The Effect of Neurofeedback and Cranial Electrotherapy on Immune Function Within a Group of HIV+ Subjects: A Controlled Study

Much attention has been paid to the potential role of the immune system in the pathophysiology of major depression in humans. While activation of innate immune responses currently dominates the research landscape, early studies in depressed patients demonstrating impairment in acquired immune responses, in particular T cell responses, may warrant further consideration. Intriguing data suggest that activated T cells may play an important neuroprotective role in the context of both stress and inflammation. For example, generation of autoreactive T cells through immunization with central nervous system (CNS) specific antigens has been shown to reverse stress-induced decreases in hippocampal neurogenesis as well as depressive-like behavior in rodents. In addition, trafficking of T cells to the brain following stress, in part related to glucocorticoids, has been found to reduce stress-induced anxiety-like behavior. Data indicate that T regulatory cells may also play a role in depression through downregulation of chronic inflammatory responses. Based on the notion that T cells may subserve neuroprotective and anti-inflammatory functions during stress and inflammation, impaired T cell function may directly contribute to the development of depression. Indeed, increased sensitivity to apoptosis as well as reduced responsiveness to glucocorticoids, may not only decrease the availability of T cells in depressed patients, but also may reduce their capacity to traffic to the brain in response to relevant neuroendocrine or immune stimuli. Further elucidation of T cell pathology may lead to new insights into immune system contributions to depression. Moreover, enhancement of T cell function may represent an alternative strategy to treat depression.

Posttraumatic stress disorder (PTSD) is associated with an enhanced susceptibility to various somatic diseases. However, the exact mechanisms linking traumatic stress to subsequent physical health problems have remained unclear. This study investigated peripheral T lymphocyte differentiation subsets in 19 individuals with war and torture related PTSD compared to 27 non-PTSD controls (n=14 trauma-exposed controls; n=13 non-exposed controls). Peripheral T cell subpopulations were classified by their characteristic expression of the lineage markers CD45RA and CCR7 into: naïve (CD45RA(+) CCR7(+)), central memory (T(CM): CD45RA(-) CCR7(+)) and effector memory (T(EM): CD45RA(-) CCR7(-) and T(EMRA): CD45RA(-) CCR7(-)) cells. Furthermore, we analyzed regulatory T cells (CD4(+)CD25(+)FoxP3(+)) and ex vivo proliferation responses of peripheral blood mononuclear cells after stimulation with anti-CD3 monoclonal antibody. Results show that the proportion of naïve CD8(+) T lymphocytes was reduced by 32% (p=0.01), whereas the proportions of CD3(+) central (p=0.02) and effector (p=0.01) memory T lymphocytes were significantly enhanced (+22% and +34%, respectively) in PTSD patients compared to non-PTSD individuals. To a smaller extent, this effect was also observed in trauma-exposed non-PTSD individuals, indicating a cumulative effect of traumatic stress on T cell distribution. Moreover, PTSD patients displayed a 48% reduction in the proportion of regulatory T cells (p<0.001). Functionally, these alterations were accompanied by a significantly enhanced (+34%) ex vivo proliferation of anti-CD3 stimulated T cells (p=0.05). The profoundly altered composition of the peripheral T cell compartment might cause a state of compromised immune responsiveness, which may explain why PTSD patients show an increased susceptibility to infections, and inflammatory and autoimmune diseases.

Recent neurophysiological findings in relation to thalamocortical mechanisms for sensory processing, together with established anatomical and expanding functional evidence, have provided a rational theoretical framework for the interpretation of normal and abnormal EEG rhythmic activities. This perspective is integrated here with earlier animal studies which were the foundation for many current applications of EEG self-regulation as a clinical tool. Basic evidence concerning the origins, frequency modulation, and functional significance of normal EEG rhythmic activities is reviewed here in an effort to provide guiding principles for the interpretation of clinical abnormalities and their remediation with EEG feedback training.