43 results on '"Pogue-Geile MF"'
Search Results
2. Evidence of factorial variance of the Mayer-Salovey-Caruso Emotional Intelligence Test across schizophrenia and normative samples.
- Author
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Eack SM, Pogue-Geile MF, Greeno CG, Keshavan MS, Eack, Shaun M, Pogue-Geile, Michael F, Greeno, Catherine G, and Keshavan, Matcheri S
- Abstract
The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) is a key measure of social cognition recommended by the MATRICS committee. While the psychometric properties of the MSCEIT appear strong, previous evidence suggested its factor structure may have shifted when applied to schizophrenia patients, posing important implications for cross-group comparisons. Using multi-group confirmatory factor analysis, we explicitly tested the factorial invariance of the MSCEIT across schizophrenia (n=64) and two normative samples (n=2099 and 451). Results indicated that the factor structure of the MSCEIT was significantly different between the schizophrenia and normative samples. Implications for future research are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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3. Neurocognitive endophenotypes in a multiplex multigenerational family study of schizophrenia.
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Gur RE, Nimgaonkar VL, Almasy L, Calkins ME, Ragland JD, Pogue-Geile MF, Kanes S, Blangero J, and Gur RC
- Abstract
OBJECTIVE: Genetic factors contribute to the development of schizophrenia where cognitive dysfunction is a hallmark. The purpose of this article was to examine computerized neurocognitive measures as candidate endophenotypic markers of liability for schizophrenia in a genetically informative cohort. METHOD: European Americans from 35 multiplex multigenerational families (N=349) and healthy participants (N=154) underwent clinical assessments and neurocognitive measurements and provided blood samples. The neurocognitive measures included performance (accuracy and speed) from a computerized battery that assessed abstraction/mental flexibility; attention; verbal, face, and spatial memory; spatial processing; sensorimotor processing; and emotion intensity discrimination. RESULTS: Probands, relatives, and comparison subjects differed from each other in performance. Probands demonstrated greatest impairment relative to comparison subjects, followed by family members. Liability for schizophrenia affected the speed-accuracy tradeoff differently for specific neurocognitive domains. Significant heritability estimates were obtained for accuracy of verbal, facial, and spatial memory and spatial and emotion processing. For speed, estimates of heritability were significant for abstraction/mental flexibility, attention, face memory, and spatial and sensorimotor processing. CONCLUSIONS: In a multigenerational multiplex design, the authors demonstrated that neurocognitive measures are associated with schizophrenia, differentiate unaffected relatives from comparison subjects, and may have significant presumed heritability. Therefore, they are endophenotypes suitable for genetic studies. Accuracy and speed can be differentially sensitive to presumed genetic liability. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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4. Allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cardiovascular reactivity in young adult male and female twins of European-American descent.
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McCaffery JM, Bleil M, Pogue-Geile MF, Ferrell RE, Manuck SB, McCaffery, Jeanne M, Bleil, Maria, Pogue-Geile, Michael F, Ferrell, Robert E, and Manuck, Stephen B
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- 2003
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5. Genetic and environmental causes of covariation among blood pressure, body mass and serum lipids during young adulthood: a twin study.
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McCaffery JM, Pogue-Geile MF, Debski TT, Manuck SB, McCaffery, J M, Pogue-Geile, M F, Debski, T T, and Manuck, S B
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- 1999
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6. Symptoms of Attenuated Psychosis Syndrome in Relatives of Clinical High-Risk Youth: Preliminary Evidence.
- Author
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Tarbox-Berry SI, Walsh BC, Pogue-Geile MF, and Woods SW
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- Humans, Adolescent, Syndrome, Family, Anxiety, Siblings, Prodromal Symptoms, Psychotic Disorders genetics, Psychotic Disorders diagnosis
- Abstract
Background and Hypothesis: Attenuated Psychosis Syndrome (APS) impacts functioning and predicts increased risk of psychosis. Risk for developing APS itself has received minimal attention. Knowledge of familial and environmental contributions to APS symptoms would advance understanding of APS and risk for psychosis. As an initial step, this report presents the first data on APS symptoms in family members of APS patients., Study Design: This study utilized a discordant sibling-pair family study design. The Structured Interview for Psychosis-risk Syndromes (SIPS) was administered to 17 APS probands and 26 non-APS biological siblings. Probands and siblings were compared on positive, negative, disorganized, and general SIPS symptom scales and factors derived from those scales., Study Results: There was significantly greater symptom severity in probands compared to siblings on nine of 19 SIPS scales. Negative/anxiety, functioning, and positive symptom factors were identified. Probands showed significantly greater severity than siblings on the negative/anxiety and positive factors. Elevated pathology on the negative/anxiety factor best differentiated between probands and siblings, over and above the contribution of the positive factor. No difference was found for the functioning factor., Conclusions: Results support the importance of non-familial effects on risk for APS and suggest differences in familial contribution to APS symptoms. Understanding the relative contribution of familial and environmental effects on APS symptoms may reveal important differences among APS patients, with implications for risk characterization, symptom course, and treatment selection., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2023
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7. Age-dependent patterns of schizophrenia genetic risk affect cognition.
