MITOCHONDRIAL DYSFUNCTION IN SCHIZOPHRENIA: EVIDENCE FOR COMPROMISED BRAIN METALOLISM AND OXIDATIVE STRESS
Mol Psychiatry 9:684-697, 2004
Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, Wayland M, Freeman T, Dudbridge F, Lilley KS, Karp NA, Hester S, Tkachev D, Mimmack ML, Yolken RY, Webster MJ, Torrey EF, Bahn S
The etiology and pathophysiology of schizophrenia remains unknown. A parallel transcriptomics, proteomics and metabolomics approach was employed on human brain tissue to explore the molecular disease signatures. Almost half the altered proteins identified by proteomics were associated with mitochondrial function and oxidative stress responses. This was mirrored by transcriptional and metabolite perturbations. Cluster analysis of transcriptional alterations showed that genes related to energy metabolism and oxidative stress differentiated almost 90% of schizophrenia patients from controls, while confounding drug effects could be ruled out. We propose that oxidative stress and the ensuring cellular adaptations are linked to the schizophrenia disease process and hope that this new disease concept may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.