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Sensory gating and schizophrenia: Critical methodological issues
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51. ANXIETY AS A FACTOR IN AGITATION IN THE DEMENTED INSTITUTIONALIZED ELDERLY: RANDOMIZED SINGLE ~LIND TREATMENT WITH AZAPIRONES VERSUS NEUROLEPTICS M. Cantillon, D. Molina, & R. Brunswick Beth Israel Nursing Home, Mount Sinai School of Medicine, New York Alzheimer's dementia is a disease of cognitive and behavioral abnormalities. The most common request for psychiatric intervention in residential settings for the elderly concerns agitated behaviors. Factor analysis of a host of clinical symptoms of agitated behavior in nursing homes suggested three central behaviors: physical aggression, verbal assault and inappropriate motor behavior (Cohen-Mansfield and Billig, 1986). ,~.nxiety scales and classification have not been described in this population. Of 38 moderate to severely demented non-depressed patients on chronic neuroleptic treatment ( age range 73- 90), identified as behavior problems by nursing, 14 were randomly switched to buspirone 15rag daily. 2 subjects became psychotic and were put on neuroleptics again. Overall, the buspirone group had behavior amelioration compared with the neuroleptic group. Over 8 weeks treatment, Zung somatic anxiety scores improved on average over 10% in the buspirone group (pc: 0.05) though Spielberger subjective anxiety scores were too variable to show reliable changes. Clinical assessment scales as the Sandoz Clinical Assessment Geriatric (SCAG) and the Nursing Observation Scale (NOSIE) showed a trend towards improvement. Sleep length increased and there was less daytime sedation. BPRS, HAMD and MMSE were essentially unchanged suggesting that psychosis, depression and cognitive functions may not be relevant to the behavioral improvement with 5 liT ! A agonists as buspirone.
52. CHANGES IN PATFERN OF ACCELERATION OF BEHAVIOR IN PATIENTS WITH ALZHEIMER'S DISEASE T. Fujimoto, T. Tamura, & T. Togawa Institute for Medical and Dental Engineering, Tokyo Medical and Dental University Although the existence of unusual behavior due to Alzheimer's disease is widely known, its evaluation has so far been based essentially on the subjective observation of the clinician. We developed a portable unconfined acceleration monitoring system and applied this system to investigate changes of pattern of acceleration in the behavior of patients with AIzhelmet's disease. The patients showed no elementary neurologic findings and were not treated with tranquilizers. The accelerations in the waist, the right hand and right ankle were continuously measured over a 3 to 7 hour period using acceleration sensors. The patterns (accelerogram) of f~quency of the occurrences and amplitude of accelerations were obtained and displayed on a muitichannel chart recorder. Histograms of the occurrence and amplitude were also calculated from the recording of the acceleration. The accelerogram of normal controls showed continuous, smooth and complicated patterns. However, the accelerogram of the patients demonstrated simple and discontinuous patterns. Changes of patterns in the behavior of the patients may reflect pathologic mental state and cerebral dysfunction including prefrontal dysfunction, in the histogram of the patients, amplitudes of the waist and the ankle are larger than normal subjects. This is probably because behavior of the patients has few preparatory movements and is not efficient. Our portable unconfined acceleration monitoring system was useful to objectively evaluate changes of behavior in patients with Alzheimer's disease.
BIOL PSYCHIATRY 629 1994;35:615-747
53. A STUDY OF HPA AXIS FUNCTION IN ALZHEIMER'S DISEASE I. Schweitzer, J.T. O'Brien, D. Ames, & P. Colman Departmentof Psychiatry,
University of Melbourne
HPA axis dysfunction has been described in Alzheimer's disease (AD), although the mechanism and clinical significance remains unclear. This study used the ACTH stimulation test and the insulin hypoglycaemia (IH) test to systematically assess HPA axis function in AD. 17 subjects with AD (NINCDS/ADRDA) and 18 control subjects underwent a fasting IH test (0.1 U Actrapid/Kg iv) and ACTH stimulation (0.05 mcg/Kg) test at ! 400 h on consecutive days. For IH blood for glucose, cortisol and ACTH estimation was taken through an indwelling venous cannula at -15, 0, 5, 10, 15, 30, 45, 60, 75, 90, 120 and 150 minutes. For ACTH stimulation tests blood for cortisol was taken at -15, 0, 30, 60, 90, 120, 180 and 240 minutes. PeakD (peak - baseline) and area under the curve (AUC) estimations were made for ACTH and cortisol response to 1H and for cortisol release after ACTH. Severity of dementia was assessed by score on CAMCOG. Patients with AD had significantly higher PeakD and AUC for cortisol after ACTH stimulation compared with controls (p ' 0.05). Consistent with this, after IH AD subjects showed shorter time to peak cortisol response. ACTH response to IH inversely correlated with CAMCOG. Significant blunting of ACTH response to IH occurred. AD subjects showed evidence of adrenal hyper-responsiveness and blunting of ACTH response to IH. The correlation with dementia severity suggests that HPA axis dysfunction in AD may reflect structural brain changes.
