Given all the activity and advances in genetic research, you might expect researchers to have mapped the entire human genome by now and identified the gene or genes responsible for bipolar disorder and other diseases that appear to have a genetic component. Obviously, that hasn’t happened. The best that researchers seem to have come up with are associations of certain gene variations with bipolar – hardly the smoking gun we would hope for.

Even the researchers seem to be getting a little discouraged, as is evident in a two articles I have recently come across. The first, published in the April 2011 edition of the American Journal of Psychiatry is entitled “After GWAS: Searching for Genetic Risk for Schizophrenia and Bipolar Disorder,” (by Elliot S. Gershon, Ney Alliey-Rodriguez, and Chunyu Liu). In their abstract, the authors explain:

Ten years ago it was widely expected that the genetic basis of common disease would be resolved by genome-wide association studies (GWAS), large-scale studies in which the entire genome is covered by genetic markers. However, the bulk of heritable variance remains unexplained.

In a study published in the journal Molecular Psychiatry entitled “A genome-wide association study of attempted suicide,” a group of Johns Hopkins researchers (Willour, et al.) report the discovery of a “a small region on chromosome 2 that is associated with increased risk for attempted suicide.”

Willour and her colleagues studied DNA samples from nearly 2,700 adults with bipolar disorder, 1,201 of them with a history of suicide attempts and 1,497 without. They found that those with one copy of a genetic variant in the region of chromosome 2 where ACP1 is located were 1.4 times more likely to have attempted suicide, and those with two copies were almost three times as likely.

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Kelly Asks…

About a month ago, I was taken off my Lamictal, lithium, Seroquel, and Zoloft. I have a new Dr. who has prescribed me 150mg of Wellbutrin SR and 600mg of Neurontin. I became very depressed, had sleeping problems, and then as the third week hit, I became suicidal.

She increased my Wellbutrin SR to 150 mg twice a day and Neurontin up to 900mg (300mg morning and 600mg in the evening). I feel she is not treating me for my rapid-cycling Bipolar. I am either up or real real down, more down moments than my manic high, which often occurs.

Is she helping me or going to hurt me? I do not want to visit any more hospitals as a result of a doctor not giving me the right doses or too little or, as it is now, I have no antipsychotic meds, which is worrying me. Is this why I feel so depressed and suicidal thinking?

Please help. I am 43. I am not a child with Bipolar. Is this weak for my case? I have been hospitalized twice with Bipolar and I really wish to stay out of them. HELP PLEASE!!!!

Dr. Fink Answers…

Hi, Kelly. I am so sorry to hear that you are struggling like this right now. Most importantly, you should continue to express to your new doctor how badly you are feeling and insist that she explain to you what she is doing and why.

Kim Asks…

Is there a way to combat the headaches and joint pains when taking the lithium?

Dr. Fink Answers…

Hi, Kim. Good question. Most importantly discuss these side effects with your doctor immediately. Your doctor may want to run a blood test to determine your lithium level and make sure your lithium level is not toxic. Headaches can indicate toxicity. Headaches may also be a sign of dehydration, which can occur with lithium, so keeping hydrated is important.

Until recently, doctors and researchers had believed that brain volume loss in schizophrenia was caused primarily by the disease itself. One recent study, however, questions this long-held belief and identifies antipsychotics, the medications most commonly used to treat schizophrenia, as the more likely culprits.

With the increased long-term use of antipsychotics to treat schizophrenia and other forms of mental illness, especially bipolar mania, it’s important to determine whether the illness or the medication (or both) contribute to the potential loss of brain volume.

In an article published in the Archives of General Psychiatry (February, 2011) entitled “Long-term Antipsychotic Treatment and Brain Volumes,” Beng-Choon Ho, MRCPsych, et al. conclude the following:

I recently read an interesting article by Kristy Foster on the Farm and Dairy website entitled “A healing place: Farming has a hand in recovery for those suffering from mental illness.” The article shines a spotlight on Hopewell Farm in Mesopotamia, Ohio – a unique 300-acre treatment center for adults with “schizophrenia, schizoaffective disorder, bipolar disorder, major depression, and other forms of serious mental illness.”

Hopewell has the capacity to serve 40 adults, each of whom is expected to work on a crew, when well enough to do so. Each work crew serves a specific need in the community: housekeeping, kitchen, maintenance and grounds, farm and garden. In addition to requiring residents to serve on a work crew, Hopewell’s program includes:

One of the problems with using traditional anti-depressants, especially selective serotonin reuptake inhibitors (SSRI’s) to treat bipolar depression is the potential risk of triggering a switch from depression to mania. Another issue is that traditional anti-depressants may not be effective in treating depression in some patients.

SSRI’s work by inhibiting the reabsorption of the neurotransmitter serotonin, effectively increasing the level of serotonin in the synapses of the brain – the space between the brain cells (neurons). This reduces the symptoms of depression and anxiety in many people.

While insufficient serotonin may be one cause of depression, researchers are exploring another possible cause – dysregulation of glutamate. Glutamate is the most abundant excitatory neurotransmitter in the body. Riluzole (Rilutek), a prescription drug commonly used to treat Lou Gehrig’s disease, amyotrophic lateral sclerosis (ALS), reduces the release of glutamate while increasing its uptake. Some studies have shown that Riluzole is effective in treating acute bipolar depression alone or in combination with other anti-depressants.

The March, 2011 Issue of the Archives of General Psychiatry has published a study entitled “Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative” (Kathleen R. Merikangas, PhD, et al.). Of the 11 nations included in the study, the United States was found to have the highest lifetime rate of bipolar disorder (4.4%). India was lowest with a rate of 0.1%.

This doesn’t necessarily mean that bipolar disorder is more prevalent in the United States. It merely means that the rate of diagnosis is higher. This may be due to numerous factors, including possibility of increased awareness of bipolar disorder and perhaps a greater willingness and opportunity to seek medical treatment in the U.S. than in some of the other countries in the study.

Photo by Marxchivist, available under a Creative Commons attribution license.

Psych Central’s Senior News Editor Rick Nauert recently posted a piece entitled “Genetic Variant Heightens Risk for Bipolar Disorder.” In it, he calls attention to a recent study published in the American Journal of Human Genetics that’s “based on a relatively new technique for the study of the genetics of bipolar disorder” termed genome-wide association studies (GWAS).

We invite you to check out the post, especially if you’re interested in keeping up on the latest breakthroughs in identifying the genetic component of bipolar disorder. Although it may be years before these genetic studies translate into any sort of gene therapy, if that’s even possible, they deliver an immediate benefit in three important ways:

February’s online edition of The American Journal of Psychiatry contains an article entitled “Longitudinal Follow-Up of Bipolar Disorder in Women with Premenstrual Exacerbation: Findings from STEP-BD,” by Dr. Rodrigo Dias and colleagues. The objective of their research was to shed light upon “the impact of hormonal fluctuation during the menstrual cycle on the course of bipolar disorder,” frequency of relapse, and severity of symptoms.

The study followed 293 pre-menopausal-age women with bipolar disorder for one entire year as part of the Systematic Treatment Enhancement Program for Bipolar Disorder, commonly known as STEP-BD, and compared mood episode frequency and severity between 191 (65.2%) of the participants with premenstrual exacerbation (significant mood changes around their menstrual cycle) and 102 without.

The study examined the baseline hormone/mood relationship during each woman’s regular monthly cycle and whether that relationship could be related to the severity of her mood disorder.