Neuropsychological Deficits in Neuroleptic Naive Patients With First-Episode Schizophrenia

Saykin, Andrew J.; Shtasel, Derri; Gur, Raquel E.; Kester, D. Brian; Mozley, Lyn Harper; Stafiniak, Paul; Gur, Ruben C.

doi:10.1001/archpsyc.1994.03950020048005

Cited by 1,011 publications

(597 citation statements)

References 43 publications

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“…Cognitive impairment often accompanies (Saykin et al, 1994) or precedes (Fuller et al, 2002;Hawkins et al, 2004) the onset of psychosis, and remains throughout the course of illness (Green and Braff, 2001;Heinrichs and Zakzanis, 1998;Bilder et al, 2000). The range of cognitive impairments is diverse and can include impairment of verbal memory, attention, general intelligence, spatial ability, and executive function.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Donepezil in Patients with Schizophrenia or Schizoaffective Disorder: Significant Placebo/Practice Effects in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Keefe

Malhotra

Meltzer

et al. 2007

Neuropsychopharmacol

135

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Altered expression of central muscarinic and nicotinic acetylcholine receptors in hippocampal and cortical regions may contribute to the cognitive impairment exhibited in patients with schizophrenia. Increasing cholinergic activity through the use of a cholinesterase inhibitor (ChEI) therefore represents a possible strategy for cognitive augmentation in schizophrenia. We examined the efficacy and safety of the ChEI donepezil as cotreatment for mild to moderate cognitive impairment in schizophrenia or schizoaffective disorder in a prospective, 12-week, placebo-controlled, double-blind, parallel-group study. In total, 250 patients (18-55 years) with schizophrenia or schizoaffective disorder who were clinically stabilized on risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole, alone or in combination, were enrolled at 38 outpatient psychiatric clinics in the United States. Patients were randomized to donepezil 5 mg q.d. for 6 weeks then 10 mg q.d. for 6 weeks, or placebo administered as oral tablets. The primary outcome measure was the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) neurocognitive battery composite score. In the intent-to-treat sample (donepezil, n ¼ 121; placebo, n ¼ 124), both treatments showed improvement in the composite score from baseline to week 12. At week 12, cognitive improvement with donepezil was similar to that with placebo (last-observation-carried-forward effect size, 0.277 vs 0.411; p ¼ 0.1182) and statistically significantly inferior for the observed-cases analysis (0.257 vs 0.450; p ¼ 0.044). There was statistically significant improvement in the Positive and Negative Syndrome Assessment Scale negative symptoms score for placebo compared with donepezil, while total and positive symptom scores were similar between both treatments. Statistically significant improvements in positive symptoms score and Clinical Global Impression-Improvement for donepezil compared with placebo were noted at Week 6. Treatment-emergent adverse events (AEs) were observed for 54.5% of donepezil-and 61.3% of placebo-treated patients; most AEs were rated as mild to moderate in severity. Donepezil was safe and well-tolerated but was not effective compared with placebo as a cotreatment for the improvement of cognitive impairment in this patient population. A significant and surprisingly large placebo/practice effect was observed among placebotreated patients, and is a serious consideration in future clinical trial study designs for potential cognitive enhancing compounds in schizophrenia.

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Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Donepezil in Patients with Schizophrenia or Schizoaffective Disorder: Significant Placebo/Practice Effects in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Keefe

Malhotra

Meltzer

et al. 2007

Neuropsychopharmacol

135

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“…Patients with schizophrenia demonstrate severe neurocognitive deficits that affect not only higher-order cognitive function (Goldberg and Gold, 1995;Goldman-Rakic, 1994;Green and Nuechterlein, 1999b;Jaeger et al, 2003;Saykin et al, 1994) but also early levels of perceptual processing (Braff et al, 1991;Javitt et al, 1999;Turetsky et al, 2003). In the visual system, deficits have been shown to include increased visual thresholds (Cadenhead et al, 1997;Schechter et al, 2003), greater sensitivity to backward masking (Braff et al, 1991;Butler et al, 1996;Green and Nuechterlein, 1999a;Schechter et al, 2003), and decreased contrast sensitivity (Butler et al, 2005;Keri et al, 2002;Slaghuis and Curran, 1999), as well as motion perception (Chen et al, 1999;Li, 2002;Schwartz et al, 1999) and eye tracking deficits (Holzman et al, 1974;Levy et al, 1993;Trillenberg et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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

Schechter

Butler

Zemon

et al. 2005

Clinical Neurophysiology

136

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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

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“…Neurocognitive deficits represent an integral feature of schizophrenic pathology and include deficits in higher cognitive functions such as attention, executive functions, and memory (Bilder, 1998;Cornblatt and Keilp, 1994;Pantelis et al, 1998;Saykin et al, 1994). Patients are also impaired in simple tasks probing sensory memory across different modalities (Javitt et al, 1997Strous et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Effects of the 5-HT2A Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Performance Task: Implications for the Neuropharmacology of Cognitive Deficits in Schizophrenia

Umbricht

Vollenweider

Schmid

et al. 2003

Neuropsychopharmacol

164

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Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an 'AX'-type continuous performance test (AX-CPT)Fmeasures of auditory and visual context-dependent information processingFin a similar manner as observed in schizophrenia. This placebo-controlled study investigated effects of the 5-HT 2A receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin administration induced significant performance deficits in the AX-CPT, but failed to reduce MMN generation significantly. These results indirectly support evidence that deficient MMN generation in schizophrenia may be a relatively distinct manifestation of deficient NMDAR functioning. In contrast, secondary pharmacological effects shared by NMDAR antagonists and the 5-HT 2A agonist (ie disruption of glutamatergic neurotransmission) may be the mechanism underlying impairments in AX-CPT performance observed during both psilocybin and ketamine administration. Comparable deficits in schizophrenia may result from independent dysfunctions of 5-HT 2A and NMDAR-related neurotransmission.

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Neuropsychological Deficits in Neuroleptic Naive Patients With First-Episode Schizophrenia

Cited by 1,011 publications

References 43 publications

Efficacy and Safety of Donepezil in Patients with Schizophrenia or Schizoaffective Disorder: Significant Placebo/Practice Effects in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Efficacy and Safety of Donepezil in Patients with Schizophrenia or Schizoaffective Disorder: Significant Placebo/Practice Effects in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

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

Effects of the 5-HT2A Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Performance Task: Implications for the Neuropharmacology of Cognitive Deficits in Schizophrenia

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