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Cognitive development in schizophrenia: Some heuristic offerings from the study of abnormal cognitive development in epilepsy
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the left hippocampus (p<0,008). Both the non-psychotic epileptics ( p < 0.0001 left, and p < 0.001 right) and the psychotic epileptics (p<0.0001 left and p<0.0001 right) showed a significant reduction in NAA. The reduction in left NAA was progressively greater going from controls (8.00 mM ), to schizophrenics (6.40 mM ), to non-psychotic epileptics (5.53 mM ) to psychotic epileptics 14.54 mM ). In the right hippocampus there was no difference between controls (7.34mM) and schizophrenics (7.59 raM), whereas non-psychotic epileptics (4.93 mM) and psychotic epileptics (4.65 mM ) showed similar significant reductions. The asymmetry in hippocampal NAA seen in schizophrenics was not evident in the psychotic epileptic group. The volume of the hippocampal/amygdala complex in the four groups showed no significant differences.
COGN ITIVE DEVELOPMENT IN SCHIZOPHRENIA: SOME HEURISTIC OFFERINGS FROM THE STUDY OF ABNORMAL COGNITIVE DEVELOPMENT IN E P I L E P S Y D.J. Done ~, S.J. Leask 2, P. Harvey 3, E. Ross a, P. T o o k e y , T.J. Crow"
t D~Tt P~vcholoKv, University O[ Her([brdshire, Ha([ield, Hefts ALIO 9AB, UK: 2(bTiversity q[O.x/brd, UK: 3Motmt Sinai Ho.witctl. New York, 4King's College School ~[ Medicine, London, UK," Shlst. ('hild Health, Lomhm, UK Neuropsychological studies of epilepsy have offered- many useful heuristics for research in schizophrenia. Here we examine cases of well diagnosed epilepsy in a national UK birth cohort (NCDS). These cases had age of onset of fits which varied from immediately after birth through to onset in their twenties. Psychometric tests of cognitive abilities (NB reading comprehension and maths) and social behaviour were recorded for all cohort members at the ages of 7, 1I and, for cognitive abilities only at age 16. We report that cases with cognitive impairments have developed these impairments before the onset on first fit and that onset itself has no detrimental effect. In contradistinction social behaviour is unimpaired before onset of fits but, in most cases, shows some decline as a result of the onset. Longer term cognitive decline is found in some (i.e. early onset) but not all cases, and degree of cognitive impairment is also affected by age of onset. By drawing a parallel between onset of fits in epilepsy and onset of psychotic symptoms in schizophrenia important questions are raised about the development of cognitive impairments in schizophrenia.
SCHIZOPHRENIA AND EPILEPSY; ALTERNATIVE RESPONSES TO BRAIN INJURY OR MALDEVELOPMENT J.R. Stevens. D. Denney
Oregon Health Sciem'es Univer.~ity, Portland, OR 97201, USA Epilepsy is a disorder characterized by episodic excessive neuronal excitatory activity leading to clinical seizures. Modern
treatment of epilepsy is directed toward decreasing neuronal excitability or enhancing inhibition. In contrast, many symptoms of schizophrenia are simulated by agents that block excitation or enhance inhibitory (e.g., monoamine) neurotransmission and treatment of schizophrenia is directed toward blocking one or more of these inhibitory networks. These facts suggest that both epilepsy and schizophrenia represent alternative "final common paths' in which excessive excitation or inhibition predominate, disturbing the homeostatic equilibrium necessary for normal brain function. Clozapine. the most proconvulsant of the antipsychotics in current use. is also one of the most effective agents against 'negative' symptoms of schizophrenia. We have shown that clozapine produces dose dependent myoclonus in rats and that myoclonus can be kindled with repeated very small weekly submyoclonic doses of the drug. Kindled myoclonus is associated with excitation of deep subcortical structures important for arousal. Trial of very small repeated ~kindling' doses of dozapine in patients with schizophrenia has not caused myoclonus, seizures or other side effects and may be associated with clinical improvement in some cases. Just as different agents optimally relieve the excessive neuronal excitation and synchrony expressed in specific types of epilepsy, the variable therapeutic efficacy of clozapine and other antipsychotics may depend on the capacity of these agents to relieve localized excessive inhibition mediated by monoamine systems or glutamate antagonism and that are differentially expressed by different individuals.
A NEUROPSYCHOLOGICAL COMPARISON OF SCHIZOPHRENIA AND THE SCHIZOPHRENIA-LIKE
PSYCHOSES
OF
EPILEPSY J.D.C. Mellers, B.K. Toone, W.A. Lishman
hTstitute q[' P~ychiatrv. De Crespigny Park, London SE5 8A F. UK Aim. The schizophrenia-like psychoses of epilepsy (SLPE) might represent a secondary form of schizophrenia in which the pathology is relatively confined to the temporal lobe. To test this possibility we have compared the neuropsychological profile of schizophrenia and SLPE. Our main hypothesis was that both psychotic groups would show deficits of temporal lobe function but that prefrontal impairment, as measured by tests of executive function, would be found only in the primary schizophrenic group. Subjects. Four groups were studied: 1) Patients wilh SLPE (77=25); 2) Patients with epilepsy but no psychiatric history (77=24): 3) Patients with schizophrenia (H~22t: 4t healthy volunteers ( n - 2 4 ) . Mefllods." Neuropsychological testing comprised measures of premorbid IQ, current verbal and performance IQ, information processing, digit span, motor speed, verbal and visual learning and memory, verbal fluency, the Wisconsin Card Sorting Task, the Stroop test and the trail making task. Results: Patients with schizophrenia and those with SLPE
the left hippocampus (p<0,008). Both the non-psychotic epileptics ( p < 0.0001 left, and p < 0.001 right) and the psychotic epileptics (p<0.0001 left and p<0.0001 right) showed a significant reduction in NAA. The reduction in left NAA was progressively greater going from controls (8.00 mM ), to schizophrenics (6.40 mM ), to non-psychotic epileptics (5.53 mM ) to psychotic epileptics 14.54 mM ). In the right hippocampus there was no difference between controls (7.34mM) and schizophrenics (7.59 raM), whereas non-psychotic epileptics (4.93 mM) and psychotic epileptics (4.65 mM ) showed similar significant reductions. The asymmetry in hippocampal NAA seen in schizophrenics was not evident in the psychotic epileptic group. The volume of the hippocampal/amygdala complex in the four groups showed no significant differences.
