Tardive dyskinesia and substrates of energy metabolism in CSF.
OBJECTIVE
This study was undertaken to assess the relationships among CSF concentrations of substrates of mitochondrial energy metabolism, neuroleptic medication, and neurological side effects.


METHODS
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.
Goff
D C
DC
Schizophrenia Research Program, Erich Lindemann Mental Health Center, Boston, MA, USA.
Tsai
G
G
Beal
M F
MF
Coyle
J T
JT
D000328:Adult; D000409:Alanine / Q000134:cerebrospinal fluid / Q000378:metabolism; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001224:Aspartic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D002952:Citric Acid Cycle; D004409:Dyskinesia, Drug-Induced / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007773:Lactates / Q000134:cerebrospinal fluid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011773:Pyruvates / Q000134:cerebrospinal fluid / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism
D014150:Antipsychotic Agents; D007773:Lactates; D011773:Pyruvates; D001224:Aspartic Acid; D000409:Alanine