Biomedical subjects

Raquel E Gur

Publications and source records attributed to Raquel E Gur.

At least 19 recordsLinked to original sources

PubMed2026

Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative Fluid Biomarkers.

BACKGROUND AND HYPOTHESIS: Schizophrenia spectrum disorders (SSDs) produce severe symptoms, disability, and premature mortality, but only partially effective symptomatic treatments exist. Treatment development is impeded by lack of insight into disease mechanisms or objective biomarkers for clinical trials. Advances in genetics and neurobiology have converged on strong pathogenic hypotheses for SSDs centered on synapse dysfunction and excessive pruning, pathogenic processes that may produce measurable proteomic evidence in cerebrospinal fluid (CSF). Leveraging design precedents from successful fluid biomarkers discovery for Alzheimer's disease, we undertook a pilot study to test the feasibility of repeated CSF and blood samples collection from individuals with SSDs. Here we report on successful implementation of longitudinal bio-behavioral phenotyping in SSDs and establishment of a repository to permit broad sample and data sharing. STUDY DESIGN: The Schizophrenia Spectrum Biomarkers Consortium (SSBC) study principles included longitudinal study design, paired CSF and plasma collection associated with robust phenotypic characterization, at 3 academic sites and the establishment of a biorepository. Participants underwent clinical and cognitive assessments, neuroimaging, blood draws, and CSF collection via lumbar puncture (LP) every 6 months. STUDY RESULTS: SSBC successfully enrolled 48 SSD and 41 Healthy Controls with a 73% longitudinal retention. Clinical, cognitive, and neuroimaging results were consistent across sites and with existing studies. Study procedures were well tolerated, and almost all LPs (99%) resulted in either no or minor headache/backache that resolved without medical interventions. CONCLUSIONS: The pilot SSBC study demonstrates that a multi-site, longitudinal study with repeat CSF collection is feasible, with excellent participant acceptability and retention.

Humans↗

PubMed2007

Phenylthiocarbamide (PTC) perception in patients with schizophrenia and first-degree family members: relationship to clinical symptomatology and psychophysical olfactory performance.

The inability to taste phenylthiocarbamide (PTC; "taste-blindness") has been associated with a number of medical and neurological illnesses not typically related to taste. We examined PTC sensitivity in 67 schizophrenia patients, 30 healthy controls, and 30 first-degree relatives to determine whether taster status could represent a simple vulnerability marker. A higher prevalence of non-tasters was seen in patients and family members relative to healthy controls. Among patients, non-tasters exhibited increased levels of negative and first-rank symptoms as well as poorer right nostril odor identification skills relative to PTC tasters. These differences were not explained by age, sex, education, smoking, or intensity differences. Phenotypic variation in PTC sensitivity is thought to be genetic in origin and suggests greater illness risk for those subjects with recessive taster alleles.

Adult↗

PubMed2007

Hemodynamic responses in neural circuitries for detection of visual target and novelty: An event-related fMRI study.

The oddball paradigm examines attentional processes by establishing neural substrates for target detection and novelty. Event-related functional imaging enables characterization of hemodynamic changes associated with these processes. We studied 36 healthy participants (17 men) applying a visual oddball event-related design at 4 Tesla, and performed an unbiased determination of the hemodynamic response function (HRF). Targets were associated with bilateral, albeit leftward predominant changes in frontal-parietal temporal and occipital cortices, and limbic and basal ganglia regions. Activation to novelty was more posteriorly distributed, and frontal activation occurred only on the right, while robust activation was seen in occipital regions bilaterally. Overlapping regions were left thalamus, caudate and cuneus and right parietal precuneus. While robust HRFs characterized most regions, target detection was associated with a negative HRF in the right parietal precuneus and a biphasic HRF in thalamus, basal ganglia, and all occipital regions. Both height of the HRF and longer time to peak in the right cingulate were associated with slower response time. Sex differences were observed, with higher HRF peaks for novelty in men in right occipital regions, and longer time to peak in the left hemisphere. Age was associated with reduced peak HRF in left frontal region. Thus, indices of the HRF can be used to better understand the relationship between hemodynamic changes and performance and can be sensitive to individual differences.

