Video summary
Kathryn Paige Harden addresses whether there are sex-based differences in the heritability of antisocial behavior, noting that while genetic liabilities for aggression and risk-taking affect both boys and girls similarly, men generally exhibit higher average levels due to social opportunities rather than fundamental biological disparities. She explains that genes associated with physical or relational aggression influence women as well; however, societal norms have historically discouraged behaviors like drinking in women, narrowing the observed gap between sexes. As these restrictions loosen, the underlying genetic similarities become more apparent, though men's ability to enact violence remains magnified by factors such as suicide rates and access to weapons. The discussion shifts focus from the 22 pairs of autosomes commonly studied due to technical reasons to the X chromosome, which holds specific significance because males possess only one copy while females have two. This biological difference makes men more vulnerable to X-linked genetic variants that lack a compensatory second copy. Harden illustrates this vulnerability using color blindness as an analogy before introducing a rare variant on the MAOA gene located on the X chromosome. The MAOA enzyme functions like "Pac-Man," breaking down neurotransmitters such as serotonin and dopamine; when defective, it leads to a dangerous buildup of these signals in the brain. Harden recounts a famous 1990s study involving a family in the Netherlands where this rare MAOA mutation caused severe antisocial behaviors in all male members, including arson, rape, and stabbing, while their female relatives remained unaffected despite inheriting the same genetic risk. The disparity arose because women with two X chromosomes could compensate for one defective copy of the gene, whereas men faced a 50/50 chance of expressing the disorder based solely on which maternal X chromosome they inherited. This case demonstrates how profoundly biological factors can disrupt moral faculties and behavior without necessarily resulting in legal defenses like "not guilty by reason of insanity," as these individuals were treated identically to other offenders until their familial genetic patterns revealed the cause. Ultimately, Harden argues that this rare variant serves two critical purposes: it highlights the fragility of our moral capacity when disrupted by a single letter change in the genome and suggests there may be undiscovered neurobiological explanations for persistent violence in families. While most deeply antisocial individuals do not carry this specific MAOA mutation, her lab is now investigating common genetic variants on the X chromosome to understand their cumulative effects. The findings challenge simplistic views of criminality by showing that what appears as random or purely behavioral deviance can sometimes be rooted in specific biological mechanisms we are only beginning to map and understand through modern genomics research.
Read the full video transcript
Is there a difference in heritability
of antisocial behavior
that's sexed?
Do men
>> Yeah. inherit more
uh
accurately? More Is is is is is the
heritability greater effect on boys than
it is on girls? Generally, no, but I
there's one exception that I want to
come back to. So,
what we see is that the genes that are
associated with antisocial behavior in
boys
also affect girls. If you have a
fraternal twin If you're female and you
have a fraternal twin that's a male
sibling,
then his antisocial behavior predicts
your likelihood of manifesting it. Um
that the same liabilities are
uh reflected in the same way. So, the
same genetic liabilities make you more
likely to be physically aggressive, they
make you more likely to be relationally
aggressive, they make you more likely to
be
substance using, they make you more
likely to be risk taking.
It's just for everything the mean for
men, the average for men, is shifted up.
>> Mhm.
So,
>> Oh, so the same impact would have a
Sorry, the the same raw materials would
have a greater impact in real life.
Yeah, yeah, yeah. Yeah. Yeah, the same
way as women commit suicide Sorry, women
attempt suicide more than men, but men
commit suicide more than women. Their
ability to enact
violence, antisocial stuff, tends to be
greater, so it's magnified. Right,
interesting.
>> And So, you know, part of that is around
social opportunity. Like for many years,
you know, women were very discouraged
from drinking, very different were
discouraged from smoking. So, you saw a
big sex difference in smoking and
drinking. Now, it's more socially
acceptable for women to smoke and drink,
and so that average difference has
narrowed, and it's the same genes that
seem to be involved in both.
The exception there is that most of our
current studies have focused on what are
called the autosomes. So, we have 23
pairs of chromosomes. One pair is the
sex chromosomes, XY or XX in typically
developing children. And then the other
22 pair
are the same across sexes.
And nearly all of our contemporary
studies have focused just on those 22
pairs of autosomes for kind of boring
technical reasons that I'm not going to
get into. We're just now really diving
in to the X chromosome
to see is there something about the X
chromosome that might have specific
effects on antisocial behavior. And the
reason why that's interesting is because
men only have one X, whereas women have
two.