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Kuo SS, Musket CW, Rupert PE, Almasy L, Gur RC, Prasad KM, Roalf DR, Gur RE, Nimgaonkar VL, and Pogue-Geile MF
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- Adolescent, Adult, Aged, Aged, 80 and over, Cognition, Humans, Middle Aged, Phenotype, Risk Factors, Young Adult, Schizophrenia epidemiology, Schizophrenia genetics
- Abstract
Cognition shares substantial genetic overlap with schizophrenia, yet it remains unclear whether such genetic effects become significant during developmental periods of elevated risk for schizophrenia, such as the peak age of onset. We introduce an investigative framework integrating epidemiological, developmental, and genetic approaches to determine whether genetic effects shared between schizophrenia and cognition are significant across periods of differing risk for schizophrenia onset, and whether these effects are shared with depression. 771 European-American participants, including 636 (ages 15-84 years) from families with at least two first-degree relatives with schizophrenia and 135 unrelated controls, were divided into three age-risk groups based on ages relative to epidemiological age of onset patterns for schizophrenia: Pre-Peak (before peak age-of-onset: 15 to 22 years), Post-Peak (after peak age-of-onset: 23-42 years), and Plateau (during plateau of age-of-onset: over 42 years). For general cognition and 11 specific cognitive traits, we estimated genetic correlations with schizophrenia and with depression within each age-risk group. Genetic effects shared between deficits in general cognition and schizophrenia were nonsignificant before peak age of onset, yet were high and significant after peak age of onset and during the plateau of onset. These age-dependent genetic effects were largely consistent across specific cognitive traits and not transdiagnostically shared with depression. Schizophrenia genetic effects appear to influence cognitive traits in an age-dependent manner, supporting late developmental and perhaps neurodegenerative models that hypothesize increased expression of schizophrenia risk genes during and after the peak age of risk. Our findings underscore the utility of cognitive traits for tracking schizophrenia genetic effects across the lifespan., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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8. Age-dependent effects of schizophrenia genetic risk on cortical thickness and cortical surface area: Evaluating evidence for neurodevelopmental and neurodegenerative models of schizophrenia.
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Kuo SS, Roalf DR, Prasad KM, Musket CW, Rupert PE, Wood J, Gur RC, Almasy L, Gur RE, Nimgaonkar VL, and Pogue-Geile MF
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- Brain pathology, Cerebral Cortex diagnostic imaging, Humans, Magnetic Resonance Imaging, Temporal Lobe pathology, Schizophrenia diagnostic imaging
- Abstract
Risk for schizophrenia peaks during early adulthood, a critical period for brain development. Although several influential theoretical models have been proposed for the developmental relationship between brain pathology and clinical onset, to our knowledge, no study has directly evaluated the predictions of these models for schizophrenia developmental genetic effects on brain structure. To address this question, we introduce a framework to estimate the effects of schizophrenia genetic variation on brain structure phenotypes across the life span. Five-hundred and six participants, including 30 schizophrenia probands, 200 of their relatives (aged 12-85 years) from 32 families with at least two first-degree schizophrenia relatives, and 276 unrelated controls, underwent MRI to assess regional cortical thickness (CT) and cortical surface area (CSA). Genetic variance decomposition analyses were conducted to distinguish among schizophrenia neurogenetic effects that are most salient before schizophrenia peak age-of-risk (i.e., early neurodevelopmental effects), after peak age-of-risk (late neurodevelopmental effects), and during the later plateau of age-of-risk (neurodegenerative effects). Genetic correlations between schizophrenia and cortical traits suggested early neurodevelopmental effects for frontal and insula CSA, late neurodevelopmental effects for overall CSA and frontal, parietal, and occipital CSA, and possible neurodegenerative effects for temporal CT and parietal CSA. Importantly, these developmental neurogenetic effects were specific to schizophrenia and not found with nonpsychotic depression. Our findings highlight the potentially dynamic nature of schizophrenia genetic effects across the lifespan and emphasize the utility of integrating neuroimaging methods with developmental behavior genetic approaches to elucidate the nature and timing of risk-conferring processes in psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
- Published
- 2022
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9. Heritable anisotropy associated with cognitive impairments among patients with schizophrenia and their non-psychotic relatives in multiplex families.
- Author
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Prasad KM, Gertler J, Tollefson S, Wood JA, Roalf D, Gur RC, Gur RE, Almasy L, Pogue-Geile MF, and Nimgaonkar VL
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- Anisotropy, Brain, Diffusion Tensor Imaging methods, Humans, Cognitive Dysfunction genetics, Schizophrenia genetics, White Matter diagnostic imaging
- Abstract
Background: To test the functional implications of impaired white matter (WM) connectivity among patients with schizophrenia and their relatives, we examined the heritability of fractional anisotropy (FA) measured on diffusion tensor imaging data acquired in Pittsburgh and Philadelphia, and its association with cognitive performance in a unique sample of 175 multigenerational non-psychotic relatives of 23 multiplex schizophrenia families and 240 unrelated controls (total = 438)., Methods: We examined polygenic inheritance (h2r) of FA in 24 WM tracts bilaterally, and also pleiotropy to test whether heritability of FA in multiple WM tracts is secondary to genetic correlation among tracts using the Sequential Oligogenic Linkage Analysis Routines. Partial correlation tests examined the correlation of FA with performance on eight cognitive domains on the Penn Computerized Neurocognitive Battery, controlling for age, sex, site and mother's education, followed by multiple comparison corrections., Results: Significant total additive genetic heritability of FA was observed in all three-categories of WM tracts (association, commissural and projection fibers), in total 33/48 tracts. There were significant genetic correlations in 40% of tracts. Diagnostic group main effects were observed only in tracts with significantly heritable FA. Correlation of FA with neurocognitive impairments was observed mainly in heritable tracts., Conclusions: Our data show significant heritability of all three-types of tracts among relatives of schizophrenia. Significant heritability of FA of multiple tracts was not entirely due to genetic correlations among the tracts. Diagnostic group main effect and correlation with neurocognitive performance were mainly restricted to tracts with heritable FA suggesting shared genetic effects on these traits.
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- 2022
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10. Why does age of onset predict clinical severity in schizophrenia? A multiplex extended pedigree study.
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Musket CW, Kuo SS, Rupert PE, Almasy L, Gur RC, Prasad K, Wood J, Roalf DR, Gur RE, Nimgaonkar VL, and Pogue-Geile MF
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- Adult, Age Factors, Age of Onset, Family psychology, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Pedigree, Psychiatric Status Rating Scales, Schizophrenic Psychology, Severity of Illness Index, Schizophrenia genetics, Schizophrenia physiopathology
- Abstract
Schizophrenia has substantial variation in symptom severity, course of illness, and overall functioning. Earlier age of onset (AOO) is consistently associated with negative outcomes and yet the causes of this association are still unknown. We used a multiplex, extended pedigree design (total N = 771; 636 relatives from 43 multigenerational families with at least 2 relatives diagnosed with schizophrenia and 135 matched controls) to examine among the schizophrenia relatives (N = 103) the relationship between AOO and negative and positive symptom severity, cognition, and community functioning. Most importantly, we assessed whether there are shared genetic effects between AOO and negative symptoms, positive symptoms, cognition, and community functioning. As expected, earlier AOO was significantly correlated with increased severity of negative and positive symptoms and poorer cognition and community functioning among schizophrenia patients. Notably, the genetic correlation between AOO of schizophrenia and negative symptoms was significant (R
g = -1.00, p = .007). Although the genetic correlations between AOO and positive symptoms, cognition, and community functioning were estimated at maximum and in the predicted direction, they were not statistically significant. AOO of schizophrenia itself was modestly heritable, although not significant and negative symptoms, positive symptoms, and cognition were all strongly and significantly heritable. In sum, we replicated prior findings indicating that earlier AOO is associated with increased symptom severity and extended the literature by detecting shared genetic effects between AOO and negative symptoms, suggestive of pleiotropy., (© 2020 Wiley Periodicals LLC.)- Published
- 2020
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11. On understanding variability in brain structure volumes in schizophrenia: A reply to De Peri and Vita.
