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The psychopathological status of 25 inpatients suffering from clinically definite multiple sclerosis (MS) according to Poser criteria was assessed by using standardized methods (Structured Clinical Interview for DSM-III-R, Inpatient Multidimensional Psychiatric Scale, Hamilton and Montgomery-Asberg Depression Rating Scales and the Structured Interview for the Diagnosis of Alzheimer Dementia and Dementias of other Aetiology (SIDAM). Magnetic resonance (MRT) (0.5 T; T2-weighted sequence) of the brain was analysed by measuring the ventricular brain ration (VBR), the area of the corpus callosum (CC) and the extension of hyperintense lesions of the brainstem, the temporal lobes and the brain at all. Six of 25 (24%) of these moderately disabled patients (mean Extended Disability Score (EDSS) 3.3) were diagnosed to suffer from depressive mood disorder (major depression or dysthymia); 2 were demented. In correlation analysis, depression was unrelated to age, gender, duration of illness, status of disability (EDSS) or the results of cognitive assessment. No relationship between the depression scores and the different MRT measures could be identified. The presence or absence of gadolinium enhancement was also uncorrelated to depressive symptoms. Fatigue as measured by the Fatigue Severity Scale was unrelated to depression or subcortical brain atrophy (increased VBR) but significantly correlated to the area of hyperintense MRT changes in brainstem and midbrain. Cognitive impairment (decreased SIDAM scores) was correlated to the total area of hyperintense MRT changes of the brain parenchyma. The type of clinical course (relapsing-remitting vs chronic progredient) was not found to influence the affective or cognitive state in our MS patient's sample.