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L Elliot Hong

Publications and source records attributed to L Elliot Hong.

17 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

Familial aggregation of eye-tracking endophenotypes in families of schizophrenic patients.

BACKGROUND: Abnormal smooth pursuit eye movements (SPEMs) are some of the most reproducible biological changes associated with the susceptibility for schizophrenia. Recent studies have suggested that deficit in predictive pursuit, a specific component of the SPEMs, marks schizophrenia susceptibility. OBJECTIVE: To test whether predictive pursuit contains less extraneous noise and may be under more direct genetic control than the traditional measure of overall pursuit performance using maintenance pursuit gain. DESIGN: Familial aggregation estimation of the predictive pursuit measure and the traditional maintenance pursuit measure in sibling pairs from families of schizophrenic patients. SETTING: Outpatient clinics. PARTICIPANTS: Patients with schizophrenia and their full siblings were recruited, provided that at least 1 sibling pair could be formed per family. Ninety-two siblings were recruited into the study. They formed 70 sibling pairs. Ninety healthy control subjects were also recruited using targeted local community advertisements based on patients' county of residence, aiming to capture the basic demographics of the regions from which the patients were recruited. MAIN OUTCOME MEASURES: Familial correlations and heritability estimates of 2 SPEM measures: maintenance pursuit gain and predictive pursuit gain. RESULTS: The sibling intraclass correlation coefficient of the predictive pursuit gain (r = 0.45-0.48) was significantly higher than that of maintenance pursuit gain (r = 0.02-0.20) (P = .005-.007). Variance component analysis suggested a high genetic loading for predictive pursuit (heritability = 0.90, SE = 0.22; P<.001) but relatively low heritability in the traditional maintenance pursuit measure (heritability = 0.27, SE = 0.21; P = .08). CONCLUSION: These results suggest that predictive pursuit may index stronger genetic effect and may be better suited for genetic studies than the traditional SPEM measure of maintenance pursuit gain.

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

Role of anticipation in schizophrenia-related pursuit initiation deficits.

Schizophrenia patients exhibit several smooth pursuit abnormalities including poor pursuit initiation. Velocity discrimination is also impaired and is correlated with pursuit initiation performance-suggesting that pursuit deficits are related to impairments in processing velocity information. Studies suggest that pursuit initiation is influenced by prior target motion information and/or expectations and that this is likely caused by expectation-based changes in the perceptual inputs to the pursuit system. We examined whether poor pursuit initiation in schizophrenia results from inaccurate encoding of immediate velocity signals, or whether these deficits reflect a failure to use prior target motion information to "optimize" the response. Twenty-eight patients and 24 controls performed an adapted version of a "remembered pursuit task." Trials consisted of a series of target motions, the first of which occurred unexpectedly, followed by four to seven identical targets each preceded by an auditory cue and a "catch target" in which a cue was given followed by target extinction. Initiation eye velocity in response to unexpected, first targets was similar in the patient and control groups. In contrast, patients showed lower eye velocity in response to repeated, cued targets compared with controls. Patients also showed reduced eye velocity in response to catch targets. Reduction in pursuit latency across repeated targets was less robust in patients. Results suggest that processing of immediate velocity information is unaffected in schizophrenia and that pursuit initiation deficits reflect an inability to accurately generate, store, and/or access "remembered" velocity signals.

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

Response to unexpected target changes during sustained visual tracking in schizophrenic patients.

BACKGROUND: Evidence supports an association between liability to schizophrenia and smooth-pursuit eye movement (SPEM) abnormalities. Knowledge of the biological mechanisms of SPEM abnormalities may provide critical insights into the etiology of schizophrenia. SPEM is elicited by sensory motor information from the movement of the object's image on the retina (retinal motion signal) and subsequent extraretinal motion signals. Previous studies suggest that a deficit in predictive responses to extraretinal motion signals may underlie the SPEM phenotype in schizophrenia. Data suggest that at-risk individuals for schizophrenia depend less on extraretinal and more on retinal motion signals to maintain pursuit than healthy individuals. METHODS: We designed a pursuit task that employs unexpected changes in target direction during smooth pursuit. The unpredictable task is unique in that performance is expected to be better if the subject's response is biased towards retinal motion. RESULTS: The study included 23 schizophrenia patients and 22 normal controls. Results showed that schizophrenia patients showed significantly superior performance (i.e. higher smooth pursuit gain) for a brief period after an unexpected change in target direction compared with healthy subjects. CONCLUSION: Findings of superior performance by schizophrenic patients are interesting because they circumvent confounds of generalized deficits. These results provide further evidence of specific deficit in the predictive pursuit mechanism and over-reliance on retinal error signals to maintain pursuit in schizophrenia.

