- Email: [email protected]
Normal P300 in acute schizophrenics during a continuous performance test
792
BIOL PSYCHiATRY 1989;25:788-792
Brief Repons
micro and ultra-micro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab 27:973990. Myers ED (1984): Serial Dexamethasone sion Tests in male chronic schizophrenic Am J Psychiatry 141904-905.
Supprespatients.
Overall JE (1984): The Brief Psychiatric Rating Scale in psychopharmacology research. In Pichot P (ed), Pharmacopsychiatry. Basel: Karger, pp 6778. Shima S, Kitamura T, Takahashi Y, Asai M (1986): Dexamethasone Suppression Test and negative symptoms of schizophrenics. Keio J Med 35:203207. Spitzer RL, Endicott J, Robins E (1978): Research Diagnostic Criteria: Rationale and reliability. Arch Gen Psychiatry 35773-782.
Tandon R, &eden JF (1988a): Cholinergic excess and the negative syndrome. In Greden JF, Tan-
don R, Pathophysiology of Negative Schirophrenic Symptoms. 141st annual meeting of the American Psychiatric Association, Montreal. Tandon R, Greden JF (1988b): Cholinergic hyper activity and negative schizophrenic symptoms: A model of cholinergic/dopaminergic interactions in schizophrenia. Arch Gen Psychiatry (in press). Tandon R, Greden JF, Silk KR (1988): Treatment of negative schizophrenic symptoms with trihexiphenidyl. J Clin Psychopharmacol 8:2 12215. Targum SD (1983): Neuroendocrine dysfunction in schizophreniform disorder: Correlation with sixmonth clinical outcome. Am J P.rychiany 140:309313. Wik G, Wiesel F-A, Eneroth P, et al (1986): Dexamethasone Suppression Test in schizophrenic pa tients before and during neuroleptic treatment. Acta Psychiatr Stand 74: 16 I-l 67.
Normal P300 in Acute Schizophrenics During a Continuous Performance Test Michael Wagner, Gabriele Kurtz, and Rolf R. Engel
Introduction Evidence from many studies indicates that the vigilance deficit tapped by a visual continuous performance test (CPT) may be a promising vulnerability marker of schizophrenia (Nuechterlein 1985). A reduced P300 component of the cortical event-related potential (ERP) in schizo-
From tbe Psychiatric Hospital, University of Munich, Federal Republic of Germany. Address reprint requests to Michael Wagner, Psychiatric Hospital, University of Munich. Nu~baumshlt~ 7,8tXlO MUnchen 2, Federal Republic of Germany. Received February 20, 1988; revised September 13. 1988.
0 1989 Society of Biological
Psychiatry
phrenics has been reported almost consistently and is considered to be related to such attentional impairments (Pritchard 1986). So far, only Pass et al. (1980) have recorded ERPs of schizophrenics during the CPT. They also found a smaller P300 amplitude in acute psychotic patients. We obtained contrasting results in a similar study.
