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Biomedical subjects

Dawn I Velligan

Publications and source records attributed to Dawn I Velligan.

15 recordsLinked to original sources
PubMed2006

Dissociable mechanisms for memory impairment in bipolar disorder and schizophrenia.

BACKGROUND: Although memory deficits are consistently reported in schizophrenia and bipolar disorder, the mechanisms underlying these impairments are poorly understood. Clarifying the nature and degree of overlap in memory deficits between the two illnesses could help to distinguish brain systems disrupted in these illnesses, and indicate cognitive remediation strategies to improve patient outcomes. METHOD: We examined performance on a non-verbal memory task in clinically stable out-patients with bipolar disorder (n=40), schizophrenia (n=40), and healthy comparison subjects (n=40). This task includes conditions in which distinct mnemonic strategies -- namely, using context to organize familiar stimuli or using holistic representation of novel stimuli -- facilitate performance. RESULT: When compared to a reference condition, bipolar patients had deficits consistent with organizational dysfunction and poor detection of novel information. Although patients with schizophrenia performed worse than the other groups, they were only differentially impaired when organizational demands were significant. Task performance was not correlated with severity of clinical symptomatology. CONCLUSIONS: This pattern of distinct memory impairments implies disturbances in partially overlapping neural systems in bipolar disorder and schizophrenia. Evidence of impairment in detection of novel stimuli that is unique to bipolar disorder suggests that, while the absolute level of cognitive dysfunction is less severe in bipolar disorder as compared to schizophrenia, subtle disruptions in memory are present. These findings can be used to plan targeted cognitive remediation programs by helping patients to capitalize on intact functions and to learn new strategies that they do not employ without training.

Adult↗
PubMed2006

Defining and assessing adherence to oral antipsychotics: a review of the literature.

The definition and assessment of adherence vary considerably across studies. Increasing consensus regarding these issues is necessary to improve our understanding of adherence and the development of more effective treatments. We review the adherence literature over the past 3 decades to explore the definitions and assessment of adherence to oral antipsychotics in schizophrenia patients. A total of 161 articles were identified through MEDLINE and PsycINFO searches. The most common method used to assess adherence was the report of the patient. Subjective and indirect methods including self-report, provider report, significant other report, and chart review were the only methods used to assess adherence in over 77% (124/161) of studies reviewed. Direct or objective measures including pill count, blood or urine analysis, electronic monitoring, and electronic refill records were used in less than 23% (37/161) of studies. Even in studies utilizing the same methodology to assess adherence, definitions of an adherent subject varied broadly from agreeing to take any medication to taking at least 90% of medication as prescribed. We make suggestions for consensus development, including the use of recommended terminology for different subject samples, the increased use of objective or direct measures, and the inclusion in all studies of an estimate of the percentage of medication taken as prescribed in an effort to increase comparability among studies. The suggestions are designed to advance the field with respect to both understanding predictors of adherence and developing interventions to improve adherence to oral antipsychotic medications.

Antipsychotic Agents↗
PubMed2006

Cognitive rehabilitation for schizophrenia and the putative role of motivation and expectancies.

Cognitive rehabilitation (CR) approaches seek to enhance cognitive processes or to circumvent cognitive impairments in schizophrenia in an effort to improve functional outcome. In this review we examine the research findings on the 8 evidence-based approaches to cognitive remediation listed in the 2005 Training Grid Outlining Best Practices for Recovery and Improved Outcomes for People With Serious Mental Illness, developed by the American Psychological Association Committee for the Advancement of Professional Practice. Though the approaches vary widely in theoretical orientation and methods of intervention, the results are, for the most part, encouraging. Improvements in attention, memory, and executive functioning have been reported. However, many persons with schizophrenia are more impaired in real-world functioning than one would expect given the magnitude of their cognitive deficits. We may need to look beyond cognition to other targets such as motivation to identify the reasons that many persons with schizophrenia demonstrate such marked levels of disability. Although a number of current CR approaches address motivation to varying degrees, treating motivation as a primary target may be needed to maximize CR outcomes.

Adaptation, Psychological↗
PubMed2006

Trail making test errors and executive function in schizophrenia and depression.

