Researchers Found Where Depression Lives in the Brain

Last year, an estimated 16 million US adults experienced a major depressive disorder that lasted at least two weeks and included at least four other symptoms such as problems sleeping, eating, or concentrating. Considering the prevalence of this mental disorder and its capacity to significantly disrupt one's normal functioning, figuring out a way to effectively treat depression is one of the most pressing problems in neuropsychiatry.

New research from a collaborative project between the UK's University of Warwick and China's Fudan University has brought us a lot closer to effective treatments for depression by identifying the physical region of the brain that is affected in depressive episodes.

"More than one in ten people in their lifetime suffer from depression, a disease which is so common in modern society and we can even find the remains of Prozac (a depression drug) in the tap water in London," said Jiangfeng Feng, a professor of computational biology. "Our finding, with the combination of big data we collected around the world and our novel methods, enables us to locate the roots of depression which should open up new avenues for better therapeutic treatments in the near future for this horrible disease."

The big data referenced by Feng was derived from 909 Chinese subjects (approximately half of the subjects were diagnosed with major depressive disorder and half were healthy) who underwent a high-precision MRI brain scan.

What the researchers found was that depression affects a part of the brain called the lateral orbitofrontal cortex (OFC). This area of the brain seems to be associated with literally every possible brain function, although one of its most researched and data-backed functional explanations is that the OFC plays a role in decision making and adaptive behavior.

The OFC has been divided into two main subregions: the lateral OFC and the medial OFC. The lateral OFC becomes active following non-reward, such as not receiving an expected reward, or unpleasant experiences like losing money or a bad smell, and as the team discovered is also affected by depression.

The new research showed that the lateral OFC is more strongly linked to a part of the brain associated with an individual's sense of self, which is likely why those suffering from depression might feel a sense of personal loss, low self-esteem, and disappointment. The medial OFC, on the other hand, is a reward circuit. It also appears to play a role in depression insofar as the researchers saw a decrease in its connectivity to memory systems, which they suggest influences depression because fewer happy and pleasant memories are being recalled.

"Before the study was performed, we did not know which brain areas the lateral orbitofrontal cortex might be especially linked to in depression," Rolls told Motherboard. "Nor did we know that the medial OFC reward system was somewhat disconnected from memory systems in the brain."

This latest study bolsters University of Warwick psychologist and computational neuroscientist Edmund Rolls' non-reward attractor theory of depression, which posits that in depression the lateral OFC non-reward system is more easily and strongly triggered than is usual. Because the lateral OFC system fires "error neurons" in response to non-reward and maintains this firing longer than is typical, it can create a feedback loop with language systems which maintains a negative cognitive state (this may also explain the tendency for those with depression to dwell on and revisit their depressive thoughts). The thinking is if you want to treat depression, you need to disrupt this feedback loop by limiting the firing of the lateral OFC error neurons.

Now that Rolls and his colleagues have a robust data set that is not only consistent with but expounds upon his theory of depression, Rolls hopes that testing will begin to determine if genes are expressed differently in the lateral OFC.

"Genes may be differently expressed in the lateral OFC [and] that may offer clues for the development of new medicines that may influence especially the lateral OFC," Rolls said in an email. "Apart from new pharmaceutical treatments that may be more specific for the lateral OFC, the new theory helps to provide a foundation for new psychological treatments that help patients to dwell less on their ruminating, negative mood, states and thoughts."