Methods Fourteen inpatients meeting DSM-III criteria for schizophrenia (9 men) were studied. Their ages ranged from 18 to 37 years (mean age 25, SD
0006-3223/89/$03.50
BIOLPSYCHIATRY
Brief Reports
5 years). Thirteen patients had received neuroleptic medication of chlorpromiazine (CPZ) equivalents (Davis 1976) ranging from 150 to 1400 CPZ equiv/day (mean 510, SD 360). Symptoms present on the day of testing were rated with the Brief Psychiatric Rating Scale (BPRS) (Gverall and Got-ham 1%2). Total scores ranged from 35 to 69 (mean 50, SD 12). The control group consisted of 14 healthy volunteers (students and hospital staff, 7 men) with no history of psychiatric or neurological illness. Controls were slightly older, with ages ranging from 20 t0 37 (IrKan age 29, SD 5 years; f(26)= 2.21, p < 0.05). All subjects had vision that was normal or corrected to normal. Subjects performed the CPT in a shielded and dimly lit room. Five blocks of 125 stimuli (upper-case letters B, D, E, P, and R, size 35 x 45 mm) were projected for 50 msec on a screen from the outside. The subjects sat at a distance of 1.5 m and were asked to react promptly and accurately at the appearance of the target letter ‘Y (20% of the trials). The interstimulus interval (ISI) was 1.5 set during the first, the last, and during either the second or the fourth block. For exploratory purposes, the two remaining blocks were run with ISIS varying randomly between 1.5 and 3 sec. The electroencephalogram (EEG) was recorded with Ag/AgCl electrodes at Cz referenced to the left earlobe. [Although P300 is often found to be maximal over Pz, to our knowledge, group differences between schizophrenics and controls were also always found at Cz. Technical limitations at the time this study was conducted allowed only for single-channel recording. We chose Cz to correspond with the similar study of Pass et al. (1980).] A low-pass filter was set at 30 Hz and the time constant was 15 sec. To control for electrooculogram (EGG) artifacts, electrodes were attached above and below the left eye, and the EEG was corrected on-line in accord with the method of Barlow and Remond (198 1). Signals were digitized and stored with a sampling rate of 200 Hz for 700 msec following stimulus onset. EEG sweeps with correct reactions were averaged separately according to stimulus type (target/nontarget) and
1989;25:792-195
793
Table 1. Means (SD) of P300 Amplitude and Latency, Reaction Time, and Errors (Collapsed across All Blocks) Normals
(n = 14)
Schizophrenics (n = 14)
P300
amplitude (pV) Targets Nontargets P300 latency (msec) Targets Nontargets Reaction time (msec) Omission errors(%) Comission errors(46)
13.9 (4.3) 8.4 (3.1)
14.0 (7.1) 6.1 (3.2)
458 (34) 380 (98) 401 (54) 3.1 0.2
479 (48) 424 (64) 464 (54)” 6.86 0.2
“Differs from nommls, p < 0.01. “Differs from normals, p < 0.1.
block. The P300 was defined as the most positive peak between 300 and 650 msec poststimulus. Amplitudes were measured with respect to an average voltage during the Ilrst 30 msec poststimulus. (During this epoch, event-related activity is generally low.) Reaction time and errors were also recorded. A three-way Analysis of Variance (ANOVA) with one group factor (patient/control) and two trial factors (block x stimulus category) was carried out for the physiological and behavioral variables.
Results Table 1 summarizes the main results, which are collapsed across all blocks. Neither amplitude nor latency of the P300 differed between schizophrenics and controls. A significant group x block interaction for P300 amplitude (Fonz, = 3.32, p < 0.05, Greenhouse-Geisser corrected) was found due to a decrease of P300 in schizophrenics, but not in controls, from the Brst to the last block. Reaction times of schizophrenics were generally slower (FoX) = 9.05, p < 0.01) and more variable within each subject (F(i,26) = 8.63, p < 0.01). The number of omission errors was only marginally higher for patients than for controls (Mann-Whitney U-test, p < 0.1). Commission errors rarely occurmd. In both groups, variable interstimulus intervals caused
194
EIIOLPSYCHIATRY 1989;25:792-7%
Brief Reporb
an increase in P300 latency (F, , ,26J= 7.90, p < 0.01) and a slowing of reaction time (F(,.26) = 37.8, p < 0.001). Pearson product-moment correlations revealed that neither P300 nor reaction time were significantly affected by medication dosage. A high degree of psychopathology (as reflected in the BPRS total score) was related to a reduced P300 amplitude (r = -0.64, p < 0.05) and to slower reactions (r = 0.60, p < 0.05). More specifically, reaction time was closely related to the anergia subscale of the BPRS (r = 0.75, p < O.Ol), and thought disorder was the only subscale that was significantly related to P300 amplitude (r = -0.58, p < 0.05).
al. (1984) found that P300 amplitude in schizophrenics diminished in response to auditory targets, but was normal for visual targets at central and parietal electrode sites. Our results support the assumption that a reduced visual P300 amplitude occurs only in untreated psychotic states, whereas a reduced auditory P300 may be more persistent. A recent study employing regional cerebral blood flow found a similar modalityspecific physiological dysfunction in schizophrenics during vigilance performance: frontal blood flow in schizophrenics was found to be reduced during auditory sustained attention (Cohen et al. 1987), but was normal during a visual CPT (Berman et al. 1986).
