4.4  The neurotrophic hypothesis of mood disorders

The most significant problem with the monoamine hypothesis in its original form is that, even though ADMs such as SSRIs raise the levels of serotonin in the brain almost immediately, it is many weeks before depressive symptoms are eased (Duman et al., 1997). Clearly, such a long delay is incompatible with the idea that monoamine levels per se are linked to mood.

What might be the reason for the delay? One influential idea is that processes such as the birth of neurons (or neurogenesis), or the growth or remodelling of connections between neurons, or changes to the number of receptors, which take time, are involved.

A class of brain chemicals called brain growth factors may play an important part in this. Such chemicals ‘nurture’ existing neurons and promote neurogenesis. Brain-derived neurotrophic factor (BDNF), one of these brain growth factors, is known to operate in many areas of the brain, and significantly for our purposes, this includes the hippocampus and prefrontal cortex, which we already know are implicated in affective disorders. (Neurotrophic means, literally, ‘brain-feeding ‘ or ‘brain- nurturing’.)