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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
PubMed2006

Effects of rivastigmine on cognitive function in patients with traumatic brain injury.

OBJECTIVE: To compare the efficacy and safety of rivastigmine (3 to 6 mg/day) vs placebo over 12 weeks in patients with traumatic brain injury and persistent cognitive impairment. METHODS: This prospective, randomized, double-blind, placebo-controlled study was conducted in 157 patients at least 12 months after injury. The primary efficacy measures were the Cambridge Neuropsychological Test Automated Battery (CANTAB) Rapid Visual Information Processing (RVIP) A' subtest and the Hopkins Verbal Learning Test (HVLT). The primary efficacy outcome was the proportion of patients who demonstrated 1.0 SD or greater improvement from baseline at week 12 on CANTAB RVIP A' or HVLT. RESULTS: The percentage of responders at week 12 on either the CANTAB RVIP A' or HVLT was 48.7% for rivastigmine and 49.3% for placebo (p = 0.940). Furthermore, for the overall study population, there were no significant differences for any of the secondary efficacy variables. In a subgroup of patients with moderate to severe memory impairment (n = 81), defined as 25% impairment or greater on HVLT at baseline, rivastigmine was significantly better than placebo for a number of measures, including the proportion of HVLT responders and CANTAB RVIP mean latency. CONCLUSIONS: Rivastigmine was safe and well tolerated in patients with traumatic brain injury with cognitive deficits. Rivastigmine shows promising results in the subgroup of patients with traumatic brain injury with moderate to severe memory deficits.

Adolescent↗
PubMed2006

Three-month change in cerebral glucose metabolism in patients with nonarteritic ischemic optic neuropathy.

BACKGROUND: No specific therapy is available for non-arteritic ischemic optic neuropathy (NAION), a blinding disease, which is related to microvascular insufficiency of the optic disc and white matter lesions in brain MRI representing ischemia. We hypothesize that pentoxifylline, traditionally used for treatment of peripheral vascular disease due to its ability to decrease viscosity and increase erythrocyte flexibility, may be useful to improve blood flow in patients with NAION. Positron emission tomography (PET) to determine the change in glucose metabolic rate in the visual cortex of patients with NAION versus age-matched controls was performed after 3 months' administration of pentoxifylline. METHODS: Eight patients clinically diagnosed with NAION underwent clinical and laboratory evaluation, brain MRI and PET with fluoride-18 fluorodeoxyglucose (FDG). All patients were treated with oral pentoxifylline 400 mg three times a day for a period of at least 3 months. Three patients were included in the final PET data analysis. RESULTS: At baseline, PET revealed bilateral metabolic decreases especially in the ventral visual stream in all patients compared with 56 age- and gender-normalized controls. Metabolic changes were seen in the dorsal stream areas 17, 18, and 19, cerebellar region, dorsolateral prefrontal cortex, medial temporal lobe, and frontal eye fields 8 and 6. At 3 months following pentoxifylline, all three patients included in the final PET data analysis showed partial normalization from the baseline metabolism. CONCLUSIONS: Metabolic imaging with FDG-PET in NAION provides functional information not attainable with conventional brain MRI. The exact relevance of these results, and the role of pentoxifylline in these metabolic changes, should be determined by means of a larger randomized and controlled trial.

Administration, Oral↗
PubMed2003

D1 receptor alleles predict PET metabolic correlates of clinical response to clozapine.

A goal of pharmacogenetics is to clarify associations between allelic variation and risk factors in psychiatric illness. We report changes in regional brain metabolism based on dopamine alleles. Treatment-resistant schizophrenic subjects were positron emission tomography scanned with 18F-fluorodeoxyglucose after 5 weeks each of placebo and clozapine treatment. Significant regional brain metabolic effects were found for the D1 receptor genotypes (P < 0.05), adjusted for multiple comparisons. Metabolic decreases for the 2,2 genotype but not the 1,2 genotype were observed in all major sectors of the brain, with the exception of the ventral parts of the caudate and putamen. Frontal, temporal, parietal, and occipital neocortices showed decreased metabolism as did the cingulate juxta-allocortex and the parahippocampal allocortex. Decreases were also observed in the thalamus, amygdala, and cerebellum bilaterally. No significant metabolic differences by genotype were observed for D3, 5HT(2A), and 5HT(2C) polymorphisms. In terms of clinical response, the DRD1 2,2 genotype significantly improved with clozapine treatment, demonstrating a 30% decrease in the Brief Psychiatric Rating Scale positive symptoms in contrast to a 7% worsening for the 1,2 genotype (P < 0.05). In this preliminary study, brain metabolic and clinical response to clozapine are related to the D1 receptor genotype.

Adult↗
PubMed2001

Stability of exploratory eye movements as a marker of schizophrenia--a WHO multi-center study. World Health Organization.

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Adult↗
PubMed2001

Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatients.

Serotonergic mechanisms have been implicated in panic disorder, and several preliminary studies suggest that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is helpful in its treatment. This 8-week double-blind parallel-group study compared fluvoxamine with a placebo in 188 patients with DSM-III-R defined panic disorder with or without agoraphobia. Efficacy assessments included a Daily Panic Attack Inventory, the Sheehan Disability Scale, the Clinical Anxiety Scale and the Clinical Global Impression Scale. When compared with the placebo, fluvoxamine produced highly significant improvements in most measures of the frequency and severity of panic disorder and in the more global aspects of disability and distress. Significant improvement was evident as early as week 1 for some panic variables. Fluvoxamine is a potent anti-panic agent with a relatively rapid onset of action.

Adolescent↗
PubMed2001

Sex-related difference in amygdala activity during emotionally influenced memory storage.

We tested the possibility suggested by previous imaging studies that amygdala participation in the storage of emotionally influenced memory is differentially lateralized in men and women. Male and female subjects received two PET scans for regional cerebral glucose-one while viewing a series of emotionally provocative (negative) films, and a second while viewing a series of matched, but emotionally more neutral, films. Consistent with suggestions from several previously published studies, enhanced activity of the right, but not the left, amygdala in men was related to enhanced memory for the emotional films. Conversely, enhanced activity of the left, but not the right, amygdala in women was related to enhanced memory for the emotional films. These results demonstrate a clear gender-related lateralization of amygdala involvement in emotionally influenced memory, and indicate that theories of the neurobiology of emotionally influenced memory must begin to account for the influence of gender.

Adult↗
PubMed2001

Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis: a double-blind, randomized trial.

RATIONALE: Intramuscular (IM) conventional antipsychotics and/or benzodiazepines are effective in the short-term treatment of acutely agitated psychotic patients but may be associated with adverse effects. A short-acting IM formulation of the novel antipsychotic, ziprasidone, which may offer advantages over conventional agents, has been developed. OBJECTIVE: To compare ziprasidone IM 2 mg (n=38) and 20 mg (n=41) in the acute control and short-term management of agitated psychotic patients. METHODS: A prospective, randomized, double-blind, 24-h study assessed efficacy using the Behavioral Activity Rating Scale (BARS) and the PANSS. The BARS is a validated rating scale for the assessment of treatment response in acute agitation associated with psychosis. Following the initial dose, three more doses could be given 4 h apart if needed during the 24-h period. RESULTS: The mean BARS score had decreased 15 min after the first 20 mg IM dose and was statistically significantly lower than the 2 mg group at 30 min post-dose. The improvement with the 20 mg dose increased until 2 h, and was maintained until at least 4 h post-dose (P<0.001). Two hours after the first injection, almost all of the patients receiving ziprasidone 20 mg were BARS responders compared with just one-third of those receiving 2 mg ziprasidone (P<0.001). The calming effect of ziprasidone was also evident by the significant reduction in PANSS agitation items (P<0.05) and CGI-severity at 4 h (P=0.008). Both ziprasidone doses were very well tolerated. Ziprasidone IM 20 mg was not associated with EPS, dystonia, akathisia, respiratory depression or with excessive sedation. CONCLUSIONS: Ziprasidone IM 20 mg substantially and significantly reduced the symptoms of acute agitation in patients with psychotic disorders. Ziprasidone 20 mg IM was very well tolerated and produced no dystonia or akathisia.

Adult↗
PubMed2001

Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease.

In-vivo metabolic measures with positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, frontal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic functioning. Cholinesterase inhibitors have demonstrated efficacy in improving cognition and behaviour in AD. In this study, we demonstrate the usefulness of FDG-PET in measuring the progression of untreated AD and its modification by treatment with rivastigmine (Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA), a centrally selective cholinesterase inhibitor of the carbamate type. Patients with mild to moderate probable AD (Mini-Mental Status Exam scores of 10-26, inclusive) were enrolled in a double-blind, placebo controlled comparison of three fixed daily doses of rivastigmine (3, 6, or 9 mg/d) or placebo for 26 wk. FDG-PET scans were obtained on 27 patients at baseline and following 26 wk of treatment using the Snodgrass Picture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients treated with rivastigmine (chi2 = 4.8; p & 0.03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinicianaposs Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p <0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal system. These metabolic changes were not observed in the placebo-treated patients or the rivastigmine non-responders. Of note is that responders increased hippocampal metabolism by 32.5% (p < 0.03) compared to a non-significant decrease in the non-responders (6.4%) and placebo-treated patients (4.1%). These results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors. Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients.

