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Ikwunga Wonodi

Publications and source records attributed to Ikwunga Wonodi.

13 recordsLinked to original sources
PubMed2007

Independent domains of inhibitory gating in schizophrenia and the effect of stimulus interval.

OBJECTIVE: Patients with schizophrenia are known to have inhibitory gating deficits in the suppression of evoked potential P50 response to repeated stimuli and the prepulse inhibition of the startle response. In the current study, the authors aimed to determine whether these two inhibitory gating measures are related in schizophrenia patients or whether abnormal P50 suppression and abnormal prepulse inhibition are independent neurophysiological characteristics of schizophrenia. The authors hypothesized that the relationship of the two measures may vary as a function of interstimulus intervals of stimulus presentations. METHOD: Fifty-nine schizophrenia patients and 17 healthy comparison subjects were tested on both P50 suppression and prepulse inhibition. P50 suppression was measured using paired clicks with 500-msec interstimulus intervals. Prepulse inhibition was measured by using a series of prepulse-pulse pairs with interstimulus intervals ranging from 30 to 500 msec. RESULTS: Patients showed reduced P50 suppression and prepulse inhibition in relation to healthy comparison subjects. Concordance analysis showed that abnormal P50 suppression and abnormal prepulse inhibition do not necessarily occur together. Prepulse inhibition was most prominent at the 120-msec interstimulus interval, which was not correlated to P50 suppression. At the 500-msec interstimulus interval, prepulse inhibition was significantly but negatively correlated to P50 suppression. Prepulse inhibition at the other interstimulus intervals was not correlated with P50 suppression. CONCLUSIONS: These neurophysiological measures lack robust and direct relationships and likely mark independent aspects of abnormal brain inhibitory functions in schizophrenia.

Acoustic Stimulation↗
PubMed2006

Lack of association between COMT gene and deficit/nondeficit schizophrenia.

BACKGROUND: The dopamine dysregulation hypothesis of schizophrenia posits that positive, negative and cognitive symptoms correlate with cortical/subcortical imbalances in dopaminergic transmission. A functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene is implicated in the pathophysiology of schizophrenia by its effect on prefrontal dopamine transmission, and its unique impact on prefrontal cognitive and behavioral phenotypes. Cognitive impairments and negative symptoms in schizophrenia have been hypothesized to be associated with hypodopaminergic states. Schizophrenia patients with the deficit syndrome are characterized by primary enduring negative symptoms, impairment on neurocognitive tasks sensitive to frontal and parietal cortical functioning, and poorer functional outcome compared to non-deficit patients. METHODS: Eighty-six schizophrenia cases that met DSM-IV criteria for schizophrenia were recruited. Additional categorization into deficit and nondeficit syndrome was performed using the Schedule for the Deficit Syndrome (SDS). A healthy comparison group (n = 50) matched to cases on age and ethnicity was recruited. Allele and genotype frequencies of the Val158Met polymorphism were compared among healthy controls, and schizophrenia cases with the deficit (n = 21), and nondeficit syndrome (n = 65). RESULTS: There was a significant difference in Val/Val genotype frequencies between schizophrenia cases (combined deficit/nondeficit) and healthy controls (p = 0.004). No significant differences in allele or genotype frequencies were observed between deficit and nondeficit cases. CONCLUSION: Results from this preliminary analysis failed to show an effect of COMT gene on deficit schizophrenia.

Journal Article↗
PubMed2006

Effects of repeated amphetamine administration on antisaccade in schizophrenia spectrum personality.

Repeated amphetamine administration is used to examine the responsivity of cerebral dopaminergic systems. Schizophrenia spectrum personality (SSP) provides a unique opportunity to study the pathophysiology of schizophrenia because of shared neurobiology without the confounding factors of acute psychosis and psychotropic exposure. Previously we noted that on repeated amphetamine administration, dyskinesia and SSP symptoms were less likely to worsen in SSP than in healthy volunteers. In the current study, we report the effects of repeated amphetamine on antisaccade task performance. Eleven SSP and seven healthy subjects were given placebo once and amphetamine (30 mg) twice, in randomized double-blind fashion at least 1 week apart. Antisaccade eye measurements (error rate and latency) were recorded over 30 trials in each direction. Analysis of error rate showed no significant main effects of the drug. There was a significant group by field by drug interaction effect on the antisaccade latency. The SSP group showed a significant reduction in antisaccade latency for right field targets whereas no significant effects were noted in healthy control subjects. Findings from this preliminary study suggest SSP may be more receptive to the beneficial effects of repeated amphetamine on cognition than healthy controls.