Discussion
References
As the CPT in this study was relatively slowpaced, the small difference in vigilance performance between patients and controls is most likely due to a psychometric ceiling effect of the task employed. Furthermore, no attempt was made to select patients with a family history of schizophrenia-a group prone to vigilance deficits even in a low-demand CPT (Walker & Shaye 1982). However, this cannot explain the “normal” P300 of our patients, as a reduced P300 in schizophrenics has often been reported despite good performance levels (Pritchard 1986). Rather, subject characteristics and stimulus modality seem to account for this result. Most of the ERP studies with schizophrenics used auditory simuli. A diminished visual P300 amplitude was found by Pass et al. (1980) in patients hospitalized during the previous 48 hr and by Brecher and Begleiter (1983) in unmedicated patients. Although the BPRS ratings of our sample indicate a moderate to severe degree of psychotic symptomatology , 11 of our patients were hospitalized for more than 1 week, 6 of them for more than 1 month, and all but one were treated with neuroleptics. In a study with both visual and auditory stimuli, Duncan et al. (1987) found that the P300 in response to visual, but not to auditory, stimuli normalized when patients received neuroleptic medication (only Cz data were reported). Also, Pfefferbaum et
Barlow JS, Remond A (1981): Eye movement artifact nulling in EEGs by multichannel on-line EOG subtraction. Electroencephalogr Clin Neurophysiol 5214 18-423. Berman KF, Zec RF, Weinberger DR (1986): Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. II. Role of neuroleptic treatment, attention, and mental effort. Arch Gen Psychiatry 43: 126135. Brecher M, Begleiter H (1983): Event-related brain potentials to high-incentive stimuli in unmedicated schizophrenic patients. Biol Psychiatn 18:661-675. Cohen RM, Semple WE, Gross M, Nordahl TE, DeLisi LE, Holcomb HH, King AC, Morihisha JM, Pickar D (1987): Dysfunction in a prefrontal substrate of sustained attention in schizophrenia. Life Sci 40:2031-2039. Davis JM (1976): Comparative doses and costs of antipsychotic medication. Arch Gen Psychiatq 33:858-861. Duncan CC, Morihisha JM, Fawcett RW, Kirch DG ( 1987): P300 in schizophrenia: State or trait marker? Psychopharmacol Bull 23:497-501. Nuechterlein KH (1985): Converging evidence for vigilance deficit as a vulnerability indicator for schizophrenic disorders. In Alpert M (ed), Controversies in Schizophrenia. New York: Guilford Press, pp 175-198. Overall JE, Gorham DR (1962): The Brief Psychiatric Rating Scale. Psycho1 Rep 10:799-8 12. Pass HL, Klorman R, Salzmann LF, Klein RH, Kaskey GB (1980): The late positive component of
BIOL PSYCHIATRY 1989:25:792-795
Brief Reports
the evoked potential in acute schizophrenics during a test of sustained attention. Biol Psychiatry 15:9-20. Pfefferbaum A, Wenegrat BG, Ford JM, Roth W’I’, Kopell BS (1984): Clinical application of the P3 component of event-related potentials. II. Dementia, depression and schizophrenia. Electroen-
795
Pritchard WS (1986): Cognitive event-related potentials in schizophtenics. Psycho1 Bull 100:43-66. Walker E, Shaye J (1982): Familial schizophrenia: A predictor of neuromotor and attentional abnormalities in schizophrenia. Arch Gen Psychiatry 39:1153-1156.
cephalogr Clin Neurophysiol59:104-124.
