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S G Potkin

Publications and source records attributed to S G Potkin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Clozapine increases EEG photic driving in clinical responders.

Photically driven electroencephalography was tested in 17 chronic schizophrenia patients who were treated with clozapine for 5 weeks. Eight of the 17 patients showed clinical improvement on the Brief Psychiatric Rating Scale (delta BPRS > 30%) while the other 9 patients remained unchanged (delta BPRS < 15%). In comparison with the nonresponders, clozapine responders had a significantly greater increase in photic driving in the electroencephalogram (EEG), primarily in the low-frequency range of alpha band (7.2 hertz [Hz], 8.3 Hz, 9.0 Hz, and 9.6 Hz, but not 12.0 Hz). The difference in the resting EEG between the responders and nonresponders did not reach statistical significance. These findings suggested that EEG photic driving might be more sensitive than the resting EEG in detecting the central nervous system drug effect. Further analysis revealed that the increase of EEG photic driving was positively correlated with patients' clinical improvement. Combined with our previous observation in the drug-free schizophrenia patients who had lower EEG photic driving, present results supported the hypothesis that the amount of EEG alpha activity, particularly its synchronization to the external stimuli, could reflect the thalamic function in sensory information processing in schizophrenia.

Adult↗
PubMed1995

Topographic analysis of EEG photic driving in normal and schizophrenic subjects.

In a 19-channel EEG photic driving paradigm the steady-state evoked response was studied in schizophrenic patients and normal controls. Seventeen drug-free patients and 15 normal controls were compared. Schizophrenic patients had lower EEG photic driving in the alpha range, particularly in the high alpha frequency band (p = 0.08). Topographic analysis revealed that the group differences were primarily located in the mid-frontal, central and parietal areas (p < 0.05). Temporal and lateral frontal lobe alpha remained the same in the two groups. Separate analysis of eye movement (EM) showed an opposite effect on the alpha-frequency photic driving as compared to that on the resting alpha EEG. EM decreased the resting alpha EEG and increased the photic driving. This finding suggested that the lower EEG photic driving in the schizophrenic patients could not be explained by the eye movement artifact. We hypothesize that the 10 Hz range photic driving that reflects the intrinsic EEG spindle generation in the thalamus may play an important role in the psychophysiology of schizophrenia.

Adult↗
PubMed1995

New morphological and neuropathological findings in schizophrenia: a neurodevelopmental perspective.

This article reviews evidence for morphological abnormalities in schizophrenia as assessed by brain imaging and neurohistochemical techniques including immunohistochemistry and in situ hybridization. Localized deficits in schizophrenic brain appear in many regions including frontal and temporal lobes, anterior cingulate, mediodorsal thalamic nucleus, and corpus callosum. These areas are interconnected and may provide the basis for a "psychosis circuitry." Neuronal disruption of elements in this circuitry may result in a hypothesized dysconnection syndrome. Evidence suggests an alteration in neuronal development related to either genetic and/or environmental factors. Primary and secondary anterograde and retrograde effects may accompany this neurodevelopmental defect and may further alter intrinsic and extrinsic neuronal communications. A number of studies are consistent with the second trimester of gestation being a critical period for fetal brain development, especially for neuronal migration. Fetal trauma due to environmental insults (e.g., influenza) during this trimester may increase the incidence of schizophrenia. Recent advances in the identification of factors that modulate neuronal development including axon guidance molecules, neurotrophins, and programmed cell death genes provide intriguing new areas for potential investigation. Future research may focus on the factors controlling neuronal migration and programmed cell death in the schizophrenic brain.

Autopsy↗
PubMed1994

Patterns of cortical activity in schizophrenia.

