Depression linked to chronic brain inflammation

Chronic depression is an adaptive, reparative neuro-biological process gone wrong, say two University of California, San Diego School of Medicine, researchers, positing in a new theory that the debilitating mental state originates from more ancient mechanisms used by the body to deal with physical injury, such as pain, tissue repair and convalescent behaviour.

In a paper published in the September online edition of Neuroscience and Biobehavioral Review, Athina Markou, PhD, professor of psychiatry, and Karen Wager-Smith, a post-doctoral researcher, integrate evidence from diverse clinical, biological and behaviural studies to create a novel theory they hope will lead to a shift in thinking about depression.

''In contrast to other biological theories of depression, we started with a slightly different question,'' said Wager-Smith. ''Other theories address the question: 'What is malfunctioning in depression?' We took a step back and asked the question, 'What is the biology of the proper function of the depressive response?' Once we had a theoretical model for the biology of a well-functioning depressive response, it helped make sense of all the myriad differences between depressed and non-depressed subjects that the biomedical approach has painstakingly amassed.''

According to the new theory, severe stress and adverse life events, such as losing a job or family member, prompt neurobiological processes that physically alter the brain. Neurons change shape and connections. Some die, but others sprout as the brain rewires itself. This neural remodeling employs basic wound-healing mechanisms, which means it can be painful and occasionally incapacitating, even when it's going well.

''It's necessary and normal so that an individual can adapt, change behavior and deal with altered circumstances,'' Markou said. Real problems occur only ''when these restructuring processes go into overdrive, beyond what is necessary and adaptive, and for longer periods of time than needed. Then depression becomes pathological.''

The theory extends findings made by other researchers that the neuro-biological substrates of physical and emotional pain overlap. Just as the body's repair mechanisms for physical injury can sometimes result in chronic pain and inflammation, so too can the response to psychological trauma, resulting in chronic depression.