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173. Age of onset of psychotic symptoms predicts information processing deficits in schizophrenia
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BIOL PSYCHIATRY 2000;47:1S–173S
a near-threshold weak stimulus, the ‘prepulse’) is a well validated animal model for the investigation of information processing deficits in patients with schizophrenia. PPI is reduced in people with schizophrenia, and in rats if treated with dopamine/serotonin agonists, N-methyl-D-aspartate antagonists or reared in isolation.1 We assessed PPI of the acoustic startle response (prepulse-to-pulse intervals: 30-ms, 60-ms, and 120-ms; PPI expressed as percent reduction of non-prepulse trials) in two groups of male schizophrenic patients: (i) on an atypical antipsychotic drug, risperidone (n ⫽ 10), and (ii) on a range of typical antipsychotics (n ⫽ 20), and compared them to a group of healthy male volunteers (n ⫽ 20). Patients on typical antipsychotics showed impaired PPI with 30-ms and 60-ms prepulse trials as compared to healthy volunteers. Risperidone– treated patients showed normal levels of PPI with all three prepulse trials. These data indicate that risperidone, like clozapine,2 is superior to typical antipsychotics in normalising information processing deficits, as assessed by PPI of the acoustic startle response, in schizophrenia. [1] Swerdlow NR, Geyer MA (1998). Schizophr Bull. 24, 285–301 [2] Kumari V, Soni W, Sharma T (1999) Am J Psychiatry, 156, 1046 –1051 Financial support: Psychmed Ltd and Gronsvenor House Group Estates.
172. NEURAL CORRELATES OF PROCEDURAL LEARNING: A FUNCTIONAL MRI STUDY V. Kumari, W. Soni, G.D. Honey, S.C.R. Williams, N. Vythelingum, P.J. Corr, J.A. Gray, T. Sharma Section of Cognitive Psychopharmacology and Department of Psychology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK This study examined the neural correlates of procedural learning (PL) using functional resonance magnetic imaging (fMRI). Six normal subjects and six schizophrenic patients (all males) participated as subjects. All patients were on conventional antipsychotics and served as negative controls (i.e., not expected to show PL). All subjects carried out a 5-minute task while undergoing fMRI. The task consisted of two 30-s alternating experimental conditions: Random Trials (OFF) and Pattern Trials (ON). Subjects were presented with a white target stimulus on the black screen. This target moved between four locations on the screen, which was divided into four equal quadrants by two intersecting white lines. The target movements were predictable during the Pattern Trials but were random during the Random Trials. The increase (over five blocks) in difference between the mean reaction times to Random and Pattern Trials represented the amount of PL. The number of activated pixels and degree of signal intensity change between ON and OFF conditions were inferred using the techniques developed at the Institute of Psychiatry. Normals showed significant PL (p ⬍ 0.05), but schizophrenic patients, as expected, did not. The ON condition, contrasted with the OFF condition, elicited significant activation in normals in anteriormiddle cingulate gyrus (right), striatum (caudate nucleus; left), thalamus (right), insula (left), cerebellum (left), and precuneus (left) regions, but not in patients. Our findings are consistent with previous clinical and pharmacological literature in showing the involvement of striatum, cerebellum, thalamus and cingulate regions in PL. Financial support: VK is supported by the Wellcome Trust.
Thursday Abstracts
173. AGE OF ONSET OF PSYCHOTIC SYMPTOMS PREDICTS INFORMATION PROCESSING DEFICITS IN SCHIZOPHRENIA V. Kumari, W. Soni, V.M. Mathew, T. Sharma Section of Cognitive Psychopharmacology, Department of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF Prepulse inhibition (PPI) of the startle reflex, a cross species measure, has been extensively used to index abnormalities in processing of rapidly presented information in schizophrenia. PPI refers to a reduction in response to an intense startling stimulus, the pulse, if this is preceded shortly (30 –100 milliseconds) by a weak nonstartling prestimulus, the prepulse. This effect is found to be reduced in people with schizophrenia, as compared to healthy people. This study investigated whether age of onset of psychotic symptoms predicts disruption of PPI in schizophrenia. We measured PPI (expressed as percent reduction of non-prepulse trials) of the acoustic startle response (indexed electromyographically as the eyeblink) in 40 male individuals with schizophrenia and 20 healthy male volunteers. We observed that patients with an early onset of psychotic symptoms (at 20 years or younger; range 10 –20 years) showed markedly reduced PPI, as compared to patients with a relatively later onset of psychotic symptoms and healthy volunteers. These data indicate that onset of psychotic symptoms during adolescence is associated with remarkably impaired information processing functions, as indexed by PPI of the acoustic startle response, in males with schizophrenia. It is concluded that PPI may provide an important objective experimental tool to investigate heterogeneity in schizophrenia. Financial support: Psychmed Ltd and Grosvenor House Group Estates.