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Kuo SS and Pogue-Geile MF
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- Brain, Humans, Magnetic Resonance Imaging, Schizophrenia
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- 2019
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12. Variation in fourteen brain structure volumes in schizophrenia: A comprehensive meta-analysis of 246 studies.
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Kuo SS and Pogue-Geile MF
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- Animals, Brain Stem pathology, Brain Stem physiopathology, Cerebral Cortex pathology, Gray Matter pathology, Hippocampus pathology, Humans, Magnetic Resonance Imaging methods, Schizophrenia diagnosis, Cerebral Cortex physiopathology, Gray Matter physiopathology, Hippocampus physiopathology, Schizophrenia physiopathology
- Abstract
Despite hundreds of structural MRI studies documenting smaller brain volumes on average in schizophrenia compared to controls, little attention has been paid to group differences in the variability of brain volumes. Examination of variability may help interpret mean group differences in brain volumes and aid in better understanding the heterogeneity of schizophrenia. Variability in 246 MRI studies was meta-analyzed for 13 structures that have shown medium to large mean effect sizes (Cohen's d≥0.4): intracranial volume, total brain volume, lateral ventricles, third ventricle, total gray matter, frontal gray matter, prefrontal gray matter, temporal gray matter, superior temporal gyrus gray matter, planum temporale, hippocampus, fusiform gyrus, insula; and a control structure, caudate nucleus. No significant differences in variability in cortical/subcortical volumes were detected in schizophrenia relative to controls. In contrast, increased variability was found in schizophrenia compared to controls for intracranial and especially lateral and third ventricle volumes. These findings highlight the need for more attention to ventricles and detailed analyses of brain volume distributions to better elucidate the pathophysiology of schizophrenia., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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13. Cognition and community functioning in schizophrenia: The nature of the relationship.
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Kuo SS, Almasy L, Gur RC, Prasad K, Roalf DR, Gur RE, Nimgaonkar VL, and Pogue-Geile MF
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- Adult, Female, Humans, Independent Living psychology, Male, Middle Aged, Neuropsychological Tests, Cognition, Schizophrenia genetics, Schizophrenic Psychology, Social Behavior
- Abstract
Although cognition is one of the most important predictors of community functioning in schizophrenia, little is known about the causes of this correlation. To our knowledge, this study is the first to examine the extent to which this correlation is genetically mediated and whether the genetic correlation is specific to schizophrenia. Six hundred thirty-six participants from 43 multigenerational families with at least two relatives with schizophrenia and 135 unrelated controls underwent diagnostic interview and cognition and functioning assessment. Quantitative genetic analyses were conducted using maximum-likelihood variance decomposition methods implemented in SOLAR (Almasy & Blangero, 1998). Among patients with schizophrenia, cognition and community functioning were positively correlated and genetic effects shared between them were significant contributors to this relationship whereas environmental effects shared between them were not. In contrast, genetic effects were not shared significantly between cognition in depressed or nondiagnosed relatives and community functioning in schizophrenia. In all analyses, the contributions of social cognition to community functioning were accounted for by general cognition. These findings support heritable factors that contribute to the correlation between cognition and community functioning that are relatively specific to schizophrenia and are not significantly shared with depression or a lack of psychopathology. This suggests the possibility of identifying specific genetic variants that contribute to this correlation and to these important individual differences among schizophrenia patients. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)
- Published
- 2018
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14. Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance.
- Author
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Kos MZ, Carless MA, Peralta J, Curran JE, Quillen EE, Almeida M, Blackburn A, Blondell L, Roalf DR, Pogue-Geile MF, Gur RC, Göring HHH, Nimgaonkar VL, Gur RE, and Almasy L
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Family, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mental Status and Dementia Tests, Middle Aged, Neurocognitive Disorders diagnosis, Neurocognitive Disorders epidemiology, Risk Factors, Schizophrenia complications, Young Adult, Exome, Genetic Markers, Neurocognitive Disorders genetics, Polymorphism, Single Nucleotide, Schizophrenia genetics
- Abstract
Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder. In total, 11,878 non-synonymous variants from 6,396 genes were tested for their association with schizophrenia spectrum disorders. Pathway enrichment analyses were conducted on gene-based test results, protein-protein interaction (PPI) networks, and epistatic effects. Using a significance threshold of FDR < 0.1, association was detected for rs10941112 (p = 2.1 × 10
-5 ; q-value = 0.073) in AMACR, a gene involved in fatty acid metabolism and previously implicated in schizophrenia, with significant cis effects on gene expression (p = 5.5 × 10-4 ), including brain tissue data from the Genotype-Tissue Expression project (minimum p = 6.0 × 10-5 ). A second SNP, rs10378 located in TMEM176A, also shows risk effects in the exome data (p = 2.8 × 10-5 ; q-value = 0.073). PPIs among our top gene-based association results (p < 0.05; n = 359 genes) reveal significant enrichment of genes involved in NCAM-mediated neurite outgrowth (p = 3.0 × 10-5 ), while exome-wide SNP-SNP interaction effects for rs10941112 and rs10378 indicate a potential role for kinase-mediated signaling involved in memory and learning. In conclusion, these association results implicate AMACR and TMEM176A in schizophrenia risk, whose effects may be modulated by genes involved in synaptic plasticity and neurocognitive performance., (© 2017 Wiley Periodicals, Inc.)- Published
- 2017
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15. Exome Sequence Data From Multigenerational Families Implicate AMPA Receptor Trafficking in Neurocognitive Impairment and Schizophrenia Risk.
