other health problems." (said at 1:25:35)

Per- and polyfluoroalkyl substances (PFAS) are well-documented endocrine-disrupting chemicals. Systematic reviews and meta-analyses show that PFAS exposure is linked to reduced fecundability, increased risk of infertility, and altered sex and thyroid hormone levels in humans. Preclinical and emerging epidemiological studies also demonstrate that PFAS exposure induces gut microbiota dysbiosis and impairs intestinal barrier integrity.

1:30:25Kathryn Paige Hardensupportedlow

Mice establish rigid social hierarchies through aggression.

"I have a theory that a lot of scientific fields and men in scientific fields are a little bit like mice in that mice have very rigid social hierarchies that they establish through aggression." (said at 1:30:25)

Extensive ethological and behavioral laboratory research demonstrates that mice (particularly male mice, but also female groups) establish stable, linear, and often despotic social dominance hierarchies that are formed and maintained through aggressive interactions, such as chasing, fighting, and offensive biting.

1:42:52Kathryn Paige Hardensupportedmoderate

Adolescent boys and girls have similar trajectories of sensation seeking, but girls mature in impulse control faster, taking men until about age 24 to match the control of a 15-year-old girl.

"What you see is that actually in adolescence boys and girls have very similar trajectories of sensation seeking. Where they differ is in the evolution of their inhibitory control. So girls mature in terms of their impulse control faster than boys do. We did a study maybe 10 years ago now. It was basically it took until men around the age of 24 to be as controlled as your average 15-year-old girl was. There's like a decade-long gap in the maturation of impulse control." (said at 1:42:52)

The speaker is referencing a 2015 longitudinal study (Shulman, Harden et al., N = 8,270 from the NLSY Child and Young Adult Survey) investigating sex differences in developmental trajectories of impulse control and sensation-seeking from ages 10 to 25. The study found that while both sexes follow the general pattern of the dual-systems model (sensation seeking rises and falls, impulse control increases into the 20s), females mature in impulse control more rapidly than males, who increase in impulse control much more gradually, resulting in a substantial lag where young adult males take until their mid-20s to reach the impulse control levels of adolescent females.

  • supports: Sex differences in the developmental trajectories of impulse control and sensation-seeking… (Journal of youth and adolescence 2015)
    "The present study investigates sex differences in the developmental trajectories of self-reported impulse control and sensation-seeking between the ages of 10 and 25 using longitudinal data from the National Longitudinal Study of Youth 1979 Child and Young Adult Survey (N = 8,270; 49% female; 33% Black, 22% Hispanic, 45% Non-Black, Non-Hispanic)... As expected, males exhibit higher levels of sensation-seeking and lower levels of impulse control than females. Differences also emerged in the shapes of the developmental trajectories... Also, males increase in impulse control more gradually than females. Consequently, sex differences in both impulse control and sensation-seeking increase with age." (abstract, results, passage verified)
    pubmedfull study (doi)
1:56:05Kathryn Paige Hardensupportedmoderate

Neuroimaging shows that seeing an ordinary person shocked activates the anterior insula (empathy), but observing someone punished who was portrayed as a moral wrongdoer activates brain reward circuitry (dopamine).

"There is a reward that we can see in the brains of people when they see someone suffer if that person is first portrayed as a wrongdoer. So ordinarily, if you see someone be shocked, you have anterior insula—it's like you're being shocked, too. Unless that person is first portrayed as violating some moral or social norm, in which case dopamine: you get a reward out of seeing that person punished." (said at 1:56:05)

The claim accurately summarizes landmark neuroimaging research by Singer et al. (2006). In that fMRI study, observing a fair player receive electric shocks activated empathy- and pain-related brain regions, specifically the fronto-insular (anterior insula) and anterior cingulate cortices. When observing an unfair player (a norm violator) receiving pain, empathic brain activation was diminished and replaced by activation in reward-related brain regions (such as the nucleus accumbens/striatum), which correlated with an expressed desire for revenge (an effect observed predominantly in male participants).

1:44:05Kathryn Paige Hardensupportedhigh

The sex difference between men and women in healthspan is smaller than the sex difference in lifespan.

"And they die earlier, but women have that long—you know, they're alive, but they're not healthy on average at the end of their life. The difference in healthspan is less different than lifespan, as you know." (said at 1:44:05)

Demographic and epidemiological data consistently confirm the 'male-female health-survival paradox': while women have longer life expectancies (lifespans) than men globally, the female advantage in healthy life expectancy (healthspan) is smaller. Consequently, women live more absolute and proportional years in poor health or disability (a larger healthspan-lifespan gap). Large-scale global analyses, including data across 183 WHO member states and Global Burden of Disease estimates, confirm that the sex difference in healthspan is narrower than the sex difference in lifespan.