Aged↗
PubMed2001

Lack of association between serotonin-2A receptor gene (HTR2A) polymorphisms and tardive dyskinesia in schizophrenia.

Tardive dyskinesia (TD) is a disabling neurological side effect associated with long-term treatment with typical antipsychotics. Family studies and animal models lend evidence for hereditary predisposition to TD. The newer atypical antipsychotics pose a minimal risk for TD which is in part attributed to their ability to block the serotonin-2A (5-HT(2A)) receptor. 5-HT(2A) receptors were also identified in the basal ganglia; a brain region that plays a critical role in antipsychotic-induced movement disorders. We tested the significance of variation in the 5-HT(2A) receptor gene (HTR2A) in relation to the TD phenotype. Three polymorphisms in HTR2A, one silent (C102T), one that alters the amino acid sequence (his452tyr) and one in the promoter region (A-1437G) were investigated in 136 patients refractory or intolerant to treatment with typical antipsychotics and with a DSM-IIIR diagnosis of schizophrenia. We did not find any significant difference in allele, genotype or haplotype frequencies of polymorphisms in HTR2A among patients with or without TD (P > 0.05). Further analysis using the ANCOVA statistic with a continuous measure of the TD phenotype (Abnormal Involuntary Movement Scale (AIMS) score) found that the AIMS scores were not significantly influenced by HTR2A polymorphisms, despite controlling for potential confounders such as age, gender and ethnicity (P > 0.05). Theoretically, central serotonergic function can be subject to genetic control at various other mechanistic levels including the rate of serotonin synthesis (tryptophane hydroxylase gene), release, reuptake (serotonin transporter gene) and degradation (monoamine oxidase gene). Analyses of these other serotonergic genes are indicated. In summary, polymorphisms in HTR2A do not appear to influence the risk for TD. Further studies evaluating in tandem multiple candidate genes relevant for the serotonergic system are warranted to dissect the genetic basis of the complex TD phenotype.

Adult↗
PubMed2001

Clozapine enhances neurocognition and clinical symptomatology more than standard neuroleptics.

Neurocognition and clinical symptomatology were evaluated in 27 patients with schizophrenia during a double-blind, placebo-controlled, cross-over study involving clozapine, an atypical antipsychotic agent, and haloperidol, a conventional neuroleptic. Patients were assessed 5 to 6 weeks after initiation of each phase. Clinical symptomatology, based on Brief Psychiatric Rating Scale and Scale for the Assessment of Negative Symptoms ratings, markedly improved after treatment with both haloperidol and clozapine. The beneficial effects of clozapine were statistically significantly greater than the effects from the haloperidol treatment. Regarding neurocognition, both agents proved efficacious in improving performance on nearly all measures compared with placebo. In addition, as compared with haloperidol, clozapine significantly improved performance on Trails B, Verbal Fluency, and measures of delayed verbal memory, and it tended to increase performance on most measures. Additional analyses indicated that the improvement on neurocognitive measures was not because of symptom amelioration; rather, neurocognitive deficits seem to be an intrinsic enduring feature of schizophrenia. The superiority of clozapine over haloperidol may be related to clozapine's unique psychopharmacologic profile.

Adult↗
PubMed2000

EEG resonant responses in schizophrenia: a photic driving study with improved harmonic resolution.

Twenty seven drug-free schizophrenic patients and 25 normal controls were studied in an EEG photic driving paradigm with an improved harmonic resolution. Consistent with previous results, the present data show that schizophrenics have lower EEG responses to photic stimulation in alpha frequency. The differences between normal and schizophrenic subjects were distributed across major brain areas except centro-temporal regions. It also demonstrated that 1-Hz narrow-pulsed stimulation was feasible in EEG photic driving studies. The enhanced harmonic resolution produced significantly more information in the frequency domain about EEG oscillatory responses to visual stimulus. Using this new technique, the authors showed for the first time that alpha photic driving was a well defined resonant system and that the group differences in harmonic responses were primarily confined in the high frequency portion of alpha band, suggesting a peak frequency shift of EEG resonance in schizophrenia.

Adult↗
PubMed2000

Subnucleus-specific loss of neurons in medial thalamus of schizophrenics.