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Kos MZ, Carless MA, Peralta J, Blackburn A, Almeida M, Roalf D, Pogue-Geile MF, Prasad K, Gur RC, Nimgaonkar V, Curran JE, Duggirala R, Glahn DC, Blangero J, Gur RE, and Almasy L
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- Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins genetics, Microfilament Proteins genetics, Pedigree, Phosphoproteins genetics, Quantitative Trait Loci, Cognition Disorders genetics, Exome genetics, Intracellular Signaling Peptides and Proteins metabolism, Microfilament Proteins metabolism, Phosphoproteins metabolism, Receptors, Glutamate metabolism, Schizophrenia genetics
- Abstract
Schizophrenia is a mental disorder characterized by impairments in behavior, thought, and neurocognitive performance. We searched for susceptibility loci at a quantitative trait locus (QTL) previously reported for abstraction and mental flexibility (ABF), a cognitive function often compromised in schizophrenia patients and their unaffected relatives. Exome sequences were determined for 134 samples in 8 European American families from the original linkage study, including 25 individuals with schizophrenia or schizoaffective disorder. At chromosome 5q32-35.3, we analyzed 407 protein-altering variants for association with ABF and schizophrenia status. For replication, significant, Bonferroni-corrected findings were tested against cognitive traits in Mexican American families (n = 959), as well as interrogated for schizophrenia risk using GWAS results from the Psychiatric Genomics Consortium (PGC). From the gene SYNPO, rs6579797 (MAF = 0.032) shows significant associations with ABF (P = .015) and schizophrenia (P = .040), as well as jointly (P = .0027). In the Mexican American pedigrees, rs6579797 exhibits significant associations with IQ (P = .011), indicating more global effects on neurocognition. From the PGC results, other SYNPO variants were identified with near significant effects on schizophrenia risk, with a local linkage disequilibrium block displaying signatures of positive selection. A second missense variant within the QTL, rs17551608 (MAF = 0.19) in the gene WWC1, also displays a significant effect on schizophrenia in our exome sequences (P = .038). Remarkably, the protein products of SYNPO and WWC1 are interaction partners involved in AMPA receptor trafficking, a brain process implicated in synaptic plasticity. Our study reveals variants in these genes with significant effects on neurocognition and schizophrenia risk, identifying a potential pathogenic mechanism for schizophrenia spectrum disorders., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2016
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16. Cognitive Enhancement Therapy in substance misusing schizophrenia: results of an 18-month feasibility trial.
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Eack SM, Hogarty SS, Greenwald DP, Litschge MY, McKnight SA, Bangalore SS, Pogue-Geile MF, Keshavan MS, and Cornelius JR
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- Adult, Alcoholism psychology, Alcoholism therapy, Cognition, Feasibility Studies, Female, Humans, Male, Marijuana Abuse psychology, Marijuana Abuse therapy, Psychotic Disorders complications, Psychotic Disorders psychology, Schizophrenia complications, Schizophrenic Psychology, Social Adjustment, Social Perception, Treatment Outcome, Alcoholism complications, Cognitive Behavioral Therapy methods, Marijuana Abuse complications, Psychotic Disorders therapy, Schizophrenia therapy
- Abstract
Substance use is a frequent problem in schizophrenia, and although many substance misusing patients with the disorder also experience considerable cognitive impairments, such individuals have been routinely excluded from clinical trials of cognitive remediation that could support their functional and addiction recoveries. This study conducted a small-scale feasibility trial of Cognitive Enhancement Therapy (CET) in substance misusing schizophrenia patients to assess the feasibility and efficacy of implementing comprehensive neurocognitive and social-cognitive remediation in this population. A total of 31 schizophrenia outpatients meeting addiction severity criteria for alcohol and/or cannabis use were randomized to 18months of CET or usual care. Feasibility findings indicated high degrees of satisfaction with CET, but also presented significant challenges in the recruitment and retention of substance misusing patients, with high levels of attrition (50%) over the study period, primarily due to positive symptom exacerbation. Intent-to-treat efficacy analyses showed large and significant improvements in neurocognition (d=.86), social cognition (d=1.13), and social adjustment (d=.92) favoring CET. Further, individuals treated with CET were more likely to reduce alcohol use (67% in CET vs. 25% in usual care) during treatment (p=.021). These results suggest that once engaged and stabilized, CET is a feasible and potentially effective treatment for cognitive impairments in patients with schizophrenia who misuse alcohol and/or cannabis. Substance misusing patients who are able to engage in treatment may be able to benefit from cognitive remediation, and the treatment of cognitive impairments may help improve substance use outcomes among this underserved population., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2015
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17. Heritability of subcortical and limbic brain volume and shape in multiplex-multigenerational families with schizophrenia.
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Roalf DR, Vandekar SN, Almasy L, Ruparel K, Satterthwaite TD, Elliott MA, Podell J, Gallagher S, Jackson CT, Prasad K, Wood J, Pogue-Geile MF, Nimgaonkar VL, Gur RC, and Gur RE
- Subjects
- Adult, Cohort Studies, Endophenotypes, Family, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, United States, White People, Brain pathology, Schizophrenia genetics, Schizophrenia pathology
- Abstract
Background: Brain abnormalities of subcortical and limbic nuclei are common in patients with schizophrenia, and variation in these structures is considered a putative endophenotype for the disorder. Multiplex-multigenerational families with schizophrenia provide an opportunity to investigate the impact of shared genetic ancestry, but these families have not been previously examined to study structural brain abnormalities. We estimate the heritability of subcortical and hippocampal brain volumes in multiplex-multigenerational families and the heritability of subregions using advanced shape analysis., Methods: The study comprised 439 participants from two sites who underwent 3T structural magnetic resonance imaging. The participants included 190 European-Americans from 32 multiplex-multigenerational families with schizophrenia and 249 healthy comparison subjects. Subcortical and hippocampal volume and shape were measured in 14 brain structures. Heritability was estimated for volume and shape., Results: Volume and shape were heritable in families. Estimates of heritability in subcortical and limbic volumes ranged from .45 in the right hippocampus to .84 in the left putamen. The shape of these structures was heritable (range, .40-.49), and specific subregional shape estimates of heritability tended to exceed heritability estimates of volume alone., Conclusions: These results demonstrate that volume and shape of subcortical and limbic brain structures are potential endophenotypic markers in schizophrenia. The specificity obtained using shape analysis may improve selection of imaging phenotypes that better reflect the underlying neurobiology. Our findings can aid in the identification of specific genetic targets that affect brain structure and function in schizophrenia., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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18. Neuroimaging predictors of cognitive performance across a standardized neurocognitive battery.
