Biology of Depression - Genetics and Imaging

Genetics

For a long time, doctors have known that depression runs in families. Many individuals with depression can identify other family members who also struggle with the same or similar illness. Early studies on the genetics of depression were conducted with twins. Identical twins share the same genes, while fraternal twins (and non-twin siblings) share only 50% of their genetic material. Researchers from all over the world have found that when one identical twin is depressed, the other twin will also have depression 76% of the time. With fraternal pairs, the twin of a person with depression experiences depression only 19% of the time. Research studies examining twins raised in different homes have further strengthened the evidence for a genetic link, and not just environmental causes of depression. Among identical twins who were raised in separate homes; when one twin has depression, the other twin also developed the same disorder 67% of the time.

Is there a "depression gene"? Some diseases are caused by a single defective gene such as cystic fibrosis or Huntington's disease. But many conditions like depression, diabetes and high blood pressure are influenced by several genes rather than caused by a single gene. In these conditions, there are combinations of genetic changes that cause illness. At this time, it is not known how many genes are involved in depression.  It is very doubtful that any one gene causes depression in any large number of people. Scans of genomes (whole genetic codes of individuals) of people with depression has confirmed that there is linkage to major depressive disorder on chromosome 15 and some suspected linkage on chromosomes 8 and 17.  More research is needed to understand what this means and how to use this information for diagnosis and treatment. It is also important to remember that environment and life experiences have a huge influence on major depressive disorder. It is difficult to say that purely genetics are to blame. At the present time, we can perhaps assume that a certain set of genes make some people more vulnerable to major depressive disorder when they are exposed to certain environmental stress.  

Imaging

While measuring bodily and biochemical changes in the body is a source of important information, brain imaging technology has also given us significant insights into the causes of depression.

Brain imaging technologies are a group of non-invasive techniques that allow scientists to examine the whole brain or portions of it without having to perform surgery. Imaging procedures provide doctors with information about brain structure.  This can include what different parts of the brain look like, as well as brain function and how the brain is behaving during different activities. Structural brain imaging techniques produce photographs or models of the brain. In contrast, functional imaging techniques produce "brain movies" that show how the various parts of the brain interact through time. Functional imaging technologies depend upon measurements of brain metabolism (e.g., oxygen and glucose use) and blood flow rates to make these movies possible. These imaging techniques include:

• Computed Axial Tomography (CT or CAT) - uses special x-ray equipment to measure the amount of radiation being absorbed throughout a person's body. This measurement is used to build a picture of the brain.
• Magnetic Resonance Imaging (MRI) - MRI uses radio frequency waves and a strong magnetic field to create 3D computer images of internal organs and tissues.
• Positron Emission Tomography (PET) - uses trace amounts of short-lived radioactive material (called a tracer) to map functional processes in the brain. This technique allows scientists to determine the metabolic rates of the brain by measuring oxygen and blood sugar (glucose) use. Areas of the brain that are active use more oxygen and glucose than areas that are not active. A computer records a 3D image of the brain, and the areas that are actively metabolizing sugar and oxygen "light up" with different colors.
• Functional MRI (fMRI) - also allows us to determine which parts of the brain are active. Rather than glucose levels, fMRI measures blood flow. Magnets in the fMRI scanner use the natural magnetic properties of blood and water in the body, and create a color-coded image on a computer screen. The fMRI image shows researchers which areas of the brain have the highest (more activity) and lowest (low activity) blood flows.
• Electroencephalography (EEG) - this is a measurement of the electrical activity of the brain and shows an electrical signal from a large number of neurons. By placing electrodes on the scalp, clinicians and researchers get a read-out in graph form called an electroencephalogram rather than an image.
• Magnetoencephalography (MEG) - an imaging technique used to measure the magnetic fields produced by electrical activity in the brain. It is a powerful technique because it measures ongoing brain activity on a millisecond-by-millisecond basis.
• Near infrared spectroscopy (NIRS) - an optical technique for measuring oxygen in the brain. It works by shining near-infrared light (700-900nm) through the skull and measuring how much light comes back out of the brain. The light that comes back out depends on how much oxygen is in the blood, so it is an indirect measure of brain activity.

Using these techniques, researchers have found that people with depression have less activity in certain parts of the brain. Scientists think that the prefrontal cortex enables us to regulate emotions. More specifically, it helps us inhibit inappropriate or crippling emotions. If our prefrontal cortex is less active, then negative emotions (such as depressed mood) may be displayed more frequently and more intensely. Functional brain imaging also suggests that certain parts of the brain work more slowly in people with depression. The activity in these areas is connected to our ability to focus on the outside world.  This may explain in part, why people with depression are focused more on their own thoughts and internal feelings than their surroundings.

Recently, neurosurgeons have reported successful treatment of severe and treatment-resistant depression by implanting a pacemaker-like device into particular areas of patients' brains known to be involved in their depression. This Deep Brain Stimulation (DBS) has a noticeable anti-depressant effect. Though the results of this experimental neurosurgery speak for themselves, exactly why this treatment appears to work is not clear. Further research will be necessary before we understand why this treatment works.  However, it is encouraging work.