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Biomedical subjects

S G Potkin

Publications and source records attributed to S G Potkin.

At least 19 recordsLinked to original sources
PubMed1999

Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group.

In this double-blind study, patients with an acute exacerbation of schizophrenia or schizoaffective disorder were randomized to receive either ziprasidone 80 mg/day (n = 106) or 160 mg/day (n = 104) or placebo (n = 92), for 6 weeks. Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total, BPRS total, BPRS core items, CGI-S, and PANSS negative subscale scores (p < .05). Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinically significant depression at baseline (MADRS > or = 14, over-all mean 23.5) (p < .05) as compared with placebo. The percentage of patients experiencing adverse events was similar in each treatment group, and resultant discontinuation was rare. The most frequent adverse events associated with ziprasidone were generally mild dyspepsia, nausea, dizziness, and transient somnolence. Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain. The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive, negative, and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder.

Acute Disease↗
PubMed1999

Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia.

OBJECTIVE: The focus of this study was the systematic evaluation of the clinical effects of glycine as an adjunct to the atypical antipsychotic clozapine in the treatment of schizophrenia. METHOD: In a double-blind, placebo-controlled study, 19 patients with chronic, treatment-resistant schizophrenia who were maintained on optimal doses of clozapine (400-1200 mg/day) were administered either 30 g/day of glycine (N=9) or placebo (N=10) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, and the Simpson-Angus movement scale were completed biweekly. RESULTS: The use of glycine as an adjunct to clozapine was not effective in decreasing positive or negative symptoms. In contrast, the patients treated with clozapine without glycine had a 35% reduction in positive symptoms. CONCLUSIONS: These preliminary data suggest that glycine may interfere with the antipsychotic efficacy of atypical neuroleptics such as clozapine.

Adult↗
PubMed1998

Altered ratios of alternatively spliced long and short gamma2 subunit mRNAs of the gamma-amino butyrate type A receptor in prefrontal cortex of schizophrenics.

The relative abundance of alternatively spliced long (gamma2L) and short (gamma2S) mRNAs of the gamma2 subunit of the gamma-amino butyrate type A (GABAA) receptor was examined in dorsolateral prefrontal cortex of schizophrenics and matched controls by using in situ hybridization histochemistry and semiquantitative reverse transcription-PCR (RT-PCR) amplification. A cRNA probe identifying both mRNAs showed that the transcripts are normally expressed at moderately high levels in the prefrontal cortex. Consistent with previous studies, overall levels of gamma2 transcripts in prefrontal cortex of brains from schizophrenics were reduced by 28.0%, although this reduction did not reach statistical significance. RT-PCR, performed under nonsaturating conditions on total RNA from the same blocks of tissue used for in situ hybridization histochemistry, revealed a marked reduction in the relative proportion of gamma2S transcripts in schizophrenic brains compared with controls. In schizophrenics, gamma2S transcripts had fallen to 51.7% (+/-7.9% SE; P < 0.0001) relative to control levels. Levels of gamma2L transcripts showed only a small and nonsignificant reduction of 16. 9% (+/-12.0% SE, P > 0.05). These findings indicate differential transcriptional regulation of two functionally distinct isoforms of one of the major GABAA receptor subunits in the prefrontal cortex of schizophrenics. The specific reduction in relative abundance of gamma2S mRNAs and the associated relative increase in gamma2L mRNAs should result in functionally less active GABAA receptors and have severe consequences for cortical integrative function.

Adult↗
PubMed1998

Is P50 suppression a measure of sensory gating in schizophrenia?

BACKGROUND: Abnormal P50 response has been hypothesized to reflect the sensory gating deficit in schizophrenia. Despite the extensive literature concerning the sensory filtering or gating deficit in schizophrenia, no evidence has been provided to test the relationship of the P50 phenomenon with patients' experiences of perceptual anomalies. METHODS: Sixteen drug-free DSM-IV diagnosed schizophrenic patients who reported moderate to severe perceptual anomalies in the auditory or visual modality were examined as compared to 16 schizophrenic patients who did not report perceptual anomalies, and 16 normal subjects. Both control groups were age- and gender-matched with the study group. RESULTS: Patients reporting perceptual anomalies exhibited P50 patterns that did not differ from normal subjects. In contrast, patients who did not report perceptual anomalies showed the abnormal P50 ratios previously found to be associated with schizophrenia. CONCLUSIONS: These paradoxical findings do not support the hypothetical relationship between the P50 and behavioral measures of sensory gating, suggesting that additional studies are needed to further explore the clinical correlates of the P50.

