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ABSTRACT: Individuals with schizophrenia demonstrate episodic memory (EM) deficits and abnormal EM-related brain activity. Experimental encoding manipulations significantly benefit memory performance in schizophrenia, suggesting that a strategic processing deficit may contribute to memory impairment. However, few studies have investigated the combined effects of encoding and retrieval strategies on EM in schizophrenia. The current study examined the impact of encoding and retrieval strategies on associative memory and brain activity in schizophrenia. We also assessed the role of verbal processing ability in response to strategic memory interventions in schizophrenia. Behavioral and functional neuroimaging data were collected from 23 participants with schizophrenia and 24 comparison subjects while performing associative memory encoding and recall tasks. Behaviorally, both schizophrenia participants and controls benefited from memory strategies and showed significant associations between verbal processing ability and recall. Additionally, among schizophrenia participants, encoding strategy use was associated with enhanced brain activity in multiple brain areas. Schizophrenia participants also demonstrated significant associations between verbal processing ability and encoding-related brain activity in prefrontal cortex. Findings suggest that memory performance and brain activity in schizophrenia can be enhanced via strategic manipulations, and individual differences in cognitive abilities in schizophrenia can affect behavioral and neurobiological responses to strategic memory interventions.
Journal of the International Neuropsychological Society 06/2011; 17(5):796-806. · 2.76 Impact Factor
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ABSTRACT: Recent work has demonstrated the potentially protective effects of the apolipoprotein E (APOE) ε2 allele on cognitive functioning in individuals at risk for developing Alzheimer disease. However, little is known regarding the effect of ε2 genotype on rate of change in daily functioning over time. The aim of the current study was to examine the relationship between APOE genotype and change over time in ability to perform daily activities.
We examined the relationship between APOE genotype and change in the ability to perform activities of daily living at 12- and 24-month intervals in 225 healthy comparison subjects, 381 individuals with amnestic mild cognitive impairment, and 189 individuals with Alzheimer disease who were enrolled in the Alzheimer's Disease Neuroimaging Initiative study. Neuropsychological measures were also collected at each follow-up.
Overall, individuals with at least one APOE-ε2 allele showed less functional decline over time and better performance on neuropsychological measures than those without an ε2 allele, even after controlling for potential confounders. When diagnostic groups were examined individually, presence of the ε2 allele continued to be associated with slower functional decline, although the relationship was no longer statistically significant in most cases, likely due to reduced statistical power.
Our findings suggest that the APOE-ε2 allele provides a buffer against significant changes in daily functioning over time and is associated with better neuropsychological performance across a number of measures.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 06/2011; 20(7):584-93. · 3.35 Impact Factor
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ABSTRACT: Individuals with schizophrenia demonstrate behavioral and neurobiological deficits in episodic memory. However, recent work suggests that episodic memory deficits in schizophrenia may be mitigated through specific encoding strategies. The current study directly compared brain activity and memory performance associated with two different verbal encoding orientations in the same group of schizophrenia participants, in order to more fully characterize the role of strategy in memory processing in this population. Participants included 18 individuals with schizophrenia and 15 healthy comparison participants. Participants encoded words under two conditions during separate fMRI scanning runs. During Incidental encoding, participants were required to make abstract/concrete judgments for each word. During Intentional encoding, participants were instructed to memorize each word for a later memory test. Free recall and a recognition task (utilizing the Remember/Know paradigm) were performed outside of the scanner. Consistent with prior work, schizophrenia participants recognized more words encoded Incidentally than Intentionally, although free recall remained substantially impaired. Schizophrenia participants were also less likely to give Remember judgments for old words and more likely to give Guess judgments for both old and new words. When functional magnetic resonance imaging data were examined, we found that Incidental encoding was associated with substantially fewer between-group differences (Control>Schizophrenia) than Intentional encoding. Furthermore, schizophrenia participants exhibited intact activity during encoding of items that were subsequently retrieved. Our results suggest that use of an Incidental encoding strategy improved recognition memory among individuals with schizophrenia and resulted in a pattern of encoding-related brain activity that was more similar to that seen in control participants. However, we found that Incidental encoding did not improve free recall in schizophrenia participants and abnormal brain activity in some regions was observed, despite improvements in recognition memory.
Psychiatry Research 10/2008; 164(1):1-15. · 2.52 Impact Factor
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ABSTRACT: First-degree relatives of individuals with schizophrenia show cognitive impairments that are similar to but less severe than their ill relatives. We have shown that memory impairments can be improved and prefrontal cortical (PFC) activity increased in individuals with schizophrenia by providing beneficial encoding strategies. The current study used a similar paradigm to determine whether siblings of individuals with schizophrenia (SIBs) also show increases in brain activity when presented with beneficial encoding strategies.
Twenty-one SIBs and 38 siblings of healthy comparison subjects underwent functional magnetic resonance imaging scans while engaged in deep (abstract/concrete judgments) and shallow (orthographic judgments) encoding. Subjects were then given a recognition memory test.
The groups did not differ on encoding or recognition accuracy, and the SIBs benefited from deep encoding to a similar degree as control subjects. The SIBs showed deep encoding-related activity in a number of PFC regions typically activated during semantic processing. However, SIBs showed more activity than control subjects in three subregions of PFC (left BA 44 & BA 47 bilaterally).
Siblings of individuals with schizophrenia benefit from supportive verbal encoding conditions. Like individuals with schizophrenia, SIBs also show increased task-related activity in a larger number of PFC subregions than control subjects during deep verbal encoding.
Biological Psychiatry 05/2007; 61(10):1141-7. · 8.28 Impact Factor
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ABSTRACT: Recent work suggests that episodic memory deficits in schizophrenia may be related to disturbances of encoding or retrieval. Schizophrenia patients appear to benefit from instruction in episodic memory strategies. We tested the hypothesis that providing effective encoding strategies to schizophrenia patients enhances encoding-related brain activity and recognition performance.
