MITOCHONDRIAL
DYSFUNCTION IN SCHIZOPHRENIA: EVIDENCE FOR OXIDATIVE STRESS AND ABNORMAL GROWTH
FACTOR SUPPORT
Sabine
Bahn and colleagues
Babraham
Institute and Department of Psychiatry, University of Cambridge, UK
Stanley
Labs, Bethesda and Johns Hopkins, Baltimore, USA
The
etiology and pathophysiology of schizophrenia remain unknown. A parallel
transcriptomics, proteomics and metabolomics approach was employed on human
brain tissue to explore the molecular disease signatures. Results from this
integrative study showed that pathways associated with mitochondrial function
and oxidative stress, were most prominently altered. White matter is
particularly vulnerable to free radical damage and schizophrenia white matter
showed the most prominent metabolite changes. Cluster analysis of
transcriptional alterations, showed that genes related to energy metabolism and
oxidative stress differentiated almost 90% of schizophrenia patients from
controls (n=92), whilst confounding drug effects could be ruled out. This
insight suggests a new concept for schizophrenia and may influence the approach
to treatment, diagnosis and disease prevention of schizophrenia and related
syndromes.
S.B. et al gratefully
acknowledge centre support through the Stanley Medical Research Institute