Unraveling the Mystery of Mania
March 15, 2008
Bipolar disorder (BPD) is one of the most prevalent psychiatric disorders in the world, affecting close to six million people in the U.S. alone. It is characterized by severe shifts of mood between stages of depression and mania. The depression involves traditional symptoms of a depressive episode, such as hopelessness, loss of interest in daily activities, and disruption of sleeping patterns. The manic episodes are what you might consider the exact opposite of depression, manifesting as drastically increased energy, euphoria, lack of inhibition, and delusions of grandeur. Many psychiatrists believe BPD is underdiagnosed, but it is also a term that is overused colloquially (much like depression), at least in my experience. Often someone will refer to an acquaintance as bipolar, meaning he or she has frequent mood swings. BPD is marked by severe changes in mood that last for several days at a time, quite unlike the sudden shift your significant other might experience when he/she hasn’t had their coffee yet.
BPD involves a spectrum of symptoms, and sorting out the mechanisms behind its occurrence has been expectedly complicated. No single gene has been identified as being responsible for BPD, and its complexity has prohibited scientists from being able to recreate the disorder reliably in animals for study. Recently, however, a group of scientists from the National Institutes of Health (NIH) has identified a gene that seems to be related to manic states in mice.
The gene, GRIK2 (glutamate receptor, ionotropic, kainite 2), encodes for a glutamate receptor, specifically glutamate receptor 6 (GluR6). Glutamate is the predominant excitatory neurotransmitter in the central nervous system. GRIK2 has attracted a lot of attention in BPD research since it was found to be associated with suicidal ideation brought on by antidepressant treatment. People with BPD are more prone to treatment-induced suicidal ideation, leading the group at NIH to investigate this gene in regards to BPD.
The group created knockout (KO) mice that lacked the GRIK2 gene and compared their behavior with control mice. KO organisms are those that have been genetically engineered to carry an inoperable version of a gene. This allows researchers to juxtapose their behavior with that of other animals that have the gene, and thus isolate the effect that the gene has.
The KO mice exhibited behavior that was consistent with mania. This was measured with a battery of tests, which showed the mice to be more aggressive, more active, and less inhibited. They were also overly sensitive to amphetamine administration, and their hyperactivity was mitigated by the administration of lithium, a mood stabilizer and common treatment for BPD.
This research is important, as scientists may now have an animal model for the manic episodes of BPD. The group does point out, however, that it is unknown whether GRIK2 is involved in the cyclic nature of BPD, or if it causes the euphoric and mind-altering aspects of a manic episode. While there is still much to be understood about the disorder, this may be an integral step toward elucidating its perplexing mechanism.