Affective disorders : Multivariate investigations of clinical and biological variables

Abstract: AFFECTIVE DISORDERS MULTIVARIATE INVESTIGATIONS OF CLINICAL AND BIOLOGICAL VARIABLES Björn Wahlund, MD, Dissertation, Karolinska Institute, Department of ClinicalNeuroscience, Section of Psychiatry, St. Göran's Hospital, S-112 81 Stockholm,Sweden This thesis is a methodological and clinical investigation of patients with affectivedisorders. The goal of the study was to determine the extent to which biologicaland clinical measures may cluster clinical subpopulations. Analytical and statisticalprocedures were applied for this purpose. Abnormalities in the Hypothalamic-Pituitary-Adrenal (HPA) axis have been foundin about 50 % of the depressed patients in the acute phase using the dexamethasonesuppression test (DST). To further test HPA-axis disturbances in depression, therelease of adrenal corticotropin (ACTH) after administration of corticotropin- releasinghormone (CRH) was studied in 24 depressed patients, in relation to the DST. AfterCRH-stimulation significantly lower cortisol and ACTH levels were found for DST-non-suppresserscompared to DST-suppessers. In a sample of 28 depressed patients, over a 15-year observation period, differentstatistical and clinical clusters were identified. Examination of 45 variables, testedusing Principle Component Analysis (PCA), revealed that the three biological variables;platelet monoamine oxidase activity (MAO), peak nocturnal serum melatonin and maximumpost dexamethasone cortisol, and the two clinically psychomotor symptoms; Reducedspeech and Slowness of movements, contributed most to the clustering of individuals. The patients were clinically distributed with high scores of agitation in theextreme of one direction and with high scores of retardation in the opposite direction.By using the combined clinical and biological variables a diagnostic subcategorywith latent bipolar disorder was identified. Two clusters of unipolar patients, onewith low melatonin and low psychomotor retardation scores, and one with high melatoninand high psychomotor retardation scores were found. The identification of the individualswith latent bipolar disorder may have potential therapeutic value since bipolar patientsshould be taken care of by a specialist in psychiatry, should avoid tricyclic antidepressanttherapy, and may be candidates for lithium treatment. The confounding effect of including latent bipolar patients in investigationson depression is inherent in all studies where presumably unipolar patients are selectedduring the first couple of depressive episodes. In the present study the clusteringof more homogenous subgroups of unipolar patients have been possible, because thebipolar patients have been identified and statistically analysed as a separate subpopulation.Replication studies are called for to refute, or verify, the reported findings ofthe three subgroups of patients with affective disorders, in particular a populationwith latent bipolar illness. Key words: Affective disorders, psychiatric symptoms, classification, unipolardepression, bipolar disorder, cortisol, melatonin, monoamine oxidase, principle componentanalysis. ISBN 91-628-2725-1 Björn Wahlund, Stockholm 1997