Adolescent↗

PubMed2006

The Consortium on the Genetics of Schizophrenia: neurocognitive endophenotypes.

The Consortium on the Genetics of Schizophrenia (COGS) is a 7-site collaboration that examines the genetic architecture of quantitative endophenotypes in families with schizophrenia. Here we review the background and rationale for selecting neurocognitive tasks as endophenotypic measures in genetic studies. Criteria are outlined for the potential of measures as endophenotypic vulnerability markers. These include association with illness, state independence (ie, adequate test-retest stability, adequate between-site reliability, impairments in patients not due to medications, impairments observed regardless of illness state), heritability, findings of higher rates in relatives of probands than in the general population, and cosegregation within families. The COGS required that, in addition, the measures be "neurocognitive" and thus linked to neurobiology and that they be feasible in multisite studies. The COGS neurocognitive assessment includes measures of attention, verbal memory, working memory, and a computerized neurocognitive battery that also includes facial processing tasks. Here we describe data demonstrating that these neurobehavioral measures meet criteria for endophenotypic candidacy. We conclude that quantitative neurocognitive endophenotypes need further evidence for efficacy in identifying genetic effects but have the potential of providing unprecedented insight into gene-environment interaction related to dimensions of brain and behavior in health and disease.

Cognition Disorders↗

PubMed2006

The Consortium on the Genetics of Endophenotypes in Schizophrenia: model recruitment, assessment, and endophenotyping methods for a multisite collaboration.

BACKGROUND: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health-funded, 7-site collaboration investigating the occurrence and genetic architecture of quantitative endophenotypes related to schizophrenia. The purpose of this article is to provide a description of the COGS structure and methods, including participant recruitment and assessment. METHODS: The hypothesis-driven recruitment strategy ascertains families that include a proband with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia, and at least one unaffected full sibling available for genotyping and endophenotyping, along with parents available for genotyping and (optional depending on age) endophenotyping. The family structure is selected to provide contrast in quantitative endophenotypic traits and thus to maximize the power of the planned genetic analyses. Probands are recruited from many sources including clinician referrals, local National Alliance for the Mentally Ill chapters, and advertising via the media. All participants undergo a standardized protocol that includes clinical characterization, a blood draw for genotyping, and endophenotype assessments (P50 suppression, prepulse inhibition, antisaccade performance, continuous performance tasks, letter-number span, verbal memory, and a computerized neurocognitive battery). Investigators participate in weekly teleconferences to coordinate and evaluate recruitment, clinical assessment, endophenotyping, and continuous quality control of data gathering and analyses. Data integrity is maintained through use of a highly quality-assured, centralized web-based database. RESULTS: As of February 2006, 355 families have been enrolled and 688 participants have been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44), first-degree biological relatives (n = 343, M:F = 151:192), and community comparison subjects (n = 191, M:F = 81:110). DISCUSSION: Successful multisite genetics collaborations must institute standardized methodological criteria for assessment and recruitment that are clearly defined, well communicated, and uniformly applied. In parallel, studies utilizing endophenotypes require strict adherence to criteria for cross-site data acquisition, equipment calibration and testing and software equivalence, and continuous quality assurance for many measures obtained across sites. This report describes methods and presents the structure of the COGS as a model of multisite endophenotype genetic studies. It also provides demographic information after the first 2 years of data collection on a sample for whom the behavioral data and genetics of endophenotype performance will be fully characterized in future articles. Some issues discussed in the reviews that follow reflect the challenges of evaluating endophenotypes in studies of the genetic architecture of endophenotypes in schizophrenia.

Cooperative Behavior↗

PubMed2006

Successful multi-site measurement of antisaccade performance deficits in schizophrenia.

