Objective: Based on earlier research, we hypothesized that patient response to diagnostically relevant items (paranoid (DP) and depressive (DS)) from clinical self‐assessment scale (PD‐S) could be cross‐validated when performed simultaneously with task‐based fMRI, resulting in specific and common neural circuit activations in response to the PDS items. In the current study, we tried to overcome one of the limitations of our previous research, namely, the lack of a healthy control (HC) group. Thus, our aim was to investigate the possible differences between patients with schizophrenia (SCZ) and depression and HCs using independent component analysis.Methods: A total of 72 subjects participated in this study, including 21 HCs, 26 patients with SCZ, and 25 patients with major depressive episode (DEP). Patients were scanned on a 3Т MRI system using a functional MRI task representing statements from DP‐DS scale and diagnostically neutral (DN) statements. The data were processed using group independent component analysis for fMRI toolbox (GIFT).Results: Five components were identified as task‐related, but only three of them were found to demonstrate statistical difference between SCZ, DEP, and HC, namely, components 6, 7, and 9. The contrast between SCZ and HC was presented by Component 6 (cingulate gyrus and basal ganglia), which exhibited significant difference when comparing all three active conditions. On the other hand, SCZ and DEP group differences were presented by Component 7 for DS‐DN comparison (frontoparietal network and superior temporal gyrus) and Component 9 (medial frontal gyrus, precuneus, angular gyrus, and among others) which highlighted preferential processing related to the DP‐DN and the DS‐DP comparison.Conclusion: Our results demonstrate differences in brain circuits processing preferentially diagnostic stimuli across the three groups. Those circuits involve mainly networks of cognitive and affective functioning, which provides insights in their role for pathophysiology of SCZ and DEP. This evidence fosters the theory of transdisciplinary validation, where neurobiological measure such as functional MRI is determined as external validity operation for the diagnostic assessment scales. This can facilitate the use of clinical evaluation methods as proxy measures of brain functions.