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Biomedical subjects

David C Glahn

Publications and source records attributed to David C Glahn.

29 records · Page 2Linked to original sources
PubMed2005

Magnetic resonance findings in bipolar disorder.

The MR findings reviewed in this article suggest structural, chemical, and functional abnormalities in specific brain regions participating in mood and cognitive regulation, such as the DLPFC, anterior cingulate, amygdala,STG, and corpus callosum in subjects with bipolar disorder. These abnormalities would represent an altered anterior-limbic network disrupting inter- and intrahemispheric communication and underlying the expression of bipolar disorder. Available studies are limited by several confounding variables, such as small and heterogeneous patient samples, differences in clinical and medication status, and cross-sectional design. It is still unclear whether abnormalities in neurodevelopment or neurodegeneration play a major role in the pathophysiology of bipolar disorder. These processes could act together in a unitary model of the disease, with excessive neuronal pruning/apoptosis during childhood and adolescence being responsible for the onset of the disorder and subsequent neurotoxic mechanisms and impaired neuroplasticity and cellular resilience being responsible for further disease progression. Future MR studies should investigate larger samples of first-episode drug-free patients, pediatric patients, subjects at high risk for bipolar disorder, and unaffected family members longitudinally. Such a study population is crucial to examine systematically whether brain changes are present before the appearance of symptoms (eg, maldevelopment) or whether they develop afterwards, as a result of illness course (eg, neurodegeneration). These studies will also be instrumental in minimizing potentially confounding factors commonly found in adult samples, such as the effects of long-term medication, chronicity, and hospitalizations. Juvenile bipolar patients often have a strong family history of bipolar disorder. Future studies could help elucidate the relevance of brain abnormalities as reflections of genetic susceptibility to the disorder. MR studies associated with genetic, post-mortem, and neuropsychologic studies will be valuable in separating state from trait brain abnormalities and in further characterizing the genetic determinants, the neuropathologic underpinnings, and the cognitive disturbances of bipolar disorder.

Atrophy↗
PubMed2005

Development and Validation of the Design Organization Test (DOT): a rapid screening instrument for assessing visuospatial ability.

A brief paper-and-pencil instrument was developed to rapidly assess visuospatial ability and serve as an alterative to the WAIS Block Design subtests during screening or when assessment time is limited. The Design Organization Test (DOT) consists of square black-and-white grids with visual patterns similar to those of the Block Design subtests. Administration is straightforward and requires examinees to reproduce as many designs as possible in 2 minutes using a numerical code key. For 411 college students, alternate forms of the DOT yielded reliability estimates comparable to that of the test-retest reliability of WAIS-III Block Design subtest. In a clinical sample, the DOT was significantly correlated (r = .92) with WAIS-III Block Design scores and was successfully substituted in place of Block Design raw scores without significant change in Performance IQ or Full Scale IQ. The results suggest that the DOT provides a useful and rapid screening measure of visuospatial ability.

Adolescent↗
PubMed2005

Declarative memory impairment in pediatric bipolar disorder.

OBJECTIVES: Impaired verbal declarative memory has been proposed as a trait marker for adult bipolar disorder. However, similar impairments in juvenile-onset bipolar disorder have not been yet documented. Here, we assessed declarative memory in a large sample of clinically well-characterized children with bipolar disorder. METHODS: Forty-one children and adolescents with bipolar disorder [21 bipolar I disorder (BP-I), 10 bipolar II disorder (BP-II), and 10 bipolar disorder, not otherwise specified (BP-NOS)] and 17 demographically matched healthy participants completed a standardized learning and memory test. RESULTS: BP-I children recalled and recognized significantly fewer words than healthy subjects, whereas children with BP-II and BP-NOS did not differ from controls. However, individuals with BP-NOS made more perseverative errors and intrusions than the other groups. Severity of mood symptomatology was not associated with memory performance in any bipolar subtype. CONCLUSIONS: Findings suggest that declarative memory impairments in juvenile BP-I are similar to those seen in the adult form of the illness. These impairments do not appear to be secondary to clinical state; rather, they may reflect trait-related impairments. Distinct performance patterns in BP-I, BP-II, and BP-NOS suggest that the broadly defined phenotype is significantly heterogeneous, and may not be informative for pathogenetic investigations of bipolar disorder.

Adolescent↗
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

Maintenance and manipulation of information in schizophrenia: further evidence for impairment in the central executive component of working memory.

Impairments in working memory (WM) have been proposed to underlie various cognitive and functional impairments in schizophrenia. However, the nature and extent of the dysfunction remain unclear. The present study attempted to examine the integrity of sub-components of working memory in schizophrenia within the framework of the multiple-component working memory model proposed by Baddeley. Two sets of visuospatial and verbal delayed-response tasks were developed which had comparable formats and difficulties across domains. In Experiment 1, demands on the central executive (CE) were manipulated by requiring subjects either (1) to simultaneously maintain and transform information (maintenance-and-manipulation condition) or (2) just to maintain this information (maintenance-only condition). In Experiment 2, the amount of information to be maintained over the delay was parametrically varied to evaluate demands on the temporary maintenance component of working memory. Patients (N=16) performed worse than controls (N=16) in both conditions of Experiment 1; however, simultaneous maintenance and manipulation was associated with a significantly greater performance reduction in the patients. In Experiment 2, both patients (N=15) and controls (N=15) declined in performance, at equivalent rates, with increasing memory load. Parallel findings were observed for the verbal and visuospatial tasks. These results suggest that while both maintenance and central executive aspects of working memory are impaired in schizophrenic patients, the central executive may be more severely affected.

