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  1. The current set of constructs is focused on (and constrained by) circuit definitions in order to (1) avoid an over-specification and proliferation of constructs, and (2) provide an organizing point that facilitates the integration both of genetic, molecular, and cellular levels of analysis regarding sub-components of circuits, and of behavioral and self-report levels of analysis regarding the kinds of outputs that circuits implement. The intent is not to arbitrarily exclude constructs, but rather to foster thinking about how constructs are related at various levels of analysis.
  2. The framework is directed toward constructs most germane to mental disorders, and makes no claim to span the entire gamut of functional behavior. For instance, circuits relevant to thermoregulation and reproductive behavior are not included.
  3. The number of constructs might well be viewed as sparse by many scientists. The attempt has been to include relatively high-level constructs in order to avoid an over-specification of functions that could become unwieldy and also necessitate unnecessarily frequent revisions to the list as research progresses. As one obvious example, a single “Perception” construct is listed that includes visual, auditory, and other sensory modalities. However, the framework is meant to foster, not discourage, research that explicates mechanisms within and across the constructs as listed. As stated above, the current framework should be viewed as a starting point and part of a work in progress.
  4. The complexity of the brain is such that circuits and constructs will necessarily have considerable overlap, and arbitrary separations are unavoidable. For instance, the basolateral amygdala is well-known to be involved with both threat and appetitive processing. This reflects the hierarchical nature of the nervous system, and the difficulty of creating a system that encompasses various levels in one framework. It should also be noted that some constructs, such as homeostasis, are not listed here; these are considered superordinate principles of nervous system activity that operate across many different circuits.
  5. Research with post-mortem tissue samples may be appropriate for studies within the RDoC framework, if the hypotheses and other variables are conceived in terms of relevant domains and constructs.
  6. The RDoC framework is explicitly agnostic with respect to current definitions of disorders. For instance, depression as a clinical syndrome has been related to abnormal activity in the amygdala, anterior cingulate cortex, nucleus accumbens, and multiple monoamine systems, while also strongly comorbid with multiple anxiety disorders, eating disorders, etc. The idea is that studying the individual mechanisms may lead to better understanding of current disorders, or perhaps new and novel definitions of disorders, but in either case improved information about treatment choices.
  7. As mentioned above, the aim of RDoC is to create a framework for selecting participants for research studies in order to create a foundational research literature that informs future versions of nosologies based upon genetics and behavioral neuroscience. RDoC is not intended for clinical diagnosis at the current time. In the future, research supported by RDoC could inform diagnostic approaches using new laboratory procedures, behavioral assessments, and novel instruments to provide enhanced treatment and prevention interventions.