Eye Movements↗
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

Evoked gamma band synchronization and the liability for schizophrenia.

OBJECTIVE: Electroencephalographic (EEG) synchronization in the gamma band is thought to represent a neuronal mechanism by which the brain integrates information processed in different cortical areas to build a coherent internal representation. Previous studies have reported abnormal gamma range ( approximately 40 Hz) synchronization in schizophrenic patients. We tested a group of first-degree relatives of schizophrenic probands who have schizophrenia spectrum personality symptoms, and a group of schizophrenic patients, to examine whether individuals with increased liability for schizophrenia have reduced gamma synchronization. METHOD: A steady-state auditory evoked potential paradigm was used to evaluate the brain's capacity to sustain 20, 30, and 40 Hz EEG synchronization in 11 relatives, 24 schizophrenic patients (11 on conventional, 13 on new generation antipsychotic medications), and 17 normal controls. RESULTS: Relatives with schizophrenic spectrum personality symptoms had reduced power at 40 Hz synchronization compared to normal controls (p=0.022). Previous findings of reduced steady-state gamma band synchronization in schizophrenic patients were not directly replicated in this study. Patients as a group did not significantly differ from controls, but patients taking new generation antipsychotics had significantly enhanced 40 Hz synchronization compared to patients taking conventional antipsychotics (p<0.001). There were no group differences in 20 or 30 Hz synchronization. CONCLUSIONS: Gamma band synchronization was found to be reduced in first-degree relatives with schizophrenia spectrum personality symptoms. Patients on new generation antipsychotic medications may exhibit enhanced gamma band synchronization.

Adult↗
PubMed2004

Gamma/beta oscillation and sensory gating deficit in schizophrenia.

Sensory gating can be measured by the suppression of auditory evoked potentials in a paired-click paradigm. The normal gating of the P50 response to the second stimulus (S2) is impaired in many schizophrenic patients. Various in vitro and in vivo evoked potential paradigms have shown that a stimulus evokes early gamma frequency oscillation, which is followed by beta frequency oscillation. The gamma-to-beta shift in response to the first stimulus (SI) in the paired-click paradigm may contain critical electrophysiological signals that modulate the S2 suppression. The results of the present study showed that post-SI beta frequency response was inversely correlated to the S2 P50 response in patients with schizophrenia.

Acoustic Stimulation↗
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

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

Components of the smooth pursuit function in deficit and nondeficit schizophrenia.

The diagnosis of schizophrenia likely encompasses a heterogeneous group of disorders, complicating the search for its causes. Studies of deficit schizophrenia represent an attempt to reduce this heterogeneity by identifying biologically distinct subgroups. Supplementing clinical phenotypes with biological markers of risk (e.g., eye-tracking and sensory-gating deficits) have also been used to reduce disease heterogeneity. In this study, we examined smooth pursuit eye movements in healthy controls (n = 37), and deficit (n = 18) and nondeficit (n = 32) patients with schizophrenia to determine what aspects of abnormal smooth pursuit are associated with the two patient groups, and which, if any, specifically mark the deficit phenotype. A small sample of relatives of deficit (n = 12) and nondeficit (n = 35) patients was also examined. Positive symptoms were equally present in deficit and nondeficit patients. Subtle, psychotic-like positive traits were also equally present in the relatives of both deficit and nondeficit probands, whereas negative symptoms were significantly more prevalent among the relatives of deficit probands. Deficits in predictive pursuit were present in both patient groups and both groups of relatives. Deficit patients showed significantly lower initiation acceleration. A similar pattern of results was seen in our pilot sample of relatives of deficit patients. These findings suggest that predictive smooth pursuit abnormality is associated with positive symptoms in schizophrenia, and that initiation abnormalities may be associated with the deficit syndrome.

Adult↗