Seventeen schizophrenia patients and 26 healthy comparison subjects underwent functional magnetic resonance imaging scans while performing incidental encoding tasks of words and faces. Subjects were required to make either deep (abstract/concrete) or shallow (alphabetization) judgments for words and deep (gender) judgments for faces, followed by subsequent recognition tests.
Schizophrenia and comparison subjects recognized significantly more words encoded deeply than shallowly, activated regions in inferior frontal cortex (Brodmann area 45/47) typically associated with deep and successful encoding of words, and showed greater left frontal activation for the processing of words compared with faces. However, during deep encoding and material-specific processing (words vs. faces), participants with schizophrenia activated regions not activated by control subjects, including several in prefrontal cortex.
Our findings suggest that a deficit in use of effective strategies influences episodic memory performance in schizophrenia and that abnormalities in functional brain activation persist even when such strategies are applied.
Biological Psychiatry 08/2005; 58(1):47-55. · 8.28 Impact Factor
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ABSTRACT: Mismatch negativity (MMN) is an event-related brain potential that is sensitive to stimulus deviation from a repetitive pattern. The MMN is thought primarily to reflect the activity of sensory memory, with, at most, moderate influences of higher-level cognitive processes, such as attention. The MMN is reported to be reduced in patients with chronic schizophrenia. However, it is unknown whether MMN is reduced in patients with first-episode schizophrenia (at first hospitalization).
Subject groups comprised patients with chronic schizophrenia (n = 16) and older control subjects (n = 13), and patients with first-episode schizophrenia (n = 21) and younger control subjects (n = 27). The MMN was visualized by subtracting the averaged event-related brain potential to standard tones (1 kHz [95% of all tones]) from the event-related brain potential to pitch-deviant tones (1.2 kHz [5% of all tones]). The MMN voltage was the mean voltage from 100 to 200 milliseconds.
Pitch-deviant MMN was reduced by approximately 47% in patients with chronic illness along the sagittal midline relative to controls. The MMN was not reduced in patients with first-episode schizophrenia. All 4 groups showed approximately 64% larger MMN to pitch-deviant tones over the right hemisphere compared with the left hemisphere.
The pitch-deviant MMN reductions present in patients with chronic schizophrenia are not present at first hospitalization. The sensory, echoic memory functions indexed by MMN seem unaffected early in the schizophrenia disease process. Reductions in MMN amplitude may develop over time and index the progression of the disorder, although that can only be definitively determined by longitudinal assessments.
Archives of General Psychiatry 09/2002; 59(8):686-94. · 12.02 Impact Factor
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ABSTRACT: This research addresses the following questions: what is the prevalence and severity of first-rank symptoms (FRS) during an extended period of time in patients with schizophrenia and bipolar disorder with psychosis? Are the specific FRS listed in Diagnostic and Statistical Manual of Mental Disorders DSM, Third Edition, Revised/Fourth Edition Criterion A for schizophrenia diagnosis (a voice keeping a running commentary or voices conversing) more prevalent and severe in patients with schizophrenia than bipolar disorder with psychosis? Lastly, do FRS at index hospitalization in patients with schizophrenia predict the absence of later recovery?
This research follows a sample of patients with psychotic disorders who were evaluated at index hospitalization and then prospectively followed-up at 6 evaluations during next 20 years (n = 86). All patients were evaluated as part of a prospective research study designed to measure multiple factors of phenomenology, severity of illness, course of illness, prognosis, and global outcome.
First-rank symptoms are not exclusive to schizophrenia; they also occur in some bipolar patients. However, they are more frequent and more severe in patients with schizophrenia than bipolar disorder. Schizophrenia patients with FRS during the acute phase are more likely to have poorer long-term outcome than schizophrenia patients who do not have FRS during the acute phase.
Our results indicate FRS at the acute phase are not a clinicopathologic correlate specific to schizophrenia. However, the presence and severity of any FRS and specifically of the 2 FRS associated with Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised/Fourth Edition Criterion A are more prevalent and more severe in patients with schizophrenia than patients with bipolar disorder.
Comprehensive psychiatry 52(2):126-31. · 2.08 Impact Factor
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ABSTRACT: Individuals with schizophrenia have relative deficits in cognition, although little is known regarding the course of such deficits across the life span and at various stages of the illness. Furthermore, the relationship between psychosis and cognition has not been adequately explored to this point. Prospective, longitudinal, multi-assessment studies of the same patients across time are rare in the field and provide a unique opportunity to examine long-term changes in cognition among individuals with schizophrenia. As part of The Chicago Follow-up Study, we prospectively assessed 244 psychiatric inpatients, including individuals with schizophrenia, other psychotic disorders, and nonpsychotic depression. Assessments were conducted 7 times (once at index hospitalization and then 6 times subsequently for the next 20 years) to provide longitudinal data about cognition and symptoms, with a focus on 2 aspects of cognition: processing speed and the ability to access general knowledge. The Digit Symbol-Coding and Information subtests from the Wechsler Adult Intelligence scale were used to measure the 2 cognitive domains at each assessment. At all 7 assessments, individuals with schizophrenia performed more poorly than the other diagnostic groups on the 2 cognitive measures. However, after the acute phase (index hospitalization), individuals with schizophrenia demonstrated significant improvements in cognition and did not show evidence of cognitive decline over the remaining 6 assessments spanning 20 years. Our data support the presence of relative cognitive impairment in schizophrenia, as well as a pattern of stability in some cognitive areas after the acute phase. In addition, we find evidence for an association between relative cognitive impairment and psychosis.
Comprehensive psychiatry 51(5):471-9. · 2.08 Impact Factor