Eighty-three patients with schizophrenia and 47 healthy controls received positron emission tomography (PET) with 18F-2-deoxyglucose uptake while they were executing the Continuous Performance Test (CPT). The entire cortex was divided into 16 regions of interest in each hemisphere, four in each lobe of the brain, and data from corresponding right and left hemispheric regions were averaged. Data from the schizophrenic patients were subjected to a factor analysis, which revealed five factors that explained 80% of the common variance. According to their content, the factors were identified and labelled 'parietal cortex and motor strip', 'associative areas', 'temporal cortex', 'hypofrontality' (which included midfrontal and occipital areas) and 'frontal cortex'. Hemispheric asymmetry was only confirmed for the temporal cortex. Factor weights obtained in the schizophrenic group were applied to the metabolic data of the healthy controls and factors scales computed. Schizophrenics were significantly more hypofrontal than the controls, with higher values on the 'parietal cortex and motor strip' factor and a trend towards higher values in the temporal cortex. A canonical discriminant analysis confirmed that the 'hypofrontality' and 'parietal cortex and motor strip' factors accurately separated the schizophrenic group from the healthy controls. Hemispheric asymmetry was only confirmed for the temporal lobe. Significantly higher factor scores for the left temporal lobe in schizophrenics than in normals were obtained when calculated for the right and left hemisphere separately. Taken together, our results confirm the importance of hypofrontality as a pattern of cortical metabolic rate and point to the potential importance of parietal and motor strip function in schizophrenia.

Adult↗
PubMed1994

S-adenosylmethionine blood levels in major depression: changes with drug treatment.

INTRODUCTION: The relationship between plasma levels of S-adenosylmethionine (SAMe), an endogenous methyl donor, and clinical response were studied in patients with a DSM-III-R diagnosis of major depression. MATERIAL AND METHODS: A double-blind randomized protocol comparing oral SAMe with oral desipramine, involving a total of 26 patients, was employed. RESULTS: At the end of the 4-week trial, 62% of the patients treated with SAMe and 50% of the patients treated with desipramine had significantly improved. Regardless of the type of treatment, patients with a 50% decrease in their Hamilton Depression Scale (HAM-D) score showed a significant increase in plasma SAMe concentration. CONCLUSION: The significant correlation between plasma SAMe levels and the degree of clinical improvement in depressed patients regardless of the type of treatment suggests that SAMe may play an important role in regulating mood.

Adult↗
PubMed1994

Plasma clozapine concentrations predict clinical response in treatment-resistant schizophrenia.

Steady-state blood clozapine concentrations in 58 schizophrenic patients varied more than 45-fold (40-1911 ng/mL) after fixed-dose treatment (400 mg/day). Discriminant function analysis determined that a blood clozapine concentration of 420 ng/mL optimally distinguished responders from nonresponders. After 4 weeks of treatment, only 8% of those patients with a blood clozapine concentration < 420 ng/mL responded compared with 60% of those who had a blood clozapine concentration > 420 ng/mL. When plasma concentrations were increased above 420 ng/mL (by a double-blind random assignment procedure), nonresponders increased their response rate to 73% if their plasma concentrations at Week 12 exceeded 420 ng/mL compared with a response rate of 29% if their Week 12 levels remained below 420 ng/mL (chi 2 = 4.2, p < .04).

Adult↗
PubMed1994

Clozapine effects on glucose metabolic rate in striatum and frontal cortex.

Eighteen patients with schizophrenia had cerebral metabolic rates assessed with positron emission tomography during a double-blind, placebo-controlled crossover study of clozapine treatment. Relative metabolic rates were increased in the basal ganglia, especially on the right side. In the frontal lobe, metabolic rates were lowered, more on the left than on the right. The anterior nuclei of the thalamus also showed lower metabolic rates after clozapine. We have previously observed patients with schizophrenia to have low metabolic rates in the basal ganglia and to lack the normal right > left asymmetry; in this study, clozapine normalized striatal activity. In the frontal lobe, asymmetry was normalized, but hypofrontal function was, if anything, exaggerated. This effect in the frontal lobe was not observed with haloperidol in earlier studies. The cortical effects of clozapine may be related to its unique clinical properties and suggest important differences between typical and atypical antipsychotic drugs.

Adult↗
PubMed1993

Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development.

