Affective disorders : multivariate investigations of clinical and biological variables

Abstract: This thesis is a methodological and clinical investigation of patients with affective disorders. The goal of the study was to determine the extent to which biological and clinical measures may cluster clinical subpopulations. Analytical and statistical procedures were applied for this purpose. Abnormalities in the Hypothalamic-Pituitary-Adrenal (HPA) axis have been Found in about 50 % of the depressed patients in the acute phase using the dexamethasone suppression test (DST). To further test HPA-axis disturbances in depression, the release of adrenal corticotropin (ACTH) after administration of corticotropin- releasing hormone (CRH) was studied in 24 depressed patients, in relation to the DST. After CRH-stimulation significantly lower cortisol and ACTH levels were found for DST-non-suppressers compared to DST-suppessers. In a sample of 28 depressed patients, over a 15-year observation period, different statistical and clinical clusters were identified. Examination of 45 variables, tested using Principle Component Analysis (PCA), revealed that the three biological variables; platelet monoamine oxidase activity (MAO), peak nocturnal serum melatonin and maximum post dexamethasone cortisol, and the two clinically psychomotor symptoms; Reduced speech and Slowness of movements, contributed most to the clustering of individuals. The patients were clinically distributed with high scores of agitation in the extreme of one direction and with high scores of retardation in the opposite direction. By using the combined clinical and biological variables a diagnostic subcategory with latent bipolar disorder was identified. Two clusters of unipolar patients, one with low melatonin and low psychomotor retardation scores, and one with high melatonin and high psychomotor retardation scores were found. The identification of the individuals with latent bipolar disorder may have potential therapeutic value since bipolar patients should be taken care of by a specialist in psychiatry, should avoid tricyclic antidepressant therapy, and may be candidates for lithium treatment. The confounding effect of including latent bipolar patients in investigations on depression is inherent in all studies where presumably unipolar patients are selected during the first couple of depressive episodes. In the present study the clustering of more homogenous subgroups of unipolar patients have been possible, because the bipolar patients have been identified and statistically analysed as a separate subpopulation. Replication studies are called for to refute, or verify, the reported findings of the three subgroups of patients with affective disorders, in particular a population with latent bipolar illness.