NEUROBIOLOGY AND

DEPRESSION TREATMENT
 BACKGROUND

• 20-30% Treated with commonly used antidepressants do not achieve complete

recovery and develop a treatment resistant depression. Need to find new treatments.
• Need to consider various NT systems that require a common molecular pathway which
then involves more than one NT receptor.
• Neuroanatomical Circuit of Depression: limbic-cortical-pallidal-thalamic-tract
• HPA feedback loop, PFC, Amygdala, Mesolimbic Dopamine System, Hypothalamus
 DIFFERENT HYPOTHESES
Monoamine Hypothesis:
• Depression is due to functional
imbalance or deficiency of
monoamine-series NTs:
Dopamine, serotonin (5-HT), &
norepinephrine (NE)
• Antidepressants enhance short-
term monoamine functions by
inhibiting the function of
monoamine transporters
• But.. Cannot explain why it
takes 3-4 weeks to receive a
treatment response when
monoamine levels increase at
administration.
Monoamine Receptor Hypothesis: 5-HT2A Receptor Sensitivity
Hypothesis:
• Monoamines are continuously
secreted with an antidepressant • Suggested to explain time gap
& receptors at pre and post- • Depression develops due to
synapse are activated abnormal somatodendritic 5-
HT1A autoreceptor function
• Depression is induced by • Antidepressants: down-regulate
monoamine receptor up-
presynaptic 5-HT1A receptor
regulation
• Long-term antidepressant use
results in down regulation of the
β-adrenergic receptor ligand
binding site within the limbic SOOO… Not appropriate to explain
system & 5-HT2A receptor
depression using only 1 monoamine
• But…not all antidepressants fit deficiency model.
this model & time gap issue
NEURAL PLASTICITY & NEUROGENESIS
NEUROTROPHIC & BDNF HYPOTHESIS
HPA FEEDBACK LOOP
NEUROENDOCRINE & NEUROIMMUNE
INTERACTIONS
MTOR PATHWAY

 Activation of protein translation signaling pathway plays a key role in long-term

regulation of neural circuits: effects development, differentiation, growth,
synapse formation, nervous branch formation, & axonal growth-differentiation.
 Figure 2: mTOR pathway
 NMDA receptor agonists (like ketamine) protect nerve cell and inhibit nerve cell
damage due to hyperactivity and Calcium influx.
 Ketamine as an antidepressant:
 Increased BDNF protein translation
 Antidepressant effects
ERK ½ & Akt = significant in depression
mTOR & eEF2 kinase = significant in rapid antidepressant results of Ketamine
 SPECIFIC QUESTIONS & ANSWERS

1) What cells? Function?

Neural cells: Hippocampus. In depression these cells and circuits are unable to adapt and can be damaged:
neuroplasticity and neurogenesis
2) How do cells usually work? Cellular process examined?
Normally are able to adapt and have normal neuroplasticity and neurogenesis. The signal cascades involved in
depression and its treatment. Info on how these cascades work can help to create improved antidepressants.
Demonstrated in the line drawings.
3) How does function contribute to how larger system works? Critical role in these cells?
The functioning of certain proteins or circuits can effect the outcome of neuroplasticity and neurogenesis. The
effect or treatment of depression and allowing the brain to function normally.
4) How do the cells contribute to behavior?
Can effect the symptoms of depression: cognitive impairment, depressive mood, working memory
impairment, psychomotor retardation, anhedonia, insomnia, weight gain, etc.
The effects of these signal cascades can effect the working of the circuitry which can effect the brain
structure’s functionality which effects behavior. The signal cascades can help to identify a treatment for these
issues.
REFERENCE

Jeon, S., & Kim, Y.-K. (2016). Molecular neurobiology and promising new treatment
in depression. International Journal of Molecular Sciences, 17(3),
381. doi:10.3390/ijms17030381