Chapter 2: Brain Differences in Bipolar Disorder

This is a hard chapter. If there are any in this series of five chapters you might wish to skip, this would probably be it. The others lead more directly to implications for treatment. This chapter is for those people who would like to see with their own eyes what is going on in the brain of people with bipolar disorder that might be different from what is going on in those who do not have this condition.

The bottom line: psychiatry is making progress. Although it is hard to spot differences in the brain by doing simple tests like a CT scan, or even an MRI, there are now consistent differences which are being shown that confirm the working hunch about bipolar disorder — namely, that this is a condition in which emotions gain too much power over behavior. I know, is that not obvious? True, we already knew that just from experience, as you surely know as well. But what we can now see is at least a glimpse of the brain mechanisms by which this occurs: too much activity in emotional centers, and too little in the frontal lobes that are supposed to be able to inhibit action. Moreover, these differences are present even when no symptoms are present.

Link to Chapter 3: The Central Role of the Biological Clock

Differences in size

First the good news: many of the differences in brain size which have been shown in many studies of patients with mood problems can be reversed at least in part with effective treatment. Second, the take-home message for now: growing evidence suggests that each episode of severe mood symptoms is associated with increases in these brain size differences, and therefore aggressive pursuit of good symptom control may be associated with preventing some of the brain changes that unfortunately seem to progress in at least some forms of bipolar disorder.

Although it has taken years to be certain, because not all studies have shown the same results, there is now fairly good agreement that the frontal cortex (which is associated with decision-making and controlling impulsive behavior) shrinks in size when bipolar disorder is allowed to progress. This is basically the same result which has been seen in severe forms of depression which remain untreated, as shown in my essay on frontal atrophy in depression.

Several studies have now shown that lithium appears to be capable of reversing this trend toward frontal atrophy (the studies are referenced in the essay on treatment effects in depression).

Differences in Function

People with bipolar disorder make mistakes when interpreting the expressions on people’s faces, at least in an experimental setting. This has been shown several times, including in children,McClure where the following results were obtained:


As you can see, given the pictures that were shown in this study, everybody makes mistakes and interpreting them, but people with bipolar disorder make those mistakes more often. Interestingly, their mistake rate was even greater than patients with anxiety disorders, who did not differ greatly from controls. When the faces shown exhibited more dramatic expressions, people with bipolar disorder made over twice as many mistakes as people without a mood or anxiety problem.

All of the above findings were seen even in children who were not symptomatic at the time of the study. In other words, this difficulty with facial expression recognition may be one of the more lasting, permanent parts of the illness, not a symptom. However, the error rate may be particularly evident during mania.Altshuler, Fleck

Interestingly, these mistakes in facial recognition appear to be reduced by treatment, at least with one of the standard treatment for bipolar disorder, lamotrigine.Haldane

Making quick decisions about emotional matters

If you aren’t familiar with reading one of these pictures, and don’t want to learn (not too tough, but maybe not necessary), the bottom line here is: people with bipolar disorder, even when they don’t have any symptoms, don’t seem to use the front part of their brain when making decisions under time pressure. In this particular task, at least, they were not using the part of the brain known to inhibit impulsive action (not as much as were the control subjects).

Researchers are homing in on regions of the brain which act differently in people with bipolar disorder compared to those without the illness. Evidence is growing quite strong that a region of the brain called the medial prefrontal cortex is underactive in people with bipolar disorder even when they are having no symptoms at all. However, to see this difference show up, the the brain image study must be done when participants are working on a task that requires making decisions quickly about something with an emotional overtone. In a recent study, a team from AustraliaLagopoulos found the following result:


The red region is the medial prefrontal cortex. You see here the portion of it which is more active during the task in people without bipolar disorder, compared to those with the illness (the task required a complex sorting of words, some of which had emotional implications). The blue/green region is the hippocampus, which was more active during the task in people with bipolar disorder.

The authors note that this region of the frontal cortex is thought to be important in being able to change one’s behavior from a routine response to a new, flexible response based on circumstances. One of my patients to whom I showed this picture asked about her sense that she is no longer able to “multitask”. She cannot rely on her brain to make choices between routine or flexible responses unless she really concentrates. She pointed out that people often take up the ability to multitask as a marker of intelligence; and unfortunately, the opposite as well: if you cannot multitask, you aren’t “smart”. Increasingly, this somewhat subtle cognitive impairment is being recognized as one of the unfortunate consequences of bipolar disorder.

Medications may make a difference, however, at least somewhat. In a study similar to the one shown above,Strakowski researchers compared patients who were not receiving medications with those who were. The following series of MRI slices shows regions of the brain which were more active in those taking medications. As you can see, a region of the brain similar to that emphasized above, the medial frontal cortex, became more active with treatment. Another region which changes substantially is the anterior cingulate gyrus, which has been shown in other studies to play a central role in emotion control.


In general the picture which seems to be developing here is that people with bipolar disorder are working harder with their emotional centers when doing basic thinking work, compared to those without the illness. This may be some form of compensation for decreased activity in more frontal regions of the brain.

The Upside of Bipolar Disorder

Isn’t there some good news to go along with all this?

This is a popular line of thought, lately. Several authors have written recently about the benefits of hypomania (The Hypomanic Edge; Exuberance; The Bipolar Advantage; an article by a NY Times science writer). In general, these authors emphasize the high degree of productivity and creativity associated with bipolar-like traits. In the last chapter of my little miniseries here, you’ll see a science-based speculation on how bipolar genes might lead to these very positive social outcomes.

Unfortunately, I fear that for many people with bipolar disorder, this line of thought is not going to help much, and could be harmful — if people look at this supposed benefit of bipolar disorder and wonder why they never saw any kind of benefits like that in their own lives. However, I must admit that one of the reasons why I have specialized in bipolar disorder is because it seems like nearly every single person with bipolar disorder I see is unusually creative or intelligent or charismatic or something. Quite a few have been really profoundly intelligent to the point where I have trouble keeping up with their minds.

Perhaps the following might serve as the metaphorical “other side” of the story in the images above:

Robert Schumann
Robert_Schumann schumann_manuscript_3

To listen to some of his works, take this link to Wikipedia and scroll to the bottom of the page.

Link to Chapter 3: The Central Role of the Biological Clock

(updated 12/2014)