PubMed Health⌕ Search

Biomedical subjects

S B Schwarzkopf

Publications and source records attributed to S B Schwarzkopf.

At least 19 recordsLinked to original sources
PubMed2001

The mentally ill in jails and prisons: towards an integrated model of prevention.

Jails and prisons have become a final destination for persons with severe mental illness in America. Addiction, homelessness, and fragmentation of services have contributed to the problem, and have underscored the need for new models of service delivery. Project Link is a university-led consortium of five community agencies in Monroe County, New York that spans healthcare, social service and criminal justice systems. The program features a mobile treatment team with a forensic psychiatrist, a dual diagnosis treatment residence, and culturally competent staff. This paper discusses the importance of service integration in preventing jail and hospital recidivism, and describes steps that Project Link has taken towards integrating healthcare, criminal justice, and social services. Results from a preliminary evaluation suggest that Project Link may be effective in reducing recidivism and in improving community adjustment among severely mentally ill patients with histories of arrest and incarceration.

Adult↗
PubMed1997

Facilitation and inhibition of the acoustic startle reflex in the rat after a momentary increase in background noise level.

Small increments in background noise were shown to increase the amplitude of a subsequently elicited acoustic startle reflex (ASR) in rats by as much as 100% under optimal conditions. Increment lead time (5-160 ms) and level (1.5-15 dB), initial noise level (30-70 dB), startle level (95-125 dB), number of test days (1-5), and drug condition (diazepam or saline ip) were varied in 6 experiments. Prepulse facilitation (PPF), measured by difference scores, was greatest for intermediate increments (3 dB) and lead times (20-40 ms) and was replaced by prepulse inhibition (PPI) for higher values, especially in the later test days. Diazepam reduced baseline ASR and diminished PPI, but it did not affect PPF. These data argue against hypotheses that attribute PPF of this sort to either temporal integration within the ASR pathways or to the elicitation of a nonspecific arousal reaction by the prepulse.

Acoustic Stimulation↗
PubMed1996

Effects of the PCP analog dizocilpine on sensory gating: potential relevance to clinical subtypes of schizophrenia.

Prepulse inhibition (PPI) of the acoustic startle reflex, a measure of sensory gating, is reduced in schizophrenic patients. Dopamine agonists and NMDA receptor antagonists such as phencyclidine (PCP) can disrupt PPI in animals, consistent with both the dopamine and glutamate hypotheses of schizophrenia. In this study, we sought to further characterize the effects of the NMDA antagonist dizocilpine on acoustic startle modulation. Fischer 344 rats were tested after one of three doses of dizocilpine (0.05, 0.2, and 0.5 mg/kg) and assessed for PPI as well as for alterations in baseline startle and prepulse facilitation (PPF). Results showed complete disruption of PPI for each inhibitory trial type after 0.2 and 0.5 mg/kg of dizocilpine. Baseline startle and PPF were enhanced by the low dose but decreased with the moderate and high doses of dizocilpine. Although dizocilpine caused alterations in prepulse modulation of startle similar to dopamine agonists, some effects differ. Unique effects of dizocilpine on sensory gating are discussed in terms of their potential for discriminating subtypes of schizophrenic illness with different underlying pathophysiology.

Animals↗
PubMed1996

Effects of haloperidol and SCH 23390 on acoustic startle in animals depleted of dopamine as neonates: implications for neuropsychiatric syndromes.

Animals depleted of dopamine (DA) in the neonatal period and tested in adulthood exhibit some similarities to patients with schizophrenia, including increased sensitivity to DA agonists, altered sensitivity to DA receptor antagonists, and abnormalities of the acoustic startle response (ASR). In this study, we examined the contributions of D1-like and D2-like DA receptors to ASR measures in animals depleted of DA as neonates. Male rat pups received intracerebroventricular injections of 6-hydroxydopamine (DA depleted) or its vehicle (controls) at 3 days of age. Animals underwent startle testing as adults (60-75 days of age) after administration of DA antagonists (haloperidol: 0.1 or 0.3 mg/kg, SCH 23390:0.01 or 0.05 mg/kg) with and without DA agonist administration (apomorphine 0.5 mg/kg). ASR amplitude and prepulse inhibition (PPI: percentage decrease in startle amplitude due to a low intensity prepulse) were measured. DA depleted animals showed increased ASR amplitude and reduced PPI compared to controls. Administration of D1-like or D2-like DA antagonists significantly reduced overall ASR and increased PPI in both control and DA depleted animals, with DA depleted animals showing a relatively greater sensitivity to the D1-like antagonist SCH 23390. Findings are discussed in terms of the role of residual DA in mediating ASR phenomena in depleted animals, differences between D1/D2 DA receptor mediation of ASR compared to other behaviors in DA depleted animals, and potential implications for neuropsychiatric syndromes such as schizophrenia.

