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Treatment Response: Linking Genes with Behavioral Phenotypes of Relevance to Patients, Families, and Policymakers

NAMHC Concept Clearance


Donna Mayo, Ph.D.
Program Chief, Functional Assessment in Mental Disorders
Assistant Director for Research Training and Career Development
Division of AIDS and Health Behavior Research


Now that new tools (e.g., high throughput genotyping and array technology) make it possible to ask if we can determine the complex genetic basis of mental disorders, how shall we decide what are the relevant phenotypes? Articles about the genetic basis of mental illness continue to use DSM categories. Behaviors outside the realm of DSM typically only include co-morbidities such as alcohol and nicotine dependence.

The activities of this initiative focus on integrating two distinct tracks of research-determining the complex genetic basis of mental disorders, and creating new strategies and tools for assessing individual functioning in the real world, with the goal of characterizing the relationship between genetic risk and functional abilities.

With this proposed initiative, behavioral researchers will be invited to team with psychiatric geneticists to investigate the links between genetic risk and practical measures of day-to-day living. As a result of this initiative, researchers may begin to look for completely different categories of genes-for example, "life-space mobility" genes or genes that are linked with getting out of the bed, out of the house, or out of the neighborhood. This is an important daily function and relates to frequently observed detrimental behaviors among people with schizophrenia and depression .

Examples of research questions that may be addressed by this initiative include:

  • What are the behaviors that may have significant genetic determinants?
  • What kinds of measures of functioning need to be developed and what kinds of instruments will these measures require? Can we create an objective outcomes assessment that can eventually be used in clinical trials?
  • What kind of statistical models should we use to compare behavioral and genetic variables?
  • Are genes and pre-treatment functioning moderators of treatment response?
  • Do genetic variables predict functioning independent of symptomatology as a mediator?
  • Can we identify non-DSM treatment targets at the level of the individual? Can these targets be used to create preventive interventions?
  • What are appropriate behavioral (as opposed to pharmacological) treatment targets and preventive interventions?

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