Epidemiological and anatomical studies support the theory that disturbances of brain development may play a contributory role in the etiology of schizophrenia. Anatomical findings suggest that the normal pattern of neuronal migration during development of the cerebral cortex may be affected in the brains of schizophrenics, with the implication that cortical connectivity and associative function will be disrupted. In the present investigation in matched schizophrenic and control brains, we examined a particular population of neurons found in the prefrontal cortex and underlying white matter and characterized by histochemical staining for the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase. In normal brains, these neurons are found in highest numbers in the white matter immediately deep to layer VI of the cortex where they remain from the subplate, an early formed, but transitory structure that plays a key role in cortical development and connection formation. The dorsolateral prefrontal area of schizophrenics showed a significant decline in nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in the superficial white matter and in the overlying cortex but a significant increase in these neurons in white matter deeper than 3 mm from the cortex. These findings are consistent with a disturbance of the subplate during development in which the normal pattern of programmed cell death is compromised and accompanied by a defect in the normal orderly migration of neurons toward the cortical plate. These are likely to have serious consequences for the establishment of a normal pattern of cortical connections leading to a potential breakdown of frontal lobe function in schizophrenics.

Adult↗
PubMed1993

Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development.

The distribution of neurons expressing the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d) in the lateral and medial temporal lobes of schizophrenic and matched control brains was investigated in a systematic blind analysis. Schizophrenics had significantly lower numbers of NADPH-d neurons in the hippocampal formation and in the neocortex of the lateral temporal lobe but significantly greater numbers of NADPH-d neurons in the white matter of the lateral temporal lobe and a tendency toward greater numbers in parts of the parahippocampal white matter. The distorted distribution of NADPH-d neurons in the lateral temporal lobe, which may be explained by developmental disturbances, such as impaired neuronal migration or an alteration in the death cycle of transitory subcortical neurons, is similar to that found in the prefrontal cortex of schizophrenics. Alterations of cortical ontogenesis, as reflected in the distribution of NADPH-d neurons, appear to be widespread among neocortical association fields in schizophrenics and may provide a clue to the cause of the disease.

Aged↗
PubMed1993

Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients.

OBJECTIVE: The cortical-striatal-thalamic circuit modulates cognitive processing and thus may be involved in the cognitive dysfunction in schizophrenia. The imaging of metabolic rate in the structures making up this circuit could reveal the correlates of schizophrenia and its main symptoms. METHOD: Seventy male schizophrenic patients underwent [18F]-fluorodeoxyglucose positron emission tomography after a period of at least 4 weeks during which they had not received neuroleptic medication and were compared to 30 age-matched male normal comparison subjects. RESULTS: Analyses revealed decreased metabolism in medial frontal cortex, cingulate gyrus, medial temporal lobe, corpus callosum, and ventral caudate and increased metabolism in the left lateral temporal and occipital cortices in the schizophrenic cohort. Consistent with previous studies, the schizophrenic group had lower hypofrontality scores (ratios of lateral frontal to occipital metabolism) than did comparison subjects. The lateral frontal cortical metabolism of schizophrenic patients did not differ from that of comparison subjects, while occipital cortical metabolism was high, suggesting that lateral hypofrontality is due to abnormalities in occipital rather than lateral frontal activity. Hypofrontality was more prominent in medial than lateral frontal cortex. Brief Psychiatric Rating Scale (BPRS) scores, obtained for each schizophrenic patient on the scan day, were correlated with regional brain glucose metabolic rate. Medial frontal cortical and thalamic activity correlated negatively with total BPRS score and with positive and negative symptom scores. Lateral frontal cortical metabolism and hypofrontality scores did not significantly correlate with negative symptoms. Analyses of variance demonstrated a reduced right greater than left asymmetry in the schizophrenic patients for the lateral cortex as a whole, with simple interactions showing this effect specifically in temporal and frontal cortical regions. CONCLUSIONS: Low metabolic rates were confirmed in medial frontal cortical regions as well as in the basal ganglia, consistent with the importance of the cortical-striatal-thalamic pathways in schizophrenia. Loss of normal lateralization patterns was also observed on an exploratory basis. Correlations with negative symptoms and group differences were more prominent in medial than lateral frontal cortex, suggesting that medial regions may be more important in schizophrenic pathology.