2:17:23Kathryn Paige Hardensupportedhigh

In experimental economics public goods games where participants can choose between an institution with punishment and one without, non-punishing institutions quickly collapse due to free-riding, driving participants to migrate to the punishment-enforcing institution where cooperation is maintained.

"There's this great study that was run by these economists where people were put into these online basically like online, you know, kind of societies where they could interact with one another and you could pick which societ which village did you want to join and you could switch villages at any time... By the end of the game, the non-punishing society has collapsed and everyone has migrated to the punishing society." (said at 2:17:23)

The speaker accurately describes the seminal experimental economics study by Gürerk, Irlenbusch, and Rockenbach published in Science (2006), as well as its recent multi-lab replication (2023). In these experiments, participants choose between an institution that allows sanctions/punishment and one without sanctions. While most participants initially prefer the sanction-free institution, free-riding causes cooperation in the sanction-free group to collapse, prompting nearly all participants to migrate over time to the sanctioning institution where high levels of cooperation and payoffs are maintained.

2:20:44Kathryn Paige Hardensupportedvery low

Genetically identical animals—such as inbred mice, nine-banded armadillo quadruplets, and clonal fish—exhibit emergence of individual behavioral variability even when reared in identical environments, a phenomenon scientists term developmental noise.

"We see this in other genetically identical animals. There's studies of inbred mice. There's studies of we were talking earlier about armadillos who give birth to four identical quadruplets. There studies of clonal fish. And what there seems to be is what some scientists have called developmental noise. Uh which is this emergence of individuality that's neither nature nor nurture, but is something about the, like, initial chaos and then path dependence of development." (said at 2:20:44)

Experimental research confirms that genetically identical animals reared under highly standardized and controlled environments develop persistent, unique behavioral differences. In clonal Amazon molly fish (Poecilia formosa), substantial behavioral individuality emerges even when isolated immediately after birth in identical conditions. Similarly, studies tracking large cohorts of inbred mice show that individual behavioral trajectories and brain plasticity diverge over time. Scientists characterize these non-genetic, non-environmental differences as emerging from developmental noise and stochastic developmental processes.

2:32:13Kathryn Paige Hardensupportedmoderate

If one identical twin has schizophrenia, there is approximately a 50% chance that the other twin will also develop it, compared to a general population base rate of 1%.

"If you have one twin who has schizophrenia, there's only a 50% chance that the other one will. 50% is way higher than 1%, which is the base rate, but it's not not destiny." (said at 2:32:13)

The speaker's figures accurately reflect standard epidemiological and twin-study literature on schizophrenia. In identical (monozygotic) twin studies, probandwise concordance rates for schizophrenia typically range from approximately 33% to 48-50% (e.g., 48% in structured DSM-III-R clinical twin cohorts), compared to a general population lifetime baseline risk of approximately 1%. This substantial discordance among identical twins demonstrates both strong genetic heritability (~70-80%) and the essential role of non-shared environmental or epigenetic factors.

2:36:16Kathryn Paige Hardensupportedmoderate

There is a scientific hypothesis proposing that individuals with ancestry from equatorial climates are more susceptible to schizophrenia when living in colder climates due to the activation of genetic risk factors.

"there is one hypothesis about how basically people whose ancestors are from equatorial climates, if they are in colder climates, if they are more susceptible to, um, schizophrenia because of activation of risk genes for that." (said at 2:36:16)

The speaker accurately describes an established scientific hypothesis in psychiatric epidemiology. Prominent researchers (such as John McGrath and colleagues) proposed the developmental vitamin D deficiency hypothesis, noting that individuals of dark-skinned/equatorial ancestry living in colder, higher-latitude climates have higher rates of schizophrenia, potentially mediated by gene-environment interactions and altered neurodevelopmental gene expression.

7 No source found (not proven false)
0:11:00Kathryn Paige Hardenunverifiedvery low

Genetically engineering mice to go through puberty earlier causes them to die earlier.

"If you genetically engineer mice to go through puberty earlier, they die earlier." (said at 0:11:00)

No published experimental studies were found demonstrating that genetically engineering mice specifically to accelerate pubertal onset causes them to die earlier. While evolutionary life-history models and mouse strain comparisons (such as cross-strain analyses linking developmental timing, IGF-1 signaling, and longevity) observe correlations between maturation timing and lifespan, direct causal evidence from genetic models engineered specifically for precocious puberty showing reduced lifespan is unverified in the published literature.

0:12:46Andrew Huberman (host)unverifiedvery low

In animal models, gonadectomy (such as ovariectomy or castration) to prevent pubertal onset does not extend the critical period for neuroplasticity.

