Expert Perspectives on the Clinical Management of Bipolar 1 Disorder - Episode 3

Symptoms Associated with Bipolar 1 Disorder

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Drs Vladimir Maletic and Andrew Cutler explore symptoms associated with bipolar I disorder, such as sensory acuity, recurrent depression, and manic episodes.

Vladimir Maletic, MD, MS: You opened a very interesting discussion, and I hate to say it, who could fill up the entire hour with that discussion, but I think you’re making a very good point. That is, as we elucidate some of the pathophysiology underlying bipolar disorder, we are realizing that symptoms of bipolar illness map more easily on dysfunction of a functional brain network and their communication than they do to transmitter systems. To provide a global picture, it appears that in a manic state the network has heightened activity, and this may translate into sensory acuity. You have seen it in our bipolar patients where people chewing loudly, conversation at workplace, and any sounds in the background including ticking of the clock can be innervating. In addition to that, there are issues with increased motoric activity in mania. These individuals are restless and agitated and often pacing. On the other hand, salience network also seems to have heightened activity, and therefore there is possibly a relationship with grandiosity where one believes that one may have been slighted yesterday by not being granted Nobel Prize for one’s discoveries, and maybe this year is not our year, but next year it’ll definitely be. People tend to be expansive, overly interested in enjoyable activities, so sensory motor network in mania seem to have elevated activity. Additionally, default mode network, which in part has to do with self-reflection of monitoring, seems to have decreased activity in mania.

Andrew Cutler, MD: In depression, it’s the opposite.

Vladimir Maletic, MD, MS: It’s the opposite, exactly. For sensory motor activity individuals, when it comes to sensory cues from the periphery diminish sensitivity and somewhat increase sensitivity for internal stimuli. People tend to be preoccupied with bodily aches and pains, but when it comes to motoric activity, as with psychomotor retardation, it’s often reduced in depression and salience in terms of finding meaning in terms of having emotional echo in the events in one’s life; interest is lower, enthusiasm is lower, ability to enjoy life is lower. On the other hand, heightened activity, and default mode network, which is sometimes associated with ruminations. Nonproductive reviewing of the Rolodex of miserable events in our lives which does nothing but deepen heart depression. The part that is intriguing to me is, in these large genome-wide association studies, it has been appreciated that bipolar disorder, like other psychiatric conditions, is not homogeneous. Individuals who have bipolar disorder will have risk genes for MDD [major depressive disorder, for ADHD, for substance use disorders, and schizophrenia. There are studies that have looked at individuals, top 10% highest presence of schizophrenia risk genes versus bottom 10% lowest presence of schizophrenia risk genes, and in terms of response to lithium, individuals who had highest presence of schizophrenia risk genes have three and a half full less chance of responding to lithium.

Andrew Cutler, MD: Less chance quite interesting. I wasn’t aware of that.

Vladimir Maletic, MD, MS: Versus individuals who don’t have schizophrenia risk genes that have bipolar disorder, so not readily translatable to clinical practice.

Andrew Cutler, MD: Unfortunately.

Vladimir Maletic, MD, MS: How often have you had patients with bipolar disorder who didn’t respond to lithium, but did respond to either typical or atypical agents?

Andrew Cutler, MD: Yes, absolutely. It is fascinating. It would be nice, wouldn’t it, if we had some biomarker like that to guide us to an appropriate therapy?

Vladimir Maletic, MD, MS: Indeed, and phenotypically there is no clear-cut separation. There is some suggestion that there is mood incongruency between delusions and patients’ mood state. But again, that is not a reliable phenotypical marker.

Transcript edited for clarity