Adult↗
PubMed2006

Deficits on the Continuous Performance Test within the schizophrenia spectrum and the mediating effects of family history of schizophrenia.

Individuals with schizophrenia spectrum personality disorders (SSPD) and schizophrenia show similar cognitive impairments. The authors examined the contributions of SSPD symptoms and familial risk for schizophrenia to impairments on the Continuous Performance Test--Identical Pairs Version. Participants included 103 schizophrenia patients, 66 first-degree relatives (29 SSPD), and 103 community controls (26 SSPD) screened for family history of psychosis. Patients and SSPD relatives performed significantly worse than non-SSPD relatives and SSPD and non-SSPD community controls. No differences in performance were observed among non-SSPD relatives and SSPD and non-SSPD community controls. Results suggest a continuum in which risk for schizophrenia-related cognitive impairments is highest among patients and SSPD relatives, intermediate among non-SSPD relatives, and lowest among SSPD and non-SSPD community controls. Results suggest that SSPD in the absence of a family history of psychosis may be a phenocopy.

Adult↗
PubMed2005

Dihydropyrimidinase-related protein 2 (DRP-2) gene and association to deficit and nondeficit schizophrenia.

A previous study has shown an association between the *2236T > C allele polymorphism of the dihydropyrimidinase-related protein 2 (DRP-2) gene and schizophrenia in a Japanese sample [Nakata et al. (2003); Biological Psychiatry 53:571-576]. DRP-2 is an important molecule in guiding neuronal development and its gene is located in 8p21, a chromosomal region that was previously shown to have significant linkage to schizophrenia and to several deficit symptoms of schizophrenia. We compared the frequency of the DRP-2 *2236T > C polymorphism between subjects with (n = 117) and without (n = 72) schizophrenia, and then further evaluated whether the association was specific for the deficit (n = 24) and nondeficit (n = 93) forms of schizophrenia. In both Caucasians and African-Americans, the C allele occurred more frequently in schizophrenia cases than controls, with this difference achieving statistical significance in Caucasians (C allele frequency: 42.0% in cases vs. 25.0% in controls, P = 0.014) but not African Americans (52.6% in cases vs. 50.0% in controls, P = 0.93). In Caucasians, the frequency of the C allele was significantly higher in both the deficit (allele frequency 53.3%, P = 0.009) and nondeficit (39.2%, P =0.050) forms of schizophrenia compared to controls (allele frequency 25.0%). We conclude that the DRP-2 *2236 C allele may mark another polymorphism in DRP-2, or in a nearby gene, that may influence susceptibility to schizophrenia.

Adult↗
PubMed2005

Specific motion processing pathway deficit during eye tracking in schizophrenia: a performance-matched functional magnetic resonance imaging study.

BACKGROUND: The neural mechanisms underlying smooth pursuit eye movement (SPEM) abnormalities in schizophrenia are not well understood. Previous evidence suggests that a deficit in the processing of internal representations of object motion (extraretinal motion) contributes to SPEM deficits in patients. Functional magnetic resonance imaging (fMRI) activation was compared between patients and control subjects to determine whether schizophrenia patients exhibit abnormal cerebral activation in regions associated with extraretinal motion processing during SPEM. METHODS: Patients and control subjects were selected based on matched performance in the closed-loop gain. Despite similar performance on closed-loop pursuit gain, patients showed consistent deficits in extraretinal motion based on predictive pursuit. In the magnet, subjects were tested using a traditional smooth-pursuit task that elicits closed-loop response. RESULTS: Patients had reduced pursuit-related activation in several known extraretinal motion processing areas including frontal and supplemental eye fields, medial superior temporal cortex, and anterior cingulate. Patients also showed increased activation in medial occipitotemporal cortex. CONCLUSIONS: These results provide functional anatomic evidence supporting reduced function in the extraretinal motion processing pathway in schizophrenia. Increased activation in medial occipitotemporal cortex suggests an increased dependence on immediate retinal motion information, which may be used to compensate for reduced extraretinal signaling during sustained visual tracking.

