Bipolar Disorder


Bipolar Disorder is a severe mental disorder characterized by mood instability which results in periods of mania and depression,  which can last days to weeks and be of varying severity, as well as chronic symptoms including but not limited to emotional dysregulation and  disturbances in circadian rhythm. Including all major subtypes of Bipolar Disorder, 4.4% of the population is affected by this disease (Leboyer et. al, 2010). Currently, the understanding of Bipolar Disorder is that it is a disease with multiple causative factors, none of which are fully understood. However, significant findings have pointed towards a number of potential molecular targets, mainly proteins related to serotonin and melatonin biosynthesis (neurotransmitters that play a role in mood regulation and regulation of circadian rhythm, respectively) (Kripke, et. al. 2011, Etain, et. al. 2012), as well as proteins like GSK-3 which have been found to be affected by common treatments of Bipolar Disorder, in this case lithium (Can, et. al. 2014, Freland and Beaulieu, 2012).

A graphic representation of the range of moods experienced in bipolar. Not all Bipolar individuals experience all of these. From University of Colorado Colorado Springs
A graphic representation of the range of moods experienced in bipolar. Not all Bipolar individuals experience all of these. From University of Colorado Colorado Springs

This focus on current treatment methods highlights the difficulties of studying mental disorders, as most of the current research that is suggesting biochemical reasoning for the disease state has been arrived at not by studying the disease directly but rather by looking for the targets of the treatments, most of which were discovered only after the treatments went into use. The number of different treatments used is significant and varied, ranging from mood stabilizers like lithium and valproic acid, to atypical anti-psychotics  (resperidone, etc.) and antidepressants (sertraline, paroxetine, etc.) (from the NIMH, The National Institute of Mental Health).  These treatments were, for the most part, developed and used prior to any biochemical mechanisms for their action being proven (Ginsberg et. al. 2012), as such the research community is now working backwards by studying the current treatment methods and determining what sorts of interactions they have in the body, and using these findings to figure out what sorts of molecules and proteins are involved in the disease state of Bipolar Disorder.

15 Replies to “Bipolar Disorder”

  1. You mention that over the different subtypes of Bipolar disorder, 4.4% of the population has it-but you don’t mention what those subtypes are and how they differ from each other. What are the differences, and do these variations affect how they are treated?

    1. There are 4 major subtypes of Bipolar Disorder recognized by the DSM-IV, Bipolar I Disorder, Bipolar II Disorder, Cyclothymic Disorder, and Bipolar Disorder Not Otherwise Specified. Bipolar I is characterized by the occurrence of Manic or mixed (manic and depressive) episodes, usually with major depressive episodes. Bipolar II is the opposite, with a predominance of Major depressive episodes and at least one Hypomanic episode (hypomania is mania of a much less severe degree, to the untrained eye it can sometimes come across as someone who is simply very energetic and driven).
      Cyclothymic disorder is a more moderate form of Bipolar, where the individual has several episodes of hypomania and periods of depression, but no full Manic Episodes or Major Depressive Episodes.
      Bipolar Disorder Not Otherwise Specified is a catch-all term for conditions and situations that do not meet the criteria for any of the other Bipolar categories, but that do display traits related to Bipolar more than other disorders. It also covers people whose symptoms are not yet well documented, as Bipolar Disorder is diagnosed based on the patients mental history, which is often self reported.

      1. having recently reviewed the newer DSM V, the primary diagnostic types of bipolar have been parsed down to the first three I mentioned, with the last type being added to the end of the list with drug induced bipolar, bipolar caused by another medical condition, other specified bipolar and unspecified bipolar.

  2. Overall, I think your language is very accessible.
    It might be interesting to write more about who is most affected by bipolar disorder — or, is it pretty evenly distributed across all demographics?

    1. Thank you for the comment! From what I have seen in the literature, occurrence seems to be pretty evenly distributed across demographics and geographic regions, although I am not 100% certain that this is the case.

  3. I think the diagram is very helpful and makes the information more understandable. You didn’t mention anything about genetics, are there any genetic components of the disease? Also what are the characteristics of severe mania and severe depression? What sets these two apart?

    1. Thanks for the comment. The genetics of this disease, although i did not mention them explicitly here, are indeed important. It is suspected that the disease is strongly genetic, with a tendency to run in families. However, there are currently a few too many genes being implicated in the disease for me to get into the specifics on this page, especially since a lot of the individual genes and gene clusters that have been linked to the disease have only been linked in a speculative manner, with decidedly little understanding of the particular effects any of these genes are having.
      As for what sets severe mania and severe depression apart, let us consult the DSM V: a full manic episode is characterized by, among other things, elevated, expansive or irritable mood, and abnormally increased goal-oriented activity, and very high energy. These symptoms persist for at least 1 week and are present most of the day every day during that time. A person in a manic episode will talk very quickly, experience racing thoughts, and potentially engage in unusually risky behavior. In summation, a manic episode is a period of intense high energy, to the point that it significantly impairs a persons ability to function normally. In the case of a major depressive episode, the person will experience a loss of interest in things that used to interest them, pleasure will also no longer be something they seem to experience. The person will experience a sense of hopelessness, sadness, and/or emptiness. They may also become suicidal. This state, if it lasts for two weeks or more, along with other common symptoms of depression (insomnia or hypersomnia, loss of energy, change in appetite, etc.) is classified as a major depressive episode.

