Increased rate of P300 latency prolongation with age in schizophrenia. Electrophysiological evidence for a neurodegenerative process.
BACKGROUND
The latency of the P300 event-related potential is prolonged in disorders associated with neural damage and degeneration and also becomes prolonged in the course of neural changes that accompany aging. We tested whether the rate of P300 latency increase with age was greater in male schizophrenic patients than in normal subjects because a steeper slope in schizophrenia would suggest a progressive neurodegenerative process. We also evaluated a subset of these subjects for changes in brain volumes as determined by magnetic resonance imaging.


METHODS
The P300 component was elicited during an auditory "oddball" paradigm and was recorded from 47 male patients with chronic schizophrenia whose mean age at onset was 22.4 years and from 47 age-, handedness-, and gender-matched control subjects. The relation of P300 latency and amplitude to age within each group was evaluated using correlation and regression analyses. Brain volumes determined via magnetic resonance imaging were evaluated by quantitative volumetric analyses of images acquired with three-dimensional Fourier transform and double echo-spin echo-pulse sequences.


RESULTS
The slope of P300 latency on age was steeper for schizophrenic patients than for normal control subjects at midline frontal and central electrode sites. The slope of N100 latency did not differ, implying that the P300 differences were not likely to be due to peripheral hearing loss or damage affecting the initial stages of neural processing. Posterior superior temporal gyrus gray matter volume determined via magnetic resonance imaging significantly diminished with age on the left side in patients with schizophrenia but not on the right side or in controls; these slopes were not, however, statistically significantly different from each other.


CONCLUSIONS
These findings provide preliminary evidence that male patients with chronic schizophrenia experience a neurodegenerative process that becomes evident in adulthood and is reflected by the rate of change of P300 latency with age. Whether this process is due to the primary effects of schizophrenia or is secondary to factors associated with schizophrenia's chronic course and treatment remains a question for future investigation.
O'Donnell
B F
BF
Department of Psychiatry, Harvard Medical School, Boston, Mass, USA.
Faux
S F
SF
McCarley
R W
RW
Kimble
M O
MO
Salisbury
D F
DF
Nestor
P G
PG
Kikinis
R
R
Jolesz
F A
FA
Shenton
M E
ME
D000161:Acoustic Stimulation; D000328:Adult; D000367:Age Factors; D000375:Aging / Q000473:pathology; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology