Biomedical subjects

Gail Silipo

Publications and source records attributed to Gail Silipo.

9 recordsLinked to original sources

PubMed2006

Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments.

Visual processing deficits are an integral component of schizophrenia and are sensitive predictors of schizophrenic decompensation in healthy adults. The primate visual system consists of discrete subcortical magnocellular and parvocellular pathways, which project preferentially to dorsal and ventral cortical streams. Subcortical systems show differential stimulus sensitivity, while cortical systems, in turn, can be differentiated using surface potential analysis. The present study examined contributions of subcortical dysfunction to cortical processing deficits using high-density event-related potentials. Event-related potentials were recorded to stimuli biased towards the magnocellular system using low-contrast isolated checks in Experiment 1 and towards the magnocellular or parvocellular system using low versus high spatial frequency (HSF) sinusoidal gratings, respectively, in Experiment 2. The sample consisted of 23 patients with schizophrenia or schizoaffective disorder and 19 non-psychiatric volunteers of similar age. In Experiment 1, a large decrease in the P1 component of the visual event-related potential in response to magnocellular-biased isolated check stimuli was seen in patients compared with controls (F = 13.2, P = 0.001). Patients also showed decreased slope of the contrast response function over the magnocellular-selective contrast range compared with controls (t = 9.2, P = 0.04) indicating decreased signal amplification. In Experiment 2, C1 (F = 8.5, P = 0.007), P1 (F = 33.1, P < 0.001) and N1 (F = 60.8, P < 0.001) were reduced in amplitude to magnocellular-biased low spatial frequency (LSF) stimuli in patients with schizophrenia, but were intact to parvocellular-biased HSF stimuli, regardless of generator location. Source waveforms derived from inverse dipole modelling showed reduced P1 in Experiment 1 and reduced C1, P1 and N1 to LSF stimuli in Experiment 2, consistent with surface waveforms. These results indicate pervasive magnocellular dysfunction at the subcortical level that leads to secondary impairment in activation of cortical visual structures within dorsal and ventral stream visual pathways. Our finding of early visual dysfunction is consistent with and explanatory of classic literature showing subjective complaints of visual distortions and is consistent with early visual processing deficits reported in schizophrenia. Although deficits in visual processing have frequently been construed as resulting from failures of top-down processing, the present findings argue strongly for bottom-up rather than top-down dysfunction at least within the early visual pathway. Deficits in magnocellular processing in this task may reflect more general impairments in neuronal systems functioning, such as deficits in non-linear amplification and may thus represent an organizing principle for predicting neurocognitive dysfunction in schizophrenia.

Adult↗

PubMed2006

Reading impairment and visual processing deficits in schizophrenia.

Individuals with schizophrenia show magnocellular visual pathway abnormalities similar to those described in dyslexia, predicting that reading disturbance should be a common concomitant of schizophrenia. To date, however, reading deficits have not been well established, and, in fact, reading is often thought to be normal in schizophrenia based upon results of tests such as the WRAT, which evaluate single word reading. This study evaluated "real world" reading ability in schizophrenia, relative to functioning of the magnocellular visual pathway. Standardized psychoeducational reading tests and contrast sensitivity measures were administered to 19 patients and 10 controls. Analyses of between group differences were further refined by classification of participants into reading vs. non-reading impaired groups using a priori and derived theoretical models. Patients with schizophrenia, as a group, showed highly significant impairments in reading (p<0.04-p<0.001), with particular deficits on tests of rate, comprehension and phonological awareness. Between 21% and 63% of patients met criteria for dyslexia depending upon diagnostic model vs. 0-20% of the controls. The degree of deficit correlated significantly with independent measures of magnocellular dysfunction. Reading impairment in schizophrenia reaches the level of dyslexia and is associated with compromised magnocellular processing as hypothesized. Findings related to symptoms, functioning and recommendations for reading ability assessment are discussed.

Adolescent↗

PubMed2006

Neurocognitive and symptom correlates of daily problem-solving skills in schizophrenia.

Functional outcome for individuals with schizophrenia has been associated with cognitive impairment. Deficits in attention, memory, speed of information processing and problem-solving skills affect independent functioning, vocational performance, and interpersonal functioning. This study investigated the relationship between neurocognitive functioning, clinical symptoms and daily problem-solving skills in seriously and persistently ill persons. Thirty-eight inpatients and outpatients were administered a neurocognitive battery for attention, working memory, processing speed, perceptual organization, and executive functioning; and semi-structured clinical interviews using the BPRS and SANS. Estimates of daily problem-solving skills were obtained using the relevant factor subscale from the Independent Living Scales (ILS-PB). Daily problem-solving skills were significantly correlated with negative symptoms, processing speed, verbal memory, and working memory scores. A regression model using an enter method suggests that working memory and negative symptoms are significant predictors of daily problem-solving skills and account for 73.2% of the variance. Further analyses demonstrate that daily problem-solving skills and negative symptoms were significantly different for inpatients and outpatients and significantly correlated with community status. The findings suggest the ILS-PB has utility as a proxy measure for assessing real-world functioning in schizophrenia.