The antisaccade task is a promising schizophrenia endophenotype; it is stable over time and reflects neurophysiological deficits present in both schizophrenia subjects and their first-degree relatives. Meaningful genetic research requires large sample sizes that are best ascertained using multi-site study designs. To establish the criterion validity of the antisaccade task in a multi-site design, the Consortium on the Genetics of Schizophrenia (COGS) examined whether seven sites could detect previously reported antisaccade deficits in schizophrenia subjects. Investigators presented 3 blocks of 20 antisaccade stimuli to 143 schizophrenia subjects and 195 comparison subjects. Frequent collaborator communication, standardized training, and ongoing quality assurance optimized testing uniformity. Data were discarded from only 1.2% of subjects due to poor quality, reflecting the high fidelity of data collection and scoring methods. All sites detected a significant difference in the proportion of correct antisaccades between schizophrenia and comparison subjects (p<.02 at all sites); group differences in gain and latency were less robust. Regression analyses to adjust for the effects of group, site, age, gender, smoking, and parental education on the proportion of correct antisaccades revealed a significant effect of group, site, and age but no effect of gender, smoking, or parental education, and no group-by-site interactions. Intraclass correlations between proportion of correct antisaccades across the blocks of stimuli ranged from 0.87 to 0.93, demonstrating good within-session reliability at sites. These results confirm previous findings of antisaccade deficits in schizophrenia subjects and support the use of the antisaccade task as a potential schizophrenia endophenotype in multi-site genetic studies.

Adolescent↗

PubMed2006

Self-face recognition and theory of mind in patients with schizophrenia and first-degree relatives.

OBJECTIVE: The hypothesized relationship between theory of mind (ToM) and self-face recognition as well as its potential genetic associations has not been previously explored in patients with schizophrenia and in first-degree relatives with schizotypal personality traits. METHOD: Ten patients diagnosed with schizophrenia, 10 of their first-degree relatives and 10 healthy controls were included. To assess self-face recognition (SFR), participants were presented images of faces of themselves and others and asked to make rapid 'unfamiliar', 'familiar' and 'self' judgments. As a measure of ToM, subjects were administered the Revised Mind in the Eyes Test (MET [Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., and Plumb, I., 2001. The "Reading the Mind in the Eyes" Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. J Child Psychol Psychiatry 42(2), 241-251.]). Schizotypal characteristics in relatives and controls were assessed using a modified version of the Schizotypal Personality Questionnaire (SPQ [Raine, A., 1991. The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophrenia Bulletin 17(4), 555-564.]). RESULTS: Patients took longer and were less accurate on the SFR task than their relatives who in turn performed worse than healthy controls. Specific ToM deficits in schizophrenia were replicated. There was a relationship between accuracy rates on the MET and SFR tasks. High levels of schizotypal traits such as social anxiety, constricted affect and no close friends were important for both tasks. CONCLUSIONS: Face recognition deficits and ToM deficits in schizophrenia are apparent. The critical influence of high levels of select schizotypal traits is also highlighted. A deficit in relatives of schizophrenia patients raises the possibility that ToM and face recognition deficits may be candidate endophenotypes for schizophrenia. Support for the hypothesized link between ToM and face recognition is provided.

Adult↗

PubMed2006

Project among African-Americans to explore risks for schizophrenia (PAARTNERS): recruitment and assessment methods.

The Project among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) is a multi-site, NIMH-funded study that seeks to identify genetic polymorphisms that confer susceptibility to schizophrenia among African-Americans by linkage mapping and targeted association analyses. Because deficits in certain dimensions of cognitive ability are thought to underlie liability to schizophrenia, the project also examines cognitive abilities in individuals affected by schizophrenia and their extended family members. This article describes PAARTNERS study design, ascertainment methods and preliminary sample characteristics. We aim to recruit a sample of 1260 African-American families, all of whom have at least one proband with schizophrenia or schizoaffective disorder. The data collection protocol includes a structured Diagnostic Interview for Genetic Studies, Family Interview for Genetic Studies, focused neurocognitive assessment, medical records review, and the collection of blood or buccal cells for genetic analyses. We have currently completed study procedures for 106 affected sib-pair, 457 case-parent trio and 23 multiplex families. A total of 289 probands have completed the best estimate final diagnosis process and 1153 probands and family members have been administered the computerized neuropsychological battery. This project lays the foundation for future analysis of cognitive and behavioral endophenotypes. This novel integration of diagnostic, neurocognitive and genetic data will also generate valuable information for future phenotypic and genetic studies of schizophrenia.

