The Chemical Imbalance Myth of Depression - Here are Some Better Explanations

Patient Expert

It is time to retire the idea that depression is caused by a "chemical imbalance of the brain." The chemical imbalance myth creates the false impression that our brains are some form of neurotransmitter porridge that can be rendered just right with squirts of serotonin and dopamine.

Thanks to at least two decades of research, we now have a number of good working models on what tends to go wrong in the brain during a depressive episode. A review article by Murali Rao and Julie Alderson in this month"s Current Psychiatry outlines four overlapping theories of depression. Letâ�™s look at three of them:

  • Differences in neuron densities in various regions of the brain.
  • The effect of stress on neural growth and death.
  • Alterations in feedback pathways connecting the pre-frontal cortex to the limbic system.

The common denominator is what happens when the brain is exposed to chronic stress. Among other things, stress promotes the release of glucocorticoids. Over time, this may induce neural atrophy in the prefrontal cortex and hippocampus.

The hippocampus is of special interest, as this is the one part of the brain where neural growth (neurogenesis) takes place. The hippocampus plays a major role in memory and emotional processing and mediating the stress response. Hippocampal neurons are dense in glucocorticoid receptors, which makes them especially vulnerable to glucocorticoid bombardment.

It is estimated that we need at least four months to recover from six months of chronic glutcocorticoid exposure.

The hippocampus does not operate in isolation. It interacts with the amygdala to provide context to emotional stimuli. The two structures constitute part of the limbic system - the emotional brain - which is wired to the prefrontal cortex.

The prefrontal cortex - our rational brain - plays a major role in moderating the reactive responses of the limbic system. Once the prefrontal cortex (with the hippocampus) determines an emotion is inappropriate, it will signal the nucleus acumbens in the midbrain to inhibit the release of dopamine from the ventral tegmental area (above the brain stem) to the amygdala.

Don't worry about the fine details. We are simply offering an appreciation of what brain circuitry is all about. Basically, the front and back ends of the brain need to be fully operational and talking to each other, but not too loud.

So imagine what can happen to these circuits when say the hippocampus goes offline.

Okay, this is where it gets interesting: The stress response diverts energy from the thinking and modulatory parts of the brain to the reactive parts of the brain, such as the amygdala.

This is part of "fight-or-flight" that also goes on below the neck, where energy is pumped into various muscles at the expense of digestion and other functions.

Brain scans show the cortical areas deprived of glucose and oxygen. The front part of the brain literally shuts down. At the same time, there is an excess build-up of the neurotransmitter glutamate, which can literally excite brain cells to death.

Ordinarily, following a stressful situation, the brain reboots back to normal. But the brain under constant siege is a different story. Weakened cells lose their capacity to fend off the next round of stress. Something has to give.

The black hole of depression is going full force. Literally, we cannot think. We cannot feel. Our senses and perceptions are blunted. We are not motivated. It is virtually impossible to get two neurons to spark.

Yet, the back end of our brain may be over-stimulated. We may experience agitation and anxiety. We may lose the capacity to rein in our impulses. To add insult to injury, the modulatory signals from the front end of the brain are not up to strength.

"Depression" does no justice to the cascade of catastrophes taking place in our brain. There is no quick fix. There is no short path to pulling out of the disaster.

Lest you blame yourself for lack of ability to cope, the authors point out that researchers have implicated a number of genes. One of these has to do with a certain variation in the serotonin transporter gene. Those with this variation tend to display over-reactive amygdalae and experience depression in response to stressful situations.

Another one involves BDNF, a protein that is responsible for brain cell maintenance, particularly in the hippocampus.

Note, we are not talking about a "depression gene," per se. Rather, we are looking at the possibility of many genes relating to different types of brain function. A picture of depression is emerging, but an extremely complex one. No single explanation can do justice to this complexity, especially when we have so much more to learn.

"Chemical imbalance of the brain" is something doctors tell their patients. Don't believe a word of it.