54. SENSORY GATING AND SCHIZOPHRENIA: CRITICAL METHODOLOGICAL ISSUES D.L. Braff, B. Clementz, & M. A. Geyer Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804" Gating and inhibitory deficits are cardinal features of the group of schizophrenias. One major strategy for assessing inhibitory functions in schizophrenic patients has been the use of the conditioning-test (CT) i)50 event related potential (ERP) paradigm, in this paradigm, the early positive wave that occurs about 50 msec after stimulus delivery (the I)50 wave) is measured in response to each of two clicks that are typically separated by a 500 msec interstimulus interval. The first (conditioning) I)50 wave is typically large and the second (test) 1:'50 wave is normally inhibited or gated in amplitude, in numerous studies, schizophrenic patients and their relatives are reported to show a loss of this normal inhibitory function. We have replicated a sensory gating (I)50) deficit in schizophrenic patients and continue to search for critical methodological issues that will allow investigators to optimize this paradigm. Based on testing 50 schizophrenic patients, 50 unaffected relatives, and 50 controls, we will review the optimal strategies for assessing the P50 wave and 1)50 gating. These issues include: 1) the use of 60 or more pairs of stimuli versus the standard lower number (eg, 30) of stimuli; 2) the use of "jittering" the interstimulus interval rather than using a fixeft interval; 3) the use of multiple electrode sites; 4) the optimal formula for measuring the P50 wave itself (ie, "peak picking") versus the use of more sophisticated dipole localization formulae; and 5) the critical importance of "off-line" blind wave rating rather than "on.line" non-blind rating of the P50. Since the !)50 wave is being increasingly utilized in schizophrenia research, these methodological questions are very important to answer so that a standardized methodology can be utilized in various research programs.
51. ANXIETY AS A FACTOR IN AGITATION IN THE DEMENTED INSTITUTIONALIZED ELDERLY: RANDOMIZED SINGLE ~LIND TREATMENT WITH AZAPIRONES VERSUS NEUROLEPTICS M. Cantillon, D. Molina, & R. Brunswick Beth Israel Nursing Home, Mount Sinai School of Medicine, New York Alzheimer's dementia is a disease of cognitive and behavioral abnormalities. The most common request for psychiatric intervention in residential settings for the elderly concerns agitated behaviors. Factor analysis of a host of clinical symptoms of agitated behavior in nursing homes suggested three central behaviors: physical aggression, verbal assault and inappropriate motor behavior (Cohen-Mansfield and Billig, 1986). ,~.nxiety scales and classification have not been described in this population. Of 38 moderate to severely demented non-depressed patients on chronic neuroleptic treatment ( age range 73- 90), identified as behavior problems by nursing, 14 were randomly switched to buspirone 15rag daily. 2 subjects became psychotic and were put on neuroleptics again. Overall, the buspirone group had behavior amelioration compared with the neuroleptic group. Over 8 weeks treatment, Zung somatic anxiety scores improved on average over 10% in the buspirone group (pc: 0.05) though Spielberger subjective anxiety scores were too variable to show reliable changes. Clinical assessment scales as the Sandoz Clinical Assessment Geriatric (SCAG) and the Nursing Observation Scale (NOSIE) showed a trend towards improvement. Sleep length increased and there was less daytime sedation. BPRS, HAMD and MMSE were essentially unchanged suggesting that psychosis, depression and cognitive functions may not be relevant to the behavioral improvement with 5 liT ! A agonists as buspirone.
