RESUMO
OBJECTIVE: The deficit syndrome is a subtype of schizophrenia characterized by primary and enduring negative features of psychopathology. It appears to reflect a distinct subtype within the syndrome of schizophrenia. Little is known about the familial or genetic aspects of the deficit syndrome. The purpose of this study was to determine whether deficit versus nondeficit subtypes are correlated in sibling pairs affected with schizophrenia. METHOD: The present study was based on the Irish Study of High-Density Schizophrenia Families. From the earlier study the authors selected a subset of patients who were members of sibling pairs in which both siblings had been diagnosed with "core" schizophrenia, which included schizophrenia, simple schizophrenia, and schizoaffective disorder with poor outcome. The Schedule for the Deficit Syndrome was used to make deficit versus nondeficit diagnoses, which were based on chart examinations by reviewers blind to sibling status. This method resulted in 65 patients being diagnosed with the deficit syndrome and 401 patients diagnosed as nondeficit (prevalence=13.9%). This group included 347 full sibling pairs, which were analyzed for resemblance with respect to deficit versus nondeficit subtype by means of logistic regression. RESULTS: Deficit versus nondeficit subtypes were significantly correlated in sibling pairs concordant for core schizophrenia. CONCLUSIONS: Familial factors contribute significantly to whether a person has the deficit subtype of schizophrenia. This familial contribution could be genetic or environmental.
Assuntos
Família , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Psicologia do Esquizofrênico , Adulto , Feminino , Humanos , Irlanda/epidemiologia , Modelos Logísticos , Masculino , Fenótipo , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/genética , Análise de Regressão , Esquizofrenia/diagnósticoRESUMO
Phencyclidine (PCP) produces psychotomimetic effects in humans that resemble schizophrenia symptoms. In an effort to screen compounds for antipsychotic activity, preclinical researchers have investigated whether these compounds block PCP-induced behaviors in animals. In the present study, the atypical antipsychotic clozapine was tested in combination with an active dose of PCP in two-lever drug discrimination and mixed signalled-unsignalled differential-reinforcement-of-low-rates (DRL) procedures. PCP produced distinctive effects in each task: it substituted for the training dose in PCP discrimination and it increased the number of responses with short (<3 s) interresponse times as well as increasing overall response rates in the DRL schedule. Acute dosing with clozapine failed to alter the behavioral effects of PCP in either procedure even when tested up to doses that produced pharmacological effects alone. These results suggest that acute dosing with clozapine would not affect behaviors most closely associated with PCP intoxication. Further, they bring into question the utility of using PCP combination procedures in animals to screen for antipsychotic potential. Since chronic dosing is required for therapeutic efficacy of antipsychotics, future studies should focus on investigation of chronic dosing effects of these drugs in combination with PCP.
Assuntos
Antipsicóticos/farmacologia , Clozapina/farmacologia , Condicionamento Operante/efeitos dos fármacos , Aprendizagem por Discriminação/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios , Fenciclidina , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Inibição Psicológica , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
N-Methyl-D-aspartate (NMDA) antagonists and gamma-aminobutyric acid agonists share a number of common pharmacological properties, including motor and anticonvulsant effects. In the present study, site-selective NMDA antagonists were evaluated for potential anxiolytic efficacy and motor impairment in a modified Geller-Seifter conflict procedure, an animal model widely used to screen drugs for anxiolytic effects. Male Sprague-Dawley rats were trained to respond for food reward under a multiple FI 30 s (food only), FR 10 (food + shock) operant schedule. Consistent with the results of previous studies, the benzodiazepines chlordiazepoxide and diazepam selectively increased punished responding and increased response durations at higher doses. The competitive NMDA antagonist CGP 37,849 increased punished responding at some doses, though not selectively, and also increased response duration in both schedule components. The glycine-site modulators milacemide, ACEA 1011 and ACEA 1021, the NR2B-selective polyamine site antagonist eliprodil and NMDA did not produce anticonflict effects at any dose and had inconsistent effects on response durations. These results suggest that the anticonflict effects of NMDA antagonists are not as reliable as those of the benzodiazepines. Further research is needed to clarify the experimental conditions under which the anxiolytic potential of NMDA antagonists is most evident.
Assuntos
2-Amino-5-fosfonovalerato/análogos & derivados , Ansiolíticos/farmacologia , Clordiazepóxido/farmacologia , Condicionamento Operante/fisiologia , Conflito Psicológico , Diazepam/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Transmissão Sináptica/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , Acetamidas/farmacologia , Animais , Condicionamento Operante/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletrochoque , Masculino , Quinoxalinas/farmacologia , Ratos , Ratos Sprague-Dawley , RecompensaRESUMO
OBJECTIVE: To examine the relationship between smooth pursuit eye movements and tardive dyskinesia (TD) in schizophrenia. METHODS: Forty schizophrenic patients with TD and 25 non-TD patients had smooth pursuit eye movements tested with infrared oculography. In addition to the diagnosis of TD (present or absent), each patient had ratings of severity of TD. RESULTS: There was no significant or strong association between TD and poor smooth pursuit eye movements. CONCLUSION: The results stand in contrast to those of several previous studies, which were based on limited methodology. However, this study was not able to exclude definitively the possibility that TD is associated with poor smooth pursuit, perhaps with a small to moderate effect. Furthermore, these conclusions are limited to simple eye tracking protocols in which distractions are minimized. The question of whether or not TD is associated with poor smooth pursuit in schizophrenia needs to be resurrected.
