John W. Mason - US grants

The principal purpose of this program is to explore the usefulness of basic psychoendocrine concepts and guiding principles in the development of clinical research strategies for the study of psychiatric and psychosomatic disorders. While a primary emphasis is on the study of mechanisms of pathogenesis of stress-related illnesses, it is hoped that new leverage in the diagnosis and treatment of such disorders may also eventually emerge from this approach. A key and rather unique feature of the research strategy is emphasis on the need to study the neuroendocrine apparatus as nearly as a whole as possible, by measurement of multihormonal patterns, since the many interdependent neuroendocrine systems are apparently coordinated in a broadly organized way by the central integrative machinery. The first project is a psychoendocrine study of bereavement in older men after the death of their wife. An extensive psychological and endocrine assessment of their adjustment 2 months following the loss will provide new information on the grief process itself, as well as a prospective view of high risk factors for the subsequent development of illness. A companion epidemiologic study will provide much subsequent development of illness. A companion epidemiologic study will provide much additional social, psychological, and outcome data for correlation with hormonal findings. A second project is a combined psychological, neuroendocrine, and neurochemical study of the stages of clinical change during the course of schizophrenic psychosis. This study will also provide an opportunity to evalute some concepts concerning the possible role of hormones in the pathophysiology of schizophrenia, which were suggested by early clinical psychoendocrine workers, but which remain untested by modern research methods. Another feature of the program is an emphasis on the training of young investigators in psychoneuroendocrine research by involving them in the major projects or guiding them in innovative pilot research aimed at exploring the extent to which our present basic science foundation in psychoneuroendocrinology can be applied to develop useful new strategies for clinical research on both psychiatric and medical disorders.

There is an increasingly pressing need for methods to permit more objective, precise, and systematic assessment of patients with Post- traumatic Stress Disorder (PTSD), as the prevalence and clinical importance of this disorder is becoming more widely recognized. Because the clinical presentation of patients with PTSD can often be complex and varied there is a particular need for innovative methods to increase specificity in the definition and differential diagnosis of this disorder. As yet, there has been very little exploration of biological approaches to the characterization and the understanding of PTSD and its underlying mechanisms. We have been evaluating an innovative multidimensional hormonal approach to the assessment of PTSD in contrast to the conventional univariate approach focussing on one biological marker at a time in psychiatric patients. We have obtained pilot data with a profile of hormones, including cortisol, norepinephrine, epinephrine, testosterone, and thyroxine, in PTSD inpatients in comparison with 4 other inpatients groups: Major depressive disorder, endogenous; Bipolar I, manic; Paranoid schizophrenia; and Undifferentiated schizophrenia. We have found a very unusual dissociation between the cortisol and norepinephrine systems in PTSD, with sustained high urinary norepinephrine levels in the face of low urinary free-cortisol levels. As a results, the mean ration (norepinephrine/corticol) is about twice as high in PTSD as in all the other diagnostic groups, with a diagnostic sensitivity of 78% and specificity of 94%. Moving from a bivariate to a multivariate approach with 3 or more hormones, we found that Stepwise Discriminant Analysis provided 100% correct diagnostic classification of PTSD versus Major depressive disorder and that Multidimensional Scaling classified all but one patient out of 17 correctly in comparing these two diagnostic groups. These findings indicate that multidimensional hormonal assessment provides the promise of important advances in the use of biological criteria in psychiatric diagnosis and that this approach may be particularly useful in the investigation of PTSD.

There is an increasingly pressing need for methods to permit more objective, precise, and systematic assessment of patients with Post- traumatic Stress Disorder (PTSD), as the prevalence and clinical importance of this disorder is becoming more widely recognized. Because the clinical presentation of patients with PTSD can often be complex and varied there is a particular need for innovative methods to increase specificity in the definition and differential diagnosis of this disorder. As yet, there has been very little exploration of biological approaches to the characterization and the understanding of PTSD and its underlying mechanisms. We have been evaluating an innovative multidimensional hormonal approach to the assessment of PTSD in contrast to the conventional univariate approach focussing on one biological marker at a time in psychiatric patients. We have obtained pilot data with a profile of hormones, including cortisol, norepinephrine, epinephrine, testosterone, and thyroxine, in PTSD inpatients in comparison with 4 other inpatients groups: Major depressive disorder, endogenous; Bipolar I, manic; Paranoid schizophrenia; and Undifferentiated schizophrenia. We have found a very unusual dissociation between the cortisol and norepinephrine systems in PTSD, with sustained high urinary norepinephrine levels in the face of low urinary free-cortisol levels. As a results, the mean ration (norepinephrine/corticol) is about twice as high in PTSD as in all the other diagnostic groups, with a diagnostic sensitivity of 78% and specificity of 94%. Moving from a bivariate to a multivariate approach with 3 or more hormones, we found that Stepwise Discriminant Analysis provided 100% correct diagnostic classification of PTSD versus Major depressive disorder and that Multidimensional Scaling classified all but one patient out of 17 correctly in comparing these two diagnostic groups. These findings indicate that multidimensional hormonal assessment provides the promise of important advances in the use of biological criteria in psychiatric diagnosis and that this approach may be particularly useful in the investigation of PTSD.