174. MEDICATION EFFECT IN FIRST EPISODE SCHIZOPHRENIA MEASURED BY PROTON MAGNETIC RESONANCE SPECTROSCOPY D. Fannon, A. Glover, V.C. Doku, S. O’Ceallaigh, L. Tennakoon, A. Simmons, T. Sharma Section of Cognitive Psychopharmacology, Department of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF The hippocampal region is implicated prominently in the pathophysiology of schizophrenia. Hippocampal N-acetylaspartate (NAA) signal intensity has been shown to be reduced in schizophrenia suggesting neuronal damage or malfunction. It is suggested that 1H-MRS findings are unrelated to medication status although few studies have specifically examined medication effects with MRS. A PRESS pulse sequence yielded clearly resolved NAA, choline and creatine/phosphocreatine (CRE) peaks in a 6 cm3 volume of the hippocampus in 25 first episode patients, 10 of whom were neurolepticnaı¨ve and 14 healthy controls. Subjects were matched for gender, age, ethnicity, handedness and parental socio-economic status. Data were analysed using the LC-model method of Provencher. Results were expressed in terms of metabolite peak area ratios. The neuroleptic-naı¨ve group showed a significant reduction of NAA/ CRE (F 8.597, p ⬍ 0.002) in the hippocampus compared to controls. No differences were found in the medicated group or in the combined patient group. No group differences were noted for choline. The two patient groups did not differ in symptomatology or age of onset. Neither duration of illness nor length of treatment was correlated with NAA levels.
BIOL PSYCHIATRY 2000;47:1S–173S
a near-threshold weak stimulus, the ‘prepulse’) is a well validated animal model for the investigation of information processing deficits in patients with schizophrenia. PPI is reduced in people with schizophrenia, and in rats if treated with dopamine/serotonin agonists, N-methyl-D-aspartate antagonists or reared in isolation.1 We assessed PPI of the acoustic startle response (prepulse-to-pulse intervals: 30-ms, 60-ms, and 120-ms; PPI expressed as percent reduction of non-prepulse trials) in two groups of male schizophrenic patients: (i) on an atypical antipsychotic drug, risperidone (n ⫽ 10), and (ii) on a range of typical antipsychotics (n ⫽ 20), and compared them to a group of healthy male volunteers (n ⫽ 20). Patients on typical antipsychotics showed impaired PPI with 30-ms and 60-ms prepulse trials as compared to healthy volunteers. Risperidone– treated patients showed normal levels of PPI with all three prepulse trials. These data indicate that risperidone, like clozapine,2 is superior to typical antipsychotics in normalising information processing deficits, as assessed by PPI of the acoustic startle response, in schizophrenia. [1] Swerdlow NR, Geyer MA (1998). Schizophr Bull. 24, 285–301 [2] Kumari V, Soni W, Sharma T (1999) Am J Psychiatry, 156, 1046 –1051 Financial support: Psychmed Ltd and Gronsvenor House Group Estates.