  4. I like the diagram, and this was easy to read and understand. I was curious to know what the multiple causative factors are?

    1. Good question! The short answer is that they aren’t known. the slightly longer answer is that some factors, such as the presence of certain mutations and the increased or decreased expression of certain proteins has been implicated in the disease, but so far there has not been concrete evidence to suggest that any one thing definitively causes bipolar disorder. Some of the proteins I mention above, like GSK-3, are strong candidates for causative factors as they interact with drugs that have proven effective at treating the disease, but beyond that only speculation based on correlative studies is available.

  5. You do a good job of highlighting the difficulty in studying mental disorders in general, which is super important to get across. Since it is so difficult and poorly understood, maybe you could talk a little bit about why the targets were targeted in the first place. Melatonin is pretty obvious based on the context, but is serotonin targeted just because it is targeted in depression? Also, linking GSK-3 to the primer page might be good to give background on that. The answer to this is probably a solid “no,” but has the “working backwards” method yielded any meaningful results yet? Also, are the different treatments prescribed based on which subtype the person has or is it just kind of arbitrary? Overall, good job organizing the information on such a complex and poorly understood disease.

    1. Ask all the hard questions, why don’t ya. I agree, I should try and talk about how the targets were decided on, which is mainly by their association with the disease state (mostly, people compared patients with bipolar with controls, saw things that were not the same, and said ‘hey, lets look at that’ or they followed the trail of one of the already present treatments). Which leads to your other question, the answer to which is in fact not a solid NO. It is more of a weak ‘sort-of?’ Protein targets like GSK-3 were arrived at by this backwards method, by looking at what molecules were being targeted by the drugs (in this case lithium) and then studying them in disease models and in people with the disease. However, I say maybe because as of yet they have only determined that these targets, like GSK-3, are being acted on by the drugs in question, but they have yet to pin point how exactly these proteins are related to the disease state.
      Finally, treatment options are decided on mainly by trial and error. No single drug is recommended specifically for one form over another except to the extent that some drugs treat manic episodes while others treat depressive episodes. There are even a select few drugs that treat both with some effectiveness. However, a single patient will often go through several different medications before finding one or a combination of drugs that works. Some drugs, such as Quetiapine (Seroquel) are approved for treating both manic and depressive episodes, but more often than not combination therapy with two different drug is used.

  6. I like the masks…. But the idea that melatonin biosynthesis has an effect is interesting considering that melatonin is sold OTC as a sleep aid.

    1. Thanks! Yes, melatonin is interesting. The reason that it is being looked at is because in bipolar, the person usually has an abnormal circadian rhythm and abnormal expression of related compounds, like melatonin. melatonin is simply one of the hormones that helps control the sleep-wake cycle, and at night your body secretes melatonin to make you tired. Some studies have found that melatonin levels differ in bipolar patients, and that their bodies secrete different amounts at different times than the average person.

  7. I liked your description of both the shifting behaviors associated with Bipolar disorders and the current methods of developing treatments (if it works give it). It could be useful going into why it is so difficult to study a mental disorder such as bipolar, and the resulting difficulties in finding a proper methodology in discovering the molecular cause of the disease. Furthermore I feel it could be interesting to relate how the very shifting behavioral aspect of bipolar disorder is related to the difficulties in finding a proper treatment. How is one supposed to treat someone currently in a manic state versus a depressive state? Should the same drug in the same quantities be given during each form of episode? Can any further understanding be made by comparing the treatment of bipolar to that of monopolar?

  8. Thanks for the comment Cyrus. I will go back and add some parts about why treating and studying mental disease is so challenging, but for now let me address your questions. For how prescribing drugs tends to work, i refer you to my answer to Matt’s question and supplement it thusly: when trying to treat bipolar, except when emergency care is needed, often a drug for both manic and depressive phases is prescribed. even when one is not experiencing an episode of either type, both types of medication will be taken at maintenance dosages in order to maintain stable mood. in the case of sudden, severe episodes, it is not uncommon for, in the case of a manic episode for example, a sizable dose of one of the antipsychotics to be administered intravenously. As far as comparing bipolar disorder to unipolar depression, strangely enough the mechanisms seem to be different. (See the page on Major Depressive Disorder for details on MAOA and the MAOIs used to treat depression). Although some of the same drugs are used, the same mechanisms do not appear to be at work, at least not in any consistent manner.

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