PubMed Health⌕ Search

Biomedical subjects

Katherine E Burdick

Publications and source records attributed to Katherine E Burdick.

16 recordsLinked to original sources
PubMed2006

DTNBP1 genotype influences cognitive decline in schizophrenia.

OBJECTIVE: Intellectual decline is common in schizophrenia and predicts functional outcome. While many patients undergo intellectual decline that typically predates the onset of symptoms, few studies have investigated the underlying mechanism through which this occurs. The current study assessed the relationship between intellectual decline in schizophrenia and genetic variation in dysbindin-1 (DTNBP1). METHODS: We assessed cognitive decline in 183 Caucasian patients with schizophrenia using a proxy measure of premorbid IQ with which current general cognitive ability (g) was compared. We then tested for a relationship between the risk haplotype identified in previous work (CTCTAC) and intellectual decline. RESULTS: We found that carriers of the CTCTAC haplotype, demonstrated a significantly greater decline in IQ as compared with non-carriers (p=0.05). CONCLUSIONS: These data suggest that DTNBP1 influences the severity of intellectual decline in schizophrenia and may represent one underlying cause for heterogeneity in cognitive course.

Adult↗
PubMed2006

Disrupted in schizophrenia 1 genotype and positive symptoms in schizophrenia.

BACKGROUND: Converging evidence has demonstrated an association between the Disrupted in Schizophrenia 1 (DISC1) gene and schizophrenia (SZ). Within the DISC1 gene, a single nucleotide polymorphism (SNP), Ser704Cys, has been associated with the structure and function of the hippocampus. Because positive symptoms in SZ have also been associated with hippocampal structure and function, we hypothesized that variation in a DISC1 haplotype containing Ser704Cys would be significantly associated with positive symptomatology in SZ. METHODS: We tested for an association between variation in a haplotype block within the DISC1 gene containing Ser704Cys and lifetime history of positive symptoms in 199 Caucasian patients with SZ. RESULTS: We detected significant associations between a DISC1 haplotype containing Ser704Cys and Ser704Cys genotype and lifetime severity of delusions in SZ. CONCLUSIONS: These data suggest that that the effect of DISC1 genetic variation might be associated with positive symptoms in patients with SZ.

Cysteine↗
PubMed2006

COMT genotype and manic symptoms in schizophrenia.

Inconsistencies in the relation between COMT variation and schizophrenia may be clarified by careful delineation of a target phenotype. The present study reports a significant association between a COMT haplotype and the severity of manic symptoms in 162 patients with schizophrenia or schizoaffective disorder (SZ). These data suggest that the effect of COMT variation may be associated with comorbid manic symptoms in SZ.

Adult↗
PubMed2006

Ziprasidone-induced cognitive enhancement in schizophrenia: specificity or pseudospecificity?

OBJECTIVE: Ziprasidone may improve cognition in schizophrenia; however, this could be related to clinical symptom improvement, reflecting "pseudospecificity". We tested the hypothesis that ziprasidone improves cognition in the absence of clinical improvement. METHODS: We conducted a 12-week, open-label study of ziprasidone in 10 schizophrenia patients who met non-response criteria (<20% reduction in BPRS scores over 12 weeks). We conducted comprehensive cognitive testing and assessed change from baseline to end of study. RESULTS: We detected significant improvement on three measures of episodic memory (p<0.01) in these clinically non-responsive patients. Trend-level improvements were noted on tests involving processing speed and executive function. CONCLUSIONS: These data suggest that ziprasidone has cognitive benefits unrelated to an influence on other disease parameters.

Adolescent↗
PubMed2006

Decision-making impairments in adolescents with early-onset schizophrenia.

Adolescence is a time of vulnerability for risk-taking behaviors. This is particularly true of adolescents with schizophrenia who present with high rates of substance use as compared to the general population. Using the Iowa Gambling Task (IGT), the authors compared decision-making processes in adolescents with early-onset schizophrenia (onset of psychosis by age 18) to that of healthy volunteers. Fifteen adolescents with schizophrenia (aged 12-21 years) and 25 demographically similar healthy volunteers were administered the IGT. Overall, adolescents with schizophrenia performed significantly worse on the IGT than healthy adolescents as measured by a significant group by block interaction. Post-hoc testing revealed that adolescents with schizophrenia performed more poorly than healthy adolescents during the last two blocks of the task. Mathematical modeling further indicated that adolescents with schizophrenia allocated significantly more attention to monetary gains than losses encountered during the task, suggesting a hypersensitivity to rewards and relative insensitivity to future consequences. This is similar to what has been reported for adults with externalizing forms of psychopathology, such as those who abuse substances. These findings have potential implications for understanding the increased vulnerability for the development of substance abuse in adolescents with schizophrenia.

Adolescent↗
PubMed2006

Deficits in memory strategy use are related to verbal memory impairments in adolescents with schizophrenia-spectrum disorders.

