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Girls and the Genetic Link Between Childhood Adversity and Adult Depression
A hormone regulatory gene known as “CRH receptor 1,” or the CRHR1 gene—
may play a role in protecting some men from depression and anxiety in the face
of adversity.
Kerry Ressler, MD, PhD, professor of psychiatry and behavioral sciences at
Emory University School of Medicine, is a leading expert on the neurobiology
of how fear changes the long-term health of the brain. Even though there is a
high correlation between childhood adversity and adult depression, not all
individuals who experience childhood trauma develop depression. Women are
clearly more vulnerable, but some men—and women—remain resilient even
when exposed to stressors in adolescence or adulthood.
Ressler examined the relationship between genetic makeup, the type of abuse,
and sex differences that might lead to specific outcomes, and specifically
focused on a variant of the CRHR1 gene that he suspected might be protective
against the effect of childhood trauma—and the production of stress hormones—
which he referred to as protective allele “A.”
His team found, as have many studies, that the prevalence of depression was
significantly higher among women than in men. They also saw, as Felitti and
Anda had, a higher prevalence of women having had fairly high levels of
childhood abuse. Forty-four percent of women reported having experienced
moderate to severe childhood maltreatment, compared to 35 percent of men.
And this difference was almost entirely due to the greater degree to which
women had experienced sexual abuse as children. Men, on the other hand, were
more likely to have experienced physical abuse as kids.
Ressler recruited more than a thousand subjects from the waiting rooms of a
public urban hospital and an urban obstetrical-gynecological clinic and divided
them into groups: those who’d suffered emotional abuse, those who’d
experienced physical abuse, and those who’d faced sexual abuse. Researchers
also subdivided participants into subgroups: those who’d experienced moderate
or severe abuse of at least one type and those who’d experienced no abuse at all.
And all three types of maltreatment—emotional, physical, sexual—were
significantly correlated with adult depression. But several startling insights
emerged that researchers hadn’t seen before.
When researchers added in the factor of
gender
, the results were mind-
boggling: men with the protective “A” variant of the CRHR1 gene were
“significantly protected from developing depression after childhood abuse.”
Boys with this gene variant who experience childhood trauma are less likely
to develop adult depression, whereas it seemed to make no such difference for
women. This is highly significant, Ressler says, “because this is a genetic site
that is highly involved in stress regulation,” and may play a role in why women
have a 2:1 ratio of depression compared with men.
Certainly young men suffer from depression all too frequently—but for some
lucky young men, CRHR1 may be a kind of Teflon gene that prevents
depression from developing and taking hold after childhood adversity. Other
research backs this up. Researchers at the Medical University of South Carolina
found that women who had suffered from childhood adversity had higher overall
stress-hormone and cortisol responses when they faced a current stressor—in
this case, a stress test in the lab—than did men who had a similar history of
childhood adversity and had faced the same stressor.
Margaret McCarthy is studying one other sex difference that may affect why
women suffer more depression from Adverse Childhood Experiences. She and
colleagues have discovered a big sex difference in the growth of new neurons, or
neurogenesis, in developing rat pup brains. Males make about twice as many
new neurons during the first week of life as females. This is significant, says
McCarthy, because making more neurons may allow males to later “forget”
some of the bad things that happened to them, including early life adverse
events. “Theoretically, this may mean that, as adults, males don’t remember their
lousy childhood as well as females do, because as they make more neurons,
those neurons crowd out old ones and replace them, replacing the memories, as
well.” If studies bear out this hypothesis, it may give greater insight into why
women are affected differently by early adversity.
So, here is what we do know: Adversity more often leads to both autoimmune
disease and depression in women. Women may carry a biological predisposition
to both an increased cortisol response and greater dysregulation of that
inflammatory response, following childhood adversity, making us more prone to
later health problems in general. Women who have faced childhood adversity
show greater disruptions in connections between the areas of the brain that help
moderate anxiety and stress reactivity—which in turn leads to a greater chance
of depression later in life. And men may have some protective gene variants
against developing depression after childhood trauma, but may be more prone to
behavior and attention disorders.
Perhaps what is most surprising, given this research, is that even though
studies repeatedly show that many girls experience more forms than boys of
childhood CUTS, or Chronic Unpredictable Toxic Stress—which affects girls in
unique biophysical ways that can lead to depression and autoimmune disease—
very few physicians have even a clue that these relationships exist and that they
matter.
Vincent Felitti puts it this way. “Every physician will see several patients with
high ACE Scores each day. Typically, they are the most difficult patients of the
day. More often than not, they are women. And so, all too often, their symptoms,
and the underlying causes that play a role both in illness and in healing, will be
missed and dismissed.”
How extraordinary it is, then, that those 64 percent of Americans—women
and men—who have had Adverse Childhood Experiences, nevertheless so often
build remarkably loving and decent lives, exhibit such courage and forbearance,
and prosper emotionally so much of the time.
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