Adult↗

PubMed2006

Functional magnetic resonance imaging of internal source monitoring in schizophrenia: recognition with and without recollection.

Patients with schizophrenia tend to have impaired source monitoring and intact item recognition, suggesting an over-reliance of familiarity effects. We previously demonstrated that providing patients with a levels-of-processing (LOP) semantic encoding strategy normalized source monitoring. The current blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) study tests the hypothesis that patients will have abnormally increased fronto-temporal activation despite intact performance. fMRI was measured in 13 patients and 13 demographically matched healthy controls during a LOP source monitoring paradigm. SPM2 was used for standard pre-processing and statistical analyses, with a corrected significance threshold of p<.05. Examination of accuracy and speed measures did not reveal any group differences in task performance. Regardless of source retrieval success both groups activated expected prefrontal and parietal regions, with no areas of relatively greater control versus patient activation. In support of the hypothesis, patients showed abnormally increased activation in temporolimbic areas including middle and superior temporal gyrus, thalamus, and parahippocampal gyrus. Activation in these areas was associated with worse positive and negative symptoms, but did not correlate with performance, suggesting inefficient rather than compensatory activation.

Adolescent↗

PubMed2006

Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia.

Recent molecular genetics studies implicate neuregulin 1 (NRG1) and its receptor erbB in the pathophysiology of schizophrenia. Among NRG1 receptors, erbB4 is of particular interest because of its crucial roles in neurodevelopment and in the modulation of N-methyl-D-aspartate (NMDA) receptor signaling. Here, using a new postmortem tissue-stimulation approach, we show a marked increase in NRG1-induced activation of erbB4 in the prefrontal cortex in schizophrenia. Levels of NRG1 and erbB4, however, did not differ between schizophrenia and control groups. To evaluate possible causes for this hyperactivation of erbB4 signaling, we examined the association of erbB4 with PSD-95 (postsynaptic density protein of 95 kDa), as this association has been shown to facilitate activation of erbB4. Schizophrenia subjects showed substantial increases in erbB4-PSD-95 interactions. We found that NRG1 stimulation suppresses NMDA receptor activation in the human prefrontal cortex, as previously reported in the rodent cortex. NRG1-induced suppression of NMDA receptor activation was more pronounced in schizophrenia subjects than in controls, consistent with enhanced NRG1-erbB4 signaling seen in this illness. Therefore, these findings suggest that enhanced NRG1 signaling may contribute to NMDA hypofunction in schizophrenia.

Animals↗

PubMed2006

Flat affect in schizophrenia: relation to emotion processing and neurocognitive measures.

Impaired emotional functioning in schizophrenia is a prominent clinical feature that manifests primarily as flat affect. Studies have examined the perception, experience, and expression of emotions in schizophrenia and reported normal ratings of experience but impaired affect identification. However, the relation between flat affect and performance on facial affect identification and cognitive tasks has not been systematically examined in relation to premorbid adjustment and clinical outcome. We report a prospective study of 63 patients with at least moderate severity of flat affect and 99 patients without flat affect, who were compared on functional domains, emotion processing tasks, and neurocognitive measures. Flat affect was more common in men and was associated with poorer premorbid adjustment, worse current quality of life, and worse outcome at 1-year follow-up. Patients overall performed more poorly on emotion processing tasks, one that required identification of happy and sad emotions and one that required differentiating among intensities within these emotions. They responded inaccurately yet faster than controls for the intensity differentiation task, suggesting a decomposition of the normal relation between accuracy and speed. Flat affect ratings, compared with other negative symptoms, uniquely predicted performance on emotion processing tasks. Patients with flat affect showed greater impairment in both emotion processing tasks, with the most pronounced impairment for the intensity differentiation task. However, the 2 patient groups did not differ in the neurocognitive profile except for verbal memory. We conclude that flat affect is an important clinical feature of schizophrenia that exacerbates the course of illness.