The hypoactivity of dorsolateral prefrontal cortex in schizophrenics is well known. One cause of this hypoactivity may be defective corticocortical or thalamocortical connections. Recent imaging studies of the thalamus suggest reductions in volume of the whole thalamus and reduced activity in the medial group of thalamic nuclei, which may indicate loss of functional input to the cortex. Using stereological techniques in six pairs of individually matched brains from schizophrenics and controls, we measured the volumes and obtained estimates of the number of neurons in the three subnuclei (parvocellular, pc; densocellular, dc; magnocellular, mc) of the mediodorsal nucleus (MD) and from the ventral posterior medial nucleus. There was a significant reduction in total neuron number in MD as a whole but this neuron loss was largely restricted to MDpc and MDdc [-30.9 and -24.5%, respectively (P </= 0.01)]. MDmc and the control ventral posterior medial nucleus showed no significant changes in cell number. Because the subnuclei of MD have different connections and project to different areas of the frontal cortex, the specific loss of neurons in MDpc and MDdc has implications for the functional defects observed in schizophrenia.

Adult↗
PubMed2000

Relative sparing of emotionally influenced memory in Alzheimer's disease.

Studies suggest that emotionally influenced events enhance long-term memory. This study aimed to uncover whether this phenomenon exists in Alzheimer's Disease (AD) by comparing patients' performance with that of controls on a memory task. Overall, controls performed better than AD subjects on a delayed recognition task of a story containing emotional elements (95.8+/-2.4% vs 66.6+/-28.5%; mean +/- s.d.), respectively. Among AD subjects, there was relative sparing of emotionally influenced memory, which was not seen in controls because of a ceiling effect. Retention of the emotional phase of the story differed significantly from that of the neutral phases. These findings suggest that the influence of emotion on memory is spared, at least to some degree, in AD.

Aged↗
PubMed2000

A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia.

Tardive dyskinesia (TD) is a common and potentially irreversible side effect associated with long-term treatment with typical antipsychotics. Approximately, 80% or more of patients with schizophrenia are smokers. Smoking is a potent inducer of the CYP1A2 enzyme, and is known to cause a significant decrease in plasma concentrations of some antipsychotics. Therefore, person-to-person differences in the extent of CYP1A2 induction by smoking may contribute to risk for the development of TD. Recently, a (C-->A) genetic polymorphism in the first intron of the CYP1A2 gene was found to be associated with variation in CYP1A2 inducibility in healthy volunteer smokers. The aim of this study was to test the clinical importance of the (C-->A) polymorphism in CYP1A2 in relation to TD severity. A total of 85 patients with schizophrenia were assessed for TD severity using the Abnormal Involuntary Movement Scale (AIMS), and were subsequently genotyped for the (C-->A) polymorphism in CYP1A2. The mean AIMS score in patients with the (C/C) genotype (associated with reduced CYP1A2 inducibility) was 2.7- and 3.4-fold greater than in those with the (A/C) or (A/A) genotype, respectively (F[2,82] = 7.4, P = 0.0007). Further, a subanalysis in the 44 known smokers in our sample, revealed a more pronounced effect. The means AIMS score in smokers was 5.4- and 4. 7-fold greater in (C/C) homozygotes when compared to heterozygotes and (A/A) homozygotes, respectively (F[2,41] = 3.7, P = 0.008). These data suggest that the (C-->A) genetic polymorphism in the CYP1A2 gene may serve as a genetic risk factor for the development of TD in patients with schizophrenia. Further studies in independent samples are warranted to evaluate the applicability of our findings to the general patient population receiving antipsychotic medications.

Adult↗
PubMed2000

An unstable trinucleotide-repeat region on chromosome 13 implicated in spinocerebellar ataxia: a common expansion locus.

Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual's DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA)n (CTG)n, which is very long ( approximately 1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (>100 repeats) were observed in 14 (1. 25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d'Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology.

Adult↗
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

Association of the MscI polymorphism of the dopamine D3 receptor gene with tardive dyskinesia in schizophrenia.

In 112 schizophrenic patients previously treated with typical neuroleptics, we investigated the putative role of the dopamine D3 receptor gene (DRD3) in tardive dyskinesia (TD). Patients were assessed for TD severity using the Abnormal Involuntary Movement Scale (AIMS) and were subsequently genotyped for the MscI polymorphism that identifies a serine to glycine substitution in DRD3. A modified analysis of covariance model, which incorporated several clinical risk factors for TD, was utilized to detect differences in TD severity among the various genotypic groups. The glycine allele of DRD3 was found to be associated with typical neuroleptic-induced TD (F[2,95] = 8.25, p < .0005). Higher mean AIMS scores were found in patients homozygous for the glycine variant of the DRD3 gene, as compared to both heterozygous and serine homozygous patients. Although replication is necessary, this finding supports a role for the dopamine D3 receptor in the pathogenesis of TD.

Adolescent↗