Biochemistry and neuropathology of bipolar disorder

Professor Wayne Drevets discusses the amygdala, striatum, and prefrontal cortex as neural correlates of bipolar disorder. Mania and depression may link to the dopamine system.

Bipolar disorder has also been associated with abnormalities of function and structure in the amygdala. It also has been associated with abnormalities of function in areas like the ventral striatum, where the so-called accumbens area is, and in parts of the prefrontal cortex like the medial prefrontal cortex which get involved in modulating stress and response to stress and in anxiety and response to stimuli that would cause one to feel anxious. Bipolar disorder is also associated with some ability to swing back and forth in the response of the emotion system. So if you think about the nature of a manic episode, it’s almost the phenomenological antithesis of a depressive episode. Instead of the mood being low in depression it can be high in mania. The self-esteem and self-concept is very low in depression, but it’s expansive and elated in the manic phase of bipolar disorder. Some individuals will even get grandiose delusions during a manic phase. In depression, one feels fatigued and worn out; in mania in contrast one feels energized like you have a boundless energy. In depression you want to socially withdraw and are less active; in mania you’re much more active and you are very much more socially outgoing and so you get this complete flip between systems. We don’t know what the nature of that flip is; we’ve hypothesized various neurobiological mechanisms for that, but we really don’t know of any at this point. The dopamine system that I referred to earlier has been one of the targets of a lot of hypotheses because the dopamine system, when it’s decreased, for example in an illness like Parkinson’s disease, is associated with low mood and loss of ability to enjoy things just like in depression. Whereas when you have high dopamine states you feel this increased motivational drive, things are much more rewarding, you feel euphoric. And so that’s been one of the systems where it has the capability for low versus high, giving this kind of range of symptoms that you see in the depression versus the mania phase of bipolar disorder.