Introduction to Brain Signaling
The brain contains roughly 100 billion nerve cells (or neurons), with each neuron forming connections (called synapses) with up to thousands of other neurons. The specificity of this staggering number of synaptic connections underlies all aspects of brain function and illustrates the remarkable complexity of the brain.
Depression is thought to be caused by complex interactions between an individual's genes (nature) and his or her environment (nurture). An individual's genes influence mood under normal conditions by encoding the proteins that mediate all aspects of the brain's functions. Environment influences mood and depression by modifying that genetic potential. People who develop depression likely does so through a combination of having genes that make them more sensitive to environmental challenges and exposure to those challenges, with the degree of genetic and non-genetic factors likely varying considerably from one individual to the next.
Stress and other environmental stimuli affect the brain initially by influencing the communication between nerve cells at synapses, a process called synaptic transmission (Figure 4). At the synapse, an electrical impulse in one neuron triggers the release of a chemical substance (called neurotransmitter), which acts on specialized receptor proteins on the nearby neurons. The neurotransmitter signal is turned off in most cases by reuptake proteins that pump the neurotransmitter back into the nerve terminal. The tricyclic, SSRI, NRI, and SNRI antidepressants act by inhibiting these reuptake pumps for serotonin or norepinephrine. The binding of a neurotransmitter to its receptor regulates proteins called ion channels, which triggers electrical impulses in that cell that travel to the next cell and so on. The binding also activates a cascade of biochemical events in the cell, which alter all aspects of that neuron's function. This occurs through the regulation of signaling molecules called G proteins, second messengers, protein kinases, and protein phosphatases, among many others. Regulation of these signaling pathways ultimately causes long-lived changes in gene expression in the neuron's nucleus. Repeated exposure to stress would, therefore, be expected to produce molecular and cellular adaptations as a result of repeated perturbation of these intracellular pathways. We believe that these adaptations are ultimately responsible for many features of depression.