Adult↗
PubMed2004

Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms.

Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships.

Brain↗
PubMed2004

The feasibility of neuropsychological endophenotypes in the search for genes associated with bipolar affective disorder.

OBJECTIVE: Efforts to identify genetic loci for bipolar disorder (BPD) have thus far proved elusive. The identification of processes mediating between genotype and phenotype (endophenotypes) may help resolve the carrier status of family members in genetic studies of polygenetic disorders with imperfect penetrance, such as BPD. We reviewed the literature to determine if neuropsychological measures could be used as effective endophenotypes to aid molecular genetic studies searching for genes predisposing to BPD. METHODS: Four prerequisites for endophenotypic markers are described, and a critical review of relevant literature was undertaken to determine if neurocognitive measures satisfy these four requirements in BPD. RESULTS: We found evidence that executive functions and declarative memory may be candidate neurocognitive endophenotypes for BPD. However, we cannot exclude other areas of cognition as being affected by BPD susceptibility genes, given the limits of the current knowledge of the neuropsychology of BPD. In particular, the paucity of studies measuring cognition in healthy relatives of BPD patient limits conclusion regarding familial aggregation of particular neurocognitive deficits (i.e. attention). Furthermore, the effects of clinical state and/or medication usage on cognitive functioning in BPD probands should be further explored. CONCLUSIONS: Molecular genetic studies of BPD may benefit from the application of select neuropsychological measures as endophenotypic markers. The use of these markers, once defined, may improve power for detecting genes predisposing to BPD and may help to better define diagnostic criteria.

Bipolar Disorder↗
PubMed2003

Spatial working memory as an endophenotype for schizophrenia.

BACKGROUND: Spatial working memory impairments are among the neurocognitive deficits that may mark genetic predisposition toward schizophrenia. We previously reported that impairment on the spatial span subtask of the Wechsler Adult Intelligence Scale-Revised increased in a dose-dependent manner with increasing genetic predisposition toward schizophrenia in a sample of discordant twins; however, it remains to be determined whether these deficits reflect difficulties with encoding, maintenance, manipulation, time-tagging of visual spatial information, storage capacity, or complex motor response. METHODS: We developed a spatial delayed response task in which memory set size was parametrically varied, holding constant manipulation and decision processes. We then reassessed 80 of the previously studied twins (17 probands with 8 monozygotic co-twins and 13 dizygotic co-twins, and 42 healthy twins). RESULTS: The spatial delayed response task was sensitive to genetic loading for schizophrenia but did not provide evidence for capacity limitations in probands or their co-twins. CONCLUSIONS: The findings suggest that deficits in the encoding or storage aspects of short-term spatial mnemonic processing may be an effective endophenotypic marker for schizophrenia.

Female↗
PubMed2002

Elucidating continuities and discontinuities between schizotypy and schizophrenia in the nervous system.

Genetic epidemiological studies indicate that schizophrenia is a complexly inherited disorder, whereby multiple genes, additively and in interaction with environmental factors, contribute to increasing risk for phenotypic expression. Linkage studies have identified a number of chromosomal regions as likely to harbor susceptibility genes for schizophrenia, but the linked regions span relatively large chromosomal segments in each case. These efforts have been hindered in part by a lack of means to detect nonpenetrant carriers of predisposing genes and in part by uncertainties concerning the nature of the nongenetic factors involved and their mechanisms of action in relation to genetic factors. Our strategy has focused on elucidating changes in central nervous system structure, physiology, and function that mark an inherited genotype for schizophrenia and on identifying specific environmental and etiological contributors and their modes of action in relation to genetic factors. The research reviewed in this paper, making use of family and twin designs, suggests that certain neural system deficits in schizophrenia (e.g., prefrontal cortex, working memory) are reflective of an inherited diathesis to the disorder, while others (e.g., temporal cortex, episodic memory) result from the interacting influences of genetic factors and particular types of biologically disruptive environmental events (e.g., fetal hypoxia). These findings help to reveal continuities and discontinuities in the neural disturbances characteristic of the schizophrenia genotype and phenotype and encourage the use of quantitative neural trait measures in the search for schizophrenia susceptibility genes.

Cognition Disorders↗
PubMed1997

Reliability, performance characteristics, construct validity, and an initial clinical application of a visual object learning test (VOLT).

Whereas verbal learning has received considerable attention by cognitive neuropsychology, spatial object learning has been more resistant to study. The paucity of visual learning data has hampered attempts to clarify if visual learning has unique features with specialized neural substrates. In schizophrenia, severe verbal learning impairment has been established, but lack of comparable visual learning measures has thwarted the dissociation of verbal and visual abilities. The Visual Object Learning Test (VOLT) was developed to examine aspects of visual-spatial learning and memory in a manner analogous to available verbal tests. Studies were performed to establish normative performance characteristics, convergent and divergent validity, and the sensitivity of the VOLT to detection of individual differences in normal (through sex and age) and pathologic variability (through persons with schizophrenia). The results indicated excellent internal consistency, convergent and divergent validity, and sensitivity to the effects of aging and pathology. Persons with schizophrenia were impaired in both learning and retention. The authors conclude that memory impairment in schizophrenia may not be specific to verbal learning.

Adolescent↗