Physical injury and illness can cause depression

Individuals with MS are extremely predisposed to depression, thus supporting the immune system model of depression. The association of depression with MS was first documented by Charcot in 1881, and had been repeatedly confirmed since. About half of those with MS suffer from depression. Those that distinguished between severity and incidence of depression found that it is more severe during the active stage. Those with MS even exhibit more depression than other patients who are physically ill but do not have MS. Depressed individuals with MS likewise seem to have greater difficulty with it.

Parkinson's disease is also associated with depression. It is a movement disorder that results from the degeneration of a small structure in the brain called the substantia nigra. It results in fatigue, aching limbs, slowed movement, depression and mental slowness. About 40 percent of those with PD have depression. Interestingly enough, the depression usually occurs early in the disease, indicating that the depression is not a psychological result of becoming aware of the disease. Individuals with PD have been shown to have much higher levels of IL1, IL6 and TNF when compared with healthy controls. In studies, individuals with Parkinson's disease have much higher levels of IL2, IL6 and TNF in their cerebrospinal fluid.

Alzheimer's disease results in the degeneration of several parts of the brain, especially the cerebral cortex. It is the most common cause of dementia. There is overwhelming evidence that links Alzheimer's with inflammation, and this inflammation is mediated by activated microglia and lymphocytes. Cytokines, acute phase proteins and other markers of immune activation exist in much higher levels in individuals with AD. This includes cytokines such as IL1, IL6, TNF and IL2 receptors. Cellular pathology in those with AD is easily accounted for in light of unusual immune activation. While depression is highly correlated with all forms of dementia, this is especially the case with AD, especially in its early stages. Of 28 depressed patients, one study found that half of them developed AD in the following three years. Another study of 44 older patients with depressive pseudodementia found that almost 90 percent of these developed AD in the next 8 years. Indeed, depressive pseudodementia, or depression with reversible dementia, is a powerful predictor of Alzheimer's disease onset.

In one study, Smith points out, 75 percent of 50 AD patients were found to be depressed at the beginning of the disease. A review of 30 studies found that most of the studies had a rate of 50 percent. The co-occurrence of inflammation in the brain with depression suggests that inflammation may indeed be a cause of depression.

Stroke patients are highly predisposed to depression. Studies have found that between 30 to 60 percent of stroke survivors suffer from depression. Those with depression have poorer outcomes. They do not recover as well as those who are not depressed. Stroke survivors exhibit unusually high levels of IL1, IL6 and TNF in animal studies in which experimental stroke has been produced. This is also true of the cerebrospinal fluid of human stroke symptoms. The greater the brain damage, the higher the levels of cytokines.

Survivors of traumatic brain injury have been found to exhibi t rates of depression between 33 to 50 percent. High levels of IL1 and IL6 were found in serum and brain-ventrical fluid of individuals with serious head injuries. This suggests that cytokines activated in response to brain injuries may result in depression.

AIDS patients, of course, exhibit massive immune system response. HIV itself enters the brain very early in the disease. It is possible that HIV infected monocytes pass through the blood-brain barrier. Next, the monocytes transform into cytokine-secreting macrophages. It is also possible that the cells lining the blood-brain barrier become infected. Finally, lymphocytes with HIV may pass through the blood-brain area. Whatever the cause, very high amounts of cytokines are produced in the brains of those with HIV. The macrophages themselves exhibit high levels of IL1, IL6 and TNF. Neuropsychiatric problems are very serious and common in HIV patients. Approximately 65 percent of such patients experience AIDS dementia complex, which results in various psychiatric and cognitive problems. About 83 percent of individuals with HIV exhibit severe depressive symptoms. This depression occurs prior to the symptoms of HIV. Indeed, it has been found that depression occurs 18 months prior to initial diagnosis, indicating that depression occurring with HIV infection cannot be explained away as a mere psychological response to knowledge of the infection.

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