Acoustic Stimulation↗
PubMed1998

Bipolar affective disorder partially cosegregates with a balanced t(9;11)(p24;q23.1) chromosomal translocation in a small pedigree.

Analysis of an extended pedigree in which a balanced t(9;11)(p24;q23.1) translocation was found to cosegregate with bipolar affective disorder revealed that five of 11 translocation carriers had bipolar affective disorder and one carrier had unipolar depression. There were no affected individuals in the pedigree without the balanced translocation. We hypothesized that gene(s) or gene regulatory regions disrupted by the translocation might be contributing to the bipolar affective disorder in a dominant fashion. To test this hypothesis, we isolated the derivative chromosome 9 and derivative chromosome 11 in somatic cell hybrids and identified the nearest flanking markers on chromosome 9 (D9S230 and D9S2011E/HRFX3) and chromosome 11 (EST00652 and CRYA2). YAC contigs were constructed in the region of flanking markers for both chromosomes 9 and 11. Chromosome 11 breakpoint was localized within an 8-kb region in a small insert (100 kb) YAC. Chromosome 9 breakpoint was localized within approximately 2 Mb region. Several genes and ESTs including EST00652, CRYA2, DRD2, 5HTR3 on chromosome 11 and VLDLR and SLC1A1 on chromosome 9 were mapped within the vicinity of the breakpoint but were shown not to be disrupted by the translocation breakpoint. Although several possibilities exist regarding the role of the balanced translocation in developing bipolar affective disorder in this pedigree, including a chance cosegregation, identification of a disrupted gene or gene regulatory region with the help of physical mapping resources described in this study may help to identify the presence of a susceptibility gene for this disorder.

Bipolar Disorder↗
PubMed1998

Topographic analysis of EEG photic driving in patients with schizophrenia following clozapine treatment.

Reduced EEG photic driving has been found to be diagnostically sensitive and specific for schizophrenia. Thirty-one patients with schizophrenia were tested in this study to identify the typical and atypical neuroleptic effects on the photic driving. Compared with the placebo, clozapine significantly enhanced the photically driven EEG in theta and low alpha frequency band, while haloperidol did not have the same effect. These changes with clozapine appeared to be symmetrical and located primarily in the frontal, central and mid-parietal areas but not in the lateral parietal, temporal and occipital regions. Results were consistent with previous findings and suggested that the atypical EEG profile of clozapine might be associated with 5-HT2 antagonistic property.

Adult↗
PubMed1997

Effects of P50 temporal variability on sensory gating in schizophrenia.

The conditioning-testing (S1-S2) P50 auditory evoked potential (EP) has been well-documented and accepted as an important tool for measuring sensory gating in schizophrenia research. However, the physiological mechanism of the phenomenon is not known. In this study a single-trial analysis was used to determine the influence of the latency variability of the responses in the formation of the averaged P50. Ten schizophrenic patients and 10 normal controls were tested in the dual-click EP paradigm. Using ensemble averaging analysis, we replicated the previous finding of a lower S1 P50 amplitude and higher S2/S1 ratio in schizophrenics compared with normal controls. The single-trial analysis revealed that patients had significantly higher trial-to-trial latency variability in S1 responses than normal subjects, while the S2 showed the same variability as in controls. Measured by the single-trial procedure, the arithmetic mean amplitudes of P50 responses to S1 and S2 were similar between normal and schizophrenic subjects. The same measure also eliminated the difference in averaged P50 amplitude between S1 and S2 for both groups. Temporal variability appears to be an important factor in the assessment of averaged EPs and thus contribute to the change of P50 amplitude observed in schizophrenia.