Adolescent↗
PubMed1993

Measuring the psychological construct of control. Discriminant, divergent, and incremental validity of the Shapiro Control Inventory and Rotter's and Wallstons' Locus of Control Scales.

The psychological construct of control is increasingly thought to be an important variable in psychosomatic medicine, but there are limitations with how it has been measured by previous instruments. The current study details four limitations of previous instruments as a rationale for developing a new multi-faceted, multi-dimensional instrument to measure control, the Shapiro Control Inventory (SCI). Discriminant, divergent, and incremental validity of the SCI is compared with the Rotter's Internal/External Locus of Control Scale and Wallstons' Multidimensional Health Locus of Control Scales on five groups, one normal and four clinical groups (depression, generalized anxiety disorder, borderline personality, and panic disorder). Analysis of variance showed significant differences among populations on each of the nine SCI scales. The majority of these results were highly significant, whereas for Rotter's scale the results were barely significant, and for Wallstons' three scales, not at all significant. Correlations of the SCI scales with Rotter's and Wallstons' scales were small to moderate, but in no case explained more than 15% of the variance. The SCI also provided incremental validity over Rotter's and Wallstons' scales both for sensitivity (clinical versus normal) and specificity (between clinical groups). The discussion section provides suggestions for future research.

Adolescent↗
PubMed1992

Frontostriatal disorder of cerebral metabolism in never-medicated schizophrenics.

We scanned 18 patients with schizophrenia who had never received neuroleptic medication and 20 age- and sex-matched controls by positron emission tomography with 18-F-fluorodeoxyglucose (fludeoxyglucose F 18) as a tracer of glucose metabolism. Subjects performed the Continuous Performance Test during 18-F-fluorodeoxyglucose uptake. Scan results were converted to metabolic rates, and computer algorithms were used to identify cortical regions. Previous reports of relative hypofrontality in schizophrenia were confirmed, indicating that this finding is not an artifact of previous treatment. Significantly reduced ratios of inferior and medial frontal regions to occipital cortex were found, together with diminished metabolism in the basal ganglia. This suggests the presence of a combined frontostriatal dysfunction in schizophrenia.

Adult↗
PubMed1992

Striatal metabolic rate and clinical response to neuroleptics in schizophrenia.

A low metabolic rate in the caudate nucleus and putamen in schizophrenic patients while they were not receiving medication was found to predict a favorable clinical response to haloperidol. Twenty-five patients (21 men and four women) entered a double-blind crossover trial of haloperidol and placebo; to our knowledge, this is the first such trial with positron emission tomography to be reported. Patients received either placebo or medication for the first 5 weeks, and they received the other treatment for the second 5 weeks. Positron emission tomographic scans were obtained at weeks 5 and 10. Patients with low relative metabolic rates in the caudate nucleus and putamen while they were receiving placebo were more likely to show decreases in their Brief Psychiatric Rating Scale scores with haloperidol treatment than individuals with normal or high metabolic rates. Among responders, haloperidol treatment had a "normalizing" effect on metabolic activity in the striatum, with the metabolic rate while they were receiving haloperidol being higher than that while they were receiving placebo. Nonresponders were more likely to show a worsening of hypofrontality while they were receiving medication and an absence of change in the striatum.

Adult↗
PubMed1992

A method for fixation of previously fresh-frozen human adult and fetal brains that preserves histological quality and immunoreactivity.

A method is described that enables fixation of previously fresh-frozen and stored adult and fetal human or animal brains. The method involves fixing during thawing under controlled, cryoprotected conditions and is compatible with good histological quality and the preservation of enzymatic activity and immunoreactivity of many neural antigens. It offers considerable advantages for the storage of large amounts of tissue from which multiple samples can be taken and processed under fixation and other conditions that can be optimized for a variety of methods, many of which may be incompatible if the whole brain is fixed in a single fixative prior to storage.