Chronic Treatment with Lithium Produces Supersensitivity to Nicotine Steven C. Dilsaver and M. Hariharan
Introduction Dilsaver et al. ( 1988) reported that amitriptyline produces supersensitivity of a nicotinic mechanism involved in the regulation of core temperature. We now present data indicating that chronically administered lithium ion also has this effect. We will discuss the potential theoretical significance of this finding and review other data indicating that treatments for depression alter sensitivity to nicotine.
Methods The dependent variable in the experiments reported here was change in core temperature in
From the Depsrtmentof Psychiatry, Ohio State University, Columbus, OH (S.C.D.), and the Cliiical Laboratory, Mental Health ResesxchInstitute,Departmentof Psychiatry, University of Michigan, AM Arbor, MI (M.H.). Supportedby Physician Scientist CareerDevelopment Award (Musmink Recepor Abnormdities in Affective Ilbxss) MHCKl55032 and NIH 2mo5383-25. Address reprintrequests to Dr. S. C. Dilsaver, Dcpamnm of Psychiatry, Ohio State University College of Mediiine, 473 West 12th Avenue, Columbus. OH 43201-1228. Received August 20. 1987; revised lum 21, 1988.
0 1989 Society of Biological Psychiatry
response to nicotine (base), 0.40 or 1.0 mgkg intraperitoneally (ip) in adult male SpragueDawley rats housed individually. Core temperature was telemetrically measured with the model VM Mini-Mitter (Mini-Mitter Co., Sun River, OR). These instruments, which emit radio waves at a rate directly proportional to temperature, are implanted into the peritoneal cavity. The rats were allowed 5 days to recover prior to starting an experiment. A digital frequency counter (model 5001 Universal counter-timer; Global Specialties, New Haven, CT) connected to an AM receiver was used to determine the emission rates of each Mini-Mitter. This measurement was converted to temperature in degrees Celsius (“C) using a linear regression equation derived by measuring the emission profile of each instrument in a temperature-controlled water bath (Dilsaver et al. 1989). The principles governing the use of the Mini-Mitter in psychopharmacological research is described in detail elsewhere (Dilsaver and Alessi 1988). Each of the three experiments below required the measurement of temperature prior to the injection of saline or nicotine (at t = 0) and every 10 min
00063223~89603.50
BIOL PSYCHiATRY 1989;25:788-792
Brief Repons
micro and ultra-micro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab 27:973990. Myers ED (1984): Serial Dexamethasone sion Tests in male chronic schizophrenic Am J Psychiatry 141904-905.
Supprespatients.
Overall JE (1984): The Brief Psychiatric Rating Scale in psychopharmacology research. In Pichot P (ed), Pharmacopsychiatry. Basel: Karger, pp 6778. Shima S, Kitamura T, Takahashi Y, Asai M (1986): Dexamethasone Suppression Test and negative symptoms of schizophrenics. Keio J Med 35:203207. Spitzer RL, Endicott J, Robins E (1978): Research Diagnostic Criteria: Rationale and reliability. Arch Gen Psychiatry 35773-782.
Tandon R, &eden JF (1988a): Cholinergic excess and the negative syndrome. In Greden JF, Tan-
don R, Pathophysiology of Negative Schirophrenic Symptoms. 141st annual meeting of the American Psychiatric Association, Montreal. Tandon R, Greden JF (1988b): Cholinergic hyper activity and negative schizophrenic symptoms: A model of cholinergic/dopaminergic interactions in schizophrenia. Arch Gen Psychiatry (in press). Tandon R, Greden JF, Silk KR (1988): Treatment of negative schizophrenic symptoms with trihexiphenidyl. J Clin Psychopharmacol 8:2 12215. Targum SD (1983): Neuroendocrine dysfunction in schizophreniform disorder: Correlation with sixmonth clinical outcome. Am J P.rychiany 140:309313. Wik G, Wiesel F-A, Eneroth P, et al (1986): Dexamethasone Suppression Test in schizophrenic pa tients before and during neuroleptic treatment. Acta Psychiatr Stand 74: 16 I-l 67.