Adult↗
PubMed1997

Lateralized attentional deficits in drug-free and medicated schizophrenic patients.

Performance on a cued reaction time (RT) task, theoretically linked to posterior and anterior neuroanatomical systems in the brain (Posner, M. I. et al., Science, 1988, 210, 1627-1631; Archives of General Psychiatry, 1988, 15, 811-821), was used to assess sensory orienting and maintenance of attention. In schizophrenic patients, Posner et al. found a lateralized abnormality in RT (longer RTs to uncued targets in the right visual field than in the left visual field), as did Maruff et al. (Neuropsychologia, 1995, 33, 1205-1223), but Strauss et al. (Journal of Psychiatric Research, 1991, 37, 139-146), among others, did not replicate this effect. However, the subjects in these studies differed in the percentage of schizophrenic patients taking neuroleptic medication at the time of testing and in the chronicity of the illness. In the present study, we used two groups of schizophrenic subjects to control for the use of neuroleptic medication. The lateralized abnormality in RT was observed in the drug-free group of schizophrenic subjects, but not in the group of drug-treated schizophrenic subjects.

Adolescent↗
PubMed1997

REM sleep eye movement counts correlate with visual imagery in dreaming: a pilot study.

Based on the findings of our previously published positron emission tomography study, we proposed that recorded eye movements during REM sleep are visually targeted saccades. In the present study, we examined the correlation between the number of eye movements in REM sleep (EM) and visual imagery in dreaming (V) and provided further support for our proposal. All the observations (N = 11) were made with one individual to eliminate interindividual variation and were made during the second REM sleep period to control for a time-of-night effect. V, with or without dream report length partialled out, was strongly associated with EM only in the 1-min interval immediately preceding awakening. The time course of the association suggests that the strong EM-V association reflects a phasic, localized activation of the eye-movement-control system in association with REM sleep eye movements.

Adult↗
PubMed1996

Decrease in sigma but no increase in striatal dopamine D4 sites in schizophrenic brains.

[3H]Nemonapride differentially defines sigma and dopamine receptor sites depending upon assay conditions. In post-mortem schizophrenic brain tissues, [3H]nemonapride-labeled sigma receptor binding is decreased compared to match normal controls. No striatal dopamine D4/D4-like receptor differential was observed between the schizophrenic or control tissues, using the [3H]nemonapride minus [3H]raclopride subtraction method.

Adult↗
PubMed1996

Gender differences in gating of the auditory evoked potential in normal subjects.

Central nervous system (CNS) inhibitory mechanisms hypothesized to "gate" repetitive sensory inputs have been implicated in the pathology of schizophrenia. The present study investigated gender differences in inhibitory gating of evoked brain responses to repeated stimuli in normal subjects (30 women and 30 men) using an auditory conditioning-testing paradigm. Pairs of click stimuli (S1 and S2) were presented with a 0.5 s intrapair and a 10 s interpair interval. The amplitudes and latencies of the P50, N100, P180 components of the auditory evoked response to the conditioning (S1) and test response (S2) were measured, and the gating ratios were computed (T/C ratio = S2/S1 * 100). The amplitudes to S1 were not significantly different between men and women at P50, N100, or P180. However, women had significantly higher amplitudes to S2 at P50 (p = 0.03) and N100 (p = 0.04). The T/C ratios for women were higher (i.e., less suppression of response to S2) for P50 (p = 0.08) and N100 (p = 0.04) compared to men. The results suggested that differences in auditory gating between men and women were not due to biological differences in the P50 and N100 generators but possibly to differential influence of inhibitory mechanisms acting on the generator substrates of these evoked responses.

Adolescent↗
PubMed1996

Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients.