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Roalf DR, Ruparel K, Gur RE, Bilker W, Gerraty R, Elliott MA, Gallagher RS, Almasy L, Pogue-Geile MF, Prasad K, Wood J, Nimgaonkar VL, and Gur RC
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Regression Analysis, Young Adult, Brain physiology, Brain Mapping, Cognition physiology, Magnetic Resonance Imaging, Neuropsychological Tests
- Abstract
Objective: The advent of functional MRI (fMRI) enables the identification of brain regions recruited for specific behavioral tasks. Most fMRI studies focus on group effects in single tasks, which limits applicability where assessment of individual differences and multiple brain systems is needed., Method: We demonstrate the feasibility of concurrently measuring fMRI activation patterns and performance on a computerized neurocognitive battery (CNB) in 212 healthy individuals at 2 sites. Cross-validated sparse regression of regional brain amplitude and extent of activation were used to predict concurrent performance on 6 neurocognitive tasks: abstraction/mental flexibility, attention, emotion processing, and verbal, face, and spatial memory., Results: Brain activation was task responsive and domain specific, as reported in previous single-task studies. Prediction of performance was robust for most tasks, particularly for abstraction/mental flexibility and visuospatial memory., Conclusions: The feasibility of administering a comprehensive neuropsychological battery in the scanner was established, and task-specific brain activation patterns improved prediction beyond demographic information. This benchmark index of performance-associated brain activation can be applied to link brain activation with neurocognitive performance during standardized testing. This first step in standardizing a neurocognitive battery for use in fMRI may enable quantitative assessment of patients with brain disorders across multiple cognitive domains. Such data may facilitate identification of neural dysfunction associated with poor performance, allow for identification of individuals at risk for brain disorders, and help guide early intervention and rehabilitation of neurocognitive deficits., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)
- Published
- 2014
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19. Neurocognitive performance stability in a multiplex multigenerational study of schizophrenia.
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Roalf DR, Gur RC, Almasy L, Richard J, Gallagher RS, Prasad K, Wood J, Pogue-Geile MF, Nimgaonkar VL, and Gur RE
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- Adolescent, Adult, Aged, Aged, 80 and over, Cognition Disorders etiology, Cognition Disorders genetics, Female, Genetic Predisposition to Disease, Humans, Longitudinal Studies, Male, Middle Aged, Schizophrenia complications, Schizophrenia genetics, Task Performance and Analysis, Time Factors, White People genetics, White People psychology, Young Adult, Cognition Disorders diagnosis, Neuropsychological Tests statistics & numerical data, Schizophrenia diagnosis
- Abstract
Certain cognitive measures are heritable and differentiate individuals at risk for schizophrenia from unaffected family members and healthy comparison subjects. These deficits in neurocognitive performance in patients with schizophrenia appear stable in the short-term. However, the duration of most, but not all, longitudinal studies is modest and the majority have relied on traditional average performance measures to examine stability. Using a computerized neurocognitive battery (CNB), we assessed mean performance (accuracy and speed) and intra-individual variability (IIV) in a longitudinal study aimed to examine neurocognitive stability in European-American multiplex families with schizophrenia. Thirty-four patients with schizophrenia, 65 unaffected relatives, and 45 healthy comparison subjects completed the same computerized neurocognitive assessment over approximately 5 years. Measures of mean performance showed that patients had stable accuracy performance but were slower in many neurocognitive domains over time as compared with unaffected family members and healthy subjects. Furthermore, patients and family members showed dissociable patterns of change in IIV for speed across cognitive domains: compared with controls, patients showed higher across-task IIV in performance compared with family members, who showed lower across-task IIV. Patients showed an increase in IIV over time, whereas family members showed a decrease. These findings suggest that measures of mean performance and IIV of speed during a CNB may provide useful information about the genetic susceptibility in schizophrenia.
- Published
- 2013
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20. The nature of schizotypy among multigenerational multiplex schizophrenia families.
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Tarbox SI, Almasy L, Gur RE, Nimgaonkar VL, and Pogue-Geile MF
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- Adult, Case-Control Studies, Depressive Disorder, Major genetics, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Pedigree, Psychiatric Status Rating Scales, Substance-Related Disorders genetics, Schizophrenia genetics, Schizophrenic Psychology, Schizotypal Personality Disorder etiology
- Abstract
Identification of endophenotypes (Gottesman & Gould, 2003; Gottesman & Shields, 1972) that genetically correlate with schizophrenia and are genetically homogeneous is an important strategy for detecting genes that affect schizophrenia risk. Symptoms of schizotypy may familially correlate with schizophrenia; however, there are critical limitations of the current literature concerning this association. The present study examined the genetic architecture and genetic associations between schizotypy and schizophrenia among multigenerational, multiplex schizophrenia families. Genetic schizotypy factor scales were developed that genetically correlated with schizophrenia, although some relations were unexpected in direction suggesting minimization of "psychotic-like" symptoms. These genetic schizotypy factor scales did not genetically correlate with major depressive disorder or substance dependence indicating specificity to schizophrenia. The results highlight the possibility of significant response bias in schizophrenia families, particularly among close relatives, and suggest an important consideration when acquiring self-report information. This is a topic that deserves future study as the origins of this putative bias in relatives are unclear. In addition, the results support the identification of genetic schizotypy factors as a promising technique for maximizing genetic correlation of endophenotypes with schizophrenia.
