The contemporary epistemic status of mental health disciplines does not allow the cross-validation of mental disorders among various genetic markers, biochemical pathway or mechanisms, and clinical assessments in neuroscience explanations. We attempt to provide a meta-empirical analysis of the contemporary status of the cross-disciplinary issues existing between neurobiology and psychopathology. Our case studies take as an established medical mode an example cross-validation between biological sciences and clinical cardiology in the case of myocardial infarction. This is then contrasted with (…) the incoherence between neuroscience and psychiatry in the case of bipolar disorders. We examine some methodological problems arising from the neuroimaging studies, specifically the experimental paradigm introduced by the team of Wayne Drevets. Several theoretical objections are raised: temporal discordance, state independence, and queries about the reliability and specificity, and failure of convergent validity of the interdisciplinary attempt. Both modern neuroscience and clinical psychology taken as separate fields have failed to reveal the explanatory mechanisms underlying mental disorders. The data acquired inside the monodisciplinary matrices of neurobiology and psychopathology are deeply insufficient concerning their validity, reliability, and utility. Further, there have not been developed any effective transdisciplinary connections between them. It raises the requirement for development of explanatory significant multidisciplinary ‘meta-language’ in psychiatry. We attempt to provide a novel conceptual model for an integrative dialogue between psychiatry and neuroscience that actually includes criteria for cross-validation of the commonly used psychiatric categories and the different assessment methods. The major goal of our proactive program is the foundation of complementary ‘bridging’ connections of neuroscience and psychopathology, which may stabilize the cognitive meta-structure of mental health knowledge. This entails bringing into synergy the disparate discourses of clinical psychology and neuroscience. One possible model accomplishment of this goal would be the synergistic (or at least compatible) integration of the knowledge under transdisciplinary convergent cross-validation of the commonly used methods and notions.