Adult↗
PubMed2005

Reliability of a portable head-mounted eye tracking instrument for schizophrenia research.

Smooth pursuit eye movement (SPEM) abnormalities are some of the most consistently observed neurophysiological deficits associated with genetic risk for schizophrenia. SPEM has been traditionally assessed by infrared or video oculography using laboratory-based fixed-display systems. With growing interest in using SPEM measures to define phenotypes in large-scale genetic studies, there is a need for measurement instruments that can be used in the field. Here we test the reliability of a portable, head-mounted display (HMD) eye movement recording system and compare it with a fixed-display system. We observed comparable, modest calibration changes across trials between the two systems. The between-methods reliability for the most often used measure of pursuit performance, maintenance pursuit gain, was high (ICC = 0.96). This result suggests that the portable device is comparable with a lab-based system, which makes possible the collection of eye movement data in community-based and multicenter familial studies of schizophrenia.

Data Display↗
PubMed2005

Psychopathological and cognitive correlates of tardive dyskinesia in patients treated with neuroleptics.

Even though new cases of TD are on the decline in North America and other western countries, TD remains a public health concern for patients with chronic schizophrenia, PAD, and for nonpsychiatric patients treated with dopamine receptor antagonists. The new generation of atypical antipsychotic medications is believed to pose less risk for TD. However, identifying the cognitive and disease-related correlates of TD should equip clinicians with the necessary tools to reduce the prevalence of this iatrogenic movement disorder. No effective treatments for TD are available. This lack of effective therapy is problematic, especially in the few patients in whom the disorder causes functional impairment and other complications, and in whom it may be irreversible.

Affective Disorders, Psychotic↗
PubMed2004

Naltrexone treatment of tardive dyskinesia in patients with schizophrenia.

OBJECTIVE: Treatment of dyskinetic disorders, in general, and of tardive dyskinesia (TD), in particular, is difficult. The opiate peptide enkephalin coexits with gamma aminobutyric acid in the projection neurons of striatum forming the "indirect" pathway. Several lines of preclinical evidence implicate this enkephalin-comediated pathway in the pathophysiology and therapeutics of dyskinesia. However, previous studies, most using relatively low doses of opioid antagonists, showed mixed results. The goal of the current study was to test whether moderately high doses of naltrexone, alone or in combination with a subtherapeutic dose of a gamma aminobutyric acid agonist, improve TD. METHODS: In 2 double-blind, placebo-controlled, randomized, crossover trials, effects of naltrexone alone (n = 9) and in combination with clonazepam (n = 14) were tested on TD. In both trials, patients' antipsychotic medication and dose remained unchanged through the trial. Naltrexone dose was increased over a period of 3 weeks to 200 mg/d and maintained at that dose for another week. In the second study, patients were first stabilized on low dose (0.25 to 0.5 mg) of clonazepam for 4 weeks or longer. In addition to the TD scores, saccadic peak velocity and latency, as measures of vigilance, and antisaccade error rate were obtained during the fourth week of placebo and naltrexone in a subgroup of patients. RESULTS: There were no significant effects of naltrexone alone on TD (mean +/- SD decrease in TD score = 0.1 +/- 4.8), psychosis scores, or eye movement measures. Low dose of clonazepam had no effect on TD. However, addition of naltrexone significantly improved TD (mean, SD decrease in TD score 4.0 +/- 3.6). There was no clinical or laboratory evidence of increased sedation during treatment with naltrexone compared to placebo. There were no significant effects on the antisaccade error rate or psychosis scores. CONCLUSION: These findings suggest effectiveness of a strategy of combining a GABA(gamma aminobutyric acid)mimetic drug with an enkephalin antagonist to treat dyskinesia.

Adult↗
PubMed2004

Ethnicity and the course of tardive dyskinesia in outpatients presenting to the motor disorders clinic at the Maryland psychiatric research center.

