- In this video I'm going to talk about
the biological basis of depression.
Depression.
And I'm not talking about just
a passing bad mood but I'm talking about
major depressive disorder.
Major depressive disorder is a major cause
of distress, disability and death from suicide.
It is the prototype of the category
of mental illnesses called the depressive disorders
which involve distress or disability
from abnormally negative mood.
In addition to negative mood
the depressive disorders often involve
related symptoms such as feelings of hopelessness
or loss of enjoyment in activities.
As of 2014 when I'm making this video
our understanding of the cause of major depressive disorder
is still very limited.
When we look at the brains of patients
that have major depressive disorder
either with the naked eye
or with traditional microscope studies
there are basically no consistent abnormalities
that have been seen in the tissues of these patients.
However special scans and research involving animal models
have suggested that there are some functional abnormalities
that can be detected in the brains of many patients
with major depressive disorder.
So here in this illustration of the brain
we're looking at the outside of the brain
and the different lobes of the cerebrum,
the top part of the brain, have been labeled
with different colors.
And in this illustration we're also looking at the brain
but it's been divided into right and left halves
and we're looking at the inside
of, in this case, the left half of the brain.
And a couple of specific areas that have seemed
to have abnormal activity in these studies
involve this part of the brain
in this light blue color
which is called the frontal lobe.
Let me just write that.
Frontal Lobe.
A lobe that's most towards the front of the brain.
And over here on the inside
that would be all of this stuff,
all of this stuff right here is also the frontal lobe.
And the other part can't be seen on the outside
it can only be seen on this inside view
involves a number of different structures
like this structure here and some others
that are behind the brain stem over here
that are called the limbic structures.
Let me just write that word down.
The limbic structures.
Limbic structures, right here.
And these studies have suggested
that there appears to be abnormally
decreased activity in areas of the frontal lobe
and areas of increased activity in areas
of the limbic structures.
These findings seem to fit well with other
studies showing a role for these parts of the brain
in regulation of the emotions
and in particular, responses to stress.
Functions of the brain that seem to be
particularly abnormal in patients with
major depressive disorder.
In regards to stress it's also been noted
that many patients with major depressive disorder
have abnormal blood concentrations of certain hormones
that are particularly associated with stress.
For example the hormone cortisol
that's a major stress hormone.
There's a particular area of the brain that controls
most hormones including the stress hormones
that's located right here.
And this area is called the hypothalamus.
Hypothalamus.
And the hypothalamus talks back and forth
to many areas of the brain
but two areas in particular that it
communicates with back and forth
are the frontal lobe and the limbic structures
of the brain.
So it's thought that perhaps abnormal communication
between the frontal lobe and the limbic structure
and the hypothalamus in major depressive disorder
play a role in why there are these abnormal
concentrations of certain hormones
related to stress in the blood stream of these patients.
These stress hormones may affect
most tissues of the body
but they also effect the brain itself
including the frontal lobes,
the limbic structures, and the hypothalamus
that actually controls their amounts
in the blood in the first place.
So for major depressive disorder
it's still unclear which abnormalities
of these stress hormones are causes
and which are effects of the disease itself.
Some features of major depressive disorder
also appear to involve abnormalities
in neuronal pathways using certain neurotransmitters,
the molecules that communicate
between neurons in the brain,
and the abnormalities of these pathways
may cause abnormally decreased
or increased activity in certain parts of the brain
like the frontal lobes and the limbic structures.
Collections of many of these neurons
that produce these neurotransmitters
have their somas, or their cell bodies,
in a few areas of the brain stem,
this structure below the cerebrum,
and then their axons project to many areas
up in the cerebrum, including the frontal lobes
and the limbic structures.
One of these pathways start in what are called
the raphe nuclei of the brain stem.
And there are several groups of raphe nuclei
at different levels of the brain stem
that send projections up to many areas of the cerebrum
including the limbic structures and the frontal lobe,
and they're responsible for much of the
serotonin that's secreted in the brain.
Serotonin.
Which appears to be abnormal in many patients
with major depressive disorder.
Another pathway starts in an area
called the locus coeruleus.
Which is located right around here in the brain stem
and it also sends long axons up to different areas
of the cerebrum and releases a lot of
the neurotransmitter called norepinephrine.
Norepinephrine.
And this also appears to be abnormal
in many patients with major depressive disorder.
Then there's a pathway that starts
with an area called the ventral tegmental area.
Which I'll just write as VTA for short,
which is located around here in the brain stem
and which also sends long axons up to
different areas of the cerebrum.
And the ventral tegmental area
supplies much of the dopamine to the brain.
Dopamine.
These neurotransmitter systems
affect the function in many parts of the brain
including the frontal lobes and the limbic structures
and supporting the idea that abnormalities
of these systems are involved in
major depressive disorder is the fact that
medications that affect these different neurotransmitters
dopamine, norepinephrine, and serotonin
often improve the symptoms of major depressive disorder.
A newer idea
that is interesting is that there may be
abnormalities of what is called neuroplasticity.
Neuroplasticity.
Which is a big word that just means
that the brain changes in response to experience
and these changes may occur down at the level
of connection between a couple of
brain cells, a couple of neurons in the brain
where the strength or efficiency
of information flow from one neuron to the next
may change based on experience.
Or it may happen that the level
of networks of neurons that are widespread,
different kinds of connections and pathways
that informations flowing through the brain
based on the experience that the brain is having.
And evidence is accumulating that
aspects of neuroplasticity appear to be
abnormal in animal models of major depressive disorder.
But like the other abnormalities that have been found so far
it's unclear if these abnormalities of neuroplasticity
are a cause or an effect of major depressive disorder.
So there have been a number of
biological abnormalities found
to go along with the mental abnormalities
we see in major depressive disorder.
Biological.
And other clues to biological factors
that may be involves in the cause
of major depressive disorder
include genetic studies that suggest that
a predisposition can be inherited.
Several genes related to brain function
have been associated with the risk
of developing the disease.
It may be that these genetic abnormalities
increase the risk of the brain developing
abnormal responses to negative or stressful events
particularly early in life when the brain is still
rapidly developing in response to experience
but like most if not all mental disorders
in addition to the biological factors
there does appear to be psychosocial factors as well.
Psychosocial factors.
Certain psychosocial factors have been linked
to the risk of developing major depressive disorder
such as childhood abuse, stressful events,
or limited social support during adverse circumstances,
so that it may be for many, if not most
people with major depressive disorders
as with most other types of mental illness
it seems that an unfortunate constellation
of both biological and psychosocial factors
combine to cause the illness.