BACKGROUND: The cortical subplate is a transitory structure involved in the formation of connections in developing cerebral cortex. Interstitial neurons, normally present in subcortical white matter (WM) of the adult brain, have escaped the programmed cell death that eliminates most subplate neurons. Previous investigations indicated a maldistribution of one population of interstitial neurons in the WM of brains of schizophrenic patients, suggesting a defect of the subplate during brain development. METHODS: Three histochemically or immunocytochemically defined neuronal populations were studied in WM beneath the middle frontal gyrus of 20 schizophrenic patients and 20 matched control subjects. RESULTS: Brains of schizophrenic patients showed significant changes in the distribution of the three neuronal populations: microtubule-associated protein 2 and nonphosphorylated neurofilament-immunoreactive neurons showed a decreased density in superficial WM and an increased density in deeper WM. Nicotinamide adenine dinucleotide phosphate-diaphorase neurons were reduced in superficial WM and showed variable densities in deeper WM. Thirty-five percent of the brains of schizophrenic patients but no brains of the control subjects showed a maldistribution of neurons toward deeper WM with at least two of the three markers. Changes in neuronal distribution were not linked to age, gender, autolysis time, or subtype of schizophrenia. CONCLUSIONS: Selective displacement of interstitial WM neurons in the frontal lobe of brains of schizophrenic patients may indicate alteration in the migration of subplate neurons or in the pattern of programmed cell death. Both could lead to defective cortical circuitry in the brains of schizophrenic patients.

Adult↗
PubMed1996

Cerebral metabolic activity correlates of subsyndromes in chronic schizophrenia.

Seventy-nine patients with schizophrenia and 47 healthy controls received positron-emission tomography (PET) with 18F-2-deoxyglucose uptake while executing the Continuous Performance Test (CPT). Patients had been off all psychoactive medication for at least four weeks. Patients' symptoms were assessed with the Brief Psychiatric Rating Scale and factor scale scores were obtained. These scores were used in cluster analysis to identify patients with predominantly delusional, negative, disorganized, and remitted symptoms. To address the interconnective nature of cerebral functioning, regions of interest were defined on the basis of the results of a factor analysis of metabolic rate in selected brain regions. This procedure identified six cortical and eight subcortical region of interest factors. Metabolic rate factor scale scores were compared between the patients' clusters and the healthy controls. The delusional cluster showed a significantly reduced hippocampal activity, while the negative symptoms cluster presented with a prominent hypofrontality and significantly increased left temporal cortex values. Concurrently, both clusters were associated with a decreased activity on the factor 'anterior cingulum and medial frontal gyrus'. The disorganized cluster was characterized by a significant overactivity in the parietal cortex and motor strip and a decreased activity in the corpus callosum. The subsyndromes of chronic schizophrenia are therefore characterized by deviant patterns of cerebral activity rather than deficits in a single location.

Adult↗
PubMed1996

Language in dreaming and regional EEG alpha power.

In an intensive single-subject design, electroencephalographic (EEG) alpha power and receptive and expressive language in dreaming were studied in 12 dreams during rapid eye movement (REM) sleep on 12 separate nights. Bilateral EEG was recorded continuously from 21 sites and digitized. We used the Fast Fourier transformation (FFT) for power spectral analysis to measure EEG power in the alpha frequency range (8-12 Hz) at each of the EEG sites. The subject was awakened after about 14 minutes into the second REM period, and dream reports were collected. We scored the dream reports for expressive and receptive language. The lower the alpha power on the left sides of those homologous pairs that roughly correspond to Broca's (C3) or Wernicke's area (P3), the more expressive or receptive language in dream reports. The largest difference between the correlation of the left and that of the right homologous pair of regions was found in the central (C3, C4) area for expressive language and in the parietal (P3, P4) area for receptive language. Our finding suggests lateralized and localized cortical activation in relation to language in dreaming.

Adult↗
PubMed1996

P50 changes with visual interference in normal subjects: a sensory distraction model for schizophrenia.

Twenty-five normal subjects were tested in a Conditioning-Testing (S1-S2) auditory P50 study. Each subject was tested twice under two experimental conditions: distraction condition (with light interference) and control condition (without interference). Results showed that S1 P50 amplitude was significantly decreased with visual interference compared with that in the control condition, while the S2 response remained unchanged. Consequently, the S2/S1 gating ratio was also increased remarkably in the distraction condition. The auditory EP changes with the visual distraction in normals closely resembled the abnormal findings in schizophrenic subjects. These data may provide an alternative model to elucidate the psychophysiological mechanism that possibly rules the changes of attention in schizophrenia.