BACKGROUND: Although newly emergent tardive dyskinesia (TD) is less of a concern, about one-fourth to one-third of patients on or previously on chronic first-generation antipsychotic agents have TD. The long-term course and outcome, as well as their predictors, are unknown. Earlier studies identify ethnicity as one of the risk factors for the development of TD, and case reports have noted a preponderance of African-American males in cohorts of patients with tardive dystonia. The current study examines the anatomic distribution and course of TD in a cohort of schizophrenia patients of European and African descent with TD who were referred to the Motor Disorders Clinic (MDC). METHODS: We evaluated data collected on 1149 TD patients who were given a focused neurologic examination for movement disorders. Movements were evaluated with the MPRC Scale for Involuntary Movements (IMS). All patients met RDC-TD criteria for diagnosis of persistent TD. One to 10-year follow-up data on 528 patients were evaluated to examine the course of TD following recommendations made to referring primary clinicians. Suggested interventions to referring primary clinicians included dose reduction of first-generation antipsychotic medication, or switching to a second-generation antipsychotic. RESULTS: Initial evaluation included 701 European American (EA) patients and 448 African-American (AA) patients. AA patients had a significantly higher proportion of males [chi(1) = 7.50, P < 0.05]. EA subjects had a higher mean age than AA patients 42.8 +/- 11.2 and 39.8 +/- 10.4, respectively [F(1,1147) = 22.27, P < 0.05]. Mean neuroleptic exposure (chlorpromazine equivalents) was similar in both groups after controlling for differences in age.Follow-up data analyzed in 528 patients (329 EA and 199AA) showed a significant ethnicity by TD interaction [F(1,504) = 4.26, P < 0.05]. Examination of body distribution of dyskinetic movements showed an effect of ethnicity. Subsequent analyses suggest EA patients experienced more improvement in TD over the course of follow up [F(1,319) = 22.39, P < 0.05] compared with AAs [F(1,189) = 1.58, P > 0.05]. These findings were unchanged when age, change in antipsychotic drug dose, and duration of follow-up were covaried. CONCLUSION: Reports from earlier studies note ethnicity (African descent) as a risk factor in the development of TD. Our study findings suggest ethnicity might be an important factor in predicting a poor course of TD.

Adult↗
PubMed2004

Catechol O-methyltransferase polymorphism and eye tracking in schizophrenia: a preliminary report.

OBJECTIVE: This study examined associations between functional polymorphism (Val(108/158) Met) in the catechol O-methyltransferase (COMT) gene and eye tracking measures in schizophrenia. METHOD: Predictive pursuit and closed-loop gains of 62 patients with schizophrenia and 53 healthy comparison subjects with Val-Val, Val-Met, and Met-Met genotypes were compared. RESULTS: There was a significant diagnosis-by-genotype interaction: patients with the Met-Met genotype showed poor predictive pursuit. The Met-Met genotype in healthy subjects was associated with significantly higher predictive pursuit gain values than the Val-Val genotype in healthy subjects. The COMT genotype explained about 10% of the variance in each group's predictive pursuit performance. DISCUSSION: These preliminary data suggest that the COMT gene is associated with predictive eye tracking performance in healthy subjects. Predictive pursuit abnormality in schizophrenia is not attributable to the Val allele. These findings suggest a complex interaction with other etiological factors (e.g., another gene), and/or with prefrontal cortical dopaminergic activity.

Adult↗
PubMed2003

Association between Val108/158 Met polymorphism of the COMT gene and schizophrenia.

Schizophrenia is a complex disorder with a multifactorial polygenic inheritance with several genes conferring susceptibility at many genetic locations, each with a small effect. An attractive candidate gene for schizophrenia is the catechol-O-methyltransferase (COMT) gene, which is a modulator of dorsolateral prefrontal cortical function. A missense G to A mutation in this gene that results in a substitution of Methionine (Met) for Valine (Val) at codon 108/158 (Val(108/158) Met) has recently been identified in association to schizophrenia. We compared allele frequencies of the variant Val allele between 96 schizophrenia cases and 80 normal controls. We selected controls from a similar pool to cases in ethnicity and gender. The frequency of the Val allele was significantly higher in schizophrenia cases compared to controls (0.620 vs. 0.506; P = 0.043). Calculation of the population attributable risk suggests that the Val allele accounts for as much as 23% of schizophrenia in this population (range: 3-38%). These results provide support for a role of this variant in the etiopathophysiology of schizophrenia.

Adult↗