I remember feeling puzzled when I first learned how antidepressants worked in medical school.  This much made sense to me: Chemicals called neurotransmitters enable neurons (nerve cells) to communicate with each other.  Some important and commonly known neurotransmitters are serotonin, norepinephrine, and dopamine.  The space between neurons is called a synapse.  When a neurotransmitter such as serotonin or norepinephrine is released and travels between neurons, some of it gets reabsorbed into the neuron that released it.  Antidepressants block serotonin, norepinephrine, and other neurotransmitters from being reabsorbed into neurons.  This allows for a greater amount of neurotransmitter to remain in the space between neurons. 

But what puzzled me as I learned about antidepressants is why having a greater amount of neurotransmitter in the space between neurons should translate into treating depression.  Recently, Scientific American published an article addressing this very question.  In it, Alan Gelenberg, a depression and psychiatric researcher at Pennsylvania State University, remarks that “there’s really no evidence that depression is a serotonin-deficiency syndrome.  It’s like saying that a headache is an aspirin-deficiency syndrome.”  Here he is saying that just because aspirin can relief a headache, this does not mean that headaches are caused by a low level of aspirin in our body.  Analogously, just because medications that raise serotonin levels in our synapses help treat depression, this does not mean that depression is due to a low level of serotonin our synapses.

The article notes that

research headed up by neuroscientists David Gurwitz and Noam Shomron of Tel Aviv University in Israel supports recent thinking that rather than a shortage of serotonin, a lack of synaptogenesis (the growth of new synapses, or nerve contacts) and neurogenesis (the generation and migration of new neurons) could cause depression. In this model lower serotonin levels would merely result when cells stopped making new connections among neurons or the brain stopped making new neurons. So, directly treating the cause of this diminished neuronal activity could prove to be a more effective therapy for depression than simply relying on drugs to increase serotonin levels.

 

Evidence for this line of thought came when their team found that cells in culture exposed to a 21-day course of the common SSRI paroxetine (Paxil is one of the brand names) expressed significantly more of the gene for an integrin protein called ITGB3 (integrin beta-3). Integrins are known to play a role in cell adhesion and connectivity and therefore are essential for synaptogenesis. The scientists think SSRIs might promote synaptogenesis and neurogenesis by turning on genes that make ITGB3 as well as other proteins that are involved in these processes. . . Of the 14 genes that showed increased activity in the paroxetine-treated cells, the gene that expresses ITGB3 showed the greatest increase in activity.

These results were published in the October 15 issue of Translational Psychiatry.  Conceiving of depression as an impairment in the generation of neurons and the connections between them makes sense of the symptoms present in severe depression.  If the neurological processes required for learning and engaging the world are not functioning, then it stands to reason that a person will have a decreased ability to concentrate, reason, retain information, and take pleasure in life.  Time will tell if this new paradigm for understanding depression will generate more effective therapies for this often debilitating condition.

The Scientific American article is linked here.