The Amygdala: Bipolar Public Enemy Number One

Patient Expert

If you’re looking to finger one particular area of the brain as a prime suspect in bipolar disorder, the amygdala certainly has to be Public Enemy Number One. But it’s not that simple. Let’s get started …

Introducing the amygdala …

The amygdala is a small structure in the mid-brain responsible for generating fight-or-flight responses. Along with nearby limbic structures such as the hippocampus, the amygdala is involved in emotion perception and regulation.

Brain scan studies reliably show amygdala over-activation (or sometimes a blunted response) in the affective reactions of bipolar subjects compared to controls, even in stable states.

Networking the amygdala …

The amygdala is in dialogue with other areas of the brain, most notably the ventral prefrontal cortex (VPFC), which, via two networks, plays a role in modulating the limbic response. One network appears to process external emotional cues (such as a scary face), the other internal stimuli (such as from inner feelings).

In a nutshell, an underperforming VPFC combined with an over-performing amygdala may form the “neuroanatomic” basis for affective symptoms. There is also the issue of “functional connectivity.”

Digging deeper …

This is spelled out in great detail in a June 2012 review article in the journal Bipolar Disorders by Stephen Strakowski of the University of Cincinnati et al. According to the article:

Effectively, with diminished prefrontal modulation, the limbic brain is hypothesized to be dysregulated, leading to the emotional extremes of mania, depression, and mixed states.

These emotional networks form feedback and feedforward systems involving various subcortical structures that in turn connect to other areas of the brain. For instance, the anterior cingulate cortex sits at the intersection of cognitive and emotional prefrontal functions, thereby integrating information processing.

According to the article, with bipolar subjects the emotional areas of the anterior cingulate may be over-activated while the cognitive aspects are under-activated. In effect, the anterior cingulate is like a confused driver, with opposite reactions to the same stimuli, one foot on the gas and the other on the brake.

It’s complicated. The authors throw around terms such as “ventral prefrontal-striatal-pallidal-thalamic iterative networks,” but the bottom line involves modulating that pesky amygdala.

How brain development fits in …

What may defeat this purpose, the authors speculate, is a hiccup in the process of brain development, typically from adolescence to adult. Part of this involves myelination, the forming of fatty sheaths along the neurons’ extending axons.

These axonal sheaths appear as the brain’s “white matter.” According to one study cited in the article, brain scans of healthy youths with bipolar parents revealed white matter abnormalities in the corpus callosum (that bundle of neural connections linking the right brain with the left), plus other areas.

Putting all this together …

Thus, a picture begins to emerge of disruptions in the brain transitioning into adulthood, leading to decreased connectivity between the VPFC and the areas it is meant to modulate, especially the amygdala.

This, in turn, may lead to a loss of “emotional homeostasis,” ie a failure in the brain to regulate its moods and reset to “normal.” This, in turn, places the individual at risk of even minor stressful events. Over time, the brain assumes a bipolar course.

The authors caution against reading too much into their review. The field is young, and we are only scratching the surface. Moreover, we need to figure out how sleep and pleasure-reward and other systems fit into the picture.

The authors also note that an over-active amygdala and a failure in connectivity is hardly exclusive to bipolar. There are many challenges ahead. The easy studies, they say, have already been done. Bring on the difficult ones …

Further reading ...

I urge you to read the following two HealthCentral pieces with this one:

Brain Development

Problems Thinking