OBJECTIVE: To assess the nature of learning and verbal memory deficits in adolescents with schizophrenia-spectrum disorders (SzS) (i.e., schizophrenia, schizoaffective disorder, and schizophreniform disorder). METHOD: Sixty patients with SzS (mean age=16.1 years, S.D. = 2.2) and 60 age- and gender-matched diagnosis-free healthy volunteers were assessed using the California Verbal Learning Test (CVLT). Planned analyses were conducted to assess the following aspects of memory: span of apprehension, verbal learning, short-term and long-term memory, rate of forgetting, interference, and organizational strategies. Adolescents with schizophrenia (Sz) were compared to those with schizoaffective disorder (SzA). Second, patients' test profiles were compared to those of controls. Relationships between initial learning and overall verbal learning with organizational strategy were explored. RESULTS: Neurocognitive profiles did not significantly differ between Sz and SzA participants. Patients performed significantly worse than healthy comparison subjects on measures of span of apprehension, verbal learning, short- and long-term memory, and organizational strategies after adjusting for differences in premorbid intelligence. No group differences were found in rate of forgetting or susceptibility to proactive or retroactive interference. CONCLUSIONS: Adolescents with SzS are characterized by significant verbal memory dysfunction similar to what has been observed in adults with first-episode schizophrenia. Deficits in consistency of learning over several trials, as well as a strong relationship between semantic organizational strategies and reduced learning capacity, implicate dysfunction of the dorsolateral prefrontal cortex as a contributor to verbal memory deficits in adolescents with SzS.

Adolescent↗
PubMed2006

Genetic variation in DTNBP1 influences general cognitive ability.

Human intelligence is a trait that is known to be significantly influenced by genetic factors, and recent linkage data provide positional evidence to suggest that a region on chromosome 6p, previously associated with schizophrenia, may be linked to variation in intelligence. The gene for dysbindin-1 (DTNBP1) is located at 6p and has also been implicated in schizophrenia, a neuropsychiatric disorder characterized by cognitive dysfunction. We report an association between DTNBP1 genotype and general cognitive ability (g) in two independent cohorts, including 213 patients with schizophrenia or schizo-affective disorder and 126 healthy volunteers. These data suggest that DTNBP1 genetic variation influences human intelligence.

Adult↗
PubMed2006

Neurocognition as a stable endophenotype in bipolar disorder and schizophrenia.

Linkage and association studies have paid increasing attention to neurocognition as a putative endophenotype. However, there exists little documentation of its trait stability in schizophrenia or bipolar disorder. Our aim was to determine the longitudinal stability of neurocognitive performance in bipolar versus schizophrenia probands. We administered a neurocognitive battery at two time points, approximately 5 years apart, in 16 schizophrenia and 16 bipolar disorder age-matched subjects. There were no significant changes over time on variables including education, estimated IQ, depression, psychosis, global functioning, or medication status. Schizophrenia subjects showed significant deterioration in one measure of executive functioning but no significant changes in seven of eight other domains. Bipolar patients showed stability over time in attentional measures but greater variability in other domains. These preliminary findings suggest that neurocognitive domains appear longitudinally stable across broad domains in schizophrenia. In contrast, stable functioning may be more limited to attentional domains in bipolar disorder.

Adult↗
PubMed2006

Dysbindin genotype and negative symptoms in schizophrenia.

OBJECTIVE: Converging evidence has demonstrated an association between variants in the dysbindin gene (DTNBP1) and schizophrenia. Recently, a DTNBP1 risk haplotype, associated with both schizophrenia and neurocognitive dysfunction, has been identified. Because neurocognitive dysfunction is commonly accompanied by negative symptoms (avolition, alogia, and affective flattening) in schizophrenia, the authors hypothesized that the presence of the risk haplotype would be significantly associated with negative symptoms. METHOD: The authors tested for an association between a DTNBP1 risk haplotype and a lifetime history of negative symptoms in 181 Caucasian patients with schizophrenia. RESULTS: A significant association was found between the presence of the risk haplotype and negative symptoms. CONCLUSIONS: These data suggest that the effect of DTNBP1 genetic variation may be associated with negative symptoms in patients with schizophrenia.

Adult↗
PubMed2005

Early-onset schizophrenia is associated with impaired adolescent development of attentional capacity using the identical pairs continuous performance test.

The authors examined performance on the Continuous Performance Test-Identical Pairs "numbers" task in adolescents with schizophrenia (n=59) and healthy controls (n=55). Adjusting for an estimate of premorbid intelligence and socioeconomic status, patients performed worse than normal controls on all three d' conditions (2-digit, 3-digit, 4-digit). However, there was a significant group-by-age-by-condition interaction (F[4,100]=4.69, p<.01) indicating an interaction between development and disease state. At the simplest level of the task (2-digit) the difference between patients with schizophrenia and controls was evident at all ages; while for the more difficult levels of the task (3-digit, 4-digit), differences between groups gradually increased across the tested age span (10 to 20 years of age). Premorbid social isolation was associated with worse attentional performance in patients, suggesting a relationship and continuity with negative symptoms. These data suggest that attentional differences in adolescents with schizophrenia are better captured by different tasks at different ages. The discrepant findings of attentional impairments reported in the literature for adolescents with schizophrenia could reflect the underlying etiological complexity of the disorder that may have a variable impact on involved brain regions and neurocognitive functioning.

