Posted on July 25, 2014 The neurotransmitter deficiency hypothesis of depression, as the gold standard model, is growing ever more wobbly under the accumulating weight of a variety of new, and disconfirming findings. Contradictory basic science data, that demonstrates these drugs to be scarcely better than placebos in many patients, and the emergence of more compelling causation theories. The inflammation hypothesis is perhaps the hottest new account of depression. Over a decade or so there has been an explosion of data emerging from many quarters suggesting that chronic low-grade systemic inflammation plays a significant role in major depressive disorder, as both cause and effect So, if not all patients suffering from inflammation get depressed, and not all depressed patients show signs or describe a history of inflammation, we must wrestle with a crucial question: when is depression an inflammatory disorder? This is the issue taken up in this excellent review article by Charles L. Raison and Andrew H. Miller of the Mind-Body Program in the Department of Psychiatry and Behavioral Sciences at the Emory University School of Medicine. In one study they lumped all treatment-resistant depressed patients together, and found that treating them with an anti-inflammatory drug had little effect. However, when they separated out those subjects who had elevated inflammatory markers, it worked as well as any antidepressant. Interestingly, patients with a baseline level of inflammation were actually rendered more depressed by the anti-inflammatory drug. This is a powerful affirmation of a foundational tenet of functional medicine: the importance of considering a patient’s biochemical individuality in any treatment. To be fair, the aim of their study was not to find an optimal treatment, but to clarify the relationship between inflammation and depression. To their credit, Raison and Miller do hold in mind the complex, multifactorial nature of depression. They describe how variables such as early life adversity (attachment trauma, loss, neglect, abuse), increased visceral fat, microbial infection, elevated evening cortisol levels and other manifestations of maladaptive stress, along with sleep deprivation, interact with inflammatory processes in the causes of depression. It appears that the stress of early adversity can program the body and brain to keep inflammation elevated, producing changes in the brain that in turn predispose toward depression. The work of investigators like Raison and Miller are expanding the ever-growing scientific foundation of the systems biology paradigm known as functional medicine.