- Published
- 2012
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21. Genetic associations between neuregulin-1 SNPs and neurocognitive function in multigenerational, multiplex schizophrenia families.
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Yokley JL, Prasad KM, Chowdari KV, Talkowski ME, Wood J, Gur RC, Gur RE, Almasy L, Nimgaonkar VL, and Pogue-Geile MF
- Subjects
- Humans, Neuropsychological Tests, Cognition, Genetic Diseases, Inborn genetics, Neuregulin-1 genetics, Polymorphism, Single Nucleotide, Schizophrenia genetics
- Abstract
Objectives: Recent work shows promising associations between schizophrenia and polymorphisms in neuregulin-1 (NRG1) and a large literature also finds strong familial relationships between schizophrenia and cognitive deficits. Given the role of NRG1 in glutamate regulation and glutamate's effect on cognition, we hypothesized that cognitive deficits may be related to variation within NRG1, providing a possible mechanism to increase risk for schizophrenia., Methods: This study examined the associations between NRG1, cognition, and schizophrenia using a multigenerational multiplex family sample (total N=419, 40 families), including 58 affected participants (schizophrenia or schizoaffective disorder-depressed type) and their 361 unaffected relatives. Participants were genotyped for 40 NRG1 single nucleotide polymorphisms (SNPs), chosen largely based on previous associations with schizophrenia. All participants completed structured diagnostic interviews and a computerized neurocognitive battery assessing eight cognitive domains. Variance component quantitative trait analyses tested for associations between individual NRG1 SNPs and cognitive performance in the total sample, a subsample of healthy participants with no Diagnostic and Statistical Manual of Mental Disorders diagnosis, and using general intelligence as a covariate., Results: Effect sizes (within-family β coefficients) ranged from 0.08 to 0.73, and 61 of these associations were nominally significant (P≤0.05), with 12 associations at P≤0.01, although none achieved the modified Bonferroni significance threshold of P<0.0003. Attention was the most frequently nominally associated domain and rs10503929, a nonsynonymous SNP, was the most frequently nominally associated SNP., Conclusion: Although not significant experiment-wise, these findings suggest that further study of the associations between variation in NRG1 and cognition may be productive.
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- 2012
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22. A multivariate perspective on schizotypy and familial association with schizophrenia: a review.
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Tarbox SI and Pogue-Geile MF
- Subjects
- Family psychology, Humans, Psychiatric Status Rating Scales, Risk, Schizophrenia diagnosis, Schizophrenic Psychology, Schizotypal Personality Disorder diagnosis, Schizotypal Personality Disorder psychology, Schizophrenia genetics, Schizotypal Personality Disorder genetics
- Abstract
Although generally accepted that schizotypal personality disorder diagnosis is more prevalent among relatives of individuals with schizophrenia and may be associated with genetic liability to schizophrenia, it seems likely that this diagnosis is itself heterogeneous and thus perhaps not as useful in identifying genes that affect schizophrenia risk (i.e. endophenotypes) as it could be. In contrast, symptoms and dimensions of schizotypal personality disorder may be more etiologically homogeneous, and thus more useful in genetic studies. The current review evaluated and consolidated evidence to date regarding specific symptoms and dimensions of schizotypal personality disorder among non-psychotic relatives of schizophrenia patients. Comparisons were made with relatives of affective disorder patients and non-psychiatric controls. Findings indicate strong support for elevation of social-interpersonal schizotypal symptoms among relatives of schizophrenia patients versus other groups along with moderate specificity. Results suggest only a small elevation of cognitive-perceptual and disorganized symptoms in relatives of schizophrenia patients and results for disorganized symptoms were inconsistent across studies. Thus, evidence to date supports further investigation of genetic associations between symptoms of schizotypal personality disorder and schizophrenia, and suggests that social-interpersonal symptoms may be particularly promising in genetic analyses of schizophrenia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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23. Mechanisms of functional improvement in a 2-year trial of cognitive enhancement therapy for early schizophrenia.
- Author
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Eack SM, Pogue-Geile MF, Greenwald DP, Hogarty SS, and Keshavan MS
- Subjects
- Adult, Cognition Disorders diagnosis, Emotional Intelligence, Female, Humans, Male, Neuropsychological Tests statistics & numerical data, Psychometrics statistics & numerical data, Psychotic Disorders diagnosis, Reproducibility of Results, Schizophrenia diagnosis, Young Adult, Cognition Disorders psychology, Cognition Disorders rehabilitation, Cognitive Behavioral Therapy methods, Psychotic Disorders psychology, Psychotic Disorders rehabilitation, Schizophrenia rehabilitation, Schizophrenic Psychology
- Abstract
Background: Cognitive rehabilitation has emerged as an effective treatment for addressing cognitive impairments and functional disability in schizophrenia; however, the degree to which changes in various social and non-social cognitive processes translate into improved functioning during treatment remains unclear. This research sought to identify the neurocognitive and social-cognitive mechanisms of functional improvement during a 2-year trial of cognitive enhancement therapy (CET) for early-course schizophrenia., Method: Patients in the early course of schizophrenia were randomly assigned to CET (n=31) or an enriched supportive therapy control (n=27) and treated for up to 2 years. A comprehensive neurocognitive assessment battery and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) were completed annually, along with measures of functioning. Mediator analyses using mixed-effects growth models were conducted to examine the effects of neurocognitive and social-cognitive improvement on functional change., Results: Improvements over 2 years in neurocognition and the emotion management branch of the MSCEIT were found to be significantly related to improved functional outcome in early-course schizophrenia patients. Neurocognitive improvement, primarily in executive functioning, and social-cognitive change in emotion management also mediated the robust effects of CET on functioning., Conclusions: Improvements in neurocognition and social cognition that result from cognitive rehabilitation are both significant mediators of functional improvement in early-course schizophrenia. Cognitive rehabilitation programs for schizophrenia may need to target deficits in both social and non-social cognition to achieve an optimal functional response.
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- 2011
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24. Assessing social-cognitive deficits in schizophrenia with the Mayer-Salovey-Caruso Emotional Intelligence Test.
