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"the Evolution of Clinical Phenotyping in Post-Mortem Brain Tissue Research: Summary of Progress and Challenges"

Saturday, 4 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
C. K. Hare1 and J. Pickett2, (1)Autism Speaks, Pittsburgh, PA, (2)Autism Speaks, San Diego, CA
"The Evolution of Clinical Phenotyping in Post-Mortem Brain Tissue Research: Summary of Progress and Challenges"


A major aim of the Autism Speaks Autism Tissue Program when it started in 1998 was to provide research-relevant clinical information on brain donors with autism spectrum disorders. At that time, brain bank programs focused on the characterization and preservation of post-mortem brain tissue while little attention was paid to standardizing essential phenotypic and

clinical data. As additional post-mortem tissue resources are currently being developed in the US and Europe, there is a mounting sense of urgency in establishing exemplary standards.  Such standards of clinical phenotyping would grant context and standardization to these rare resources and help facilitate a greater understanding of the tissue by the researchers that access them.


The purpose of this study is to explore existing clinical standards and protocols in post-mortem brain tissue research and communicate the evolution of the Autism Tissue Program’s Clinical Standard Operating Procedures. 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. 


Review discussion and recommendations made for post-mortem clinical phenotyping via the ATP’s International Post-Mortem Brain Tissue Clinical Workgroup, including survey results of Principal Investigators.  Consider Workgroup discussion and recommendations as well as advances in various clinical assessments to determine whether current ATP Clinical Protocols should be revised to maintain exemplary standards of phenotyping in post-mortem brain tissue research. 


As a result of discussion amongst the members of the Clinical Workgroup, it is evident that any modifications to clinical protocol need to be made with tremendous consideration of the additional burden and potential fatigue of donor families.   A survey of Principal Investigator’s prioritization of clinical data points was administered and yielded the following results (many of these points are addressed within the current ATP protocol):


Clinical Data Points

Usefulness (2=required, 1=somewhat useful, 0=not useful)

ADI-R validation of Autism and domain scores


ADI-R raw data


description of agonal state


seizure disorder  




GI Issues  






aggression (classification and detailed description of) 


sensory issues 


repetitive behaviors 


parental genotype/phenotype when available



  1. The Autism Tissue Program Modified its Post-Mortem Clinical Standard Operating Procedures in 2012 to include the use of the CBCL, ACBL and SRS2.   These measures were added to screen for data points not currently addressed by the ATP protocol and to minimize respondent fatigue.  The ATP should consider the addition of a seizure survey.   
  2. Due to the low response rate conflicting results* of this survey, ongoing and broader 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. 

  3. Ongoing dialogue is required across post-mortem brain tissue programs. 
This dialogue should be focused on improving upon existing processes in 
an effort to provide researchers with gold-standard phenotypic and 
clinical data. 
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