Adolescent↗

PubMed2006

A description of the process of recruitment for research studies investigating the genetics of psychotic illness.

Collecting biometric data on probands and family members is pivotal for advancing the understanding and treatment of any medical disorder with genetic contributions. The process of recruiting probands with psychosis and their family members for genetic studies has proven to be challenging. We present the recruitment strategies of two sites that are collaborating in genetic studies. We review details of referral sources at these sites. Of 69 participants recruited from the University of Pittsburgh, 23% were self-referrals, 30% were encouraged by family, and 47% were encouraged by clinicians. Of 48 probands from the University of Pennsylvania, 6% were self-referrals, 21% were encouraged by family, and 73% were encouraged by clinicians. Qualitative data from focus groups are reviewed. Strategies that helped to facilitate recruitment and foster community networking are discussed. This preliminary study has broad implications as a potential model for collaboration among patient support groups, family groups, clinicians, and researchers.

Humans↗

PubMed2006

Assessment of adolescents at risk for psychosis.

Early intervention in schizophrenia is an emerging goal of research investigating the earliest phases of the illness, which occur predominantly in adolescence and young adulthood. In order to develop strategies for early intervention, individuals at highest risk for the development of psychosis must be accurately identified. Here we briefly review the historical approaches to the assessment of risk for schizophrenia and highlight the more recently developed interview-based methods for the assessment of incipient psychosis, with particular attention paid to their applicability in adolescence. We present a prototypical assessment battery that includes an integration of historical assessment approaches to form a comprehensive assessment of threshold and subthreshold psychopathology, and other assessment procedures targeted specifically at adolescents. This battery may assist in unraveling the complex presentation of prodromal symptoms during the adolescent developmental period.

Adolescent↗

PubMed2006

Levels-of-processing effect on internal source monitoring in schizophrenia.

BACKGROUND: Recognition can be normalized in schizophrenia by providing patients with semantic organizational strategies through a levels-of-processing (LOP) framework. However, patients may rely primarily on familiarity effects, making recognition less sensitive than source monitoring to the strength of the episodic memory trace. The current study investigates whether providing semantic organizational strategies can also normalize patients' internal source-monitoring performance. METHOD: Sixteen clinically stable medicated patients with schizophrenia and 15 demographically matched healthy controls were asked to identify the source of remembered words following an LOP-encoding paradigm in which they alternated between processing words on a 'shallow' perceptual versus a 'deep' semantic level. A multinomial analysis provided orthogonal measures of item recognition and source discrimination, and bootstrapping generated variance to allow for parametric analyses. LOP and group effects were tested by contrasting recognition and source-monitoring parameters for words that had been encoded during deep versus shallow processing conditions. RESULTS: As in a previous study there were no group differences in LOP effects on recognition performance, with patients and controls benefiting equally from deep versus shallow processing. Although there were no group differences in internal source monitoring, only controls had significantly better performance for words processed during the deep encoding condition. Patient performance did not correlate with clinical symptoms or medication dose. CONCLUSIONS: Providing a deep processing semantic encoding strategy significantly improved patients' recognition performance only. The lack of a significant LOP effect on internal source monitoring in patients may reflect subtle problems in the relational binding of semantic information that are independent of strategic memory processes.

Adult↗

PubMed2006

Olfactory functioning in schizophrenia: relationship to clinical, neuropsychological, and volumetric MRI measures.

