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Updated 12 March 2008
Printable version

Live Discussion: Gene Expression Profiling of Postmortem Human Brain

Akira Sawa

Marquis Vawter

The venerable medical tradition of postmortem research would seem to be poised for a quantum leap in this era of molecular science, but old provisos and emergent issues must clearly be taken into account.

On 9 January 2008, Akira Sawa of Johns Hopkins University and Marquis Vawter of the University of California, Irvine, led an SRF online discussion of the fine art of generating and interpreting reliable gene expression data in psychiatric research. We invite you to read their background text below, along with an extensive comment by Vawter on several recent papers, particularly one in the Journal of Neuroscience Methods by Christine Miller and colleagues at Johns Hopkins University and the Stanley Medical Research Institute. We then ask that you share your ideas, warnings, horror stories, and other useful information in the form of a comment.

View Transcript of Live Discussion — Posted 12 March 2008

View Comments By:
Karoly Mirnics, Fuller Torrey — Posted 30 December 2007
Christine Miller — Posted 7 January 2008
Alberto Arregui — Posted 7 January 2008
Beth Thomas — Posted 7 January 2008
Sherry Leonard — Posted 7 January 2008
Kenji Hashimoto — Posted 7 January 2008
Tadafumi Kato, Kazuya Iwamoto — Posted 8 January 2008
Sinthuja Sivagnanasundaram, Duncan Sinclair, Cynthia Shannon Weickert — Posted 8 January 2008
Christine Miller — Posted 9 January 2008
Paul Harrison — Posted 9 January 2008
Christine Miller — Posted 9 January 2008
Barbara K. Lipska, Joel Kleinman — Posted 9 January 2008
Sinthuja Sivagnanasundaram — Posted 17 January 2008

Background Text
By Akira Sawa and Marquis Vawter

The purpose of this forum is to discuss factors that impact gene expression profiles in postmortem human brain in the context of microarray, quantitative PCR, in-situ hybridization, and other expression assessment methods.

The pathophysiology of several psychiatric disorders has been extensively studied using postmortem human brains. Enormous molecular information has been obtained from autopsied brains from schizophrenia patients through microarray and proteomic approaches. However, there are caveats to the use of this tissue as well: schizophrenia appears to be a disorder of neurodevelopmental origin; thus, major pathological events that affect neurodevelopment may be compensated for at later stages, such that they would not be seen or detected in autopsied brains. In addition, mechanisms and processes of brain maturation may be different between patients with schizophrenia and controls. More practically, confounding factors such as medication, smoking, and diet must be considered in studying autopsied brains. Gene expression profiles are affected by RNA quality, fixation, agonal factors, postmortem interval, as well as freeze-thaw effects of autopsied brains.

Thus, we plan to discuss methodological approaches for quality control in postmortem brain gene expression studies, as well as data interpretation, alternative approaches, and subject selection or matching. Our discussion will mainly focus on studies of gene expression profiles, since whole genome studies have been conducted. Similar strategies may also refer to studies targeting protein and peptide profiling.

Some provisional questions for discussion will be

1. What are the reliable parameter(s) for quality control of gene expression profiling with postmortem brains?

2. What are the appropriate strategy(ies) in data analysis and interpretation, considering possible confounding factors?

3. How can we address molecular changes associated with neurodevelopment in the autopsied brains? How can we address the question of possible differences in brain maturation and aging between patients and controls?

4. What types of tissues are to be considered as alternatives to autopsied brains?

5. What types of brain banks or collections are to be developed in the research community?

6. What kinds of data sharing systems are expected to promote research in the field?

Read Mark Vawter’s comment on several recent postmortem methods papers.

Comments on Online Discussion
Comment by:  Karoly Mirnics, SRF AdvisorFuller Torrey
Submitted 30 December 2007 Posted 30 December 2007

Summary of Workshop Regarding Future Use of Stanley...  Read more

View all comments by Karoly Mirnics
View all comments by Fuller Torrey

Comment by:  Christine Miller
Submitted 7 January 2008 Posted 7 January 2008

My view is that postmortem studies of the affected organ...  Read more

View all comments by Christine Miller

Comment by:  Alberto Arregui
Submitted 7 January 2008 Posted 7 January 2008

In research projects involving postmortem material,...  Read more

View all comments by Alberto Arregui

Comment by:  Beth Thomas
Submitted 7 January 2008 Posted 7 January 2008

I have a question about whether there is any consensus...  Read more

View all comments by Beth Thomas

Comment by:  Sherry Leonard
Submitted 7 January 2008 Posted 7 January 2008

The topics for discussion are all important! Would like to...  Read more

View all comments by Sherry Leonard

Comment by:  Kenji Hashimoto
Submitted 7 January 2008 Posted 7 January 2008

We believe that postmortem human brain samples are...  Read more

View all comments by Kenji Hashimoto

Comment by:  Tadafumi KatoKazuya Iwamoto
Submitted 7 January 2008 Posted 8 January 2008

Thanks to the endeavors of Dr. Torrey and all the other...  Read more

View all comments by Tadafumi Kato
View all comments by Kazuya Iwamoto

Comment by:  Sinthuja SivagnanasundaramDuncan SinclairCynthia Shannon Weickert (SRF Advisor)
Submitted 8 January 2008 Posted 8 January 2008

A Few Technical Comments About Evaluating RNA Quality...  Read more

View all comments by Sinthuja Sivagnanasundaram
View all comments by Duncan Sinclair
View all comments by Cynthia Shannon Weickert

Comment by:  Christine Miller
Submitted 9 January 2008 Posted 9 January 2008

Reply to Cynthia Shannon Weickert and...  Read more

View all comments by Christine Miller

Comment by:  Paul Harrison
Submitted 9 January 2008 Posted 9 January 2008

Several of the above comments pertain to the use of pH...  Read more

View all comments by Paul Harrison

Comment by:  Christine Miller
Submitted 9 January 2008 Posted 9 January 2008

Clarification to my last commment: a higher 260/280...  Read more

View all comments by Christine Miller

Comment by:  Barbara K. LipskaJoel Kleinman
Submitted 9 January 2008 Posted 9 January 2008

We have previously suggested that accurate assessment of...  Read more

View all comments by Barbara K. Lipska
View all comments by Joel Kleinman

Comment by:  Sinthuja Sivagnanasundaram
Submitted 17 January 2008 Posted 17 January 2008

Reply to Comment by Christine Miller
Thanks...  Read more

View all comments by Sinthuja Sivagnanasundaram
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