Mentalization describes the ability to understand and interpret one’s own and others’ thoughts, feelings, and motives through the attribution of mental states [1]. Particularly in patients with mental disorders, deficits in mentalization capacity have already been observed [2]. As part of a study in the psychiatric department of Klinik Favoriten, led by the Medical University of Vienna, over the course of 1 year, clinical staff were trained in a specific form of mentalization. In order to analyze the patient side as well, the significance of childhood, personality, and affect in depressive patients was examined in comparison with patients within the schizophrenia spectrum, in relation to their mentalization capacity. For the collection of data a questionnaire-based measurement procedure was used and combined with systematic interviews. The results of the study underscore the necessity of both a transdiagnostic and a disorder-specific perspective with regard to further therapeutic interventions, as well as the quality of communication in clinical-care settings: depressive and psychotic patients are similar in terms of vulnerabilities, such as childhood trauma and personality structure, but differ markedly in their affect perception and regulation. Depressive patients display more pronounced primary emotions in affect perception, such as fear and sadness, whereas psychotic patients exhibit affective flattening and inadequate emotional expression. Affect regulation in the depressive spectrum manifests as avoidant defense. The psychotic clinical picture is characterized by externalizing defense.