COGN ITIVE DEVELOPMENT IN SCHIZOPHRENIA: SOME HEURISTIC OFFERINGS FROM THE STUDY OF ABNORMAL COGNITIVE DEVELOPMENT IN E P I L E P S Y D.J. Done ~, S.J. Leask 2, P. Harvey 3, E. Ross a, P. T o o k e y , T.J. Crow"
t D~Tt P~vcholoKv, University O[ Her([brdshire, Ha([ield, Hefts ALIO 9AB, UK: 2(bTiversity q[O.x/brd, UK: 3Motmt Sinai Ho.witctl. New York, 4King's College School ~[ Medicine, London, UK," Shlst. ('hild Health, Lomhm, UK Neuropsychological studies of epilepsy have offered- many useful heuristics for research in schizophrenia. Here we examine cases of well diagnosed epilepsy in a national UK birth cohort (NCDS). These cases had age of onset of fits which varied from immediately after birth through to onset in their twenties. Psychometric tests of cognitive abilities (NB reading comprehension and maths) and social behaviour were recorded for all cohort members at the ages of 7, 1I and, for cognitive abilities only at age 16. We report that cases with cognitive impairments have developed these impairments before the onset on first fit and that onset itself has no detrimental effect. In contradistinction social behaviour is unimpaired before onset of fits but, in most cases, shows some decline as a result of the onset. Longer term cognitive decline is found in some (i.e. early onset) but not all cases, and degree of cognitive impairment is also affected by age of onset. By drawing a parallel between onset of fits in epilepsy and onset of psychotic symptoms in schizophrenia important questions are raised about the development of cognitive impairments in schizophrenia.
SCHIZOPHRENIA AND EPILEPSY; ALTERNATIVE RESPONSES TO BRAIN INJURY OR MALDEVELOPMENT J.R. Stevens. D. Denney
Oregon Health Sciem'es Univer.~ity, Portland, OR 97201, USA Epilepsy is a disorder characterized by episodic excessive neuronal excitatory activity leading to clinical seizures. Modern
treatment of epilepsy is directed toward decreasing neuronal excitability or enhancing inhibition. In contrast, many symptoms of schizophrenia are simulated by agents that block excitation or enhance inhibitory (e.g., monoamine) neurotransmission and treatment of schizophrenia is directed toward blocking one or more of these inhibitory networks. These facts suggest that both epilepsy and schizophrenia represent alternative "final common paths' in which excessive excitation or inhibition predominate, disturbing the homeostatic equilibrium necessary for normal brain function. Clozapine. the most proconvulsant of the antipsychotics in current use. is also one of the most effective agents against 'negative' symptoms of schizophrenia. We have shown that clozapine produces dose dependent myoclonus in rats and that myoclonus can be kindled with repeated very small weekly submyoclonic doses of the drug. Kindled myoclonus is associated with excitation of deep subcortical structures important for arousal. Trial of very small repeated ~kindling' doses of dozapine in patients with schizophrenia has not caused myoclonus, seizures or other side effects and may be associated with clinical improvement in some cases. Just as different agents optimally relieve the excessive neuronal excitation and synchrony expressed in specific types of epilepsy, the variable therapeutic efficacy of clozapine and other antipsychotics may depend on the capacity of these agents to relieve localized excessive inhibition mediated by monoamine systems or glutamate antagonism and that are differentially expressed by different individuals.
A NEUROPSYCHOLOGICAL COMPARISON OF SCHIZOPHRENIA AND THE SCHIZOPHRENIA-LIKE
PSYCHOSES
OF
EPILEPSY J.D.C. Mellers, B.K. Toone, W.A. Lishman
hTstitute q[' P~ychiatrv. De Crespigny Park, London SE5 8A F. UK Aim. The schizophrenia-like psychoses of epilepsy (SLPE) might represent a secondary form of schizophrenia in which the pathology is relatively confined to the temporal lobe. To test this possibility we have compared the neuropsychological profile of schizophrenia and SLPE. Our main hypothesis was that both psychotic groups would show deficits of temporal lobe function but that prefrontal impairment, as measured by tests of executive function, would be found only in the primary schizophrenic group. Subjects. Four groups were studied: 1) Patients wilh SLPE (77=25); 2) Patients with epilepsy but no psychiatric history (77=24): 3) Patients with schizophrenia (H~22t: 4t healthy volunteers ( n - 2 4 ) . Mefllods." Neuropsychological testing comprised measures of premorbid IQ, current verbal and performance IQ, information processing, digit span, motor speed, verbal and visual learning and memory, verbal fluency, the Wisconsin Card Sorting Task, the Stroop test and the trail making task. Results: Patients with schizophrenia and those with SLPE