The circadian rhythm, responsible for the sleep-wake cycle has been implicated in bipolar disorder, specifically rapid cycling.
So, what is the circadian rhythm. This is the rhythm controlled by our internal clocks to control our sleep cycle. It’s associated with CRY2 mRNA expression in our bodies. Meaning that it’s associated with a particular protein in our bodies. In our human brains, this is controlled by the suprachiasmatic nucleus, a small lobe located by the hypothalamus. Taken from wikipedia (the mother of all explanations):
The SCN takes the information on the lengths of the day and night from the retina, interprets it, and passes it on to the
pineal gland , a tiny structure shaped like a
pine cone and located on the
epithalamus . In response, the pineal secretes the hormone
melatonin . Secretion of melatonin peaks at night and ebbs during the day and its presence provides information about night-length.
Several studies have indicated that pineal melatonin feeds back on SCN rhythmicity to modulate circadian patterns of activity and other processes
So it’s a complex process as we can see above. Light modulates the SCN, then that sends signals to the pineal gland, responsible for hormonal control in our brains, releasing melatonin causing us to sleep. How does this relate to bipolar disorder?
Well, in a normal human, the expression of this is diurnal, meaning twice a day, associated with the circadian rhythm. It’s expressed more at night, and less during the day. But in patients with bipolar disorder who are depressed, even with sleep deprivation, the expression of this gene is very low, as opposed to the higher levels in normal brains. Additionally, it was nonresponsive to sleep deprivation. So something is screwy there. This also marks a difference between bipolar depression and seasonal affective disorder, which finds that there are higher levels of CRY2 mRNA expression throughout the day in SAD patients.
The findings get more interesting, there are also protective and risky haplotypes for the CRY2, AGGA and GGAC. These haplotypes were found in the seasonal affective disorder patients in sweden, indicating that there are genetic markers and genetic reasons for winter depression. But, in rapid cycling, there is a difference. The protective haplotypes were the opposite of the SAD haplotypes, they were AAAC and GGAC.
The results of this study are two fold. First, gene variations are in congruence with the usual findings that the circadian rhythm is disfunctional in bipolar individuals; where individuals have low melatonin levels. Secondly, it indicates that lithium might be a corrective agent in this process. Lithium stimulates the GSK3B regulator for the circadian rhythm. Thus, it can correct the imbalance in the circadian rhythm that is found in individuals with bipolar disorder. This adds to my previous post that lithium might actually be corrective rather than suppressive in medicating bipolar disorder.
In addition to this mumbo-jumbo, one finds an additional element to all of this there is a marked difference between bipolar 1 and bipolar 1 with rapid cycling. That is, the genetic markers were different, specifically the RORB gene variations. So in response to these findings, the study suggested that bipolar 1 was found to be corrective with just lithium, but with rapid cycling they suggested that a combination of anti-epileptic drugs and valproate acid should be used in conjunction with lithium.
I apologize for the technical nature of this piece, it’d take a lot of research to break down what each of these genetic markers do, but I think that you get the basic ideas. In summary, there are not only marked differences between Seasonal Affective Disorder and Bipolar 1, but also between Bipolar 1 and Rapid Cycling. This variation is specifically genetic and also tied to the circadian rhythm. Personally, I always find that the findings of genetic differences between the different classifications of bipolar disorder to be interesting because it provides an empirical basis for different classification as well as the possibility for testing. Not to mention, it also allows us to understand the interactions of the brain itself with bipolar disorder and how the drugs impact it. The fact that lithium appears to have corrective properties is also fascinating. But that’s it for now. Hope you enjoyed my morning research project.
References:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939397/
Philosophy, Science, Bipolar I, and Life
The circadian rhythm, responsible for the sleep-wake cycle has been implicated in bipolar disorder, specifically rapid cycling.
So, what is the circadian rhythm. This is the rhythm controlled by our internal clocks to control our sleep cycle. It’s associated with CRY2 mRNA expression in our bodies. Meaning that it’s associated with a particular protein in our bodies. In our human brains, this is controlled by the suprachiasmatic nucleus, a small lobe located by the hypothalamus. Taken from wikipedia (the mother of all explanations):
The SCN takes the information on the lengths of the day and night from the retina, interprets it, and passes it on to the pineal gland , a tiny structure shaped like a pine cone and located on the epithalamus . In response, the pineal secretes the hormone melatonin . Secretion of melatonin peaks at night and ebbs during the day and its presence provides information about night-length. Several studies have indicated that pineal melatonin feeds back on SCN rhythmicity to modulate circadian patterns of activity and other processesSo it’s a complex process as we can see above. Light modulates the SCN, then that sends signals to the pineal gland, responsible for hormonal control in our brains, releasing melatonin causing us to sleep. How does this relate to bipolar disorder?
Well, in a normal human, the expression of this is diurnal, meaning twice a day, associated with the circadian rhythm. It’s expressed more at night, and less during the day. But in patients with bipolar disorder who are depressed, even with sleep deprivation, the expression of this gene is very low, as opposed to the higher levels in normal brains. Additionally, it was nonresponsive to sleep deprivation. So something is screwy there. This also marks a difference between bipolar depression and seasonal affective disorder, which finds that there are higher levels of CRY2 mRNA expression throughout the day in SAD patients.
The findings get more interesting, there are also protective and risky haplotypes for the CRY2, AGGA and GGAC. These haplotypes were found in the seasonal affective disorder patients in sweden, indicating that there are genetic markers and genetic reasons for winter depression. But, in rapid cycling, there is a difference. The protective haplotypes were the opposite of the SAD haplotypes, they were AAAC and GGAC.
The results of this study are two fold. First, gene variations are in congruence with the usual findings that the circadian rhythm is disfunctional in bipolar individuals; where individuals have low melatonin levels. Secondly, it indicates that lithium might be a corrective agent in this process. Lithium stimulates the GSK3B regulator for the circadian rhythm. Thus, it can correct the imbalance in the circadian rhythm that is found in individuals with bipolar disorder. This adds to my previous post that lithium might actually be corrective rather than suppressive in medicating bipolar disorder.
In addition to this mumbo-jumbo, one finds an additional element to all of this there is a marked difference between bipolar 1 and bipolar 1 with rapid cycling. That is, the genetic markers were different, specifically the RORB gene variations. So in response to these findings, the study suggested that bipolar 1 was found to be corrective with just lithium, but with rapid cycling they suggested that a combination of anti-epileptic drugs and valproate acid should be used in conjunction with lithium.
I apologize for the technical nature of this piece, it’d take a lot of research to break down what each of these genetic markers do, but I think that you get the basic ideas. In summary, there are not only marked differences between Seasonal Affective Disorder and Bipolar 1, but also between Bipolar 1 and Rapid Cycling. This variation is specifically genetic and also tied to the circadian rhythm. Personally, I always find that the findings of genetic differences between the different classifications of bipolar disorder to be interesting because it provides an empirical basis for different classification as well as the possibility for testing. Not to mention, it also allows us to understand the interactions of the brain itself with bipolar disorder and how the drugs impact it. The fact that lithium appears to have corrective properties is also fascinating. But that’s it for now. Hope you enjoyed my morning research project.
References:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939397/