Depression and Anhedonia

What's anhedonia? If you're depressed, you know.

Anhedonia is one of the main symptoms of major depressive disorder (MDD). It is the loss of interest in previously rewarding or enjoyable activities. People suffering from clinical depression lose interest in hobbies, friends, work, and even food and sex. It's as if the brain's pleasure circuits shut down or short out. But do they? Some experts define hedonic function as the total amount of pleasure that it's possible to gain from a single activity. Perhaps depression reduces that hedonic capacity. Certainly, as I report in Brain Sense, we know that the brain's pleasure circuits can be modified—for example from a deep aversion to salty taste to a real orgasm of salt pleasure.

But depression may not shut down pleasure circuits entirely. An alternative theory suggests that anhedonia comes not from a reduced capacity to experience pleasure, but instead from an inability to sustain good feelings over time. In other words, maybe pleasure is experienced fully, but only briefly—not long enough to sustain interest or involvement in life's good things.

How can you find out the difference? When it comes to pleasure pathways, the brain's geographic layout is complex. Areas associated with reward and motivation include the nucleus accumbens (or NA, deep inside the "primitive brain"); and higher up, the prefrontal cortex (or PFC, the thin outer layer of the brain behind the forehead). It's likely that nerve impulses travel in both directions to maintain reward and motivation. That is, "feel good" signals travel upward to the PFC, but nerve fibers from the PFC also send signals down to the NA. Some evidence suggests that, in normal brains, signals traveling downward from the PFC to the NA may sustain interest in a pleasurable activity. If that's true, then the depressed brain might have trouble using the PFC to sustain NA activity over time.

Today, Aaron Heller and his colleagues at the University of Wisconsin and the University of Reading (UK) published a paper that sheds some light on that hypothesis. They report in the Proceedings of the National Academy of Sciences on their new functional magnetic resonance imaging (fMRI) studies of brain activation patterns in depressed and nondepressed people. The people looked at pleasant, unpleasant, and neutral pictures over a 37-minute period, but the volunteers weren't passive. They made a conscious effort to enhance the mood the picture produced, whether happy, sad, or indifferent. The study delivered five important insights:

1. In response to positive images, the depressed brains didn't sustain NA activation as well as the normal brains did—no matter how hard they tried.
2. Difficulties sustaining activity in the NA were associated with reduced activity in the PFC.
3. Those depressed persons who couldn't sustain NA activity reported less positive emotional responses to the pleasurable pictures.
4. Those depressed subjects who were better able to sustain NA activity also reported higher levels of positive emotion in their everyday lives.
5. The deficit in sustaining NA activity was specific to positive emotion. (Apparently, happiness is hard to sustain but sadness isn't. I wonder if sadness is our default setting.)

If you are depressed and suffering from anhedonia, you're probably asking, "So what?" How does knowing what's going on in the brain offer hope to individuals trapped in despair? I think it's important for at least two reasons. Pure scientific research gets to the heart of "how things work." If we can understand what goes wrong in anhedonia, we may be able to develop drugs or behavioral therapies that coax the PFC into reinstating its sustained activation of the NA. This research also provides a new way to measure whether experimental treatments work. And those possibilities for treatment and assessment—admittedly for the future—should cheer even the most stubborn anhedonia.