Normal P300 in Acute Schizophrenics During a Continuous Performance Test Michael Wagner, Gabriele Kurtz, and Rolf R. Engel
Introduction Evidence from many studies indicates that the vigilance deficit tapped by a visual continuous performance test (CPT) may be a promising vulnerability marker of schizophrenia (Nuechterlein 1985). A reduced P300 component of the cortical event-related potential (ERP) in schizo-
From tbe Psychiatric Hospital, University of Munich, Federal Republic of Germany. Address reprint requests to Michael Wagner, Psychiatric Hospital, University of Munich. Nu~baumshlt~ 7,8tXlO MUnchen 2, Federal Republic of Germany. Received February 20, 1988; revised September 13. 1988.
0 1989 Society of Biological
Psychiatry
phrenics has been reported almost consistently and is considered to be related to such attentional impairments (Pritchard 1986). So far, only Pass et al. (1980) have recorded ERPs of schizophrenics during the CPT. They also found a smaller P300 amplitude in acute psychotic patients. We obtained contrasting results in a similar study.
Methods Fourteen inpatients meeting DSM-III criteria for schizophrenia (9 men) were studied. Their ages ranged from 18 to 37 years (mean age 25, SD
0006-3223/89/$03.50
BIOLPSYCHIATRY
Brief Reports
5 years). Thirteen patients had received neuroleptic medication of chlorpromiazine (CPZ) equivalents (Davis 1976) ranging from 150 to 1400 CPZ equiv/day (mean 510, SD 360). Symptoms present on the day of testing were rated with the Brief Psychiatric Rating Scale (BPRS) (Gverall and Got-ham 1%2). Total scores ranged from 35 to 69 (mean 50, SD 12). The control group consisted of 14 healthy volunteers (students and hospital staff, 7 men) with no history of psychiatric or neurological illness. Controls were slightly older, with ages ranging from 20 t0 37 (IrKan age 29, SD 5 years; f(26)= 2.21, p < 0.05). All subjects had vision that was normal or corrected to normal. Subjects performed the CPT in a shielded and dimly lit room. Five blocks of 125 stimuli (upper-case letters B, D, E, P, and R, size 35 x 45 mm) were projected for 50 msec on a screen from the outside. The subjects sat at a distance of 1.5 m and were asked to react promptly and accurately at the appearance of the target letter ‘Y (20% of the trials). The interstimulus interval (ISI) was 1.5 set during the first, the last, and during either the second or the fourth block. For exploratory purposes, the two remaining blocks were run with ISIS varying randomly between 1.5 and 3 sec. The electroencephalogram (EEG) was recorded with Ag/AgCl electrodes at Cz referenced to the left earlobe. [Although P300 is often found to be maximal over Pz, to our knowledge, group differences between schizophrenics and controls were also always found at Cz. Technical limitations at the time this study was conducted allowed only for single-channel recording. We chose Cz to correspond with the similar study of Pass et al. (1980).] A low-pass filter was set at 30 Hz and the time constant was 15 sec. To control for electrooculogram (EGG) artifacts, electrodes were attached above and below the left eye, and the EEG was corrected on-line in accord with the method of Barlow and Remond (198 1). Signals were digitized and stored with a sampling rate of 200 Hz for 700 msec following stimulus onset. EEG sweeps with correct reactions were averaged separately according to stimulus type (target/nontarget) and
1989;25:792-195
793
Table 1. Means (SD) of P300 Amplitude and Latency, Reaction Time, and Errors (Collapsed across All Blocks) Normals
(n = 14)
Schizophrenics (n = 14)
P300
amplitude (pV) Targets Nontargets P300 latency (msec) Targets Nontargets Reaction time (msec) Omission errors(%) Comission errors(46)
13.9 (4.3) 8.4 (3.1)
14.0 (7.1) 6.1 (3.2)
458 (34) 380 (98) 401 (54) 3.1 0.2
479 (48) 424 (64) 464 (54)” 6.86 0.2
“Differs from nommls, p < 0.01. “Differs from normals, p < 0.1.
block. The P300 was defined as the most positive peak between 300 and 650 msec poststimulus. Amplitudes were measured with respect to an average voltage during the Ilrst 30 msec poststimulus. (During this epoch, event-related activity is generally low.) Reaction time and errors were also recorded. A three-way Analysis of Variance (ANOVA) with one group factor (patient/control) and two trial factors (block x stimulus category) was carried out for the physiological and behavioral variables.