- Author
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Eack SM, Greeno CG, Pogue-Geile MF, Newhill CE, Hogarty GE, and Keshavan MS
- Subjects
- Adolescent, Adult, Antipsychotic Agents therapeutic use, Cognition Disorders drug therapy, Cognition Disorders psychology, Female, Humans, Male, Psychometrics statistics & numerical data, Psychotic Disorders drug therapy, Reproducibility of Results, Schizophrenia drug therapy, Social Adjustment, Young Adult, Cognition Disorders diagnosis, Emotional Intelligence, Psychiatric Status Rating Scales statistics & numerical data, Psychotic Disorders diagnosis, Psychotic Disorders psychology, Schizophrenia diagnosis, Schizophrenic Psychology
- Abstract
The emotion management subscale of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) has recently been recommended by the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia committee as the sole measure of social cognition for trials of cognitive enhancement in schizophrenia, yet the psychometric properties of this subscale and the larger instrument in schizophrenia patients have not been thoroughly examined. This research presents a psychometric investigation of the MSCEIT in a sample of 64 early course outpatients with schizophrenia, schizoaffective, or schizophreniform disorder. Results demonstrated that the MSCEIT possesses adequate internal consistency reliability among its branch and total scales and that patients' branch and overall test performance was significantly below normative levels. Estimates of discriminant and concurrent validity indicated that the MSCEIT diverged from measures of neurocognitive functioning and psychopathology, but was only modestly related with objective measures of functional outcome. Convergent validity estimates suggested that, contrary to expectations, the MSCEIT did not correlate with a behavioral measure of social cognition. Finally, exploratory factor analyses suggested the possibility of a shift in the latent structure of emotional intelligence in schizophrenia, compared with studies with healthy individuals. These findings support the use of the MSCEIT as a reliable and potentially valid method of assessing the emotional components of social cognition in schizophrenia, but also point to a need for additional measurement development efforts to assess broader social-cognitive domains that may exhibit stronger relations with functional outcome. Further investigation is warranted to examine the instrument's latent factor structure and convergence with other measures of social cognition.
- Published
- 2010
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25. Antibodies to cytomegalovirus and Herpes Simplex Virus 1 associated with cognitive function in schizophrenia.
- Author
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Shirts BH, Prasad KM, Pogue-Geile MF, Dickerson F, Yolken RH, and Nimgaonkar VL
- Subjects
- Adolescent, Adult, Aged, Animals, Cognition Disorders diagnosis, Cognition Disorders immunology, Cytomegalovirus Infections immunology, Female, Herpes Simplex immunology, Humans, Immunoenzyme Techniques, Male, Middle Aged, Psychotic Disorders blood, Schizophrenia blood, Schizophrenia immunology, Toxoplasma immunology, Trail Making Test, Antibodies, Viral blood, Cognition Disorders blood, Cytomegalovirus immunology, Herpesvirus 1, Human immunology
- Abstract
Background: Cognitive impairment in the form of decreased working memory and executive functions has been recognized as a key deficit in schizophrenia. Neurotropic viruses have been associated with focal gray matter deficits in patients with schizophrenia. We evaluated whether such agents alter cognitive function in schizophrenia., Methods: The sample consisted of 329 patients diagnosed with schizophrenia or schizoaffective disorder. We evaluated associations between exposure to selected agents (Herpes Simplex Viruses 1 and 2 (HSV1, HSV2 respectively) cytomegalovirus (CMV) and Toxoplasma gondii) and scores on the Trail Making Test (TMT), controlling for relevant variables., Results: Serological evidence of exposure to CMV was associated with impaired performance on TMT part A time to completion (p=0.044), a measure of visual search, working memory, and psychomotor speed. Both CMV and HSV1 were significantly associated with increased errors on TMT part B (p<0.001 for both viruses). HSV2 and T. gondii exposure measures were not associated with any of the cognitive functions evaluated using TMT., Conclusions: Both CMV and HSV1 are associated with impaired cognitive function in schizophrenia as measured by the TMT. Further analyses to evaluate the impact of other illness related variables including genetic variants are warranted.
- Published
- 2008
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26. A genome screen for quantitative trait loci influencing schizophrenia and neurocognitive phenotypes.
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Almasy L, Gur RC, Haack K, Cole SA, Calkins ME, Peralta JM, Hare E, Prasad K, Pogue-Geile MF, Nimgaonkar V, and Gur RE
- Subjects
- Adult, Alleles, Cognition Disorders diagnosis, Cognition Disorders epidemiology, Female, Genetic Testing, Genotype, Humans, Male, Microsatellite Repeats, Neuropsychological Tests, Quantitative Trait Loci, Schizophrenia epidemiology, Severity of Illness Index, Brain physiopathology, Chromosomes, Human, Pair 19 genetics, Cognition Disorders genetics, Genome, Phenotype, Schizophrenia genetics, Schizophrenia physiopathology
- Abstract
Objective: Deficits in neurocognitive function have been demonstrated in individuals with schizophrenia and in the unaffected family members of these individuals. Genetic studies of such complementary traits, along with traditional analyses of diagnosis, may help to elucidate the biological pathways underlying familial liability to schizophrenia and related disorders. The authors conducted a multiplex, multigenerational family study using a genome-wide screen for schizophrenia and related neurocognitive phenotypes., Method: Participants were 1) 676 European American individuals from 43 families, ascertained through an individual with schizophrenia, and 2) 236 healthy comparison subjects. Participants were evaluated clinically and examined through the use of a computerized neurocognitive test battery that provided measures of accuracy and speed on the cognitive domains of abstraction and mental flexibility; attention; verbal, face, and spatial memory; language and reasoning; spatial and emotion processing; and sensorimotor dexterity. A genome-wide linkage screen was also performed. Healthy comparison subjects were included in order to obtain normative phenotypic data but were not genotyped., Results: Significant evidence for linkage of schizophrenia to chromosome 19q was observed. Analysis of cognitive traits revealed significant linkage to chromosome 5q for the domains of abstraction and mental flexibility. A variety of other neurocognitive traits also showed nominal evidence of linkage to the 5q region. Joint analyses with diagnosis suggested that this quantitative trait locus may also influence schizophrenia., Conclusions: Although chromosome 5 has been implicated in previous linkage studies of schizophrenia, the identification of the chromosome 19 quantitative trait locus is a novel finding. The identification of the chromosome 5 quantitative trait locus through linkage to neurocognitive phenotypes in the present study may inform functional hypotheses pertaining to how genotypes are connected to disease.