Assuntos
Antipsicóticos/efeitos adversos , Discinesia Induzida por Medicamentos/fisiopatologia , Acompanhamento Ocular Uniforme/fisiologia , Esquizofrenia , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Movimentos Sacádicos/fisiologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
The present study examined sensorimotor reactivity in rats following traumatic brain injury (TBI). Moderate injury was induced with midline fluid percussion in some of the rats. Others received identical surgery, but were not injured (sham-injured rats), or received neither surgery nor injury (naive rats). All rats were evaluated in acoustic and/or tactile startle procedures. At 8 days post-injury, the sensorimotor reactivity of TBI rats to acoustic stimuli was severely reduced compared to that of sham-injured rats. This TBI-induced deficit was enduring (> 30 days). In a separate experiment, greater sensorimotor reactivity was observed with tactile (vs. acoustic) stimulation in both TBI and naive rats although startle amplitudes for the TBI rats were lower than control levels for both types of stimuli. These results suggest that sensorimotor reactivity is altered by TBI and that the startle procedure is a promising method for investigation of information processing alterations following TBI.
Assuntos
Comportamento Animal/fisiologia , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/psicologia , Reflexo de Sobressalto/fisiologia , Estimulação Acústica , Animais , Masculino , Estimulação Física , Ratos , Ratos Sprague-DawleyRESUMO
The effects of phencyclidine (PCP) and NPC 12626 on punished responding were examined using a modified Geller-Seifter procedure in rats. Both drugs are known to antagonize N-methyl-D-aspartate (NMDA) receptor mediated neurotransmission, albeit at different sites on the NMDA receptor complex. Rats were trained to lever press for food reinforcement under a multiple schedule, with responding in one component reinforced under a fixed-interval 60-sec schedule, while each response in the other component resulted in both food and brief electric shock. Both PCP and NPC 12626 produced selective increases in punished responding, although the effects were not as large as those produced by chlordiazepoxide. Repeated daily administration of each of these drugs for 6 days resulted in increases in punished responding during different portions of the treatment. A 5 mg/kg dose of chlordiazepoxide produced increases over the last 2 days of administration. PCP (2 mg/kg) produced an increase only during the second session, whereas NPC 12626 (30 mg/kg) produced increases for all but the first and fifth days of the 6-day regimen. Both competitive and noncompetitive NMDA antagonists can have antipunishment effects in this model.
Assuntos
Aminoácidos/farmacologia , Ansiolíticos/farmacologia , Fenciclidina/farmacologia , Punição , Animais , Clordiazepóxido/farmacologia , Condicionamento Operante , Masculino , Ratos , Ratos Endogâmicos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
In Experiment 1, the benzodiazepine chlordiazepoxide (CDP), two typical antipsychotics, haloperidol (HAL) and chlorpromazine (CPZ), and the atypical antipsychotic clozapine (CLZ) were evaluated for antipunishment effects in rats in a modified Geller-Seifter conflict procedure [MULT fixed interval (FI) 60-s, fixed ratio (FR) 1 (food + shock)]. In Experiment 2, CDP and thioridazine (THD) were similarly tested. CLZ (2.5 and 5.0 mg/kg), but not HAL, CPZ, or THD, selectively increased punished responding, although the magnitude of effect was smaller than that observed for CDP. Possible serotonergic mechanisms for CLZ's action in this model and the possible importance of serotonergic activity for the development of other atypical antipsychotic drugs are discussed.
Assuntos
Antipsicóticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Punição/psicologia , Animais , Antipsicóticos/química , Antipsicóticos/metabolismo , Clordiazepóxido/farmacologia , Clorpromazina/farmacologia , Clozapina/farmacologia , Conflito Psicológico , Avaliação Pré-Clínica de Medicamentos , Haloperidol/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Relação Estrutura-Atividade , Tioridazina/farmacologiaRESUMO
Previous research has shown that the differential development of tolerance to the disruption of operant responding produced by repeated dosing with pimozide (PMZ) or clozapine (CLZ) can distinguish these two drugs. In the present study, the effects of PMZ (1 mg/kg) and CLZ (10 mg/kg) on response rate and response duration in rats lever pressing for food reward under a fixed-ratio 30 (FR-30) operant schedule were examined. PMZ suppressed response rates across all 10 days of drug dosing; CLZ produced an initial response rate decrease, with partial recovery (50%) occurring within the 10 day period. Similarly, PMZ produced an increase in response duration that persisted into the postdrug vehicle-injection period, while CLZ did not significantly change response duration. The prolonged suppression of FR responding produced by PMZ is similar to the lack of tolerance to this drug in other types of operant schedules. In contrast, CLZ's effects on response rate are schedule dependent. These results suggest that changes in response duration with repeated dosing may more reliably differentiate typical and atypical neuroleptics than do changes in response rate under FR schedules.
Assuntos
Clozapina/farmacologia , Condicionamento Operante/efeitos dos fármacos , Pimozida/farmacologia , Animais , Clozapina/administração & dosagem , Tolerância a Medicamentos , Masculino , Pimozida/administração & dosagem , Ratos , Ratos Sprague-Dawley , Esquema de ReforçoRESUMO
Impulsive behavior may represent, in part, a failure of behavioral inhibition (the ability to delay or inhibit a response). In this study, use of a multiple signaled-unsignaled differential-reinforcement-of-low-rates (DRL) 15-s schedule allowed examination of drug effects in conditions in which level of stimulus control differed. Results showed that whereas diazepam increased premature responding during signaled and unsignaled DRL components, amphetamine and delta9-tetrahydrocannabinol increased premature responding primarily during unsignaled components when timing was necessary for efficient performance on the task. In contrast, pimozide and desipramine increased long-delay responses across both components, resulting in longer mean interresponse times. Collectively, these results suggest that the use of different levels of stimulus control may aid in separation of drug effects on timing and other behavioral processes, including behavioral inhibition.