Animals↗
PubMed1996

Stimulus configuration and context effects in perceptual organization in schizophrenia.

Two studies assessed perceptual organization in schizophrenia to determine (a) whether inpatient and outpatient groups with poor premorbid schizophrenia have comparable levels of perceptual organization deficit; and (b) whether the deficit could be eliminated by task manipulations. In Study 1, inpatients demonstrated clear evidence of a perceptual organization deficit, whereas outpatients performed similarly to the control groups. In Study 2, a performance pattern that operationally defined a perceptual organization deficit was eliminated by a task manipulation thought to aid in context processing. The perceptual organization deficit is most pronounced in actively symptomatic patients with poor premorbid schizophrenia, and the deficit reflects, in part, deficient top-down influences to basic perceptual processes.

Adult↗
PubMed1995

Effects of single and repeated exposure to apomorphine on the acoustic startle reflex and its inhibition by a visual prepulse.

The acoustic startle reflex (ASR) is inhibited by startle-irrelevant stimuli that briefly precede reflex elicitation. This effect, prepulse inhibition (PPI), is reduced in strength for animals that have received dopamine agonists, such as apomorphine (APO). Reduction in PPI is most evident for weak masked noise prepulses, thus suggesting that APO disrupts the reception of stimuli to the extent that they present a low signal-to-noise ratio. Here we examine the effect of APO on PPI produced by non-masked visual prepulses. Light flashes were given at two intensities, 40, 70, 110, or 220 ms before ASR elicitation. In phase 1 (5 weeks in duration) half of the animals received one weekly injection of APO (0.5 mg/kg, IP) and one of vehicle (VEH), while the other half received two injections of VEH. Within these groups, half were tested 30 min after the injections, the other half kept test naive (four groups total). In phase 2, following a 4-week rest, all groups were tested after a low dose of APO (0.1 mg/kg) and VEH, 1 week apart. APO eliminated PPI for a dim flash and reduced PPI for a brighter flash to a level normally obtained with the dim flash, while increasing both ASR control values and activity. The bright light was maximally effective at a lead time of 70 ms and APO did not alter this value. Because in general the time of maximal inhibition varies with prepulse intensity for visual stimuli, the finding that the time of the peak remained constant reveals that APO has its effect on inhibition rather than on effective stimulus intensity. In phase 2, APO reduced PPI with no sign of sensitization from past drug exposure. However, APO increased the ASR only in groups previously exposed to APO, indicating behavioral sensitization. The differential effects of repeated exposure on these response measures suggest that neural substrates for the several behavioral effects of APO function at least in part independently.

Animals↗
PubMed1995

Filgrastim treatment of three patients with clozapine-induced agranulocytosis.

BACKGROUND: Agranulocytosis is the most serious side effect of clozapine therapy, occurring in approximately 1% of all treated patients. Despite careful blood monitoring, a significant number of cases of agranulocytosis and resulting fatalities have occurred. Strategies are needed to manage clozapine-induced agranulocytosis more safely. METHOD: This report describes the management of three state hospital inpatients who developed clozapine-induced agranulocytosis. All patients were diagnosed as having chronic paranoid schizophrenia according to DSM-III-R criteria and had previously failed to respond to treatment with standard antipsychotic medications. After onset of agranulocytosis, all patients were transferred to a medical service in a university hospital and treated with recombinant granulocyte colony-stimulating factor (filgrastim). RESULTS: White blood count and absolute neutrophil count returned to within normal limits in each patient after 5 to 8 days of treatment with filgrastim 300 micrograms/day subcutaneously. No side effects were observed during filgrastim treatment. CONCLUSION: Treatment with filgrastim appears to be safe and effective in decreasing the duration of clozapine-induced agranulocytosis. While further studies are necessary to establish the safety and effectiveness of this treatment, filgrastim should presently be considered a treatment of choice for clozapine-induced agranulocytosis.

