How Serotonin Regulation Affects Depression

In todays world we have seen an influx of many medical and psychological disorders. In fact, in todays high paced world mood elevating drugs are among the top five most highly prescribed medications due to the drastic increase in anxiety and depressive disorders. Serotonin, also known as 5-HT, is a neurotransmitter that is highly linked with depression and anxiety. One of the most common types of mood elevators are Selective Serotonin Reuptake Inhibitors (SSRIs) commonly known as Zoloft, Paxil and Prozac. SSRIs are a class of antidepressant drugs that alter serotonin levels in the brain.

Serotonin and Depression

Serotonergic neurons (neurons that produce and transmit serotonin) are widespread throughout the brain and participate in many neural functions. These neurons often show depleted serotonin activity in the synapse in the hypothalamus, amygdala, and the cortex when a person is depressed. Essentially, levels of serotonin in the synapse are too low to perpetuate the signal. Thus feelings of joy, happiness, and pleasure, that are associated with these areas of the brain, are not felt. Serotonin Under-Production Usually, an excess of serotonin is produced to ensure that once released into the synapse enough serotonin reaches the target neuron (seen as green) 1 for the nerve signal to continue. However one reason, for depleted serotonin levels, is the transmitting neurons (seen in yellow) are not producing enough serotonin to properly stimulate the post-synaptic or target neuron. Serotonin Reuptake In addition to under production of serotonin, the transmitting neuron recycles serotonin through special selective reuptake ports. This process pulls serotonin out of the synapse to be reused by the transmitting cell. This removal of serotonin does not allow it to have time to stimulate the target neuron. In addition, this removal has been found to be accelerated in patients suffering from depression leading to even lower levels of serotonin in the synapse. These problems often co-occur which leads to extreme under stimulation of the target neuron. Essentially, in a depressed persons brain not enough serotonin is produced, which when added
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to over active reuptake ports, this creates an extremely low amount of serotonin in the synapse. This halts the transmission of the signal which can result in a person being unable to experience joy and happiness.

Selective Serotonin Reuptake Inhibitors

Selective Serotonin Reuptake Inhibitors disrupt this dysfunctional process through a few simple steps. Through this correction, serotonin levels stabilize renewing the connection and allowing signals to be sent. SSRIs Absorption and Transportation SSRIs are highly engineered chemicals. They first need to be absorbed from the stomach into the blood stream and then manage to cross the blood-brain barrier. To accomplish this they are designed to mimic substances commonly found in the body to prevent any immune response and destruction. In addition, to cross the blood-brain barrier so they can enter the synapse (where they are active), they must mimic one of the substances recognized by the supportive barrier cells (called glial cells) that selectively allow chemicals into the brain. Once they have been absorbed into the brain, it is believed that there is such a high concentration of SSRI in the brain that it enters most synapses in the brain. However, due to engineering it can only act on certain cites. SSRI Synaptic Action Once in the synapse, SSRIs can only bind to one site on the transmitting neuron. This site is the selective serotonin reuptake port, which will only recycle serotonin. The name Selective Serotonin Reuptake Inhibitor describes exactly what this drug does. SSRIs are antagonists of the selective serotonin reuptake port, meaning that they bind to and inhibit its action (seen highlighted by the box)2. Thus, no serotonin is reabsorbed into the transmitting cell. Eventually, the SSRI is removed from its binding site and once again the cell can reabsorb serotonin, hence the necessity to take SSRIs daily. SSRI Effects

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With the blockage of the selective reuptake ports on the transmitting neuron, serotonin is not reabsorbed into the cell. This results in a return to normal levels of serotonin in the synapse. This helps correct for the low production of serotonin by ensuring that more of the produced serotonin hits this target cell. Due to this increase of serotonin in the synapse there is now enough to properly stimulate the target cell. With this stimulation, the target cell passes on the signal as it would in a health brain. Without this breakdown in neural communication, the patient using the SSRIs can return to normal functioning, once again experiencing feelings of joy, happiness, and pleasure. SSRI Side Effects Unfortunately, as with most medications today, there are side effects of taking SSRIs. The main and worst side effect is seen when a patient abruptly halts taking SSRIs. The brain is unable to adjust to this sudden drop in serotonin stimulation and the patient can plunge into deeper depression than they were in before. In addition, since serotonin is not just used in the pleasure centers of the brain but many other areas, these areas can become over stimulated resulting in numerous side effects such as nausea, headache, drowsiness, and, in adolescence especially, thoughts of suicide. However, as the patient adapts to the medication these side effects often lessen. Serotonin is a major part of the cause of depression and through the miracle of science we now have the ability to help change this imbalance. By simply, blocking part of the faulty mechanism, we can allow suffering patients to lead normal lives again.