Activities of Daily Living↗

PubMed2005

Early-stage visual processing and cortical amplification deficits in schizophrenia.

BACKGROUND: Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-D-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. OBJECTIVES: To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. DESIGN, SETTING, AND PARTICIPANTS: Between-group study at an inpatient state psychiatric hospital and outpatient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. MAIN OUTCOME MEASURES: (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. RESULTS: Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P = .001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P = .001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P = .002), which was in turn related to deficits in complex visual processing (P< or =.04). Both evoked potential (P< or =.04) and contrast sensitivity (P = .01) measures significantly predicted community functioning. CONCLUSIONS: These findings confirm the existence of early-stage visual processing dysfunction in schizophrenia and provide the first evidence that such deficits are due to decreased nonlinear signal amplification, consistent with glutamatergic theories. Neuroimaging studies support the hypothesis of dysfunction within low-level visual pathways involving thalamocortical radiations. Deficits in early-stage visual processing significantly predict higher cognitive deficits.

Adult↗

PubMed2005

Impairments in generation of early-stage transient visual evoked potentials to magno- and parvocellular-selective stimuli in schizophrenia.

OBJECTIVE: Patients with schizophrenia demonstrate significant impairments of early visual processing, potentially implicating dysfunction of the magnocellular visual pathway. The present study evaluates transient visual evoked potential (tVEP) responses to stimuli biased toward the magnocellular (M) or parvocellular (P) systems in patients with schizophrenia vs. normal volunteers first to evaluate relative contributions of M and P systems to specific tVEP components in schizophrenia and, second, to evaluate integrity of early M and P processing in schizophrenia. METHODS: Seventy-four patients with schizophrenia and schizoaffective disorder were compared with 59 control subjects using separate stimuli to assess the tVEP response to M, P and mixed M/P conditions. Stimuli were biased toward M vs. P processing by manipulation of chromatic and achromatic contrast. C1, P1, N1 and P2 components were compared between patients and controls. All subjects showed 20/32 vision or better. RESULTS: Waveforms were obtained to low contrast (M), chromatic contrast (P) and high contrast (mixed M/P) stimuli in both patients and controls. C1 was present to P and mixed M/P stimuli. Patients showed a significant reduction in amplitude and an increase in latency of the C1 component. P1 was elicited primarily by M and mixed M/P stimuli, whereas N1 was elicited primarily by P and mixed M/P stimuli. Patients showed reductions in both P1 and N1 amplitudes across conditions. However, only reductions in P1 amplitude survived covariation for between group differences in visual acuity. Further, P1 amplitude reductions in the M condition correlated with a proxy measure of global outcome. CONCLUSIONS: M- and P-selective stimuli elicit differential components of the tVEP. Patients with schizophrenia show significant reductions in response even to simple visual stimuli. Deficits, particularly within the M system, may correlate significantly with global outcome and level of community functioning. SIGNIFICANCE: Whereas deficits in high-order cognitive processing have been extensively documented in schizophrenia, integrity of early-stage sensory processing has been studied to a lesser degree. The present findings suggest that deficits in early-stage visual processing are significantly related to overall clinical outcome in schizophrenia. Further, between-group differences in visual acuity may influence VEP results, even for subjects with 'normal' vision (20/32 or better).

Activities of Daily Living↗

PubMed2003

Magnocellular and parvocellular contributions to backward masking dysfunction in schizophrenia.

