Background
My PhD thesis research is in John Kelsoe's (MD-psychiatry) lab at UCSD. We are searching for the genes involved in bipolar disorder (also known as manic depressive disorder). Notice I say genes. The reality is that discovering genes for most psychiatric disorders is daunting. Most likely several genes are involved, and having one defective gene may not result in illness, but rather some kind of combination of genes results in disorder. Thus, some people who have one or maybe even two defective gene(s) may function well, or perhaps they do have some symptoms but not enough for a classical diagnosis. As a result, bipolar disorder is considered to be non-Mendelian; that is, you can not trace the genes and their effects like Mendel did with peas (green vs. yellow and smooth vs. wrinkled).

Despite the fact that no gene has yet been identified for bipolar disorder (or for any other mental illness), research indicates that genetics play a role. If you have a family member with bipolar, you are much more likely than the general population to also have bipolar or other disorder (such as depression). Although environment (or nurture; how you were raised) probably plays some sort of role, studies of twins indicate that there is a genetic factor. Such studies show that if one identical twin is affected, the other identical twin (sharing 100% genetic information) is 4 times more likely to be affected than if one were comparing fraternal twins (who also share 50% genetic information). These studies also illustrate the difficulty in determining the genetic factor: bipolar disorder in one twin does not necessarily mean that the other twin will also be affected.

How can this be explained? No one really knows for sure, but there are probably at least two things involved: the above-mentioned "nurture" and the concept of genetic penetrance. In genetic terms, penetrance is how often you see a certain effect from a certain gene. For example, in a genetic disorder such a cystic fibrosis, if you have the defective gene, you will get the disease, no question. The gene for cystic fibrosis has 100% penetrance. It is thought that for mental disorders, this is not the case. Rather, a defective gene may result in a 50% or 80% chance of having a disorder. Much more research has to be done to explain why this may occur.

Even though complicated, statistical analysis of DNA samples from affected and non-affected people show evidence for genes involved in bipolar disorder on several chromosomes. At the October, 1998 psychiatric genetics meeting Germany, it was noted that many of the chromosomal regions implicated in bipolar disorder have also been independently implicated in schizophrenia research. This could help explain why there can be an overlap of symptoms of both schizophrenia and bipolar (often diagnosed as schizoaffective disorder, or we're not sure which one they are so let's classify them here).

If it is so hard to find the genes involved in bipolar disorder, why bother?
Well, there are several reasons. Undergoing treatment for bipolar disorder can be hit-and-miss at first, because some drugs work for some people and don't work well for others. (However, let me note that most bipolars are able to do very well on medication; work with your doctor to find the right meds for you.) If we actually know what genes are defective, we can use medication that is specific for the malfunctioning genes for specific individuals. Basically, we may be able to one day make customized meds based on a quick genetic test. Also, if we have medications designed to specifically target the genes involved, they are much less likely to cause side effects. In the future, we may be able to use some form of gene therapy to correct the problem permanently. Additionally, finding the genes involved will help relieve some of the stigma that is often associated with any mental illness. Those who suffer will know the molecular reason for the chaos they feel, and parents of bipolars won't have to hear comments like "you must have done something wrong when they were kids."

My research focus
Our lab is concentrating on two areas right now: the dopamine transporter gene on chromosome 5 and a possible candidate gene on chromosome 22. My research is on 22 (another grad student researches the dopamine transporter). Chromosome 22 has been implicated statistically in both bipolar disorder and schizophrenia, and I am trying to find what gene is triggering the statistical evidence. To help narrow down the search, I am genotyping (finding out what specific DNA people have) markers near a specific location of chromosome 22 called D22S278, which is the region highly implicated in our studies.