And so men are much more vulnerable to
the effects of a genetic variant that's
X-linked because they don't have another
copy to compensate.
>> Oh, that's so cool. So, that's why color
blindness, for instance, is much more
prevalent in men than versus women
because it's a sex-linked it's an X
chromosome-linked
um
genetic variant.
>> That is so sick.
So,
the reason why we think the X chromosome
might be important
um is
and again, just to back up a second,
most of what we study in our lab is what
we would call common genetic variation.
So, these are genetic differences
between people
that exist in at least 5%. Sometimes
people say at least 1% of the
population.
The thing about common genetic variants
is that um
they're common,
which means that they are likely to have
a relatively small effect in isolation.
Because if they had a big effect,
evolution would make them not common,
would weed them out very very quickly.
So, you have this trade-off between how
common is a genetic variant and how big
of an effect it how powerful it is.
Um so, what we're looking at is lots of
common genetic variants, each of which
have a tiny effect, but if you add them
all up, then you get an appreciable
effect when when that's meaningful.
But there are studies of rare genetic
variants, and there's one very famous
study that was done in the 1990s where
they looked at a
rare variant
on um a gene on the X chromosome. And
that gene was called MAOA. So um your
monoamines are how your neurons are
talking to each other. It's like
serotonins a monoamine, dopamine's a
monoamine.
So monoamine
oxidase is an enzyme that basically is
like a Pac-Man eating the
neurotransmitter in your brain.
And if it doesn't work well, then you
get this incredible build-up of
the signals that your brain ordinarily
uses to communicate with each other.
Okay, so why is that important? In this
one family where they found this genetic
variant on the X chromosome,
it made the MAOA
enzyme not work.
And all the men in that family suffered
from extremely serious antisocial
behavior problems, whereas their sisters
were completely
>> Mom. typically functioning. So the men
one raped his sister, one committed
arson, one stabbed his boss with a
pitchfork.
Huge levels of antisocial violence in
this family. And the their sisters and
their moms were like, "What the [ __ ] is
going on here? Like why why do my sons
and my brothers keep doing this, and we
don't have this problem?"
And it's because they have two X's. And
so if they inherited the mutation, it
didn't matter because there was another
functioning version of the
>> them back toward the mean. To to to kind
of dosage like they could compensate for
it. Whereas if if you're a man and you
only have one X and you got this, you
know, 50/50 shot which of your mom's X's
are you getting, 50/50 shot whether or
not you were going to be antisocial.
So, that's a rare variant.
You know,
the vast majority of people who are
deeply antisocial do not have this MAOA
problem.
>> the MAOA excuse.
>> They can't use the MAOA excuse. But, I I
think it's important for two reasons.
And one is that we think of our moral
faculties as our ability to not go
around stabbing our boss every time
we're mad at him
in moral terms, in spiritual terms, or
in cognitive terms.
And it turns out that it's very
vulnerable to disruption. You can change
one letter of your genome that changes
one gene, which changes one enzyme,
and that capacity is really
if not destroyed, very very impaired.
And so, the extent to which our morality
is a biological faculty, I think is very
much supported by the fact that we can
so profoundly disrupt it by this one
change in our genome.
And the other thing that I find so
interesting about this case study is
that
um
these men were in the criminal legal
system in the Netherlands, and no one
was like,
"Oh, this must be a genetic problem."
They weren't not guilty by reason of
insanity. They weren't you know, lacking
capacity to just stand trial. They were
indistinguishable
from the rest of the offending
population based just on their behavior.
And the only reason we know that their
behavior was due to this genetic cause
is because of the familial data that
made the pattern of transmission so
clear.
And I think that really brings up the
question, how many other people who are
persistently violent in families that
are persistently violent, there might be
some
um genetic or neurobiological
explanation that we just haven't
discovered yet. Like we just don't know
that. In the '80s, they would have
considered it ridiculous. Like, "Ugh,
this persistently violent family, it's
you're telling me it's because they have
a Mhm. one gene that's wrong." Like,
what if seemed sounded like science
fiction, but that was the case
for this family. Um so, I you know, we
haven't in modern genomics turned our
attention very often back to the X
chromosome, but my lab's doing this now,
and I'm I'm really excited about this
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