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well as people who have been impacted by this illness. The reality
of depression is that it is a debilitating and potentially deadly
medical condition that affects more than 15 million Americans every
year. The other reality of depression is that there is hope.
Down & Up Show #44: Depression: Nature and Nurture
DR. REEF KARIM:
Alright, good. Welcome to the Down and Up Show on DepressionIsReal.org.
I'm your host, Dr. Reef Karim, psychiatrist, addiction specialist
and relationship therapist. Today's guest is Dr. Gerald Haful from
the University of Notre Dame, and we'll be talking to Dr. Haful
about his recent study published in the January 2008 edition of
Psychological Science that explains how depression is caused by
both nature and nurture.
Thank you for joining us today, Dr. Haful.
DR. JERRY HAEFFEL:
It's my pleasure. Thanks for having me.
DR. REEF KARIM:
Okay, so nature versus nurture. We've heard this-this argument in
many other ways. Why did you think it was necessary first off to
research this topic of how depression was caused, whether it's nature
or nurture?
DR. JERRY HAEFFEL:
Um, I think that's a great question. Like you said so we do hear
about this distinction all the time, right, the great nature/nurture
debate with the idea that some things are caused by nature or that
it's caused by genetics. We're born that way and there's not much
we can do about it. Then in contrast some things are due to nature,
caused by environmental experiences.
Now one of the hopes of our research is to draw attention to the
nature/nurture distinction and show that things are not so clear
cut. So I think there are many misconceptions about nature and nurture
particularly the idea that these two things are independent.
There's a growing consensus among researchers that nothing is really
just nature or just nurture. So this distinction may not be that
useful any more. So this idea that both nature and nurture are always
intertwined I think is particularly important in the area of depression.
DR. REEF KARIM:
So what was the purpose of your study?
DR. JERRY HAEFFEL:
So the specific purpose of our study was to test whether a gene
related to the dopamine system interacts with internal rejection
to create risk for depression. So there's research suggesting that
dopamine which is a neuron-transmitter related to motivation and
goals and the reward system that this neuron-transmitter may play
a role in depression.
On the other hand there's also research showing that adverse environments
growing up can also increase risk for depression. So having a mother
or perceiving a mother as rejecting that can create risk for depression.
So in the past people have looked at these separately. So they looked
at either genetics or the environment, and like we've been talking
about we're sort of arguing you have to look at both. So depression
is caused by genetic and environmental factors. So the purpose of
our study was to look at both of these-a dopamine gene which is
sort of the nature and maternal rejection which is the nurture part.
DR. REEF KARIM:
Right. So like you say traditionally the sort of genetics part that's
been looked at most frequently is serotonin given the effectiveness
of the SSRIs for treating depression. There is research emerging
that shows well maybe something is going on with this dopamine and
this is mainly coming from what are called motivational theories
of depression.
So there's this idea that much of what drives our motivation might
come from two sort of fundamental systems. One of these systems
is called the approach system, and like I said the goal of this
system is to obtain goals and to go toward rewards, and there's
research showing that depression may be related to a shutdown of
this approach system.
SoŅand one of the key neuron-transmitters involved in the approach
system is dopamine. So if depression is related to a deficit in
the approach system and dopamine is related to this approach system
it looks like that might be another neuron-transmitter to start
looking at.
There's also sort of indirect evidence that you often see high rates
of depression in those who have Parkinson's Disease. And Parkinson's
again is thought to be a deficit in dopamine functioning. So there's
hints that dopamine may play a role in all of this.
DR. REEF KARIM:
Can you tell us a little bit about who your subjects were and what
the screening process was and all that.
DR. JERRY HAEFFEL:
Absolutely. So before I go into that I just want to mention my collaborator
on this study, Dr. Elaina Gregorenko (ph.) who at the Yale Child
Study Center. I was very lucky to be able to work with her, and
it's really because of her that we were able to publish this study.
So I just wanted to mention she was a big part of this. Um, but
our subjects were 176 male adolescents from a juvenile detention
center in northern Russia, and the average age of these kids was
16 years old.
DR. REEF KARIM:
Okay. And what was-one thing that's mentioned is the DAT-1 gene.
Can you talk about that a little more, what that is?
DR. JERRY HAEFFEL:
Sure, sure. So the gene of interest that we were looking at in the
study like you said it's called the DA-1-or DAT-1 gene, also called
the dopamine transporter gene. So this is a gene that is considered
to play a primary role in the uptake of dopamine in the brain and
thus is thought to be a major regulator of dopamine level in the
brain.
So again dopamine is thought to be related to this approach motivation,
people's motivation to pursue rewards, rewards, attain goals. It's
also related to positive affect. So just thinking about this then
you can imagine how a problem with dopamine might look like depression,
right.
So people with depression there's a lack of motivation, a loss of
interest in pursuing goals, hopelessness. There's a loss of positive
affect. So we think this gene is poten-was potentially related to
a lot of the symptoms of depression and the regulation of dopamine
more generally.