52. CHANGES IN PATFERN OF ACCELERATION OF BEHAVIOR IN PATIENTS WITH ALZHEIMER'S DISEASE T. Fujimoto, T. Tamura, & T. Togawa Institute for Medical and Dental Engineering, Tokyo Medical and Dental University Although the existence of unusual behavior due to Alzheimer's disease is widely known, its evaluation has so far been based essentially on the subjective observation of the clinician. We developed a portable unconfined acceleration monitoring system and applied this system to investigate changes of pattern of acceleration in the behavior of patients with AIzhelmet's disease. The patients showed no elementary neurologic findings and were not treated with tranquilizers. The accelerations in the waist, the right hand and right ankle were continuously measured over a 3 to 7 hour period using acceleration sensors. The patterns (accelerogram) of f~quency of the occurrences and amplitude of accelerations were obtained and displayed on a muitichannel chart recorder. Histograms of the occurrence and amplitude were also calculated from the recording of the acceleration. The accelerogram of normal controls showed continuous, smooth and complicated patterns. However, the accelerogram of the patients demonstrated simple and discontinuous patterns. Changes of patterns in the behavior of the patients may reflect pathologic mental state and cerebral dysfunction including prefrontal dysfunction, in the histogram of the patients, amplitudes of the waist and the ankle are larger than normal subjects. This is probably because behavior of the patients has few preparatory movements and is not efficient. Our portable unconfined acceleration monitoring system was useful to objectively evaluate changes of behavior in patients with Alzheimer's disease.
BIOL PSYCHIATRY 629 1994;35:615-747
53. A STUDY OF HPA AXIS FUNCTION IN ALZHEIMER'S DISEASE I. Schweitzer, J.T. O'Brien, D. Ames, & P. Colman Departmentof Psychiatry,
University of Melbourne
HPA axis dysfunction has been described in Alzheimer's disease (AD), although the mechanism and clinical significance remains unclear. This study used the ACTH stimulation test and the insulin hypoglycaemia (IH) test to systematically assess HPA axis function in AD. 17 subjects with AD (NINCDS/ADRDA) and 18 control subjects underwent a fasting IH test (0.1 U Actrapid/Kg iv) and ACTH stimulation (0.05 mcg/Kg) test at ! 400 h on consecutive days. For IH blood for glucose, cortisol and ACTH estimation was taken through an indwelling venous cannula at -15, 0, 5, 10, 15, 30, 45, 60, 75, 90, 120 and 150 minutes. For ACTH stimulation tests blood for cortisol was taken at -15, 0, 30, 60, 90, 120, 180 and 240 minutes. PeakD (peak - baseline) and area under the curve (AUC) estimations were made for ACTH and cortisol response to 1H and for cortisol release after ACTH. Severity of dementia was assessed by score on CAMCOG. Patients with AD had significantly higher PeakD and AUC for cortisol after ACTH stimulation compared with controls (p ' 0.05). Consistent with this, after IH AD subjects showed shorter time to peak cortisol response. ACTH response to IH inversely correlated with CAMCOG. Significant blunting of ACTH response to IH occurred. AD subjects showed evidence of adrenal hyper-responsiveness and blunting of ACTH response to IH. The correlation with dementia severity suggests that HPA axis dysfunction in AD may reflect structural brain changes.
54. SENSORY GATING AND SCHIZOPHRENIA: CRITICAL METHODOLOGICAL ISSUES D.L. Braff, B. Clementz, & M. A. Geyer Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804" Gating and inhibitory deficits are cardinal features of the group of schizophrenias. One major strategy for assessing inhibitory functions in schizophrenic patients has been the use of the conditioning-test (CT) i)50 event related potential (ERP) paradigm, in this paradigm, the early positive wave that occurs about 50 msec after stimulus delivery (the I)50 wave) is measured in response to each of two clicks that are typically separated by a 500 msec interstimulus interval. The first (conditioning) I)50 wave is typically large and the second (test) 1:'50 wave is normally inhibited or gated in amplitude, in numerous studies, schizophrenic patients and their relatives are reported to show a loss of this normal inhibitory function. We have replicated a sensory gating (I)50) deficit in schizophrenic patients and continue to search for critical methodological issues that will allow investigators to optimize this paradigm. Based on testing 50 schizophrenic patients, 50 unaffected relatives, and 50 controls, we will review the optimal strategies for assessing the P50 wave and 1)50 gating. These issues include: 1) the use of 60 or more pairs of stimuli versus the standard lower number (eg, 30) of stimuli; 2) the use of "jittering" the interstimulus interval rather than using a fixeft interval; 3) the use of multiple electrode sites; 4) the optimal formula for measuring the P50 wave itself (ie, "peak picking") versus the use of more sophisticated dipole localization formulae; and 5) the critical importance of "off-line" blind wave rating rather than "on.line" non-blind rating of the P50. Since the !)50 wave is being increasingly utilized in schizophrenia research, these methodological questions are very important to answer so that a standardized methodology can be utilized in various research programs.