Acetylcholinesterase↗
PubMed1992

Effects of clozapine and thiothixene on glucose metabolic rate in schizophrenia.

Twelve patients with schizophrenia received positron emission tomography scans with 18F-deoxyglucose before and after 4 to 6 weeks of treatment with clozapine or thiothixene. Both stereotaxic and magnetic resonance image template methods were used to position regions of interest for metabolic rate analysis. Clozapine increased and thiothixene decreased metabolic rates in the basal ganglia; these effects were most marked on the right side. Within the basal ganglia, a superior to inferior gradient in drug effect was found for thiothixene but not clozapine. This gradient resembled in some respects observations on regional differences in D2 receptors in human autoradiography. Baseline metabolic rates also predicted clinical medication response, with right inferior caudate metabolic rates differentiating clozapine and thiothixene responders. Larger sample studies are needed to replicate and extend these initial findings.

Adult↗
PubMed1990

Chronic treatment with clozapine or haloperidol differentially regulates dopamine and serotonin receptors in rat brain.

Long-term administration of the atypical neuroleptic clozapine (CLZ) poses a much lower risk of extrapyramidal side effects (EPS) than does the use of typical neuroleptics such as haloperidol (HAL). To investigate the neural mechanisms of the differing CNS activities of these two drugs, we used quantitative autoradiography to measure changes in dopamine and serotonin receptors in rats after injection with CLZ or HAL for 21 days at clinically relevant dose ratios. Levels of D1, D2, and 5-HT2 receptors were determined in frontal cortex, caudate-putamen, and nucleus accumbens. Rats that received CLZ chronically showed CNS receptor changes markedly different from those in chronic HAL-treated animals. Whereas rats treated chronically with HAL showed enhanced striatal D2 binding (average increase of 42%), those treated with CLZ did not. In contrast, chronic CLZ, but not chronic HAL, induced enhanced striatal D1 binding (average increase of 43%). Finally, CLZ treatment decreased 5-HT2 receptor binding by an average of 37%, while HAL had no significant effect. The effects of chronic HAL or CLZ treatment on receptors were similar in all forebrain areas examined. However, since D1 and 5-HT2 receptors are more abundant than D2 sites in limbic and neocortical areas, the preferential modulation of D1 and 5-HT2 receptors by CLZ suggests a greater impact of this atypical neuroleptic on activity of the limbic system than that achieved by the typical neuroleptic, HAL. These findings suggest that the clinical profile of atypical neuroleptics such as CLZ may be attributed to their effects on a receptor profile differing in pharmacological characteristics and anatomical distribution from that affected by typical neuroleptics.

Animals↗
PubMed1990

Abnormal EEG responses to photic stimulation in schizophrenic patients.

Numerous studies have differentiated schizophrenic patients and normal controls in electroencephalography (EEG) spectral patterns recorded at rest. We replicated the resting EEG spectral differences between these groups and observed significant differences in periodic photic stimuli on the EEG spectra. Drug-free schizophrenic male patients (n = 8, mean age = 23.9) and normal male controls (n = 11, mean age = 24.3) were studied. Eighty seconds of EEG were collected from each subject for each of four experimental conditions: one resting and three photic-driving conditions (2.38, 4.54, and 8.33 Hz). Eye movement and other movement artifacts were minimized by use of an automatic amplitude threshold filter. Although large eye movements could be excluded as confounding factors, the filter could not for certain exclude small eye movements. Subjects were instructed to keep their eyes closed throughout. A significant difference was found between the groups both at rest and following photic stimulation in EEG activity. This result was characterized by increased delta activity and decreased alpha activity in schizophrenic patients at rest. The EEG activity following the photic driving also differentiated the groups. Schizophrenic patients had decreased sensitivity to the photic stimulation in the alpha range for spectra derived from both fundamental and harmonic analysis.

Adult↗