Adult↗
PubMed1994

Alterations in behavioral responses to stressors following excitotoxin lesions of dorsomedial hypothalamic regions.

The dorsomedial hypothalamus is important for regulation of cardiovascular responses associated with emotional arousal. This region has also been identified as a component of neural circuitry involved in fear/anxiety, yet clear evidence as to the effects of lesioning on stress-related behaviors is missing. In this study, we lesioned the dorsomedial hypothalamic region with the neurotoxin, ibotenic acid (IBO; 2.0 micrograms in 0.2 microliter), and studied the impact on spontaneous and unlearned behavioral responses to stressors. In the open field test, we observed non-generalized increases in motility parameters in the IBO rats with the differences occurring in the latter two-thirds of the test. In the elevated plus-maze, the IBO rats displayed a classic anxiolytic response with a greater proportion of entries into (and greater time spent in) the open arms of the maze. In the environment-specific social interaction (SI) test, the IBO rats showed a normal familiar/unfamiliar environment discrimination with respect to Total SI; however, the composition of the behaviors ('curiosity' vs. physical contact) by the IBO rats was markedly altered, with there being a 2-fold increase in non-violent physical interactions. Additionally, the differences in these traditional indices of anxiety were associated with lesioned animals exhibiting greater acoustic startle responsiveness than controls as a function of prepulse intensity. Overall, the results following IBO lesions indicate an altered responsiveness to sudden stressors, particularly as relates to novelty or exploration-oriented behaviors. The hypothalamic lesion may, therefore, have resulted in a disinhibition of normally suppressed responding to innate fear or challenging stimuli. This study contributes to those that have begun to define neural interactions that are essential for integrated stress responses.

Acoustic Stimulation↗
PubMed1994

Reliability of P50 auditory event-related potential indices of sensory gating.

We examined the reliability of three traditional P50 auditory event-related potential indices under paired-click conditions: (a) the conditioning response (C), (b) the testing response (T), and (c) the testing to conditioning suppression ratio (T/C). Three alternative indices, (a) the (C - T) difference, (b) the (C - T)/(C + T) adjusted difference, and (c) the (T - T') residualized difference, where T' is the regression of T on C, were also studied. The N100 wave was used as a generalizability check. Although C and T amplitudes were reliably measured by traditional means, the T/C suppression ratio was not. For psychometric reasons that are described, the reliability of the suppression ratio is undermined principally by the correlation between C and T. The C - T difference score is a promising alternative to the unreliable T/C suppression ratio. Theoretical consequences of changed metrics are discussed.

Acoustic Stimulation↗
PubMed1993

Effects of haloperidol and SCH 23390 on acoustic startle and prepulse inhibition under basal and stimulated conditions.

1. Adult Sprague-Dawley rats underwent startle testing for assessment of baseline startle amplitude and prepulse inhibition (PPI) of the startle reflex. 2. Animals were tested after administration of either: saline, a selective D1 dopamine (DA) receptor antagonist, a relatively selective D2 DA antagonist, or combined low dose D1 and D2 antagonists. 3. Changes due to antagonists were assessed with and without administration of the D1/D2 agonist apomorphine. 4. Testing without apomorphine stimulation showed that both D1 and D2 antagonists reduce baseline startle and enhance PPI. Further, the two antagonists exhibited a synergistic interaction. 5. Testing with apomorphine showed that D1 and D2 antagonists reduce apomorphine-induced startle enhancement. Again, the two exhibited a synergistic interaction. 6. For PPI, the D2 but not D1 antagonist reduced the apomorphine effect. However, the D1 antagonist potentiated the effect of the D2 antagonist.

Acoustic Stimulation↗
PubMed1993

Within-session changes in sensory gating assessed by P50 evoked potentials in normal subjects.

