MEDI7111 Lecture Notes - Lecture 1: Neurotrophic Factors, Major Depressive Episode, Brain-Derived Neurotrophic Factor
Mental Health 1
Pathophysiology Related to Depression
It is agreed upon that there are organic causes of depression due to the changes in signalling,
response to anti-depressant medication and peripheral physiological changes seen.
The Brain
The pathology within the brain was originally found incidentally through treatment of patients with
TB with isoniazid, where this medication resulted in elevated mood. Iproniazid (a modified version of
isoniazid) was the first anti-depressant available, however at higher doses it was found to be a
convulsant therefore is not used anymore. Iproniazid is an irreversible, non-selective MAO inhibitor;
MAO is the “off signal” for monoamine neurotransmitters (NA, DA & 5-HT) therefore inhibiting MAO
results in prolonged action of these neurotransmitters. These actions include:
Noradrenaline
oMood
oAppetite
oDrives
Dopamine
oPleasure
oSex/libido
oPsychomotor activity
Serotonin (5-HT)
oAggression
oSleep
oAppetite
All of these areas are affected in depression therefore it was hypothesised that these
neurotransmitters are key to the pathophysiology of depression. Original theories proposed that
there was local deficiency in noradrenaline which caused depressive symptoms however research
into this NA levels in the brain did not support this idea.
The focus then shifted to serotonin as the deficient neurotransmitter; most current antidepressants
operate to increase the synaptic concentration of serotonin (e.g. SSRIs). Other neurotransmitters of
interest are glutamate and GABA. Glutamate modulates the activity of dopamine; therefore
inhibition of the NMDA receptor theoretically should modulate dopamine function and improve
mood. GABA is a modulator of glutamate therefore it is thought to have an effect via this
mechanism. There is some research into the role of neuropeptides in depression however only
substance P has been found to have some role by inhibiting serotonergic neurons.
Peripheral Pathophysiology
Peripheral Neuropeptides
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Document Summary
It is agreed upon that there are organic causes of depression due to the changes in signalling, response to anti-depressant medication and peripheral physiological changes seen. The pathology within the brain was originally found incidentally through treatment of patients with. Tb with isoniazid, where this medication resulted in elevated mood. Iproniazid (a modified version of isoniazid) was the first anti-depressant available, however at higher doses it was found to be a convulsant therefore is not used anymore. Mao is the off signal for monoamine neurotransmitters (na, da & 5-ht) therefore inhibiting mao results in prolonged action of these neurotransmitters. All of these areas are affected in depression therefore it was hypothesised that these neurotransmitters are key to the pathophysiology of depression. Original theories proposed that there was local deficiency in noradrenaline which caused depressive symptoms however research into this na levels in the brain did not support this idea.
