Working Backwards…

Bipolar disorder is a psychological disease characterized by extreme mood change. The highest point, termed mania, is a period of extremely good mood and impulsivity, while the lowest point, depression, is characterized by deep sadness or emptiness. Some of these intense emotional symptoms include poor judgment, spending sprees, very high self-esteem, and hyperactivity during mania which transitions into low mood, sadness, feelings of hopelessness, and thoughts of suicide during depression.[i] Interestingly, it is hypothesized that the famous historical figures Edgar Allan Poe, Vincent van Gogh, and Virginia Woolf all had bipolar disorder. In the U.S., the disorder is estimated to affect 5.7 million adults, but surprisingly only about 50% of these people are getting any treatment at all. [ii],[iii] What is stopping these people from getting adequate treatment for this debilitating disorder?
It would probably surprise you to know that bipolar disorder is one of the oldest known illnesses known today. In fact, according to some sources, its symptoms were recognized as far back as the second century.[iv] How does this make sense? How have we not figured out how to treat this disorder effectively?
Quite frankly, scientists simply don’t know what’s going on with bipolar disorder. The medications prescribed to patients for the disorder are essentially a shot in the dark. No one knows how or why they seem to work….sometimes. In fact, most scientific study into bipolar is essentially working backwards from treatment. In other words, maybe if we can figure out what the treatment is doing in the brain, we can figure out what’s wrong with the brain.
One of the front-running hypotheses as to what’s going on in the bipolar brain is called the “arachidonic acid hypothesis.” This hypothesis shows significant promise as to why mood stabilizers like lithium, valproate, and carbamazepine work to stabilize mood swings, especially in the mania stage.
Arachidonic acid, a polyunsaturated fatty acid found in our diet, plays a role in many cellular processes including neurotransmission, membrane excitability, long-term potentiation, gene transcription, membrane fluidity, neurite outgrowth, cerebral blood flow, sleep, and memory.[v] Furthermore, arachidonic acid has been implicated in the excessive neurotransmission of glutamate and dopamine observed in bipolar disorder. In one study, it was shown that NMDA activation increased arachidonic acid incorporation in controls while use of LiCl or NMDA agonist blocked this incorporation.
Lastly, it has been shown that mood stabilizers have some sort of neuroprotective effect over the brain. This makes sense in the context of the arachidonic acid hypothesis because increasing arachidonic acid levels can lead to cell damage and behavioral changes. Therefore, these mood stabilizers could be decreasing arachidonic acid’s cellular affects.[v]
There are still many unanswered questions surrounding bipolar disorder, and many psychological disorders in general. There really comes a point where you have to wonder – what is normal anymore? Will there come a time when we understand these disorders completely? Or will it take learning all the intricacies of the “normal” brain first? I don’t know the answers to these questions, but it seems like (for now at least) the arachidonic acid hypothesis is the best we’ve got.