The Trail Making Test (TMT) frequently is used as a measure of executive cognitive function. However, traditional use of test completion time as the primary outcome score does not give the more detailed information on cognitive processes that analysis of test-taking errors may provide. The present study compared TMT performance of three groups: patients with schizophrenia, patients with major depression, and healthy control participants (n = 30 for each group). Three operationally defined error types were examined: (a) tracking, (b) perseverative, and (c) proximity. Although both patient groups were slower than the healthy control group, only the schizophrenia group made significantly more errors, particularly tracking errors, suggesting a greater degree of cognitive disorganization. Within-group analysis of a larger group of schizophrenia patients (n = 84) revealed that TMT time was most strongly associated with the Withdrawal-Retardation factor of the Brief Psychiatric Rating scale. In contrast, TMT errors were most strongly associated with the Conceptual Disorganization factor. Comparisons of TMT scores and other cognitive tests showed moderate to high associations with tests of working memory, psychomotor speed, and executive function. Stepwise regression analysis revealed an independent association between Digit Cancellation and Part B Time, indicating a unique contribution of visuomotor scanning to performance. In contrast, Part B errors were uniquely associated with the Verbal Series Attention Test and the Token Test, tests of mental tracking and executive-mediated working memory, respectively. These findings demonstrate the utility of TMT error analysis in revealing cognitive deficits not traditionally captured using completion time as the sole outcome variable.

Adult↗
PubMed2006

Differential working memory impairment in bipolar disorder and schizophrenia: effects of lifetime history of psychosis.

BACKGROUND: Although bipolar disorder and schizophrenia have long been viewed as distinct illnesses, there is growing evidence that these two complex diseases share some common genes, which may manifest as overlapping neuropsychological impairments. Although working memory dysfunction has been proposed to be central to the pathophysiology of schizophrenia, it has received less attention in studies of bipolar disorder. METHOD: We applied measures of working memory to patients with schizophrenia (n = 15), patients with schizoaffective disorder (n = 15), patients with psychotic (n = 11) and non-psychotic (n = 15) bipolar disorder, and demographically matched healthy subjects (n = 32), in order to determine the extent to which these groups show common or unique impairments. RESULTS: While patients with bipolar disorder (with and without psychotic features) and those with schizophrenia/schizoaffective disorder were impaired on backward digit span, only patients with a lifetime history of psychotic features, regardless of diagnosis, were impaired on spatial delayed response task. CONCLUSIONS: Backward digit span performance is comparable in bipolar disorder and schizophrenia, and may be an appropriate endophenotypic marker that cuts across diagnostic categories. In contrast, spatial working memory performance clearly distinguishes non-psychotic bipolar disorder patients from patients with functional psychosis.

Adult↗
PubMed2006

Use of environmental supports among patients with schizophrenia.

OBJECTIVE: Cognitive adaptation training is a psychosocial treatment that uses individually tailored environmental supports, such as signs, calendars, hygiene supplies, and pill containers, to cue and sequence adaptive behavior in the client's home environment. Generic environmental supports offer a less costly treatment that provides a predetermined package of helpful supports to clients at the time of their routine clinic visit. Previous studies have demonstrated the efficacy of cognitive adaptation training. The study reported here examined the extent to which environmental supports are used by clients. METHODS: As part of an ongoing study, persons with schizophrenia were randomly assigned to one of three conditions: cognitive adaptation training, generic environmental supports, or assessment only. Rates of use of supports for the first three months of treatment were examined for the first 64 patients assigned to the first two groups. RESULTS: Rates of overall use averaged approximately 80 percent for cognitive adaptation training and 44 percent for generic environmental supports. Specific categories of supports were also significantly more likely to be used by patients who were receiving cognitive adaptation training. More than 66 percent of patients in cognitive adaptation training were classified as high users of supports (used more than 75 percent of supports provided appropriately), compared with only 13 percent of those who were receiving generic environmental supports. CONCLUSIONS: Environmental supports have been found to improve functional behaviors for patients with schizophrenia. However, supports are not likely to be used unless they are customized for individual clients and set up in the home environment.

Adaptation, Psychological↗
PubMed2005

Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia.

Although there is considerable evidence that patients with schizophrenia fail to activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal comparison subjects when performing working memory or executive tasks, hypofrontality may be coupled with relatively increased activity in other brain regions. However, most imaging studies of working memory in schizophrenia have focused on DLPFC activity. The goal of this work is to review functional neuroimaging studies that contrasted patients with schizophrenia and healthy comparison subjects during a prototypical working memory task, the n-back paradigm, to highlight areas of hyper- and hypoactivation in schizophrenia. We utilize a quantitative meta-analysis method to review 12 imaging studies where patients with schizophrenia were contrasted with healthy comparison subjects while performing the n-back paradigm. Although we find clear support for hypofrontality, we also document consistently increased activation in anterior cingulate and left frontal pole regions in patients with schizophrenia compared to that in controls. These data suggest that whereas reduced DLPFC activation is reported consistently in patients with schizophrenia relative to healthy subjects, abnormal activation patterns are not restricted to this region, raising questions as to whether the pathophysiological dysfunction in schizophrenia is specific to the DLPFC and about the relationship between impaired performance and aberrant activation patterns. The complex pattern of hyper- and hypoactivation consistently found across studies implies that rather than focusing on DLPFC dysregulation, researchers should consider the entire network of regions involved in a given task when making inferences about the biological mechanisms of schizophrenia.

