Clinical Phenotyping in Post-Mortem Brain Tissue Research- Progress and Challenges

Background: As the scientific and clinical interests in autism have increased, there has been a correlative increase in the research dedication to tissue based studies and the importance of post-mortem brain tissue in autism research. This interest is demonstrated by the elevated demand by researchers for post-mortem brain tissue from dedicated facilities such as the Autism Speaks Autism Tissue Program (ATP) and The NICHD Maryland Brain Bank.  While characterization and preservation of post-mortem brain tissue has been of paramount concern to researchers, little attention has been paid to standardizing essential phenotypic and clinical data.  Having responded to more than a dozen inquiries in 2011 from ATP board-approved researchers regarding clinical information associated with post-mortem brain tissue it is evident that clinical standards and protocols need to be established.  Furthermore, as additional post-mortem tissue resources are developed, there is a mounting sense of urgency in establishing exemplary standards.

Objectives: The purpose of this study is to explore existing clinical standards and protocols in post-mortem brain tissue research.  This exploration is conducted in consideration of:  provision of pertinent phenotypic and clinical information to researchers and collection of phenotypic and clinical date from families while providing essential bereavement support.

Methods: Interview three authors of scholarly papers utilizing phenotypic or other relevant clinical data obtained via the ATP’s Clinical Standard Operating Procedures combined with a case study of three ATP donor families' experiences participating in the ATP donation process from the point of donation through the home visit.

Results: ATP Board-approved researchers have been specifically interested in the following types of clinical data provided by the ATP:  diagnosis, regression and agonal state.  Researchers had questions regarding the consistency of data across donors (particularly diagnosis).  Additionally, clinicians need to spend more time learning about the scientific research and establishing cross-program standards for collecting and disseminating data.  The ATP has spearheaded a post-mortem brain tissue clinical workgroup in response to these needs.

Clinical information is obtained from the families utilizing a variety of clinical tools over time, but a majority of this information is collected during the home visit.  Donor families have consistently expressed appreciation for the time spent participating in this process and consider the home visit a key element of the bereavement support provided by the ATP. 

Conclusions:

1.  Ongoing dialogue is required between researchers and clinicians to increase potential for translational science to occur.  This dialogue should be focused on informing clinicians to improve the relevance of clinical data collection; likewise clinicians can encourage greater use of the clinical data that already exists.

2.   Donor families require ongoing bereavement support and recognition for making the decision to donate their loved one’s brain tissue for autism research.

3.  Ongoing dialogue is required across post-mortem brain tissue banks and the ATP.  This dialogue should be focused on improving upon existing processes in an effort to provide researchers with gold-standard phenotypic and clinical data.  The clinical workgroup spearheaded by the ATP is dedicated to engaging in this dialogue.