Deficits in odor identification and detection threshold sensitivity have been observed in schizophrenia but their relationship to clinical, cognitive, and biologic measures have not been clearly established. Our objectives were to examine the relationship between measures of odor identification and detection threshold sensitivity and clinical, neuropsychological, and anatomic brain measures. Twenty-one patients with schizophrenia and 20 healthy controls were administered psychophysical tests of odor identification and detection threshold sensitivity to phenyl ethyl alcohol. In addition, clinical symptom ratings, neuropsychological measures of frontal and temporal lobe function and whole brain MRIs were concurrently obtained. Patients exhibited significant deficits in odor identification but normal detection threshold sensitivity. Poorer odor identification scores were associated with longer duration of illness, increased negative and disorganized symptoms, and the deficit syndrome, as well as impairments in verbal and nonverbal memory. Better odor detection thresholds were specifically associated with first-rank or productive symptoms. Larger left temporal lobe volumes with MRI were associated with better odor identification in controls but not in patients. Given the relevance of the neural substrate, and the evidence of performance deficits, psychophysical probes of the integrity of the olfactory system hold special promise for illuminating aspects of the neurobiology underlying schizophrenia.

Adult↗

PubMed2006

Prognostic variables at intake and long-term level of function in schizophrenia.

OBJECTIVE: This study assessed the relationship between symptoms and cognitive measures at intake and functional outcome 2-8 years later (average 3 years) in first-episode and previously treated schizophrenia patients. METHOD: A composite cognitive score was assessed at intake to determine the influence of cognition on later functional outcome. At intake and follow-up, positive and negative symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, and affective symptoms were assessed with the Hamilton Depression Rating Scale. Level of function in seven domains (social function, occupational function, independent living, symptom severity, fullness of life, extent of psychiatric hospitalization, and overall level of function) at intake and follow-up was assessed with the Strauss-Carpenter Level of Function scale. The contributions of sex, education, and duration of illness to functional outcome were also examined. RESULTS: The results indicated that symptoms at intake had distinct patterns of prognostic significance for functional outcome in previously treated patients, compared with first-episode patients. In addition, male and female patients differed in the degree to which initial symptoms were correlated with later function. CONCLUSIONS: Initial level of function, symptoms, sex, education, and duration of illness are all important predictors for functional outcome in patients with schizophrenia.

Activities of Daily Living↗

PubMed2006

Impairment in the specificity of emotion processing in schizophrenia.

OBJECTIVE: Deficits in emotion processing are a hallmark of schizophrenia, with consequences for social functioning and subjective well-being. However, their specificity and characteristics have not been ascertained psychometrically. The authors' purpose was to examine a differential deficit for processing emotional facets of the face compared to judgment of nonemotional features (age) and facial memory. The authors also sought to establish whether the deficit affects sensitivity or specificity of performance. METHOD: Participants were 20 patients with schizophrenia and 20 healthy subjects matched for age, gender, and parental education. The authors examined emotional discrimination abilities compared to age discrimination and recognition memory for faces with standardized faces displaying the universal emotions of happiness, sadness, anger, and fear. Percent correct in each condition and for each emotion were assessed as well as sensitivity (correct identification of a target emotion) and specificity (correct rejection of a nontarget emotion) for emotion recognition. RESULTS: Patients with schizophrenia were differentially impaired in the discrimination of emotional aspects of facial expressions compared to nonemotional aspects and memory. Within the emotional task, patients showed differential impairment in specificity and insensitivity to the emotion displayed. CONCLUSIONS: When identical stimuli were used across tasks, differential impairment was seen in patients with schizophrenia for processing emotional faces, although the nonemotional task proved harder for both groups. Impairment in the specificity of emotion identification may lead to misunderstanding of social communication and may underlie difficulties in social adjustment experienced by people with schizophrenia. Emotion discrimination tests could augment the neurobehavioral evaluation of patients.

Adult↗

PubMed2006

Apolipoprotein E genotype and odor identification in schizophrenia.

The authors examined Apolipoprotein E (ApoE) genotype frequencies and unirhinal odor identification in 28 schizophrenia patients and 26 healthy comparison subjects. No significant associations between ApoE status and olfaction were observed in either diagnostic group. The authors concluded that olfactory deficits in schizophrenia do not appear to be mediated by the ApoE allele.

Adult↗