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Matthew T Avila

Publications and source records attributed to Matthew T Avila.

At least 19 recordsLinked to original sources
PubMed2006

Spatial working memory as a cognitive endophenotype of schizophrenia: assessing risk for pathophysiological dysfunction.

Research suggests that first-degree relatives and individuals with schizophrenia spectrum personality disorders (SSPD) may represent nonpenetrant carriers of the genetic diathesis for schizophrenia. This study examined visuospatial working memory (SWM) as a cognitive endophenotype of schizophrenia by expanding the concept of risk for pathophysiological dysfunction beyond overt psychosis. Risk was thus defined by familial status and the presence or absence of SSPD. SWM was assessed in the following groups, in order of decreasing likelihood of genetic vulnerability: 23 patients with schizophrenia, 17 SSPD relatives of patients with schizophrenia, 23 non-SSPD relatives of patients with schizophrenia, 14 SSPD community members with no family history of psychosis, and 36 non-SSPD community members. SWM performance during a computer task was quantified by A-Prime. Relative risk ratios for SWM deficits were compared among the groups. Compared with community non-SSPD volunteers, relative risk (RR) of SWM deficits was significantly elevated in patients with schizophrenia (RR = 3.76, p = .002) and SSPD family members (RR = 2.97, p = .027), but not in the family non-SSPD (RR = 1.88, p = .241) or community SSPD (RR = 1.03, p = .971) groups. The pattern of SWM performance deficits reflected the proposed model of latent genetic liability, upholding SWM as a viable cognitive endophenotype. The results underscore the importance of including both familial liability and the schizophrenia spectrum when considering risk for schizophrenia and schizophrenia-related traits. This is particularly relevant for research efforts to identify pathophysiological components of the disease.

Adult↗
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↗
PubMed2004

Nicotine improves delayed recognition in schizophrenic patients.

RATIONALE: Nicotine has been shown to enhance some aspects of memory, attention and cognition in normal subjects and in some patient populations such as Alzheimer's and Parkinson's disease groups. OBJECTIVES: Memory disorders are consistently observed in schizophrenic patients, so it is of interest to determine whether nicotine might improve memory performance in these patients. METHODS: Delayed recognition was assessed using yes/no recognition of visuospatial designs. Working memory was assessed in a delayed match-to-sample paradigm using unfamiliar faces. Nicotine (1.0 mg delivered via nasal spray) was administered to schizophrenic patients and normal volunteers prior to testing in the nicotine condition. Results were compared to a baseline condition in which no nicotine was given. RESULTS: On both tasks, normal volunteers performed better overall than schizophrenic patients. Significant improvement following nicotine administration was obtained only on the delayed recognition task and only for the subset of schizophrenic patients who were smokers. This improvement reflected a reduction in false alarm rates in the nicotine condition; hit rates were unaffected by nicotine. CONCLUSIONS: These results suggest that nicotine enhances delayed recognition memory in schizophrenic patients who smoke, but that similar performance enhancement is not observed for working memory.

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

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↗
PubMed2003

Effects of nicotine on leading saccades during smooth pursuit eye movements in smokers and nonsmokers with schizophrenia.

Several studies have shown that schizophrenic patients and their biological relatives generate a greater number of leading saccades during smooth pursuit eye movement (SPEM) tasks. This abnormality may reflect a failure of cortical and/or cerebellar areas to coordinate saccadic and pursuit eye movements during visual tracking. The pharmacology of this phenomenon is not known. Here, we sought to replicate and extend the findings of Olincy et al (1998), who found that nicotine transiently reduced the number of leading saccades during SPEMs. A total of 27 subjects with schizophrenia (17 males; 14 smokers), and 25 healthy comparison subjects (nine males; 14 smokers) completed an eye-tracking task after receiving a 1.0 mg nasal spray of nicotine and during drug-free conditions. Results confirm that nicotine reduces the number of leading saccadic eye movements during visual tracking in schizophrenic patients. Baseline impairments and the beneficial effects of nicotine were not restricted to patient smokers, as nonsmoker patients exhibited the greatest number of leading saccades in the no drug condition and exhibited the most pronounced improvements after nicotine administration. Improvement in patient nonsmokers was not a function of previous smoking history. No effect of nicotine was observed in control nonsmokers. In contrast to the previous study, nicotine appeared to improve performance in control smokers. Overall, the study results support a functional role of nACh receptors in improving eye-tracking performance, and are consistent with the hypothesis, articulated by several investigators, that nACh receptor system abnormalities are responsible for a number of schizophrenia-related neurophysiological deficits.

Adult↗
PubMed2003

Using neurophysiological markers of genetic risk to define the boundaries of the schizophrenia spectrum phenotype.

There is considerable evidence that schizophrenia spectrum personality (SSP) disorders mark genetic risk for schizophrenia. Use of the spectrum phenotype in genetic and neurophysiological studies may prove informative. However, the degree to which the current diagnostic criteria correspond with genetic risk is unclear. This can be assessed by observing how measures of liability among SSP subjects change as a function of diagnostic criteria. In this study the generalized estimating equation method was used to assess changes in eye-tracking performance among SSP and non-SSP family and community groups employing various diagnostic criteria. Eye-tracking deficits among SSP relatives remained statistically higher compared with the other groups across progressively more liberal SSP criteria. The results suggest that fewer traits than are used in clinical diagnoses can effectively identify the spectrum phenotype among relatives of schizophrenia patients. Thus, reduced criteria may be used in research to increase "high risk" sample size and power to detect neurophysiological and genetic differences. Our results provide suggestive evidence that the use of clinical criteria in research may, in fact, underidentify at-risk individuals--potentially distorting genetic and neurophysiological findings.

