Bipolar Disorder: Abnormalities in Brain Structures and Functions

A person experiencing bipolar disorder will feel alternately euphoric and severely depressed of they can have a mixture of those emotional states. This condition is known to e a disease, much like any other chronic medical condition, which can be mediated by a medication regimen, but not cured. It is also known that there are elements of the disease which relate to certain structures and processes in the brain. Specific physical properties in the brain that are related to bipolar disorder are more speculative than determined. Understanding what research has determined are known to be direct links to bipolar disorder and what is hypothesized and requires further study is the focus of this paper.

First the condition must be understood from a clinical perspective. "Bipolar disorder (BPD; loci MAFD1 [MIM 125480] and MAFD2 [MIM 309200]) is a chronic psychiatric disorder with a worldwide lifetime prevalence of 0.5% -- 1.5% [Mula, et al. (2008) suggests that the number is 1%-2%] and a predominantly genetic etiology, based on twin-study data" (Segurado, et al., 2003). This means that between .5% and 2% (population size depends on the research given) of people worldwide can be expected to experience bipolar disorder. Of course, this number could be much higher due to underreporting among individuals who have the symptoms and the medical profession (NIH, 2008). The etiology of the condition is also mentioned in the above quote which was stated as primarily genetic. Twin studies have been used in many cases to determine if a condition can be considered genetic or not. The prevalence of the disease in both twins, if they are identical, is considered to be significant. This genetic causation however does not answer the question of cause.

Much research has been conducted related to determining the cause of bipolar and other mood disorders. The problem has been that while there may seem to be a correlation between bipolar disorder and some brain structure or process, research has never proven a consistent direct correlation. Studies have shown that any number of physical abnormalities could be the issue, but no specific link to anything has been found.

However, there have been some breakthroughs with regard to mood disorders which have seemed to correlate well across the spectrum. Low serotonin levels have long been positively linked to a diagnosis of bipolar disorder (NIH, 2008). Several neurotransmitters, or the lack of same, have been linked to depressed and manic mood. Serotonin and dopamine both play a role in mood elevation, and when a person has a low level of either of these chemicals in their brain it can be one cause for a mood disorder. Numerous studies have been conducted to find out of there is some element within a bipolar brain that can explain this lack of serotonin and other neurotransmitters.

Recent studies have found that a certain gene may be one reason that some people lack the ability to produce adequate levels of serotonin. Brain-derived neurotrophic factor (BDNF) "was reported to promote the function and growth of serotonin (5-HT) neurons in the brain, and infusion of BDNF in the adult rat brain induced sprouting of 5-HT nerve terminals" (Neves-Pereira, et al., 2002). Since the therapy has worked in the brains of animals it is easily extrapolated to humans. However, the study in question did not go beyond examining the research that had already been conducted on animal subjects. People may be a different story altogether. However, the research is promising. Mainly "given that the principal treatment of depressive states in mood disorders consists of pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs) and that BDNF plays a significant role in serotonin system development, the BDNF gene becomes an important candidate in mood disorders" (Neves-Pereira, et al., 2002). Because of the discovery of the importance of BDNF, scientists have looked at ways that the factor can be successfully introduced to humans who are plagued with low levels. The success of introduction into animal brains has caused further research to be done into the specific genes that can be significantly associated with the disease.

It has been found that "children with a parent or sibling who has bipolar disorder are four to six times more likely to develop the illness, compared with children who do not have a family history of bipolar disorder" (NIH, 2008). Of course this speaks significantly to a genetic link, but the specific genes associated have not been definitely determined. Segurado, et al. (2003) performed a meta-analysis of studies that tried to link specific...

The researcher found that "numerous studies have investigated linkage to BPD over the past 2 decades. Early reports suggestive of linkage led to a focus on regions of chromosome 11, the X chromosome, and chromosome 18" (Segurado, et al., 2003). The group looked at more than forty different studies that had been conducted over the past two decades. Unfortunately the finding were not what the researchers had hoped for. The purpose of the meta-analysis was to see if there were any links between bipolar and these genes that single studies had missed. Unfortunately, "the present analyses provide some support for the hypothesis that regions on chromosomes 14q, 9p-q, 10q, 18p-q, and 8q could contain loci that are weakly linked to BPD in multiple populations" (Segurado, et al., 2003). This means that while some links were found between the genes that have been determined as most likely links to bipolar and other mood disorders, a direct causal link could not be adequately determined from the studies which had been done previously.
These findings have not discouraged researchers. Since there are other conditions which seem to have some link to bipolar disorder, there have been attempts to see if a cause can be found through research done into these other diseases. Epilepsy has long been known to have a population that exhibits significant symptoms of both mania and depression. Mula, et al. (2008) found that "a large U.S. survey revealed that 12.2% of patients with epilepsy screened positively, with the MDQ, for bipolar symptoms (BS), a rate twice that of people with asthma and seven times that of a healthy comparison group." The researchers did realize that much of this resort could be linked to other causes, but finding that such a high percentage had bipolar-like symptoms could mean that there was some link between the two. However, after an exhaustive search "the prevalence of true manic depressive illness in epilepsy has been demonstrated to be in line with that reported in the general population (about 2%)" (Mula, et al., 2008). The reason for the high initial number was determined to be the fact that many of the symptoms of bipolar disorder were mimicked by mania and depression common to epilepsy. Epileptic medications also caused some of the false positive information. So, any of the causes associated with epilepsy could not be positively linked as a cause of bipolar.

Bipolar has also been found in brain imaging scans which have linked it to "multi-dimensional impairment in children" (NIH, 2008). The patterns within the brain are similar, but that still does not show how the two are linked. The chemical signatures are profoundly comparable though, so some studies have looked at the comorbidity of the conditions (Segurado, et al., 2003). However, nothing has been discovered yet.

It has also been found that "the manifold signs and symptoms of manic depression may be viewed in terms of dysregulation of three major neurobiological systems: those that involve reinforcement-reward functions, central pain mechanisms, and psychomotor activities" (Murphy & Sahakian, 2003). The term dysregulation refers to a "mechanism" that is impaired (Murphy & Sahakian, 2003). Thus, bipolar disorder can have a dampening effect on these three separate functions that the brain tends to regulate. People with bipolar disorder do not have the same structure for reward and reinforcement that others do. They are unable to less able to differentiate between a reward and a negative consequence. Bipolar disorder has also been positively linked to a depression of the pain receptors within some sufferers. Also, the ability to regulate muscular motions, especially when it comes to fine motor control, can be directly correlated to bipolar disorder. It has been postulated that the mechanisms which control these functions could be linked to the neurotransmitter deficits common in bipolar disorder (since other mood disorders have the same issues), but nothing more than a tenuous link has been found (Murphy & Sahakian, 2003).

Conclusion

Bipolar then definitely has a genetic component that can be seen in both twin study data and other gene studies. However, only weak correlations have been found to exist thus far in the studies that have been conducted. Much of the research points to specific gene areas, but the ability of medical science to form a strong positive correlation is limited. Brain structures which regulate the production of the various neurotransmitters have also been investigated, and a permanent solution for adding the neurotransmitter on something like a normal schedule have been attempted, but results have…