DR. REEF KARIM:
Okay. And so is that a specific gene that you're looking at in this
study? Is that the primary or is there more involved? Or...
DR. JERRY HAEFFEL:
That was the primary gene that we looked at in the study. Now there
are other-when we think about dopamine there are other candidate
genes that I think future research will want to look at. So the
COMT gene, C-O-M-T, has been implicated in dopamine functioning
and cognitive functioning more generally. So I think that's another
gene that's gonna get looked at in the future as well as a gene
DRD-4.
So I think this was just one gene that we looked at, but I think
there's also some other ones that are gonna be the focus of future
research.
DR. REEF KARIM:
Because these genes have been looked at in regards to schizophrenia
research and other types of mental health disorder research.
DR. JERRY HAEFFEL:
Yes, yes. So some of these-yeah, these genes have been implicated
in psycho pathology sort of generally-in cognitive functioning.
But there's been a lack of support so far looking at them in depression,
and one of our hypotheses was is that if you just look at a genetic
cause of depression you might not find that relationship because
chances are the gene isn't gonna cause depression without some sort
of-without the proper environmental circumstances being there.
So there was sort of a lack of support, and we thought oh maybe
one of the reasons why is because people weren't taking into account
environment. So that's why we're looking at both in this study.
DR. REEF KARIM:
Okay. Can you tell us a little bit about your findings?
DR. JERRY HAEFFEL:
Sure. So what we found is that adolescents with a particular variant
of that dopamine transporter gene were at heightened risk for depression
and suicidal thoughts but only if they also experienced or perceiving
having a rejecting mother.
So just having this gene did not cause depression by itself, and
also just having a rejecting mother did not cause depression by
itself. You really needed both the genetic risk and the environmental
risk. So if we looked at those who just had the gene or who just
had rejection the rate of depression was only about 20% to 25%.
However for those who had both risk factors-they had both the varying
of the gene and the rejecting mother-the proportion of depression
jumped all the way up to about 70%. So that's a pretty big increase
from 25% to 70% there.
DR. REEF KARIM:
Wow. So when we talk about your childhood and what your relation
is to your mother it's pretty important there.
DR. JERRY HAEFFEL:
Um, especially if you have a particular variant of that dopamine
transporter gene.
DR. REEF KARIM:
It's interesting that you know it seems to me that dopamine is a
much bigger studied neuron transmitter now in regards to depression.
DR. JERRY HAEFFEL:
Yes, yes. I think it's-I think the motivational theories are a lot
behind that. So there's been a lot of work within the last decade
from neuron science showing that these motivational systems have
an impact on emotion. I think we followed suit from that saying
well dopamine seems to be really important in these motivational
things. I think we need to start taking those into account.
I mean and I should note that before we make any-I think these are
all good indicators that dopamine's involved, but before we really
conclude anything that it's critical in depression. We really need
to replicate the results from our study.
So you know our study found this in a sample of boys, of males,
so we'd want to see the same finding in girls, in adults. This is
really the first study to show a particular dopamine gene implicated
in depression. So it's exciting but I think what we're gonna have
to see inde-other independent labs really replicate this before
we get too excited about it.
DR. REEF KARIM:
Right. Well the Depression Is Real Coalition seeks to diminish the
stigma around depression and help people who need treatment speak
out and get that help. How do you think your study contributes to
eroding the stigma around depression?
DR. JERRY HAEFFEL:
You know I think the study highlights a couple of issues. The first
like we had talked about this study suggests that depression is
not purely a genetic problem. So I think there are a lot of people
who believe that depression is caused by having some sort of faulty
DNA, you have some bad DNA and there's nothing you can-you can do
about that.
But our study and other studies have shown that genetics are just
one part of a much bigger picture. It's a combination of things
that contribute to depression and many of which people can try to
change in order to try to increase the resilience to this disorder.
I think second it shows that depression also affects males. We know
there's a gender difference. Females are at greater risk, but this
is just a reminder that males are also at risk. So I think that's
something to just keep in mind when we're thinking about depression.
DR. REEF KARIM:
Right. What do you think is the most important point to take away
from your study? Is that it as far as treatment or do you think
there's something else as well?
DR. JERRY HAEFFEL:
I just think that one of the most important points is that there
are many contributors to depression, both genetic and environmental.
I think the goal of research is not to show that one theory is correct
or that there is only one cause of depression but rather how our
genetics, our environment, our cognition, our behavior, all of these
things are really integrated.
It's hard to tease them apart. So by looking at more of these it
can lead us to have a more comprehensive, a richer, a more complete
theory of depression.
DR. REEF KARIM:
That's great. Thank you so much for speaking with us today Dr. Haful.
DR. JERRY HAEFFEL:
My pleasure.
DR. REEF KARIM:
And join us next week for another segment of the Down and Up Show
on DepressionIsReal.org. I'm Dr. Reef Karim.