1. The authors studied within-session changes in P50 suppression occurring in a group of 28 normal subjects. 2. A conditioning-testing paradigm was used with 120 pairs of 110 Db peak intensity clicks. Clicks were of 0.04 msec duration, 500 msec separation and delivered through headphones at 10 second intervals. 3. Mean P50 suppression ranged from 60.5% during the first 30 click pairs to -19.1% during the last 30 pairs, with an overall mean suppression of 25.4%. 4. The authors concluded that P50 suppression is a dynamic process in normal subjects, and that further work is necessary to elucidate the factors affecting P50 suppression.

Acoustic Stimulation↗
PubMed1993

Cavum septum pellucidum in schizophrenia, affective disorder and healthy controls: a magnetic resonance imaging study.

Many structural brain abnormalities have been described in schizophrenia, consistent with a neurodevelopmental model for this disease. We report here a study of the cavum septum pellucidum (CSP) in schizophrenia compared to control groups, as well as the clinical correlates of this congenital anomaly in schizophrenia. We conducted a magnetic resonance imaging (MRI) study to compare rates of CSP in schizophrenia (N = 67) v. psychiatric controls (bipolar and schizoaffective, N = 60) and healthy controls (N = 37). Of the controls 18.9%, and of all psychotic subjects 18.1% had a CSP of any size and there was no difference in the frequency of large CSP among the groups. Males had higher rates of CSP than females (25% v. 9.7%, P = 0.01) in all groups. Schizophrenics had higher CSP rates than affective patients (25%, v. 10%, P = 0.02). No clinical difference was found between schizophrenics with or without CSP.

Adolescent↗
PubMed1993

Are controls in schizophrenia research "normal"?

The psychiatric assessment by structured interview and family history of mental disorder in normal volunteers recruited by advertisement for a study of brain structure and function in psychosis is described. Nine of 51 volunteers (17.6%) who passed a phone screen were excluded after a structured interview for major psychopathology. Of 35 completers, 10 (28.6%) had subthreshold mood or substance use but were included in the study. Only 16 subjects (45%) had a negative family history by FH-RDC. Diagnoses in family members included substance abuse (31%), mood disorder (11%), psychosis (9%), and other/undiagnosed (14%). Ventricular enlargement was evaluated by magnetic resonance imaging in two planes. Ventricular size was bimodally distributed in the males, and the group with larger ventricles was more educated and had higher scores on the 8 (Schizophrenia) scale of the MMPI (F = 5.44, p = .0099). Our results suggest that 'normal' volunteers for psychiatric research have personal or family psychopathology which motivates them to participate. As the sensitivity of biological instrumentation increases, the characteristics of the control group must be anticipated in the design and recruitment.

Adult↗
PubMed1993

Clinical correlates of valproate augmentation in refractory bipolar disorder.

We examined the clinical correlates of valproate (VPA) therapy in refractory bipolar disorder. Retrospective chart review was used to collect demographic and clinical data including present diagnosis, diagnosis at illness onset, duration of illness, number of hospitalizations, VPA dose, side effects, and maximum serum concentration. Global response was rated once patients serum VPA exceeded 50 mg/dL. The charts of all inpatients admitted over a two-year period and treated with VPA for acute episodes of bipolar disorder in manic, mixed, or depressed phase were reviewed. Seventeen of these patients began VPA augmentation while hospitalized and became the cohort for review. Patients were excluded if VPA was started prior to admission or the patient was discharged less than one week after drug initiation. Patients were not excluded on the basis of EEG, CT, or neurological exam findings. Overall, 12 of 17 (71%) of the patients showed a moderate or marked improvement while 5 of 17 (29%) showed mild or no response. Responders were older and had a longer duration of illness with an increased number of hospitalizations. There was a strong trend for responders to achieve a higher serum VPA level. A significant positive correlation was found between response in acute mania and psychotic symptoms at first episode of illness.

Adult↗
PubMed1992

Third-ventricle enlargement and neuropsychological deficit in schizophrenia.

