Do antidepressants really cause neurogenesis? World Jl Biological Psych, Sept 12

27.09.2012

Psychological stress can increase  cortisol and this could suppress BDNF synthesis.This can lead to neuronal damage . Antidepressants are now thought to induce BDNF expression and neurogenesis.

There are many lines sof evidence to support neurogenesis in adult brain . 1.Stress-induced suppression of neurogenesis in certain strains of rats 2. Elevated blood cortisol levels in submissive primates.3. Delayed onset of antidepressant action which could be explained by the time taken for neurogenesis to occur.4. All major classes of antidepressant drugs as well as ECT, induced neurogenesis in rodents 5.  Potent reversal of corticosteroid-induced suppression of cell proliferation by paroxetine (Lau et al. 2007; Qiu et al. 2007)  and other antidepressants. 6. sertraline increases neurogenesis in a hippocampal progenitor cell line  etc.

There are increasing number of reports of neurogenesis in adult human brain.It is thought that it occurs in a small scale only.The relationship of such genesis to age is also unclear.

Clinical benefits of antidepressants is difficult to be explained by neurogenesis ( mainly in hippocampus) alone. In rodents, hippocampal neurogenesis is associated with learning, memory and spatial orientation than with mood. All symptoms in major depression cannot be explained by defective hippocampal function alone .If neurogenesis is limited in older people, that process cannot explain the antidepressant effect in that group.

Mood stabilizers (lithium) and atypical antipsychotics also induce neurogenesis ie the effect is not specific to antidepressants.

It is interesting to note that non medication interventions like exercise is also associated with  neuronogenesis in rodents. Some studies have suggested a link between increased cognitive performance after exercise, but not all.

Neuronogenesis alone cannot explain all depressive symptoms or the reversal of symptoms after antidepressant treatment. New neurones , in rodents, are thought to be contributing to learning and memory and the link to emotional status/regulation is unclear.

Authors caution against  considering brain volume changes to necessarily mean neuronogenesis. Haloperidol causes acute (within 1–2 h), reversible (by 24 h) striatal gray matter volume reduction in human brain (Tost et al. 2010). This effect is likely to be at the synaptic level ie unlikely to be related to changes in cell number since the effects were both rapid and reversible .So synaptogenesis may be an important factor in brain area volume changes other than neurogenesis in certain circumstances.

Antidepressant drug treatment, though capable of inducing hippocampal neurogenesis, cannot treat the primary pathology of other disorders such as schizophrenia and dementia, where neuronal loss also occurs.  The authors argue that reversal of suppressed neurogenesis is not specific and also too simplistic a model to explain the therapeutic action of antidepressant drugs.

Pro inflammatory cytokines are elevated in  blood and CSF  of depressed individuals suggesting that depression is an inflammatory response. Pro-inflammatory cytokines play an active role in synaptic plasticity and will be an important area of further research. Another area of interest is the role neuroglial cells play in all these.Astrocytes are particularly important in the mainte- nance of neuronal homeostasis and are likely to play protective or damaging role depending on concentration or activation status. According to this view,  the therapeutic efficacy of antidepressants can be attributable to the repair to neuronal circuits, damaged by chronic, low-grade inflammation, in the prefrontal cortex and limbic regions by indirectly increasing synaptogenesis.

Authors suggest  that we would need to   integrate neurogenesis, synaptogenesis, inflammation and other non-neurogenesis factors  in to a new model to explain  the role of neurogenesis and neurodegeneration in depression and  the therapeutic action of antidepressant drugs.

This is the summary of the article:

Is neurogenesis relevant in depression and in the mechanism of antidepressant drug action? Acritical review.Tang SW, Helmeste D, Leonard B.World J Biol Psychiatry. 2012 Sep;13(6):402-12.

 

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