Brain↗
PubMed2004

A brief cognitive assessment for use with schizophrenia patients in community clinics.

Cognitive impairment is a prominent feature of schizophrenia. The availability of very brief measures may increase the use of cognitive assessment in routine care settings. We examined the reliability and validity of the brief cognitive assessment (BCA), a battery that takes approximately 15 min to administer and score, and that was designed to be sensitive to changes in cognition with novel antipsychotics. The BCA was administered to 340 outpatients on two occasions, 3 months apart. A sub-sample of subjects received a full battery of cognitive tests (n=97) and additional measures of functional outcome. Results indicated that the BCA had very good test-retest reliability and inter-item consistency. Moreover, the BCA was strongly correlated with a comprehensive battery (r=0.72; p<0.0001) which took 8 to 10 times longer to administer. Finally, both cognitive batteries were correlated similarly with measures of community functioning. Changes over time for individual patients can be interpreted in the context of normative data available for each test in the BCA. The data provide preliminary evidence for the reliability and validity of the BCA. Further studies examining the utility of the BCA for tracking changes in cognitive functioning with treatment are encouraged.

Adult↗
PubMed2004

The Texas medication algorithm project: clinical results for schizophrenia.

In the Texas Medication Algorithm Project (TMAP), patients were given algorithm-guided treatment (ALGO) or treatment as usual (TAU). The ALGO intervention included a clinical coordinator to assist the physicians and administer a patient and family education program. The primary comparison in the schizophrenia module of TMAP was between patients seen in clinics in which ALGO was used (n = 165) and patients seen in clinics in which no algorithms were used (n = 144). A third group of patients, seen in clinics using an algorithm for bipolar or major depressive disorder but not for schizophrenia, was also studied (n = 156). The ALGO group had modestly greater improvement in symptoms (Brief Psychiatric Rating Scale) during the first quarter of treatment. The TAU group caught up by the end of 12 months. Cognitive functions were more improved in ALGO than in TAU at 3 months, and this difference was greater at 9 months (the final cognitive assessment). In secondary comparisons of ALGO with the second TAU group, the greater improvement in cognitive functioning was again noted, but the initial symptom difference was not significant.

Adolescent↗
PubMed2004

Cognitive functioning in schizophrenia: a consensus statement on its role in the definition and evaluation of effective treatments for the illness.

BACKGROUND: Truly effective treatments for schizophrenia require much more than clinical efficacy. Symptom improvement is all that is required to demonstrate clinical efficacy. However, for a treatment to be effective in a wide-ranging manner, improvement in various life domains, such as social functioning, independent living, and employment, should also be found. Thus, a much wider range of improvements, not widely produced by previous treatments, is required to take treatment for schizophrenia to a new level of effectiveness. CONSENSUS PROCESS: A teleconference consensus meeting was held with the bylined authors on December 10, 2002, to explore the factors that hinder the most effective treatments for schizophrenia. We argue that a possible unifying factor underlying these apparently disparate domains of effective treatment is cognitive functioning, which is impaired in people with schizophrenia. Treatment of cognitive dysfunction may have a central role in increasing the breadth of effective treatment for schizophrenia. CONCLUSIONS: Novel antipsychotics and specific cognitive-enhancing medications have preliminarily been shown to have cognitive benefits that might lead to broader effectiveness of treatments, eventually reflected in improvements in the daily lives of patients. These treatments may have their greatest impact when combined with focused psychological interventions. While the research to date does not provide a large number of successes, this area will be one of considerable research interest for the next decade, with developments likely to be very important to clinicians treating patients with schizophrenia.

Antipsychotic Agents↗
PubMed2003

The effectiveness of quetiapine versus conventional antipsychotics in improving cognitive and functional outcomes in standard treatment settings.

OBJECTIVE: To examine the effectiveness of quetiapine versus conventional antipsychotics in improving cognitive and functional outcomes. METHOD: Forty stable outpatients with DSM-IV schizophrenia treated in public outpatient clinics were randomly assigned to continue taking conventional antipsychotic medications or switch to quetiapine for 6 months, beginning September 1998 and ending July 2000. Neurocognitive and functional measures were obtained at study entry, 3 months, and 6 months by raters blinded to treatment. Group differences were examined using repeated-measures analyses of covariance for mixed models. RESULTS: The mean (SD) dose of conventional antipsychotics in chlorpromazine equivalents was 348.00 (348.28) mg/day; the mean (SD) dose of quetiapine was 319.25 (142.55) mg/day. A cognitive function summary score improved in the quetiapine group relative to the group treated with conventional antipsychotics over the 6-month period (F = 5.80, df = 1,28.9; p <.023). Patients taking quetiapine did better with respect to both verbal fluency (initiation) and verbal memory. There were also statistically significant group differences with respect to quality of life favoring the quetiapine group (F = 4.87, df = 1,29; p <.04). Differences were not found with respect to adaptive functioning. CONCLUSION: Quetiapine improved cognition relative to conventional agents. After 6 months, groups differed by more than 1 standard deviation when baseline cognitive functioning was taken into account. No group differences were found with respect to improvements in community functioning. Improvements in adaptive functioning may lag behind improvements in cognition. Psychosocial programming may be necessary to translate gains in cognition into improvements in adaptive functioning.

