The Brain Circuit Model of Depression

Patient Expert

You have heard depression described as a "chemical imbalance," as if our brains were some sort of soup that could be brought back into balance by pouring in the right additives. It is far more accurate, instead, to think of depression as a breakdown in our neural circuitry. In this context, depression and other "psychiatric" disorders have a relationship to movement disorders that are the normal province of neurologists.

Basically, if the brain is working as intended, its circuits are firing right. In a TED Talk delivered in January this year, neurosurgeon Andres Lozano of the University of Toronto discussed what happened when things go wrong. In essence, he said, brain functions are localized in circuits. So, when we get malfunctions in the motor circuits we see movement disorders such as Parkinson's. When the mood circuits misfire - voila - depression.

So far, so good. The topic of Dr Lozana's talk was about a type of brain surgery known as deep brain stimulation (DBS). Let's make this clear: This is not a piece that advocates brain surgery to treat depression. Please - don't go running to your doctor requesting brain surgery.

Rather, this piece is about understanding brain circuits and how their malfunction may lead to depression. A very effective way of demonstrating the principle just happens to be by showing how DBS works. DBS involves drilling a dime-sized hole in the skull and dropping an electrode down through the folds in the brain to the particular trouble area, and connecting through a wire lead to a pacemaker-like device implanted in the chest. A remote control turns the electricity up or down.

Why on earth would anyone want that? If you happen to have Parkinson's and medications cannot control it, the procedure can be a life-saver. Indeed, Dr Lozano showed a clip of a patient in a state of extreme distress, experiencing severe Parkinson's tremors. The electricity was turned on. The tremors ceased. The patient's face lit up with blessed relief. DBS has had FDA approval for Parkinson's since 2002, and for tremors since 1997.

Fine, you say. But surely you can't turn mental illness off with a switch. Four years ago, I attended a talk delivered by Neal Swerdlow of UCSD. First, Dr Swerlow talked about Huntingtons, which involves the brain's lack of ability to screen out certain movement impulses.

Then Dr Swerdlow explained that the mental illness of OCD involves a similar malfunction of the brain. Basically, the brain cannot screen out certain thoughts. In both Huntington's and OCD, there is a failure in "gating." We don't want to push the similarities too far, but at the root we see a failure in brain circuitry. In 2009, the FDA gave a limited approval for DBS for treating OCD.

About a decade ago, I began reporting on the work of Dr Lozano and his colleague Helen Mayberg of Emory University on DBS for treating depression. Their studies have been on small groups of treatment-resistant patients, and it is premature to draw conclusions, but in the successful cases we can once again see the brain circuit model in action.

In his talk, Dr Lozano showed brain scans of his depressed subjects, with blue areas representing areas of the brain that were shut down. These areas involved motivation, drive, and decision-making. The red area represented an over-active region - area 25 in the cingulate cortex - which Dr Lozano referred to as "the sadness center of the brain."

Drs Lozano and Mayberg wondered if they could turn down the activity in area 25, in effect tell all those screaming neurons to shut up and behave. Within three to six months of turning on the switch, Dr Lozano told the Ted Conference, there is a reversal. The reds and blues normalize.

Once more I need to emphasize: This is a piece on neural circuits, not brain surgery. Moreover, even though the causes of depression are physical, the treatments can be mental. Thus cognitive behavioral therapy can be very effective in physically changing our circuits. Dr Mayberg, herself, has the brain scans to prove it. Bogggles the mind, doesn't it?