Cerebral ventricular enlargement is present in a substantial subgroup of schizophrenic patients. Most, but not all studies examining neuropsychological performance and ventricular size in schizophrenics show more severe cognitive impairment in those patients with greatest ventricular enlargement. Inconsistencies in this literature have been attributed to different neuroimaging techniques, variation in patient characteristics across studies, and the variety of neuropsychological batteries used. In the present study, schizophrenic patients (n = 49 men, n = 23 women) and normal controls (n = 13 men, n = 18 women) underwent magnetic resonance (MR) imaging of the brain and extensive neuropsychological testing including measures of frontal and temporal lobe function. A complete coronal set of MR images was used to calculate volumetric estimates of lateral and third cerebral ventricles. Highly significant associations were found between cognitive deficits and third-ventricle volume, with measures of frontal functioning, attention, and concentration showing the most robust correlations. In contrast, neuropsychological performance was not highly associated with lateral ventricular size. These findings further support the pathophysiological relevance of ventricular enlargement in schizophrenia. More specifically, third, but not lateral, ventricular enlargement was associated with greater cognitive disturbance in this sample. Results are consistent with pathological involvement of periventricular diencephalic structures resulting in dysfunctional frontal and limbic processing in a subgroup of patients.

Adult↗
PubMed1992

Sensory gating in rats depleted of dopamine as neonates: potential relevance to findings in schizophrenic patients.

Based on a recent hypothesis of reduced subcortical dopaminergic tone, evidence of early neurodevelopmental deviation, and acoustic startle abnormalities in schizophrenia, we examined acoustic startle in adult animals depleted of dopamine (DA) as neonates. Male rat pups received intracerebroventricular injections of either 6-hydroxydopamine (6-OHDA, 100 micrograms) or its vehicle on postnatal day 3. At 60 days of age, baseline startle and prepulse inhibition (PPI) of startle were assessed in a no injection condition, with all other animals receiving injections of saline or the DA agonist, apomorphine. Acoustic startle was elicited using 120 db white noise bursts alone or preceded by prepulses of 75, 80, and 85 db. Animals treated with 6-OHDA exhibited a 93% depletion of striatal DA compared to vehicle-treated controls. Whereas DA depleted animals did not differ from controls in the no injection condition, they showed greater baseline startle and reduced PPI compared to controls after saline injections. Depleted animals also showed exaggerated responses to apomorphine, with greater increases in baseline startle, loss of habituation, and decreased PPI compared to controls. Findings indicate that neonatal DA depletions lead to increased baseline startle and impaired sensory gating in adulthood after saline injections and dopamine agonists compared to controls. These findings may be relevant to a subgroup of psychotic patients that exhibit similar startle abnormalities as well as signs of hypodopaminergic function.

Acoustic Stimulation↗
PubMed1992

Bidirectional effect of beta-carboline agonists at the benzodiazepine-GABAA receptor chloride ionophore complex on GABA-stimulated 36Cl- uptake.

beta-Carboline agonists produced a left shift of the GABA concentration-chloride uptake curve or a reduction in the maximal increase in GABA-stimulated 36Cl- uptake depending on their concentration. The enhancement of the GABA effect occurs only at lower beta-carboline and GABA concentrations and is smaller for the partial agonist ZK 9126 compared to the full agonist ZK 93423. The opposite effect, inhibition of GABA-stimulated chloride conductance, is observed only at higher concentrations of beta-carboline agonists and GABA. The reduction of the GABA maximal response by the partial agonist ZK 91296 is greater than by the full agonist ZK 93423. The transformation of GABA-stimulated 36Cl- uptake data to specific chloride influx (36Cl- uptake per nM of GABA) reveals that the GABA concentration-response curve consists of three parts characterized by differences in the molar effectiveness of GABA relative to the GABA concentration. The molar effectiveness of GABA is a measure of the sensitivity of the GABAA receptor chloride ionophore complex and shows adaptive changes by this complex to increasing concentrations of GABA and/or beta-carboline. We conclude from our data that the change from GABA-sensitive to GABA-insensitive conformation of the GABAA receptor occurs with increasing concentrations of GABA and/or beta-carboline. Both conformations maintain positive heterotropic cooperativity with beta-carboline binding sites, one responsible for positive and the other responsible for negative effects of beta-carboline agonists on chloride uptake.

Animals↗