we’re faced with a huge array of behavioral choices, and it’s thought that this region of the brain helps you select the best one. When it’s not functioning, decisions are harder to make. Your brain can’t choose, so it chooses nothing.
One interesting symptom of Huntington’s that may shine light on the nature of irritability is that HD patients are apt to misconstrue situations, researchers say. Craufurd was the coauthor of a study that tested the ability of Huntington’s patients to read social cues by asking the participants to interpret cartoons. Identifying the humor in the cartoons required the viewer to infer the mental state of another person. Here’s the description from the paper in
In one cartoon, for example, a man is shown cuddling a young woman who is sitting on his lap, while with his free hand, he is tapping a ping-pong ball with a bat. The humor lies in the fact that an older woman sitting in the adjacent room, within earshot but out of view of the couple, is deceived into believing that the man is playing table tennis, whereas in reality he is otherwise occupied.{45}
Huntington’s patients were asked to describe why the cartoon was funny. Here’s a misread that one HD patient made: “They’re having a bit of nooky while the wife’s sat [
The interpretation isn’t like the paranoid delusion of a schizophrenic; it’s within the realm of possible reality, but it is not supported by the information presented. The authors of the study write, “HD patients did draw inferences that went beyond the physical contents of the cartoon. They abstracted and formulated hypotheses, including hypotheses about a character’s feelings or belief. However, those inferences deviated from the conventional interpretation.”
This tendency to misconstrue seems to exacerbate the irritability problem. We have all met someone who takes things the wrong way. Let’s say you tell your husband that his suit makes him look trim, and he responds, “Are you saying I’m fat?” People who are prone to reading too much into a statement or a situation also seem prone to getting annoyed. Kevin Craig said that many of his depressed patients are irritable, and it seems to be related to their tendency to assume the worst, even if there’s no evidence for the assumption. “They take things the wrong way,” he says. “Neutral comments become upsetting.” In the case of Huntington’s patients, the combination of being likely to misconstrue and having a short fuse because your mental brakes aren’t working well can result in disaster.
Breaking a social contract is a common source of annoyance, even for healthy people. Most of us navigate the world with expectations for how social situations should transpire, and we get annoyed when those expectations are not fulfilled: a quiet train ride is disrupted by a noisy nail-clipper, a simple meeting in India becomes a lengthy afternoon tea, or a Swiss mechanic won’t honor your appointment because you’re a little late. Now imagine that social transactions never go the way you expect. It’s like waking up in a foreign country where all of the rules are different, and you’re never able to decode them. Craufurd gives this example:
I like to tell a story of my patient who was actually on his way to the clinic. He comes from Liverpool, and he leaves his bag in the gent’s toilet in the railway station. The person who saw him do this approached a policeman who then eventually found [the patient] and reunited him with his bag and gave him a rather annoying lecture about being more careful in the future. [The patient] ended up hitting this policeman and getting arrested. One part of it is obviously being able to think through the consequences of actions, and you’d know that hitting a policeman would get you into big trouble. But aside from that, you and I wouldn’t regard that person as threatening, he’s just doing his job, and if you couldn’t really correctly infer that, you might think that he was angry and that he represented some kind of physical threat.
Compounding the problem for Huntington’s patients is that according to one of Craufurd’s studies, people with the disease are particularly bad at recognizing negative emotions, especially anger, in others.{46} Most healthy people can look at someone’s furrowed brow or other facial features and recognize anger or sadness. Huntington’s patients have a particularly hard time with this. “Patients with Huntington’s aren’t terrifically good at correctly reading another person’s emotional state, and that leaves you at a great disadvantage,” Craufurd says.
This is a social impediment because the reactions of others often direct our own behavior. Imagine how you might behave if you didn’t know you were making others feel bad. You might act much worse if you didn’t see the negative consequences to others.
For a healthy person, making your spouse upset (and having to deal with that upsetness) might deter you from making a big fuss over a trivial matter. If you couldn’t see that your spouse was upset—because your brain wasn’t functioning properly—you might not feel quite as deterred. An incentive for regulating our tendency to get annoyed may have something to do with guilt avoidance. So, it’s a triple threat for some Huntington’s patients: the disease can make a person more likely to misread a situation, make it difficult for a person to control himself, and impair his ability to recognize that his behavior is making someone sad or angry.
Worse still, HD patients don’t seem to be particularly aware of their outbursts, psychiatrists say. Mark Groves relates this story from the Huntington’s clinic at Columbia University: “This morning in the clinic there was one patient we saw recently. I asked her, ‘Have you been irritable lately?’ and she said, ‘No.’ Then her husband said, ‘Yes, you have been.’ And she screamed out, ‘?Mentira!’ [It’s a lie!] and started to lunge at him—of course, demonstrating that she was irritable.”
Because the patients are unreliable sources, David Craufurd is interested in figuring out whether irritability can be measured directly. “We started to play around a little bit with experimental paradigms to try to annoy people and see whether we could measure a response to that.” Specifically, Craufurd and colleagues, including Stefan Kloppel, put healthy people and people with the Huntington’s gene into an fMRI machine and annoyed them.{47}
The participants were playing a game—but the researchers were cheating them. “The results were a little bit confusing from that study,” Craufurd says. In the healthy participants, “when we cheated them with the computer, their imaging showed the brain changes we rather expected when people start to get annoyed.” The researchers saw activation of the amygdala—which is part of the limbic system—when the healthy participants reported feeling annoyed. “Whereas the [HD] patients showed the same sort of brain changes when they were provoked, but they said they didn’t feel annoyed, and that rather spoiled the correlations and so on,” Craufurd says. Even though their brain activity suggested annoyance, patients with HD weren’t aware of the feeling or didn’t admit to feeling annoyed.
The good news for HD patients—and perhaps even better news for their families and caretakers—is that irritability can be treated. “It’s remarkably responsive to treatment, so it’s very gratifying,” says Mark Groves, who is working on treatment guidelines for HD.
The first line of attack for irritability is drugs. When treating irritability, Groves says, “more than in any other area of psychiatry, I am confident when I give a prescription to our patients in the HD clinic that either a family member is going to call or the patient is going to call and say this is tremendously helpful.”
Four classes of medication are used to treat irritability. Groves likes to start with selective serotonin reuptake inhibitors (SSRIs)—a group that includes antidepressants such as Lexapro, Celexa, Prozac, and Zoloft. Serotonin is a neurotransmitter that helps deliver messages in the brain. SSRIs block the absorption of serotonin by certain nerve cells in the brain, leaving more serotonin floating around. If some circuits are down, as occurs in HD patients, it seems to help to make the nerve cells that are working more effective.
Groves says that unlike with depression, in HD this irritability disappears within a few weeks on these medications. “Irritability in Huntington’s seems cleaner. It’s extreme, but it also melts away on the medications. Whereas the irritability in some of the other conditions, it’s more complex, especially for personality disorders or depression or bipolar disorder.” Psychiatrist Jon Silver has seen irritability evaporate in only few days in his traumatic brain injury patients.
There are other medications that Groves uses as well, such as propranolol, a beta-blocker, which is often prescribed as a blood pressure medication. “People use propranolol all of the time for performance anxiety. It