Adult↗
PubMed2002

Frontal Systems Behavior Scale in schizophrenia: relationships with psychiatric symptomatology, cognition and adaptive function.

Schizophrenia patients often exhibit impairments in executive functioning on formal testing and exhibit behaviors consistent with executive/frontal impairment in daily life. The Frontal Systems Behavior Scale (FrSBe) assesses behaviors associated with frontal lobe damage including executive dysfunction, apathy and disinhibition. We examined the reliability and validity of the FrSBe in 131 schizophrenia outpatients. Subjects were rated on the FrSBe and received symptom, cognitive and functional assessments. Statistical tests were corrected for multiple comparisons. The FrSBe was found to have good internal consistency and test-retest reliability. All three dimensions of the FrSBe (i.e. executive dysfunction, apathy and disinhibition) were significantly correlated with poor adaptive functioning as measured by the Social and Occupational Functioning Scale and the Functional Needs Assessment. In addition, differential relationships were found for apathy and disinhibition with symptoms as rated from the Brief Psychiatric Rating Scale and with cognitive variables including Trails B and verbal fluency scores. A multivariate analysis of variance examined differences on the FrSBe between patients and a group of 51 education-matched controls. Patients had significantly greater impairment on the FrSBe than controls. These differences were found for all FrSBe subscales. Results support the use of the FrSBe to characterize goal-directed behavior in schizophrenia patients.

Adaptation, Psychological↗
PubMed2002

Does cognitive function improve with quetiapine in comparison to haloperidol?

Recent evidence suggests that schizophrenia patients taking atypical antipsychotic medications may perform better on some tests of cognitive function than those treated with older antipsychotics. The current study compared the effects of quetiapine and haloperidol on measures of executive function, memory and attention. Subjects were 58 stable outpatients with schizophrenia (DSM III-R) who received a battery of cognitive tests as part of a randomized, double-blind, multi-site clinical efficacy study conducted by AstraZeneca Pharmaceuticals. Cognitive assessments were conducted prior to randomization when patients were receiving < or =30 mg haloperidol or equivalent (mean: 9.2mg/day haloperidol equivalents), and again after 24 weeks of fixed-dose treatment with either quetiapine 600 or 300 mg/day or haloperidol 12 mg/day. Analyses of covariance with planned comparisons were used to compare scores on cognitive measures at the end of 24 weeks by treatment group with baseline cognitive function scores used as covariates. Patients receiving quetiapine 600 mg/day improved to a greater extent than patients receiving haloperidol on overall cognitive function (p<0.02). Specific differences were found for executive function (Verbal Fluency Test, p<0.04), attention (Stroop Color Word Test, p<.03) and verbal memory (Paragraph Recall Test, p<0.02). Treatment group differences were not solely due to benztropine use, medication side effects, or changes in symptomatology. Treatment with quetiapine at higher doses (600 mg/day) relative to haloperidol appears to have a positive impact on important domains of cognitive performance that have been found to predict role function and community outcomes in patients with schizophrenia.

Antipsychotic Agents↗
PubMed2002

A randomized single-blind pilot study of compensatory strategies in schizophrenia outpatients.

In a previous study, we found that cognitive adaptation training (CAT)--a manual-driven program of environmental supports designed to bypass cognitive deficits--improved multiple domains of outcome in schizophrenia patients recently discharged from a State psychiatric facility. The present study examined the efficacy of CAT in a sample of patients who had been in the community at least 3 months. Forty-five medicated schizophrenia patients were randomly assigned for 9 months to one of three conditions: (1) CAT, (2) a condition that controlled for therapist time and provided environmental changes unrelated to cognitive deficits, or (3) follow-up only. Comprehensive assessments were conducted every 3 months by blinded raters. Results of repeated measures analyses of covariance for mixed models indicated that patients participating in CAT had better adaptive function and quality of life, and fewer positive symptoms than those in the two non-CAT conditions. Results indicate that compensatory strategies may improve various outcomes in schizophrenia outpatients.

Adult↗