http://www.medpagetoday.com/Psychiatry/Depression/39794 Depression Tied to Infections, Autoimmune Disease By Crystal Phend, Senior Staff Writer, MedPage Today Autoimmune disease and severe infections may increase risk of developing depression and other mood disorders, a population-based study suggested. Any contact with a hospital for autoimmune disease was associated with an independent and significant 45% higher risk of a subsequent mood disorder diagnosis, Michael Eriksen Benros, MD, of Denmark's Aarhus University, and colleagues reported online in JAMA Psychiatry. Hospitalization for any infection was associated with a significant 62% elevated risk of later mood disorders. If that association was causal and could be eliminated, 12% of all mood disorders could be avoided, the researchers estimated. A history of both severe infection and autoimmune disease synergistically boosted the risk 2.35-fold (95% confidence interval 2.25-2.46). "These associations are compatible with the hypothesis of a general immunologic response affecting the brain in subgroups of patients with mood disorders," the researchers concluded. However, "it remains unclear precisely how the immunologic process affects the brain and whether it is a causal relationship or an epiphenomenon of underlying genetic, psychological, or non-immune-related mechanisms," they acknowledged. There is some suggestive evidence for a causal link in that proinflammatory cytokines and other immune components can alter neurotransmitter and neuroendocrine function. Animal and human experiments have shown activation of inflammatory reactions can induce mood disorder symptoms. Also, systemic inflammation can produce symptoms of fatigue, reduced appetite, sleep disturbance, and others that are similar to the symptoms of depression. Some studies have suggested progression to depression in vulnerable individuals after prolonged periods, Benros' group pointed out. While the results could spur research into preventive treatments, Linda Carpenter, MD, a psychiatrist at Brown University in Providence, R.I., predicted that the immediate impact will be to call attention to comorbidities in psychiatry. "For a long time psychiatrists have been asking people 'Tell me about your life, what's stressful, what was your early life like,'" she told MedPage Today. "We know those things create risk. We ask people about family members. But we haven't really been paying attention to the health of the immune system and inflammatory conditions in our patients." At this point, though, it would be premature to treat patients differently based on infectious and immune history, she cautioned. Their study included all 3.56 million people born from 1945 through 1996 in Denmark, followed through 2010 in national longitudinal registries. Among them, 91,637 were diagnosed with a mood disorder by a psychiatrist in a hospital, outpatient clinic, or emergency department setting at some point in their lifetime. About a third of those diagnosed with a mood disorder had a prior infection diagnosis recorded in the hospital contact databases and 5% had at least one autoimmune disease diagnosis. Both the severe infections and autoimmune disease had a dose-response relationship with the risk of hospital contact for a subsequent mood disorder. "The risk of mood disorders increased with the temporal proximity of the last infection, especially in persons with autoimmune diseases for whom an infection within the last year increased the risk of mood disorders more than four times, suggesting that the results might be due to a contemporary inflammatory process," the researchers noted. The relationships were seen across sites of infection and type of autoimmune disease, although highest for hepatitis and sepsis among infections and for autoimmune diseases with "suspected presence of brain-reactive antibodies, particularly when combined with an infection." Sensitivity analyses didn't indicate difference by substance abuse or psychiatric family history, though the effect was greater among those over age 30. Limitations included lack of data on less severe cases of infection, autoimmune disorders, and mood disorders that didn't lead to a hospital contact as well as inability to draw causal conclusions from observational data. "It remains unclear whether the results can be generalized to the more frequently occurring less severe infections and mood disorders treated by the general practitioner or to those going untreated," Benros' group noted.