Research Of The Issues In Identifying Bipolar Disorder

Abstract

This paper summarizes the diagnostic definition of bipolar disorder (BD) and the identifiable forms of it on the spectrum as well as the issues in identifying the physiology behind BD and analyzes the possible solutions. The determination of relevant brain areas is notably complicated by the prefrontal cortex and its areas “that are not well delineated at the level of anatomic resolution available with current imaging methods” (S M Strakowski, M P DelBello & C M Adler, 2005). In addition, multiple studies (Phillips, Travis, Fagiolini, Kupfer (2008) & Maletic, Raison (2014)) point to the difficulties of neuro-imaging patients on medication. While there is no conclusive agreement in the scientific community on the neural pathways that provide the symptoms of BD there are thankfully, treatments available to manage the symptoms. Identifying the ways that these treatments help alleviate the symptoms of BD will lead to improved treatment for the disease, which affects nearly 10 million people in the United States alone (Harvard Medical School, (2007)).

Keywords: Bipolar Disorder

Bipolar Disorder:

Neural Physiology and Variants

Popularized and even romanticized in the blockbuster movie “Silver Linings Playbook”, BD is one of the least understood mental health disorders by the general public. In “The Global Burden of Disease” Murray and Lopez (1996) list only road traffic accidents, depression, alcohol use, violence, tuberculosis, and war as more popular causes of ill health and premature death worldwide in men aged 15-44 than BD. In 1991 BD cost 45 billion dollars (Wyatt and Henter, 1995). With an expanding definition and increasing prevalence (Yutzy, S. H., Woofter, C. R., Abbott, C. C., Melhem, I. M., & Parish, B. S., 2012) the cost is likely much higher today. Researchers have yet to find a definitive cause for the disorder but there are many competing theories. This paper begins with a brief definition and overview of BD before exploring the proposed neural pathways and neurotransmitters involved in BD and the many difficulties in finding a conclusive theory of BD’s pathology.

The defining symptoms of BD are the oscillating periods of mania and depression. The cycles of depression and mania happen at different rates in different cases, and can vary not only from patient to patient, but from episode to episode. The manic phase is a period of time (at least a week) characterized by high energy, an inflated sense of self, euphoria, psychosis, and impulsivity. The depression phase, nearly identical to major depression disorder, is a period of time (at least two weeks) characterized by persistent feelings of sadness, hopelessness, sleep and appetite dysfunction, feelings of worthlessness, and contemplation of suicide (see DSM V, “Diagnosis of Bipolar Disorder”). The manic and depressive stages may overlap resulting in a mixed state characterized by an amalgam of symptoms from each state with complicating results such as an increased risk for suicide from the “mix” of impulsivity from mania and contemplation of suicide from depression (Swan et al., 2013). BD has three main forms that fall on a spectrum of intensities that all include one or more episodes of depression, mania or mixed state. Bipolar I disorder is diagnosed with at least one manic episode and is often accompanied by depressive episodes that are not necessary for the diagnosis. Bipolar II disorder is diagnosed with at least one hypomanic (a less intense form of mania) episode and one or more depressive episodes. Cyclothymic disorder is a combination of multiple hypomanic and “hypo-depressive” episodes that do not meet the criteria for standard mania and depression.

Current research indicates that BD has a strong genetic factor with heritability rates between 89% (McGuffin, Rijsdijk, Andrew, Sham, Katz, Cardno, 2003) and 93% (Kieseppa, Partonen, Haukka, Kaprio, Lonnqvist, 2004). The inheritance of mania and depression are independent, which lead researchers to determine that BD is two comorbid diseases (Maletic, Raison, 2014). The same study questions the diagnostic capabilities of medical professionals for BD but points to microglia over-reactivity as the mechanism for BD after multiple studies showed that “inflammation is also increased in the periphery of the body in both the depressive and manic phases of the illness”. Strakowski, et al. (2012) points to developmental issues with white matter connectivity and prefrontal pruning as the cause of BD. Phillips, Travis, Fagiolini & Kupfer (2008) highlight the problems of neuro-imaging patients with BD that were being treated with medications at the time of the study and the difficulty of taking such serious patients off medication for the trials.

In addition, Maletic and Raison (2014) point out the difficulties of past neuroimaging studies of patients with BD in that they often fail to identify the state (manic or depressive) that the patient was in when the imaging occurred and the propensity for patients being medicated during the imaging. The symptoms of BD have led all the researchers mentioned in this paper to conclude that the amygdala, thalamus, and hippocampus play some role in BD, while several others offered some combination of the ventral lateral and medial prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex, hypothalamus, and striatum as prime culprits. These findings are generally derived from the researchers' affinity for a certain model of neural pathways for emotional control that fit the symptoms of BD. Harrison, Colbourne, & Harrison (2018) provides several of these conflicting sources about the pathophysiology of BD and laments the lack of consistency and similarities between BD studies.

Conclusive research on the neural pathways of BD are inconclusive, and although there is more certainty provided by many researchers on BD neuro-chemistry, it is hard to find support for any of the pathway hypotheses from these findings. Gigante, et al. (2012) conducted a study that found elevated levels of glutamine and glutamate in BD patients, while Schür, et al. (2016) found no significant change in GABA levels in BD cases. GABA and Glutamate are often complementary neurotransmitters that tightly regulate neural activation and suppression. The high levels of glutamate combined with the normal levels of GABA would seem to indicate that there is an over-excitatory element of BD. However, there are no meaningful implications from these findings of neuro-chemistry to identifying the neural pathways of BD due to the abundance of Glutamate receptors in the brain.

In spite of the lack of agreement in the scientific community over the pathophysiology of BD, there is consistent support for the use of lithium, carbamazepine, divalproex sodium or psychotherapy as treatment (Bowden, et al. (2000). Attempting to form a connection between effective treatments and the underlying disorder is difficult. Phillips et al. (2008) researched the published literature on the topic and found, “either no significant effect or ameliorative effects of psychotropic medications on abnormal structural and functional neuroimaging measures relevant to pathophysiologic mechanisms of the disorder”. This study is another example of the difficulties in identifying the neural pathways of BD.

In conclusion, BD is a serious disorder that affects millions of people. The study of its neurophysiology is complicated by the need for medication, disagreement over the affected neural pathways, and the pathology involving common neurotransmitters. The most likely cause of the confusion surrounding BD is that it is actually two different disorders; depression and mania. Looking at BD as a case of oscillating depression with a rebounding effect that overshoots the optimal values of homeostatic brain activity may lead to a clearer definition of BD. This hypothesis would imply that Bipolar I and Bipolar II are completely different disorders, as Bipolar I doesn’t require an instance of a depressive state for its diagnosis. Because treatment remains the same regardless of the definition, there are currently no practical differences in using a unified definition over the current definition.

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