Depression: most common mood affecting disorder
Two main forms: Unipolar and Bipolar
We do not have a full understanding of what causes depression, and its pathogenesis
The current drugs are based on our current mechanistic understanding of the neurobiological changes that occu
Monoamine Theory
Pathophysiologic basis of depression is a depletion in serotonin,
noradrenaline, and/or dopamine levels, in the CNS
This theory isn't currently accepted fully, but it does explain how the
current drugs work.
Glutamatergic Signalling
Glutamate hypothesis first mentioned in 1990s (Trullas et al, 1990)
Increased glutamatergic neurotransmission may lead to NMDAR
overstimulation, which could cause neuronal death via excitotoxicity.
And neuronal loss has been implicated in many depression studies.
The increased glutamate is likely from increased synaptic release, but
post mortems show --> reduced glial density, reduced EAAT levels, so
could be compromised glutamate clearance.
Neurotrophic Hypothesis
Loss of BDNF plays a major role in depression's pathophysiology
BDNF promotes neuronal survival through the TrkB receptor, so loss of
of BDNF is detrimental to hippocampal function (involved in controlling
emotions).
Overall
Castren put forward a theor to explain BDNF inconsistencies:
BDNF may act as a critical tool in modulating plasticity within emotional processing networks
So this plasticity may be what is compromised during depression
The physiological function of this neuronal plasticity may be what is determining the magnitude and direction o
, This hypothesis may explain the contrasting behaviours of BDNF wihtin the hippocampal/prefrontal & mesolimb
So while depression's pathophysiology isn't fully clear yet, it seems like BDNF has a role in the pathogenesis, bu
Monoamine-potentiating drugs currently are not producing efficacious enough results
Because they were designed based off an incomplete understanding of depression's pathophysiology (the Mon
Glutamate furthered this MA hypothesis, and shifted research towards more beneficial targets
But no effective glutamatergic neurotransmission targeting drugs have been developed for widespread clinical u
Two main forms: Unipolar and Bipolar
We do not have a full understanding of what causes depression, and its pathogenesis
The current drugs are based on our current mechanistic understanding of the neurobiological changes that occu
Monoamine Theory
Pathophysiologic basis of depression is a depletion in serotonin,
noradrenaline, and/or dopamine levels, in the CNS
This theory isn't currently accepted fully, but it does explain how the
current drugs work.
Glutamatergic Signalling
Glutamate hypothesis first mentioned in 1990s (Trullas et al, 1990)
Increased glutamatergic neurotransmission may lead to NMDAR
overstimulation, which could cause neuronal death via excitotoxicity.
And neuronal loss has been implicated in many depression studies.
The increased glutamate is likely from increased synaptic release, but
post mortems show --> reduced glial density, reduced EAAT levels, so
could be compromised glutamate clearance.
Neurotrophic Hypothesis
Loss of BDNF plays a major role in depression's pathophysiology
BDNF promotes neuronal survival through the TrkB receptor, so loss of
of BDNF is detrimental to hippocampal function (involved in controlling
emotions).
Overall
Castren put forward a theor to explain BDNF inconsistencies:
BDNF may act as a critical tool in modulating plasticity within emotional processing networks
So this plasticity may be what is compromised during depression
The physiological function of this neuronal plasticity may be what is determining the magnitude and direction o
, This hypothesis may explain the contrasting behaviours of BDNF wihtin the hippocampal/prefrontal & mesolimb
So while depression's pathophysiology isn't fully clear yet, it seems like BDNF has a role in the pathogenesis, bu
Monoamine-potentiating drugs currently are not producing efficacious enough results
Because they were designed based off an incomplete understanding of depression's pathophysiology (the Mon
Glutamate furthered this MA hypothesis, and shifted research towards more beneficial targets
But no effective glutamatergic neurotransmission targeting drugs have been developed for widespread clinical u