"So they've done the experiments of ovariectomizing animals or taking the testicles out of animals and somewhat preventing puberty, and it doesn't seem to extend that window." (said at 0:12:46)

No published animal study was identified within the retrieved records that directly demonstrates that prepubertal gonadectomy (castration or ovariectomy) fails to extend the critical period window for neuroplasticity. While classical critical periods for sensory systems (such as visual cortex ocular dominance plasticity) typically close prior to or independently of pubertal onset, specific experimental literature assessing the effect of gonadectomy on prolonging critical period windows was not verified in the searched records. This verdict does not prove the host's claim false, but indicates that a matching primary record could not be confirmed.

1:25:20Andrew Huberman (host)unverifiedvery low

Toxic PFAS compounds are found in 80% of non-stick pans.

"Surprisingly, toxic compounds such as PFAS or forever chemicals are still found in 80% of non-stick pans, as well as utensils, appliances, and countless other kitchen products." (said at 1:25:20)

No published peer-reviewed studies were identified that verify the specific claim that exactly 80% of non-stick pans contain toxic PFAS compounds. While non-stick cookware historically and frequently utilizes fluoropolymers such as polytetrafluoroethylene (PTFE, a type of PFAS) and non-stick pans have been investigated for fluorochemical migration and degradation products, market prevalence statistics (such as '80%') typically originate from non-governmental consumer testing reports or market share estimates rather than peer-reviewed scientific literature.

1:31:40Kathryn Paige Hardenunverifiedvery low

Studies show that successful entrepreneurs by age 30 tend to be white men with social advantage, high IQ on standardized tests, and a history of adolescent delinquency.

"If you look at studies of who is a successful entrepreneur by the age of 30, they are white men. So, social advantage, high IQ as measured by a standardized test, history of a little bit of adolescent delinquency, right?" (said at 1:31:40)

No matching publication was located in PubMed or biomedical databases, as the research referenced is from the economics literature. The speaker's statement accurately describes findings from a widely cited economics study by Ross Levine and Yona Rubinstein ('Smart and Illicit: Who Becomes an Entrepreneur and Do They Earn More?', published in the Quarterly Journal of Economics, 2017). Using longitudinal data from the National Longitudinal Survey of Youth (NLSY79), the authors found that incorporated entrepreneurs were predominantly white, male, came from high-income families, scored higher on cognitive tests (AFQT), and had higher engagement in illicit or delinquent youth activities compared to other workers. However, because this literature is indexed in economics rather than biomedical databases, it could not be verified via PubMed records.

1:43:59Kathryn Paige Hardenunverifiedlow

In men, testosterone levels continue to increase through their teenage years and into their 20s after puberty has ended.

"men's testosterone is increasing—puberty is over, but their testosterone is still going up through their teen years and into their 20s." (said at 1:43:59)

A search of the biomedical literature did not retrieve records confirming or refuting the exact developmental trajectory asserted by the speaker (specifically that testosterone continues to rise steadily through the teenage years and into the 20s well after pubertal completion). While circulating testosterone rises steeply across Tanner stages of male puberty and reaches peak physiological levels in late adolescence and young adulthood (typically early 20s) before plateauing and gradually declining, specific longitudinal endocrine studies detailing post-pubertal trajectory into the 20s were not retrieved in this search session.

2:13:04Kathryn Paige Hardenunverifiedvery low

In wasp colonies, alpha queen wasps eat a proportion of the beta queens' eggs, but subordinate sisters will bite the alpha queen to enforce limits if she eats too many eggs.

"how you can have alpha queen wasps and they eat some proportion of the eggs of the beta queens in their in their colony. But if she eats too many of the eggs, her sisters will bite her. They will be like, "Okay, you're allowed this much power, but no more, and we're going to enforce those limits."" (said at 2:13:04)

No published literature matching the specific claim—that subordinate sister wasps bite an alpha queen to enforce a limit on the number of eggs she eats—was identified in the search. In social wasps (such as Polistes dominulus), reproductive conflict, oophagy, and dominance interactions are well documented, but evidence that subordinates bite the dominant queen to limit her egg consumption was not found.

2:21:37Kathryn Paige Hardenunverifiedlow

Research by psychologist Paul Bloom and colleagues indicates that people dislike unfairness rather than inequality itself, and will prefer inequality over unfairness.

"Paul Bloom who's a child psychologist has a great paper where he says people prefer uh inequality to unfairness. It's not things being unequal that they necessarily dislike. It's things being unfair. It's within it's when the inequality feels unfair that people are like" (said at 2:21:37)

Although the guest is accurately summarizing the thesis of a well-known 2017 review paper by Christina Starmans, Mark Sheskin, and Paul Bloom ('Why people prefer unequal societies', published in Nature Human Behaviour), no indexed record for this paper could be retrieved or fetched via the PubMed database tools during search. Consequently, under the fact-checking rules requiring direct citation of fetched PMIDs, the claim remains unverified in this search session. The paper itself argues based on behavioral and developmental evidence that humans have a natural aversion to unfairness rather than inequality per se, and will often favor unequal distributions over equal ones when fairness demands it (e.g., in reward allocation based on merit).

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.