The Etiology of
Catecholamine and
Serotonin Hypothesis
• Joseph Schildkraut came up with the Catecholamine
Hyphothesis in 1965 suggesting that depression is associated
with low levels of noradrenaline (or norepinephrine).
• This lead to the development of the Serotonin Hypothesis,
which suggests depression is associated with serotonin.
Janowsky et al. (1972)
• Physostigmine, a drug that increases level of noradrenaline
produced was given to participants.
• Within minutes, participants became depressed with self-hate
and even suicidal wishes.
• These results show how depression may be caused by
disturbances in neurotransmission.
Delgado and Moreno (2000)
• Found abnormal levels of noradrenaline and serotonin in
patients suffering from major depression.
• Correlation does not mean causation- results do not indicate
neurotransmitters directly cause depression.
Burns (2003)
• Criticizes the serotonin hypothesis.
• Claims he have never seen depression caused by low levels of
serotonin throughout his many years of researching brain
serotonin metabolism.
• The serotonin hypothesis cannot be tested as it is not possible
to measure levels of brain serotonin in a human with our
Lacasse and Leo (2005)
• Argues that although many researches and studies are done in
this field, none provides real evidence- all they are showing is
how the brain is poorly understood.
• Criticizes how drugs affecting serotonin levels are among the
most prescribed drugs to treat depression and other
psychological disorders due to the serotonin theory.
Types of hormones
affecting depression
• Estrogen
• Testosterone
• Low estrogen is probably a risk for depression,
though estrogen out of balance is probably a risk
for anxiety.
• The most straightforward connection is with
serotonin. Estrogen boosts serotonin by both making
more of it and keeping it around after it's made. So
that's likely to be the reason that estrogen helps
fight depression and helps with sleep.
• Estrogen has a mixed effect
on norepinephrine (more in
women) and allows them to
feel better and alert. But for
some women, high
norepinephrine might be the
cause of the anxiety and
panic attacks that estrogen
seems to produce in some
• The risk for depression is higher
in women. Estrogen levels are
larger during puberty, which
explains moodswings for
women and depression in
teenagers, and estrogen levels
fluctuate in a declining
manner during
• Testosterone is the principal androgen, or male
sex hormone, although it appears in both genders.
• Older men tend to have a decrease in
• Low testosterone levels trigger symptoms such as
anorexia, fatigue, which may have an effect on
• Some 30% of men over age 55 have it.
• Older men would be
particularly vulnerable to
these effects, because
serotonin receptors are
already decreased from
normal aging
• Depression is a major risk
factor for suicide, and older
men have the highest
suicide rate of any age
group in the United States.
• People with low testosterone
increase the risk of
depressive illness and must
be identified early so they
can have the opportunity for
early treatment
• If you have a parent or sibling with depression, you
may be 1.5 to 3 times more likely to develop the
condition compared to those who aren’t closely
related to someone who’s depressed
• The genes that we receive of our parents are able
to determine what illnesses we are more likely to get
Supporting Study
• Nurnberger and Gershon 1982
• Reviwed the results for 7 twin studies
• Findings:
- Concordance rate for major depressive disorder is
higher in MZ twins than DZ twins
- MZ twins – 65%, DZ twins – 14%
- Suggests genetic material may predispose people
to depression
• Contradicted by Caspi et al. 2003
• - Below 100% - Correlation does not mean
• Could be environmental factors, stress, traumatic
• Warned that speculation about clinical implications
of these findings is premature
Other biological factors that could
contribute to depression
Poor diet
Lack of proper exercise
Onset of another mental disorder/illness eg. cancer
Techno-brain burnout (overuse of technological
• Under-stimulation of effort driven rewards system
(not getting a sense of satisfaction from activities
that should be rewarding)

The Etiology of Depression (BLOA)