D C Goff1, G Tsai, M F Beal, J T Coyle. 1. Schizophrenia Research Program, Erich Lindemann Mental Health Center, Boston, MA, USA.
Abstract
OBJECTIVE: This study was undertaken to assess the relationships among CSF concentrations of substrates of mitochondrial energy metabolism, neuroleptic medication, and neurological side effects. METHOD: CSF was obtained from 25 patients with schizophrenia; seven were unmedicated and 11 had tardive dyskinesia. CSF concentrations of four substrates of mitochondrial energy metabolism (Krebs cycle)--alanine, aspartate, lactate, and pyruvate--were determined. Tardive dyskinesia was measured with the Abnormal Involuntary Movement Scale (AIMS), and parkinsonism was measured with the Simpson-Angus Rating Scale. RESULTS: CSF concentrations of alanine were significantly elevated in the medicated patients when tardive dyskinesia status was controlled for. CSF aspartate concentrations were significantly elevated in patients with tardive dyskinesia when medication status was controlled for and were significantly correlated with total scores on the AIMS. CONCLUSIONS: These results are consistent with a model linking neuroleptic-induced neurological side effects with impairment of mitochondrial energy metabolism, possibly mediated by inhibition of complex 1 of the electron transport chain.
OBJECTIVE: This study was undertaken to assess the relationships among CSF concentrations of substrates of mitochondrial energy metabolism, neuroleptic medication, and neurological side effects. METHOD:CSF was obtained from 25 patients with schizophrenia; seven were unmedicated and 11 had tardive dyskinesia. CSF concentrations of four substrates of mitochondrial energy metabolism (Krebs cycle)--alanine, aspartate, lactate, and pyruvate--were determined. Tardive dyskinesia was measured with the Abnormal Involuntary Movement Scale (AIMS), and parkinsonism was measured with the Simpson-Angus Rating Scale. RESULTS:CSF concentrations of alanine were significantly elevated in the medicated patients when tardive dyskinesia status was controlled for. CSFaspartate concentrations were significantly elevated in patients with tardive dyskinesia when medication status was controlled for and were significantly correlated with total scores on the AIMS. CONCLUSIONS: These results are consistent with a model linking neuroleptic-induced neurological side effects with impairment of mitochondrial energy metabolism, possibly mediated by inhibition of complex 1 of the electron transport chain.
Authors: Jeffrey A Lieberman; Frank P Bymaster; Herbert Y Meltzer; Ariel Y Deutch; Gary E Duncan; Christine E Marx; June R Aprille; Donard S Dwyer; Xin-Min Li; Sahebarao P Mahadik; Ronald S Duman; Joseph H Porter; Josephine S Modica-Napolitano; Samuel S Newton; John G Csernansky Journal: Pharmacol Rev Date: 2008-09 Impact factor: 25.468
Authors: J C Leveque; W Macías; A Rajadhyaksha; R R Carlson; A Barczak; S Kang; X M Li; J T Coyle; R L Huganir; S Heckers; C Konradi Journal: J Neurosci Date: 2000-06-01 Impact factor: 6.167
Authors: William T Regenold; Pornima Phatak; Christopher M Marano; Amritpal Sassan; Robert R Conley; Mitchel A Kling Journal: Biol Psychiatry Date: 2008-12-21 Impact factor: 13.382
Authors: Paul M Thompson; George Bartzokis; Kiralee M Hayashi; Andrea D Klunder; Po H Lu; Nancy Edwards; Michael S Hong; Michael Yu; Jennifer A Geaga; Arthur W Toga; Cecil Charles; Diana O Perkins; Joseph McEvoy; Robert M Hamer; Mauricio Tohen; Gary D Tollefson; Jeffrey A Lieberman Journal: Cereb Cortex Date: 2008-10-08 Impact factor: 5.357