Adolescent↗
PubMed2005

DISC1 and neurocognitive function in schizophrenia.

We recently reported an association between DISC1 and schizophrenia, schizoaffective disorder, and bipolar disorder. Convergent evidence suggests that DISC1 has a direct effect on central nervous system functioning. However, there is a paucity of data investigating the effects of DISC1 on neurocognition. Thus, we analyzed the relationship between five single-nucleotide polymorphisms that influenced risk for schizophrenia in our previous study and neurocognition in 250 patients with schizophrenia. DISC1 genotype was related to neurocognitive performance on measures of rapid visual search and verbal working memory, when controlling for age and premorbid intellectual capacity, and explained 3%-4% of the variance. These data suggest that DISC1 is associated with neurocognitive functioning in schizophrenia.

Adult↗
PubMed2005

Assessing cognitive deficits in bipolar disorder: are self-reports valid?

Patients with affective disorders frequently report problems with attention, concentration and memory, although little research has investigated subjective cognitive complaints relative to objective neuropsychological deficits. We compared subjective (self-rated) cognition and objective (clinician-rated) neuropsychological functioning in 37 DSM-IV bipolar outpatients. Subjects completed three standardized self-report inventories: the Cognitive Difficulties Scale (CDS), Cognitive Failures Questionnaire (CFQ), and Patient's Assessment of Own Functioning (PAOF). These were followed by a systematic neuropsychological test battery. More than 75% of our sample of bipolar patients displayed some cognitive deficits, most notably in the domains of verbal learning and memory. In general, patients' self-reports of impairment failed to reliably predict objective neuropsychological deficits. Mood ratings for mania and depression were not significantly correlated with any of the self-report inventories or the objective neuropsychological variables. The findings suggest that most bipolar patients demonstrate objective signs of cognitive impairment, but they are unable to report them accurately, at least using available self-report inventories. Such discrepancies could relate to impaired insight, efforts to conceal deficits, or to subthreshold affective symptoms.

Bipolar Disorder↗
PubMed2005

Neurocognitive profile in adolescents with early-onset schizophrenia: clinical correlates.

BACKGROUND: Neurocognitive impairments have been documented in adolescents with early-onset schizophrenia (EOS; onset by age 18) and are important treatment targets. Information concerning the severity, pattern, and clinical correlates of these deficits in EOS remains limited. METHODS: Tests assessing motor skills, attention, memory, visuospatial abilities and executive functioning were administered to 54 clinically stabilized adolescents with EOS and 52 age- and sex-matched healthy controls. Childhood-onset patients (onset by age 13) were compared to those with an adolescent onset of illness. Patients' neurocognitive profiles were compared to those of controls. Relationships between neurocognitive deficits and demographic and clinical characteristics were explored. RESULTS: Neurocognitive profiles did not differ between childhood- and adolescent-onset participants. Patients showed a generalized neurocognitive deficit of 2.0 SDs compared to controls, with relative deficit in executive functioning and relative sparing of language and visuospatial abilities. Degree of generalized neurocognitive impairment was associated with premorbid adjustment and negative symptom severity (Adjusted R(2) = .39). CONCLUSIONS: Results document both a significant generalized deficit and a relative deficit of executive functioning in adolescents with EOS. The overall pattern is similar to that observed in severely ill first-episode adult patients. The impairments across multiple neurocognitive domains suggest widespread brain dysfunction in EOS.

Adolescent↗
PubMed2004

Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression.

OBJECTIVE: Previous studies suggest that the dopamine agonist pramipexole may possess antidepressant properties. The authors conducted a preliminary randomized, placebo-controlled trial to determine the safety and antidepressant efficacy of pramipexole in treatment-resistant bipolar depression. METHOD: Twenty-two depressed outpatients with DSM-IV nonpsychotic bipolar disorder were randomly assigned to receive placebo or flexibly dosed pramipexole (mean maximum dose=1.7 mg/day, SD=1.3) added to existing mood stabilizers for 6 weeks. The primary outcome measure was response, defined as improvement in Hamilton Depression Rating Scale score of 50% or more over the baseline score; secondary analyses involved changes in Clinical Global Impression (CGI) severity scores. RESULTS: More patients given pramipexole (10 [83%] of 12) than patients given placebo (six [60%] of 10) completed the study. Eight (67%) of 12 patients taking pramipexole and two (20%) of 10 taking placebo had an improvement of at least 50% in their Hamilton depression scale scores. The mean percentage of improvement from baseline Hamilton depression scale scores was greater for patients taking pramipexole (48%) than for those taking placebo (21%). Mean improvements in CGI severity were also greater with pramipexole than placebo. No patients discontinued the study because of adverse events except for one patient who became hypomanic while taking pramipexole. CONCLUSIONS: Pramipexole was a safe and effective antidepressant among patients with bipolar depression. Larger randomized, controlled trials are needed to affirm these initial observations.

Adult↗