Adult↗
PubMed2003

Neurodevelopmental interactions conferring risk for schizophrenia: a study of dermatoglyphic markers in patients and relatives.

Schizophrenia is hypothesized to be the result of an interaction between specific genetic factors and nonspecific insults during embryonic development. Dermatoglyphic abnormalities appear to mark these putative insults--providing information about the temporal sequence of aberrant developmental events as well as the organism's vulnerability to their adverse effects. In the present study, dermatoglyphic measures thought to mark first and second trimester development were examined in patients with schizophrenia and first degree relatives and compared with those of healthy controls to examine whether genetic factors may mediate this vulnerability. Both patients with schizophrenia and relatives exhibited dermatoglyphic abnormalities compared with controls. Patients were more likely to exhibit dermatoglyphic abnormalities indicative of early second trimester development, which suggests that vulnerability interacts with the timing of insults to produce overt disease. These findings indicate that the two-hit model, in which schizophrenia-specific genetic factors combine in an additive fashion with environmental insults to produce the illness, may be oversimplified. Rather, the data are consistent with a more complex model in which nonspecific genetic factors that increase susceptibility to developmental abnormalities interact with insults and specific genetic factors.

Adult↗
PubMed2003

A model of smooth pursuit eye movement deficit associated with the schizophrenia phenotype.

Smooth pursuit eye movement (SPEM) abnormalities in schizophrenia, although well described, are poorly understood. SPEMs are initiated by motion of an object image on the retina. During initiation, the eyes accelerate until they approximate target velocity and a state of minimal retinal motion is achieved. Pursuit is maintained through predictive eye movements based on extraretinal signals and corrections based on deviations from the fovea. Here, initiation and predictive pursuit responses were used to estimate the contributions of retinal and extraretinal signals to pursuit maintenance in schizophrenia patients' relatives. Relatives exhibited normal initiation, but had lower predictive pursuit gain compared with controls. Relatives had normal gain during pursuit maintenance, presumably by greater reliance on retinal error. This was confirmed by group differences in regression coefficients for retinal and extraretinal measures, and suggests that schizophrenia SPEM deficits involve reduced ability to maintain or integrate extraretinal signals, and that retinal error may be used to compensate.

Humans↗
PubMed2002

The effects of nicotine on specific eye tracking measures in schizophrenia.

BACKGROUND: The role of neuronal nicotinic receptors in the etiology and pathophysiology of schizophrenia has been suggested by postmortem findings as well as by linkage analysis implicating chromosome 15q14, the region where the alpha-7 nicotinic receptor gene is located. In addition, drug probe studies show that acute nicotine administration reverses sensory gating and eye-tracking deficits associated with the genetic liability for schizophrenia. The purpose of the current study was to examine the effects of acute administration of nicotine on specific measures of smooth pursuit eye movements and visual attention. METHODS: Twenty nine subjects with schizophrenia (15 smokers and 14 nonsmokers), and 26 healthy comparison subjects (15 smokers and 11 nonsmokers) completed testing. The effects of 1 mg of nicotine, administered by nasal spray, on smooth pursuit initiation, pursuit maintenance, and predictive pursuit were examined. RESULTS: Nicotine significantly improved eye acceleration during smooth pursuit initiation in both smoker and nonsmoker patients but had no effects in healthy subjects. The fact that patient initiation eye acceleration in response to nicotine was significantly higher than in healthy subjects suggests that the lack of effect in healthy subjects was not due to ceiling effects. Nicotine significantly improved pursuit gain during maintenance at a target velocity of 18.7 deg/sec. There were no effects of nicotine on visually guided and memory saccades, or visual attention (d' from a continuous performance task). CONCLUSIONS: Nicotine showed differential effects in schizophrenic patients compared to healthy subjects. These effects of nicotine were unlikely the result of differences in vigilance or sustained attention, because saccadic peak velocity, a sensitive measure of vigilance, and continuous performance task measures were not affected by nicotine. These findings are not thought to be an artifact of nicotine withdrawal effects at baseline, because the abstinence period was very short, and there were similar effects of nicotine on initiation in nonsmoker patients. These findings suggest an abnormality in neuronal nicotinic system functioning in schizophrenic patients.

Administration, Intranasal↗
PubMed2002

Effects of ketamine on leading saccades during smooth-pursuit eye movements may implicate cerebellar dysfunction in schizophrenia.

OBJECTIVE: Ketamine has proved a useful probe in the study of schizophrenia. Recent studies have shown that ketamine causes abnormalities in eye tracking similar to those seen in patients with schizophrenia. The authors examined the effects of ketamine on leading saccadic eye movements, a specific component of the smooth-pursuit response shown to be abnormal in schizophrenia patients and their relatives. METHOD: Twelve normal healthy volunteers received a 0.1 mg/kg bolus injection of ketamine or placebo in double-blind fashion during a smooth-pursuit eye-movement task. The number of leading saccades and the ratios of leading saccades to smooth-pursuit response time and to total saccadic eye-movement time were measured. RESULTS: Ketamine significantly increased the number of leading saccades and increased the leading saccade ratios for more slowly moving targets. Similar nonsignificant effects were noted at higher target speeds. Ketamine-induced abnormalities were similar to those observed in relatives of schizophrenia patients under drug-free conditions. CONCLUSIONS: These results suggest that neurotransmission mediated by N-methyl-D-aspartate (NMDA) is involved in eye-tracking abnormalities. The generation of disruptive leading saccades during smooth pursuit is thought to be mediated by frontal-thalamic-cerebellar circuitry. Evidence that the locus of this and other ketamine-induced smooth-pursuit eye-movement deficits involves NMDA receptor functioning in the cerebellum is suggested.

Adult↗