Results Table 1 summarizes the main results, which are collapsed across all blocks. Neither amplitude nor latency of the P300 differed between schizophrenics and controls. A significant group x block interaction for P300 amplitude (Fonz, = 3.32, p < 0.05, Greenhouse-Geisser corrected) was found due to a decrease of P300 in schizophrenics, but not in controls, from the Brst to the last block. Reaction times of schizophrenics were generally slower (FoX) = 9.05, p < 0.01) and more variable within each subject (F(i,26) = 8.63, p < 0.01). The number of omission errors was only marginally higher for patients than for controls (Mann-Whitney U-test, p < 0.1). Commission errors rarely occurmd. In both groups, variable interstimulus intervals caused
194
EIIOLPSYCHIATRY 1989;25:792-7%
Brief Reporb
an increase in P300 latency (F, , ,26J= 7.90, p < 0.01) and a slowing of reaction time (F(,.26) = 37.8, p < 0.001). Pearson product-moment correlations revealed that neither P300 nor reaction time were significantly affected by medication dosage. A high degree of psychopathology (as reflected in the BPRS total score) was related to a reduced P300 amplitude (r = -0.64, p < 0.05) and to slower reactions (r = 0.60, p < 0.05). More specifically, reaction time was closely related to the anergia subscale of the BPRS (r = 0.75, p < O.Ol), and thought disorder was the only subscale that was significantly related to P300 amplitude (r = -0.58, p < 0.05).
al. (1984) found that P300 amplitude in schizophrenics diminished in response to auditory targets, but was normal for visual targets at central and parietal electrode sites. Our results support the assumption that a reduced visual P300 amplitude occurs only in untreated psychotic states, whereas a reduced auditory P300 may be more persistent. A recent study employing regional cerebral blood flow found a similar modalityspecific physiological dysfunction in schizophrenics during vigilance performance: frontal blood flow in schizophrenics was found to be reduced during auditory sustained attention (Cohen et al. 1987), but was normal during a visual CPT (Berman et al. 1986).
Discussion
References
As the CPT in this study was relatively slowpaced, the small difference in vigilance performance between patients and controls is most likely due to a psychometric ceiling effect of the task employed. Furthermore, no attempt was made to select patients with a family history of schizophrenia-a group prone to vigilance deficits even in a low-demand CPT (Walker & Shaye 1982). However, this cannot explain the “normal” P300 of our patients, as a reduced P300 in schizophrenics has often been reported despite good performance levels (Pritchard 1986). Rather, subject characteristics and stimulus modality seem to account for this result. Most of the ERP studies with schizophrenics used auditory simuli. A diminished visual P300 amplitude was found by Pass et al. (1980) in patients hospitalized during the previous 48 hr and by Brecher and Begleiter (1983) in unmedicated patients. Although the BPRS ratings of our sample indicate a moderate to severe degree of psychotic symptomatology , 11 of our patients were hospitalized for more than 1 week, 6 of them for more than 1 month, and all but one were treated with neuroleptics. In a study with both visual and auditory stimuli, Duncan et al. (1987) found that the P300 in response to visual, but not to auditory, stimuli normalized when patients received neuroleptic medication (only Cz data were reported). Also, Pfefferbaum et
