How Does Changes in Energy Pathway Lead to Depression?

DNA

The observation that changes in the energy pathway, that is, metabolism and mutations can be a significant cause for disease development and progression is major progress in the field of medicine. Mutations in DNA has been shown to be responsible for a wide range of diseases and molecular disorders. This is not to say that mutations are entirely bad. Some are actually good for you. But the influence of DNA mutations on diseases should not be overlooked and it has been a subject of intense research. This connection has also been observed in laboratory animals. Studies of laboratory animals have shown that these animals have had dietary energy intake decreased or increased above usual levels. These animals demonstrated symptoms similar to depression.

Recently, a group of researchers led by Brooke E. Hjelm who is an assistant professor of clinical translational genomics at the University of Southern California in Los Angeles discovered a connection between the mutation and major depressive disorders. The results of this study corroborate the enormous hypothesis that genetics is one of the major factors leading to depression. Other factors such as environmental factors, substance abuse, and brain physiology have also been identified. The result of this study is even not far-fetched owing to the observation of all the organs in the body system, the brain has the highest requirement for energy, and thus any disturbance to this finely tuned system can have drastic consequences. This results from the fact that the energy pathway is precise. The energy-producing and storing processes of various cells, including cells and tissues making up the brain, are intricately modulated by a variety of factors which are not limited to genetic composition, lifestyle choices, hormones, metabolites, and environmental fluctuations. Disturbance of one or more key regulatory systems will result in cellular abnormalities (and in some cases congenital abnormalities) that result in diseases such as depression, anxiety, and molecular disorders. Furthermore, neurological disorders, are now known to be intimately linked to energy metabolism.

The researchers that conducted the study deleted the gene Sirt1 in forebrain excitatory neurons in male mice. The result was a stark reduction in the number of mitochondria in these cells, accompanied by depression-like symptoms. Mitochondria is widely regarded as the powerhouses of the cell, are specialized compartments that function to metabolize the food we eat into the chemical units of energy that our cells need to function properly (the so-called cellular functions) Each cell has many mitochondria to ensure a smooth supply of energy. The study involved about 41 participants of which nine had been diagnosed with major depressive disorder. They found a large number of deletions in brain tissue from two of the individuals with MDD. The researchers had already identified around 800 such deletions in the mitochondrial genome. It could be said that mutations of this gene could be linked to depression in the form of decreased enzyme activity. This kind of mutation is referred to as Deletion. The several interconnected genes within these mitochondria communicate via a network to keep these cells running. This project was also supported by the contributions of Dr. Vawter who had been studying mitochondrial deletions at his laboratory for several years by specifically investigating the brain tissue of people who have mental health conditions.

This discovery will have a significant in pharmacogenomics. It is hoped that further research in this study will be able to enable drug discovery to be tailored to specific population subgroups with a similar genetic defect which will enable therapy to be individualized and hence improve their quality of life.