How Nucleus Accumbens Is Associated With Depression

In the 1950s it was discovered that the Nucleus Accumbens (NAc) was associated with the ability to feel pleasure. Robert C. Malenka, M.D., Ph.D., Pritzker Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, decided to take a closer look at this pleasure circuit since this seemed to be lacking in many diagnosed with depression. What he and his colleagues discovered was that it was not as much the specific region of the brain as much as the circuit activity that crossed through many complex areas.

Dr. Malenka has become a leading expert on the tiny gaps, called synapses, that occur during the transmission of nerve cell activation signals. The challenge is significant since there are trillions of synapses in the human brain. Recently, a melanocortin circuit’s contribution to anhedonia-like behavior was found and has high hopes in identifying a potential new pathway of intervention in depression. Melanocortin is a hormone that affects appetite in humans and further, turns off the brain’s ability to experience pleasure when an animal is stressed.

Monoamine Oxidase

Monoamine loss is the basis of another study investigated by Dr. Jeffrey Meyer, Tier 1 Canada Research Chair in the Neurochemistry of Major Depression at the Centre for Addiction and Mental Health in Toronto, Ontario. Monoamine oxidase (MAO-A) is an enzyme that breaks down chemicals like serotonin, norepinephrine, and dopamine.

Dr. Meyer discovered that there was a considerable increase (34%) in MAO-A in patients with a primary depression diagnosis. Knowing that this was a significant breakthrough in tracking monoamine transporters, his team created a model to follow, like a roadmap. This will take the guesswork out watching how chemicals, like serotonin and dopamine, increase or decrease at different rates based upon transporter density.

Researchers are now moving on to the next step in why MAO-A levels are raised in the brain and how to prevent.

Acetylcholine

Dr. Marina Picciotto, Ph.D., Professor of Neurobiology and Pharmacology, Yale University, and a team of researchers, have proven a biological cause for depression and anxiety, one which was previously dismissed in theory. Acetylcholine is a neurotransmitter that was overshadowed by a signal-carrying chemical, called serotonin, as a leading cause of depression. While serotonin is essential in the scheme of transmission, it is not nearly as powerful as acetylcholine. Also there are some plants with acetylcholine in them. They are being researched about the effectiveness herbal wise.

An enzyme called acetylcholinesterase (AChE) has been found to lower acetylcholine levels. The team discovered that while studying mice that were treated with Prozac, the AChE levels raised considerably and even higher levels of acetylcholine were noted. This once obscure area of treatment became understandable and showed why SSRI anti-depressants were valuable in alleviating depression.

The relationship between serotonin and acetylcholine signaling systems has not yet become clear, but by finding the cause of depression, treatments can now be studied from a different point of view.

Genes and Chemicals

It has already been discovered that specific genes make individuals more susceptible to low moods and how their treatment with antidepressant drugs may differ from the next person. However, by majoring this hurdle, scientists can now focus on how specific regions of the brain changes in individuals. For example, the hippocampus is smaller in some depressed people. Their hypothesis lies in the fact that new nerve cells have to be grown to combat the deteriorating cells that cause depression. In animals, it was found that the use of anti-depressants spurred the growth and enhanced branching of nerve cells in the hippocampus.

New neurons, a process called neurogenesis, that is stimulated by drugs designed explicitly for strengthening nerve cell connections, and improving the exchange of information between nerve circuits, could be the answer in treating depression. Scientists have pinpointed several types of neurotransmitters. These include Acetylcholine, Serotonin, Norepinephrine, Dopamine, Glutamate and Gamma-aminobutyric acid (GABA). By studying each one of these transmitters and creating new chemicals that enhance their existence, depression, anxiety, and S.A.D. could easily be treated.

It seems that researchers are onto something, some that can aid in treatment soon, others years down the road. While every one of these discoveries seems deserving for further testing, let us not forget that the brain is a very complicated machine and that it may take a collaboration of findings to reach an answer to different individuals.