Biomedical subjects

Monica E Calkins

Publications and source records attributed to Monica E Calkins.

16 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↗

PubMed2006

Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures.

In an effort to reveal susceptibility genes, schizophrenia research has turned to the endophenotype strategy. Endophenotypes are characteristics that reflect the actions of genes predisposing an individual to a disorder, even in the absence of diagnosable pathology. Individual endophenotypes are presumably determined by fewer genes than the more complex phenotype of schizophrenia and would, therefore, reduce the complexity of genetic analyses. Unfortunately, despite there being rational criteria to define a viable endophenotype, the term is sometimes applied indiscriminately to characteristics that are deviant in affected individuals. Schizophrenia patients exhibit deficits in several neurophysiological measures of information processing that have been proposed as candidate endophenotypes. Successful processing of sensory inputs requires the ability to inhibit intrinsic responses to redundant stimuli and, reciprocally, to facilitate responses to less frequent salient stimuli. There is evidence to suggest that both these processes are "impaired" in schizophrenia. Measures of inhibitory failure include prepulse inhibition of the startle reflex, P50 auditory evoked potential suppression, and antisaccade eye movements. Measures of impaired deviance detection include mismatch negativity and the P300 event-related potential. The purpose of this review is to systematically evaluate the endophenotype candidacy of these key neurophysiological abilities. For each candidate, we describe typical experimental procedures, the current understanding of the underlying neurobiology, the nature of the abnormality in schizophrenia, the reliability, stability and heritability of the measure, and any reported gene associations. We conclude with a discussion of the few studies thus far that have employed a multivariate approach with these candidates.

Arousal↗

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

A comparison of cognitive structure in schizophrenia patients and healthy controls using confirmatory factor analysis.

There is evidence that cognitive task performance breaks down into the same broad domains in schizophrenia as in healthy populations. However, this does not mean that the domains are independent of one another or that the interrelationships among domains are the same between groups. We used confirmatory factor analysis (CFA) to compare the latent structure of a broad neuropsychological battery in schizophrenia patients (n = 148) and healthy controls (n = 157). Main analyses examined the fit of a hierarchical six-factor model, in which associations among the factors were assumed to reflect their strong shared relationship to a general cognitive ability factor. The model incorporated the factors of verbal comprehension, perceptual organization, verbal memory, spatial memory, processing speed, and executive/working memory. The hierarchical model provided a good overall fit to data from both groups. However multiple groups CFA revealed significant differences in factor loadings between groups, reflecting a more generalized latent structure of cognitive ability in schizophrenia. This was also evident in higher bivariate correlations among cognitive domain composite scores calculated from the observed test data. Cognitive ability, as reflected in test performance, appears to be more unitary in schizophrenia than in healthy subjects. This finding may have measurement and treatment implications.

Adult↗

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↗

PubMed2005

Working memory functioning in schizophrenia patients and their first-degree relatives: cognitive functioning shedding light on etiology.

There is accumulating evidence for involvement of the prefrontal cortex (PFC) in the pathophysiology of schizophrenia. A primary function supported by the PFC is working memory (WM). Findings from WM studies in schizophrenia can provide insight into the nature of clinical symptoms and cognitive deficits associated with this disorder, as well as begin to suggest areas of underlying neuropathology. To date, studies have not adequately investigated different WM domains (e.g., verbal, spatial, or object) or processing requirements (e.g., maintenance, monitoring, or manipulation), shown to be associated with distinct patterns of neural activation, in schizophrenia patients and their well relatives. Accordingly, this study evaluated the performance of schizophrenia patients, their first-degree biological relatives, and nonpsychiatric controls on a comprehensive battery of WM tasks and investigated the association among WM deficits and schizophrenia-spectrum psychopathology. The findings indicate that schizophrenia patients are consistently impaired on WM tasks, irrespective of WM domain or processing requirements. In contrast, their unaffected relatives are only impaired on WM tasks with higher central executive processing requirements. This pattern of WM performance may further implicate DLPFC dysfunction in the liability for schizophrenia and has implications for future cognitive, genetic, and neurodevelopmental research.

Adult↗

PubMed2005

Face recognition memory deficits and visual object memory performance in patients with schizophrenia and their relatives.

OBJECTIVE: Face recognition memory deficits in schizophrenia are attributed to frontotemporal dysfunction. Biological relatives of patients have similar deficits, suggesting genetic susceptibility. Because the impairment may reflect generalized object memory deficits, the authors evaluated both face and visual object recognition. METHOD: The Penn Face Memory Test and Visual Object Learning Test were given to 102 patients with schizophrenia, 60 of their biological relatives, and 135 healthy comparison subjects. RESULTS: Significant immediate and delayed face recognition deficits were observed in patients and their relatives. Although patients were more impaired in visual object memory than comparison subjects, relatives were not. CONCLUSIONS: Face recognition deficits in patients with schizophrenia and their families are not secondary to generalized object memory deficits and may be an endophenotype reflecting frontotemporal impairment.

