In order to promote the improvement of evidence-based psychological treatments (EBPT) and/or the integration of EBPT and bio-medical treatments, we propose a change in direction in cognitive neurogenetics (CNG)—from cognitive neurogenic to cognitive behavioral-based neurogenetics—starting from a top-down analysis: from symptoms and clinical-relevant cognitions to their implementation (brain, protein, genes). To illustrate our proposal, we specifically focus trans-diagnostically on symptoms of depression and anxiety, and consider the next underlying/interrelated mechanisms: (1) specific cognitions related to EBPT clinical theory/practice (cognitions/cognitive biases); (2) involved brain areas; (3) variability in protein expression; and (4) genetic polymorphisms. The proposed CBT-based neurogenetics framework rectifies the limitations of the classical CNG paradigm, and guides a more ecological and integrative approach in CNG. We argue that using large datasets, comparative methods of data analysis, and complex modelling techniques the CNG paradigm can be transcended. Our approach offers the framework for targeting key questions that have been previously disregarded, but which could revolutionize our understanding of the human mind and mental disorders: (Q1) do biological and psychological variables reflect different things in different “realities” or in the same reality?; (Q2) are biological and psychological variables different descriptions, at the same or at a different level of the same thing?; (Q3) if they are different descriptions at different levels of the same thing, are they reducible to each other or are there some emergent properties at more abstract levels?; (Q4) if they are different descriptions at the same level of the same thing, does it make sense to use both of them? Based on the innovative multi-/inter-/trans-disciplinary paradigm we propose, we should answer these questions.
