Explain and evaluate the monoamine hypothesis of depression and how this has provided a rationale for drug

treatment
I. Hypothesis
a) Proposed by Schildkraut in 1965, attempting to provide a physical reason to explain observations of depression
b) States that depression is the result of a functional lack of the monoamine neurotransmitters serotonin (5-HT) and
noradrenaline at certain sites in the brain
c) Initially formed from clinical observations that certain drugs were able to bring about positive changes in depressed
patients (initially no hard science), and the known neurochemical changes those drugs had on the brain
d) Attempts to study direct neurochemical changes in depressed patients and observe monoamine metabolism have
been inconsistent and unsuccessful
e) There is no pharmacological evidence that either serotonin or noradrenaline are more important in this theory,
both drug types appear to have equal effects on depression
i. Drugs known to block noradrenaline or 5-HT synthesis have low mood as a side-effect
II. Elaboration on the hypothesis
a) One of the biggest observations is that although SSRIs and NRIs have a chemical effect on the brain within minutes,
the antidepressant effect of these drugs take weeks or months to appear
b) This indicates that the change in monoamine metabolism is not directly responsible for the drug effect.
i. Suggestions are a secondary effect of drugs at a higher functional level, which changes the long term cognitive
processing of the brain
c) Psychological studies on humans and rats show antidepressant treatment changes cognitive and emotional
processing bias
i. Cognitive bias may be when a person creates a subjective social reality that may not fit true reality (ie: Everyone
hates me)
ii. Emotional bias is when a persons reasoning is clouded by their emotions, either positive (leading to denial of
tough reality) or negative (leading to over-criticism ect. - Linked with depression)
iii. Does this mean that every pessimist is depressed? If their reasoning is solid are they really biasing their emotions?
Both questions someone might consider when seeing a patient. Some may be depressed, others anxious, and
others completely normal
III. Proposed Neuroendocrine mechanisms
a) It is known that the hypothalamus has 5-HT and noradrenaline neural inputs.
i. The hypothalamus controls the hypothalamic-pituitary axis required to secrete cortisol
ii. A common blood finding in depressed patients is high plasma cortisol, low GH, and high prolactin, indicating a
skewing of this axis
IV. Neuroplasticity and stimulatory (trophic) effects
a) It is thought that low Brain derived neurotrophic factor (BDNF) or receptor malfunction play a role in depression.
b) Another view is neuronal cell loss at the hippocampus and prefrontal cortex induces depression and antidepressants
stimulate regeneration of nerves in that area
i. Various studies have shown this idea to be promising