Patients with schizophrenia have repeatedly shown deficits in visual processing. These deficits have been well documented using visual backward masking (VBM). The VBM deficit in schizophrenia is thought to be due to aberrant interactions between magnocellular (M) and parvocellular (P) visual pathways. To date, no study has studied these claims with rigorous stimuli isolating M and P pathway responses. This study examined the function of each pathway and their interactions by creating M- and P-biased targets based on their known physiological properties. The M system responds to very low luminance contrast whereas the P system does not, and the P system responds to color contrast whereas the M system generally does not. Thus, to activate the P system, target letters and masks utilized color contrast, and to activate the M system, target letters and masks utilized very low luminance contrast. Four conditions were presented such that M- and P-biased targets were paired with both M- and P-biased masks. A significant Group x Mask Condition interaction was found when a P target was used in combination with an M or P mask, but not when an M target was used. In particular, schizophrenia patients needed significantly longer interstimulus intervals (ISIs) than controls to escape from masking in the P target/M mask condition, but not in any of the other three conditions. In addition, the critical stimulus durations (CSDs) for unmasked stimuli were significantly increased for both M and P targets in patients relative to controls. These findings demonstrate a significant impairment in M, but not P pathway, function in patients with schizophrenia. Furthermore, deficits of letter identification, including those of P targets, may also reflect impairment of the M pathway given the priming function of the dorsal stream.

Adult↗

PubMed2002

Placebo-controlled trial of D-cycloserine added to conventional neuroleptics, olanzapine, or risperidone in schizophrenia.

OBJECTIVE: The authors investigated the clinical effects of D-cycloserine when added to treatment with conventional neuroleptics, olanzapine, or risperidone for treatment-resistant schizophrenia. METHOD: Twenty-four patients participated in a double-blind, placebo-controlled, 6-week crossover trial with D-cycloserine, 50 mg/day, added to their fixed dose of antipsychotic medication. Clinical ratings were performed every 2 weeks. RESULTS: D-Cycloserine treatment was well tolerated and resulted in a significant reduction in negative symptoms (mean=15%). The degree of improvement did not differ between patients treated with conventional neuroleptics and those treated with olanzapine or risperidone. CONCLUSIONS: These data support the efficacy of the addition of 50 mg/day of D-cycloserine to treatment with conventional neuroleptics and suggest that therapeutic benefits may also be attained when D-cycloserine is added to olanzapine or risperidone.

Adult↗

PubMed2002

A naturalistic study of risperidone treatment outcome using prognosis-adjusted discharge rates in New York State inpatients.

BACKGROUND: Information concerning the effectiveness of newer atypical antipsychotics is derived largely from controlled clinical trials of relatively short duration. Limited information is available concerning naturalistic outcome of patients selected for clinical treatment with atypical antipsychotics. This study evaluates 1-year discharge rates among all patients treated with risperidone within the New York State inpatient psychiatric hospital system during the calendar years 1994 and 1995 ("period of interest") relative to patients treated with all other antipsychotic medications. METHOD: Data from the Integrated Research Database at Nathan Kline Institute (Orangeburg, N.Y.) were used. This database maintains complete treatment records for all inpatients within the New York State psychiatric inpatient system along with demographic, diagnostic, admission, and discharge information. Patients were identified at admission or first change in antipsychotic during the period of interest, and 1-year outcome was determined. RESULTS: 2198 risperidone-treated patients were identified versus 3259 treated with other antipsychotics. Length of hospitalization prior to treatment initiation was the primary predictor of discharge rate for both risperidone and control groups. When adjustment was made for between-group difference in prognosis (dischargeability), patients treated with risperidone within 30 days of admission were less likely to be discharged than those treated with all other agents (including clozapine), whereas risperidone was more effective in patients who had been hospitalized for 90 days or more prior to switch from another antipsychotic to risperidone. CONCLUSION: When database information is utilized to evaluate treatment effectiveness, adjustment must be made for a priori differences in prognosis or dischargeability. With appropriate methodology, database studies may indicate which patient groups are most likely to benefit from newer atypical antipsychotic agents.

Adult↗

PubMed1998

Double-blind, placebo-controlled, crossover trial of D-cycloserine adjuvant therapy for treatment-resistant schizophrenia.

Dysfunction of N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission may be relevant to the pathogenesis of negative symptoms in schizophrenia. The tuberculostatic compound D-cycloserine (DCS) acts as a partial agonist at the strychnine-insensitive glycine regulatory site on the NMDA receptor complex. Dose-finding trials suggest that DCS doses of 50-100 mg/d may be beneficial in the treatment of negative symptoms in schizophrenia. Nine treatment-resistant chronic schizophrenic patients participated in a double-blind, placebo-controlled, adjuvant treatment trial with 50 mg/d DCS. Between treatment-groups differences in symptom changes were not significant. However, a significant (p<0.05) reduction in negative symptoms was registered during treatment with DCS but not placebo. Greater reductions were registered in patients with lower baseline serum glycine levels (p<0.008). No side effects were registered. These preliminary findings indicate a potential role of DCS in the treatment of negative symptoms in schizophrenia. However, the degree of symptom reduction may be modest, at least among treatment-resistant inpatients.

Journal Article↗