Adult↗

PubMed2004

Antisaccade performance is impaired in medically and psychiatrically healthy biological relatives of schizophrenia patients.

Schizophrenia patients and their relatives have been found to exhibit increased reflexive errors on the antisaccade task, suggesting the deficit reflects genetic susceptibility for schizophrenia. To evaluate the degree to which antisaccade error is elevated in schizophrenia relatives, we carried out a meta-analysis of the existing literature and a primary study examining whether the magnitude of reported differences between relative and nonpsychiatric comparison groups could be due to differences in participant inclusion criteria. Meta-analysis yielded a moderate to large effect size across studies comparing relatives and controls (Cohen's d=0.61; Glass' d(g)=0.87). Antisaccade performance in medically and psychiatrically healthy relatives (n=45), who were selected from a larger sample of relatives based on criteria applied to healthy controls, was significantly more impaired than in healthy control participants (d=0.81, d(g)=0.93). Moreover, excluded (n=71) and included relatives did not differ (d=0.14, d(g)=0.13). The results indicate that the antisaccade deficit is a robust phenomenon in unaffected schizophrenia relatives that is not due to differences in inclusion criteria between relatives and controls, and thus are consistent with a growing literature indicating that the antisaccade deficit will be a valuable endophenotype of schizophrenia.

Adolescent↗

PubMed2004

Multiple dimensions of schizotypy in first degree biological relatives of schizophrenia patients.

Considerable research has been devoted to identifying individuals predisposed to schizophrenia, with much of the effort devoted to identifying the personality characteristics of the biological relatives of schizophrenia patients. Although resource-consuming interviews have yielded promising results, investigators have long sought self-report measures that index genetic risk for schizophrenia. The Schizotypal Personality Questionnaire (SPQ) is a self-report measure that assesses the nine features of DSM-defined schizotypy. The SPQ, modified to include validity scales, was administered to 135 nonpsychotic first degree relatives of schizophrenia patients and 112 healthy controls. Principal components analysis (PCA) yielded three factors that correlated highly with previously reported factors (social-interpersonal, cognitive-perceptual, and disorganization). Social-interpersonal deficits were found to best differentiate relatives from controls. Contrary to the hypothesis that schizophrenia relatives are more defensive in responding to schizotypy questionnaires, relatives were significantly less defensive than controls. The results demonstrate that a multidimensional paper-and-pencil measure can characterize schizotypal features in schizophrenia relatives, which will be useful for the further delineation of the heritable schizophrenia spectrum phenotype.

Child↗

PubMed2003

Smooth pursuit and antisaccade performance evidence trait stability in schizophrenia patients and their relatives.

Several forms of eye movement dysfunction (EMD) have been widely regarded as candidate endophenotypes of schizophrenia, ultimately capable of identifying individuals carrying schizophrenia susceptibility genes and elucidating the pathophysiology of schizophrenia. As an indication of their trait-like status, candidate endophenotypes optimally evidence stability over time. However, there have been few published reports of test-retest reliability of several forms of EMD in schizophrenia patients and their relatives. In the current investigation, schizophrenia patients and the first-degree biological relatives of schizophrenia patients (n=15) were administered by an eye movement battery including smooth pursuit, antisaccade and prosaccade tasks, and re-tested after an average of 1.82 years (range=14-24 months). Adequate test-retest reliabilities of smooth pursuit closed-loop gain (Pearson r=0.72), antisaccade error rate (r=0.73), saccade reaction time to correct antisaccade responses (r=0.73), and prosaccade hypometria (r=0.72) were observed. Lower reliabilities were obtained for smooth pursuit open-loop gain (r=0.52) and prosaccade reaction time (r=0.43). The results are supportive of the trait-like characteristics of particular forms of EMD in schizophrenia families and of the candidacy of EMD as an endophenotypic marker of schizophrenia.

Adult↗

PubMed2002

Recognition memory for faces in schizophrenia patients and their first-degree relatives.

It has consistently been shown that schizophrenia patients are impaired in recognition memory for faces. However, studies have not examined the specificity of this deficit relative to other cognitive functions nor the relationship between this deficit and particular schizophrenia symptoms. In addition, no studies have examined recognition memory for faces in unaffected biological relatives of schizophrenia patients who likely share some of the genetic diathesis for this disorder without presenting the potential confounds of mentally ill study samples. The Faces subtests from the Wechsler Memory Scale-Third Edition were used to evaluate recognition memory for faces in 39 schizophrenia patients, 33 of their first-degree relatives and 56 normal controls. Both schizophrenia patients and their relatives were impaired, relative to control participants, in recognition memory for faces after partialing out group differences in spatial attention or verbal memory. Further, recognition memory for faces was associated with positive symptoms in the schizophrenia group and schizotypal personality traits in the relative group. These findings may have important implications for reducing etiological heterogeneity among schizophrenia populations, identifying disorder susceptibility among their relatives and furthering understanding of disorder etiology.

Adolescent↗