Acoustic Stimulation↗
PubMed1996

Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics.

NMDA receptor antagonists can induce a schizophrenia-like psychosis, but the role of NMDA receptors in the pathophysiology of schizophrenia remains unclear. Expression patterns of mRNAs for five NMDA receptor subunits (NR1/NR2A-D) were determined by in situ hybridization in prefrontal, parieto-temporal, and cerebellar cortex of brains from schizophrenics and from neuroleptic-treated and nonmedicated controls. In the cerebral cortex of both schizophrenics and controls, mRNAs for NR1, NR2A, NR2B, and NR2D subunits were preferentially expressed in layers II/III, Va, and VIa, with much higher levels in the prefrontal than in the parieto-temporal cortex. Levels of mRNA for the NR2C subunit were very low overall. By contrast, the cerebellar cortex of both schizophrenics and controls contained very high levels of NR2C subunit mRNA, whereas levels for the other subunit mRNAs were very low, except NR1, for which levels were moderate. Significant alterations in the schizophrenic cohort were confined to the prefrontal cortex. Here there was a shift in the relative proportions of mRNAs for the NR2 subunit family, with a 53% relative increase in expression of the NR2D subunit mRNA. No comparable changes were found in neuroleptic-treated or untreated controls. These findings indicate regional heterogeneity of NMDA receptor subunit expression in human cerebral and cerebellar cortex. In schizophrenics, the alterations in expression of NR2 subunit mRNA in prefrontal cortex are potential indicators of deficits in NMDA receptor-mediated neurotransmission accompanying functional hypoactivity of the frontal lobes.

Autoradiography↗
PubMed1995

Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics.

BACKGROUND: Up-regulation of gamma-aminobutyric acidA (GABAA) receptors and decreased GABA uptake in the cerebral cortex of schizophrenics suggest altered GABAergic transmission, which could be caused by primary disturbance of GABA synapses or by decreased production of the transmitter. Decreased production could be due to a shutdown in GABA production or to loss of GABA neurons caused by cell death or their failure to migrate to the cortex during brain development. METHODS: To discriminate between these possibilities, we quantified levels of messenger RNA (mRNA) for the 67-kd isoform of glutamic acid decarboxylase (GAD), the key enzyme in GABA synthesis, and the number and laminar distribution of GAD mRNA--expressing neurons in the dorsolateral prefrontal cortex (DLPFC) of schizophrenics and matched controls, using in situ hybridization-histochemistry, densitometry, and cell-counting methods. These data were compared with the total number of neurons, the number of small, round or ovoid neurons 8 to 15 microns in diameter, and overall frontal lobe volume. As a control, mRNA levels for type II calcium-calmodulin-dependent protein kinase (CamIIK) were quantified. RESULTS: Schizophrenics showed a pronounced decrease in GAD mRNA levels in neurons of layer I (40%) and layer II (48%) and an overall 30% decrease in layers III to VI. There were also strong overall reductions in GAD mRNA levels. The CamIIK mRNA levels showed no significant differences between samples. No differences were found in the total number of neurons nor in small, round or ovoid neurons, which should include a majority of the GABA cells. Prefrontal gray and white matter volume did not differ significantly between controls and schizophrenics. CONCLUSIONS: The prefrontal cortex of schizophrenics shows reduced expression for GAD in the absence of significant cell loss. This may be brought about by an activity-dependent down-regulation associated with the functional hypoactivity of the DLPFC. The lack of significant alterations in cell numbers in the DLPFC and frontal lobe volume in schizophrenics also implies that overall cortical neuronal migration had not been compromised in development. Previous reports of altered neuronal distribution in the subcortical white matter of schizophrenic brains in comparison with that of controls may indicate disturbances of migration or programmed cell death in the cortical subplate, leading to altered connection formation in the overlying cortex of schizophrenics and activity-dependent down-regulation of neurotransmitter-related gene expression.

Adult↗