172. NEURAL CORRELATES OF PROCEDURAL LEARNING: A FUNCTIONAL MRI STUDY V. Kumari, W. Soni, G.D. Honey, S.C.R. Williams, N. Vythelingum, P.J. Corr, J.A. Gray, T. Sharma Section of Cognitive Psychopharmacology and Department of Psychology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK This study examined the neural correlates of procedural learning (PL) using functional resonance magnetic imaging (fMRI). Six normal subjects and six schizophrenic patients (all males) participated as subjects. All patients were on conventional antipsychotics and served as negative controls (i.e., not expected to show PL). All subjects carried out a 5-minute task while undergoing fMRI. The task consisted of two 30-s alternating experimental conditions: Random Trials (OFF) and Pattern Trials (ON). Subjects were presented with a white target stimulus on the black screen. This target moved between four locations on the screen, which was divided into four equal quadrants by two intersecting white lines. The target movements were predictable during the Pattern Trials but were random during the Random Trials. The increase (over five blocks) in difference between the mean reaction times to Random and Pattern Trials represented the amount of PL. The number of activated pixels and degree of signal intensity change between ON and OFF conditions were inferred using the techniques developed at the Institute of Psychiatry. Normals showed significant PL (p ⬍ 0.05), but schizophrenic patients, as expected, did not. The ON condition, contrasted with the OFF condition, elicited significant activation in normals in anteriormiddle cingulate gyrus (right), striatum (caudate nucleus; left), thalamus (right), insula (left), cerebellum (left), and precuneus (left) regions, but not in patients. Our findings are consistent with previous clinical and pharmacological literature in showing the involvement of striatum, cerebellum, thalamus and cingulate regions in PL. Financial support: VK is supported by the Wellcome Trust.
Thursday Abstracts
173. AGE OF ONSET OF PSYCHOTIC SYMPTOMS PREDICTS INFORMATION PROCESSING DEFICITS IN SCHIZOPHRENIA V. Kumari, W. Soni, V.M. Mathew, T. Sharma Section of Cognitive Psychopharmacology, Department of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF Prepulse inhibition (PPI) of the startle reflex, a cross species measure, has been extensively used to index abnormalities in processing of rapidly presented information in schizophrenia. PPI refers to a reduction in response to an intense startling stimulus, the pulse, if this is preceded shortly (30 –100 milliseconds) by a weak nonstartling prestimulus, the prepulse. This effect is found to be reduced in people with schizophrenia, as compared to healthy people. This study investigated whether age of onset of psychotic symptoms predicts disruption of PPI in schizophrenia. We measured PPI (expressed as percent reduction of non-prepulse trials) of the acoustic startle response (indexed electromyographically as the eyeblink) in 40 male individuals with schizophrenia and 20 healthy male volunteers. We observed that patients with an early onset of psychotic symptoms (at 20 years or younger; range 10 –20 years) showed markedly reduced PPI, as compared to patients with a relatively later onset of psychotic symptoms and healthy volunteers. These data indicate that onset of psychotic symptoms during adolescence is associated with remarkably impaired information processing functions, as indexed by PPI of the acoustic startle response, in males with schizophrenia. It is concluded that PPI may provide an important objective experimental tool to investigate heterogeneity in schizophrenia. Financial support: Psychmed Ltd and Grosvenor House Group Estates.
174. MEDICATION EFFECT IN FIRST EPISODE SCHIZOPHRENIA MEASURED BY PROTON MAGNETIC RESONANCE SPECTROSCOPY D. Fannon, A. Glover, V.C. Doku, S. O’Ceallaigh, L. Tennakoon, A. Simmons, T. Sharma Section of Cognitive Psychopharmacology, Department of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF The hippocampal region is implicated prominently in the pathophysiology of schizophrenia. Hippocampal N-acetylaspartate (NAA) signal intensity has been shown to be reduced in schizophrenia suggesting neuronal damage or malfunction. It is suggested that 1H-MRS findings are unrelated to medication status although few studies have specifically examined medication effects with MRS. A PRESS pulse sequence yielded clearly resolved NAA, choline and creatine/phosphocreatine (CRE) peaks in a 6 cm3 volume of the hippocampus in 25 first episode patients, 10 of whom were neurolepticnaı¨ve and 14 healthy controls. Subjects were matched for gender, age, ethnicity, handedness and parental socio-economic status. Data were analysed using the LC-model method of Provencher. Results were expressed in terms of metabolite peak area ratios. The neuroleptic-naı¨ve group showed a significant reduction of NAA/ CRE (F 8.597, p ⬍ 0.002) in the hippocampus compared to controls. No differences were found in the medicated group or in the combined patient group. No group differences were noted for choline. The two patient groups did not differ in symptomatology or age of onset. Neither duration of illness nor length of treatment was correlated with NAA levels.