There has recently been evidence of links between the central nervous system and the immune system. Stressed animals show impairment in several immune parameters and are more likely than control animals to develop cancer when inoculated with an oncogenic virus. Similar derangements in host-defense mechanisms have also been observed with injections of glucocorticoids and lesions in the anterior hypothalamus. The clinical implications of these findings have not been adequately investigated. Epidemiological studies show an increase in morbidity rates following stressful life events such as bereavement and suggest an association between depression, allergy and certain forms of cancer. A number of studies have shown an impairment of different immune parameters following psychosocial stress. Very little research has been done on the immune status of patients with depressive illness. This issue is particularly interesting in view of recent findings in depressed patients of a disturbance in the hypothalamic-pituitary-adrenal axis activity often resulting in the secretion of excessive amount of cortisol, an immunosuppressive hormone. We have recently formulated the hypothesis that depression may be accompanied by an impairment of immune responses that could explain the reported increase in the incidence of infection, allergy and cancer in depressed patients. Preliminary data from our own laboratory indicate a suppression of in vitro lymphocyte mitogenic activity in depressed patients compared to normal controls. This proposal seeks to further explore the possibility of immune dysfunction in patients with depressive illness by giving them a battery of immunological tests, including hypersensitivity skin testing, lymphocyte surface marker analysis with monoclonal antibodies, assessment of in vitro lymphoblast transformations and an assay of natural killer cell activity. Depressed patients will be studied both during the acute phase of depression and following recovery. Comparisons of immune function will also be made between clinical as well as neuroendocrine subtypes of depression. Depressed patients will also be compared to schizophrenic controls, highly stressed but otherwise psychiatrically-well controls and normal controls.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH042988-01
Application #
3382449
Study Section
Psychopathology and Clinical Biology Research Review Committee (PCB)
Project Start
1987-08-01
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Kronfol, Z; Nair, M; Zhang, Q et al. (1997) Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Psychosom Med 59:42-50
Kronfol, Z; Starkman, M; Schteingart, D E et al. (1996) Immune regulation in Cushing's syndrome: relationship to hypothalamic-pituitary-adrenal axis hormones. Psychoneuroendocrinology 21:599-608
Nair, M P; Schwartz, S A; Kronfol, Z A et al. (1994) Suppression of tumor necrosis factor production by alcohol in lipopolysaccharide-stimulated culture. Alcohol Clin Exp Res 18:602-7
Barks, J D; Nair, M P; Schwartz, S A et al. (1993) Potentiation of N-methyl-D-aspartate-mediated brain injury by a human immunodeficiency virus-1-derived peptide in perinatal rodents. Pediatr Res 34:192-8
Kronfol, Z; Nair, M; Hill, E et al. (1993) Immune function in alcoholism: a controlled study. Alcohol Clin Exp Res 17:279-83
Shain, B N; Kronfol, Z; Naylor, M et al. (1991) Natural killer cell activity in adolescents with major depression. Biol Psychiatry 29:481-4
Kronfol, Z; Hamdan-Allen, G; Goel, K et al. (1991) Effects of single and repeated electroconvulsive therapy sessions on plasma ACTH, prolactin, growth hormone and cortisol concentrations. Psychoneuroendocrinology 16:345-52
Nair, M P; Kronfol, Z A; Schwartz, S A (1990) Effects of alcohol and nicotine on cytotoxic functions of human lymphocytes. Clin Immunol Immunopathol 54:395-409
Kronfol, Z; Nair, M; Goodson, J et al. (1989) Natural killer cell activity in depressive illness: preliminary report. Biol Psychiatry 26:753-6
Kronfol, Z; House, J D (1989) Lymphocyte mitogenesis, immunoglobulin and complement levels in depressed patients and normal controls. Acta Psychiatr Scand 80:142-7

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