Putamen mitochondrial energy metabolism is highly correlated to emotional and intellectual impairment in schizophrenics

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 22; no. 3; pp. 284 - 292
• Main Authors: PRINCE, J. A, HARRO, J, BLENNOW, K, GOTTFRIES, C. G, ORELAND, L
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01.03.2000; Nature Publishing Group
• Subjects: Adult and adolescent clinical studies; Aged; Aged, 80 and over; Biological and medical sciences; Brain; Cytochrome; Dopamine; Electron Transport Complex IV - metabolism; Emotions; Energy; Energy Metabolism; Female; Humans; Intelligence; Male; Medical sciences; Metabolism; Middle Aged; Mitochondria - metabolism; Neurosciences; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Putamen - metabolism; Raclopride - pharmacokinetics; Receptors, Dopamine D2 - metabolism; Reference Values; Regression Analysis; Schizophrenia; Schizophrenia - metabolism; Schizophrenic Psychology; Sweden; Human; Energy metabolism; Enzyme; Neuroleptic; Psychotropic; Motor system disorder; Cytochrome-c oxidase; Postmortem; Central nervous system; Schizophrenia; Molecular interaction; Emotional disorder; Gene expression; In vitro; Putamen; Psychosis; Mitochondria; D2 Dopamine receptor; Intellectual deficiency; Oxidoreductases; Brain (vertebrata)
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(99)00111-6

In a recent study, we demonstrated that cytochrome-c oxidase (COX), an indicator of neuronal activity, is increased in several brain regions from chronic, medicated schizophrenics. In the present study, to address the functional significance of those findings, we have measured COX activity in a group of schizophrenics in whom antemortem geriatric measures of motor, intellectual, and emotional impairment had been assessed. COX activity in the putamen was strongly negatively correlated with emotional (r = -.76; p < .005) and intellectual impairment (r = -0.76; p < .005), but not with motor impairment (r = 0.01). No significant correlations could be found in the frontal cortex, thalamus, caudate nucleus, globus pallidus, mesencephalon, or nucleus accumbens. Dopamine D2 receptor density in the putamen, measured with [3H]raclopride, was elevated in schizophrenics as compared to controls, as were Kd values. In contrast to COX activity, D2 receptor binding was moderately, but significantly positively correlated with intellectual impairment (r = 0.64; p < .05) but not with motor impairment. Results expose a unique anomaly in the effects of neuroleptics in terms of increasing neuronal signaling in the putamen, which may underlie a reversal of cognitive deficits in schizophrenics, while at the same time, elevating D2 receptor density that seems to be detrimental.