Barlow JS, Remond A (1981): Eye movement artifact nulling in EEGs by multichannel on-line EOG subtraction. Electroencephalogr Clin Neurophysiol 5214 18-423. Berman KF, Zec RF, Weinberger DR (1986): Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. II. Role of neuroleptic treatment, attention, and mental effort. Arch Gen Psychiatry 43: 126135. Brecher M, Begleiter H (1983): Event-related brain potentials to high-incentive stimuli in unmedicated schizophrenic patients. Biol Psychiatn 18:661-675. Cohen RM, Semple WE, Gross M, Nordahl TE, DeLisi LE, Holcomb HH, King AC, Morihisha JM, Pickar D (1987): Dysfunction in a prefrontal substrate of sustained attention in schizophrenia. Life Sci 40:2031-2039. Davis JM (1976): Comparative doses and costs of antipsychotic medication. Arch Gen Psychiatq 33:858-861. Duncan CC, Morihisha JM, Fawcett RW, Kirch DG ( 1987): P300 in schizophrenia: State or trait marker? Psychopharmacol Bull 23:497-501. Nuechterlein KH (1985): Converging evidence for vigilance deficit as a vulnerability indicator for schizophrenic disorders. In Alpert M (ed), Controversies in Schizophrenia. New York: Guilford Press, pp 175-198. Overall JE, Gorham DR (1962): The Brief Psychiatric Rating Scale. Psycho1 Rep 10:799-8 12. Pass HL, Klorman R, Salzmann LF, Klein RH, Kaskey GB (1980): The late positive component of
BIOL PSYCHIATRY 1989:25:792-795
Brief Reports
the evoked potential in acute schizophrenics during a test of sustained attention. Biol Psychiatry 15:9-20. Pfefferbaum A, Wenegrat BG, Ford JM, Roth W’I’, Kopell BS (1984): Clinical application of the P3 component of event-related potentials. II. Dementia, depression and schizophrenia. Electroen-
795
Pritchard WS (1986): Cognitive event-related potentials in schizophtenics. Psycho1 Bull 100:43-66. Walker E, Shaye J (1982): Familial schizophrenia: A predictor of neuromotor and attentional abnormalities in schizophrenia. Arch Gen Psychiatry 39:1153-1156.
cephalogr Clin Neurophysiol59:104-124.
Chronic Treatment with Lithium Produces Supersensitivity to Nicotine Steven C. Dilsaver and M. Hariharan
Introduction Dilsaver et al. ( 1988) reported that amitriptyline produces supersensitivity of a nicotinic mechanism involved in the regulation of core temperature. We now present data indicating that chronically administered lithium ion also has this effect. We will discuss the potential theoretical significance of this finding and review other data indicating that treatments for depression alter sensitivity to nicotine.
Methods The dependent variable in the experiments reported here was change in core temperature in
From the Depsrtmentof Psychiatry, Ohio State University, Columbus, OH (S.C.D.), and the Cliiical Laboratory, Mental Health ResesxchInstitute,Departmentof Psychiatry, University of Michigan, AM Arbor, MI (M.H.). Supportedby Physician Scientist CareerDevelopment Award (Musmink Recepor Abnormdities in Affective Ilbxss) MHCKl55032 and NIH 2mo5383-25. Address reprintrequests to Dr. S. C. Dilsaver, Dcpamnm of Psychiatry, Ohio State University College of Mediiine, 473 West 12th Avenue, Columbus. OH 43201-1228. Received August 20. 1987; revised lum 21, 1988.
0 1989 Society of Biological Psychiatry
response to nicotine (base), 0.40 or 1.0 mgkg intraperitoneally (ip) in adult male SpragueDawley rats housed individually. Core temperature was telemetrically measured with the model VM Mini-Mitter (Mini-Mitter Co., Sun River, OR). These instruments, which emit radio waves at a rate directly proportional to temperature, are implanted into the peritoneal cavity. The rats were allowed 5 days to recover prior to starting an experiment. A digital frequency counter (model 5001 Universal counter-timer; Global Specialties, New Haven, CT) connected to an AM receiver was used to determine the emission rates of each Mini-Mitter. This measurement was converted to temperature in degrees Celsius (“C) using a linear regression equation derived by measuring the emission profile of each instrument in a temperature-controlled water bath (Dilsaver et al. 1989). The principles governing the use of the Mini-Mitter in psychopharmacological research is described in detail elsewhere (Dilsaver and Alessi 1988). Each of the three experiments below required the measurement of temperature prior to the injection of saline or nicotine (at t = 0) and every 10 min
00063223~89603.50