- Published
- 2008
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27. Development of social functioning in preschizophrenia children and adolescents: a systematic review.
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Tarbox SI and Pogue-Geile MF
- Subjects
- Adolescent, Case-Control Studies, Child, Cohort Studies, Humans, Psychology, Adolescent methods, Psychology, Child methods, Adolescent Behavior psychology, Child Behavior psychology, Child Development, Schizophrenia, Schizophrenic Psychology, Social Behavior
- Abstract
Schizophrenia is associated with severe deficits in social functioning. Similar deficits may be present prior to psychosis onset, in childhood and adolescence. If so, then prepsychosis social deficits could provide clues to the development of pathological processes in preschizophrenia children and could potentially improve early identification of the disorder and suggest targets for intervention. Evidence is reviewed from birth cohort, case- control, and familial high-risk studies within distinct periods of development to clarify the nature, timing, and specificity of social deficits in preschizophrenia children and adolescents. The results indicate that poor social functioning does differentiate preschizophrenia children and adolescents from their peers and can be a sensitive and potentially specific predictor of schizophrenia, not just psychopathology in general. Furthermore, age (but not sex) appears to be an important moderator of the strength and specificity of the association between particular social deficits (e.g., externalizing, internalizing) and later schizophrenia. Results are discussed in the context of current developmental theories of timing and pathophysiology of schizophrenia involving hypothalamic- pituitary-adrenal dysregulation. Implications for the early identification and treatment of preschizophrenia individuals are also considered., (PsycINFO Database Record (c) 2008 APA)
- Published
- 2008
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28. Are neurologic examination abnormalities heritable? A preliminary study.
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Sanders RD, Joo YH, Almasy L, Wood J, Keshavan MS, Pogue-Geile MF, Gur RC, Gur RE, and Nimgaonkar VL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Neuropsychological Tests statistics & numerical data, Psychiatric Status Rating Scales statistics & numerical data, Reproducibility of Results, Statistics as Topic, Family Health, Neurologic Examination methods, Schizophrenia genetics, Schizophrenia physiopathology
- Abstract
Background: Neurologic examination abnormalities (NEA) are more prevalent among patients with schizophrenia as well as their unaffected relatives when compared with healthy controls, suggesting that NEA may be endophenotypes for schizophrenia. We estimated the heritability of NEA in moderately sized pedigrees. We also evaluated correlations between NEA and cognitive performance in order to examine their construct validity., Methods: Members of eight extended families, each consisting of two first degree relatives with schizophrenia/schizoaffective disorders, as well as available first- to fifth-degree relatives were examined (n=96 participants). A modification of the Neurological Evaluation Scale (NES) was employed, augmented with localizing signs. Where feasible, we used untransformed data such as error counts and completion time, rather than ordinal measures. Heritability was estimated using the variance component method, implemented in SOLAR., Results: Statistically significant heritability (h2) estimates were obtained for several measures (p<0.05, h2+/-standard error: rapid alternating movements, right-sided completion time, 0.99+/-0.19; alternating fist-palm test, completion time, 0.77+/-0.19 s, errors, 0.70+/-0.32; fist-ring test, right-sided completion time, 0.53+/-0.23 s, left-sided completion time, 0.70+/-0.21 s; go-no go task, correct responses, 0.93+/-0.33; audio-visual integration, correct responses, 0.79+/-0.54). For most items, heritability analysis was hampered by insufficient data variability (infrequent errors). Correlational analyses show some degree of divergence among types of NEA, repetitive motor tasks being associated with most domains of cognitive functioning other than executive functioning, and cognitive-perceptual tasks being associated with memory and executive functioning., Conclusions: Significant familial influences on certain aspects of neurologic performance were detected. These heritable measures were also correlated with heritable neurocognitive measures.
- Published
- 2006
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29. Spontaneous dyskinesia and familial liability to schizophrenia.
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Tarbox SI and Pogue-Geile MF
- Subjects
- Adult, Female, Functional Laterality genetics, Humans, Male, Neurologic Examination, Phenotype, Siblings, Dyskinesias genetics, Genetic Predisposition to Disease genetics, Psychotic Disorders genetics, Schizophrenia genetics
- Abstract
Several factors suggest that spontaneous dyskinesia may be a useful supplemental phenotype for further elucidating the specific nature of the genetic contribution to schizophrenia. For example, involuntary movement abnormalities have been observed in both medicated and unmedicated schizophrenia patients, in individuals with schizotypal personality disorder, and sometimes in siblings of schizophrenia patients. However, there are many inconsistencies present in the literature to date. The current study thus sought to investigate the existence of spontaneous dyskinesia in schizophrenia patient probands, their non-psychotic siblings, and healthy controls in order to clarify its potential value as an "endophenotype" in genetic studies of schizophrenia. Videotaped interviews were coded for the presence of spontaneous, involuntary movement abnormalities by a trained and reliable rater using computer assisted technology who was blind to group and family status. The results of this study indicated that siblings of schizophrenia patients did not display significantly more involuntary movements compared to controls, although tremor was observed in a few siblings. In contrast, schizophrenia patients did display significantly more involuntary movements compared to controls as well as their non-psychotic siblings. The lack of significant differences between siblings and controls argues against a strong association between spontaneous dyskinesia and an "unexpressed" genetic liability to schizophrenia. Thus, it appears that involuntary movement abnormalities may be limited in their utility as endophenotypes in genetic studies of schizophrenia, despite being associated with, and perhaps predictive of, schizophrenia itself.
- Published
- 2006
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30. Indicators of genetic liability to schizophrenia: a sibling study of neuropsychological performance.
- Author
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Thompson JL, Watson JR, Steinhauer SR, Goldstein G, and Pogue-Geile MF
- Subjects
- Adolescent, Adult, Diagnostic and Statistical Manual of Mental Disorders, Genetic Markers, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Neuropsychological Tests, Phenotype, Severity of Illness Index, Trail Making Test, Cognition Disorders diagnosis, Cognition Disorders etiology, Schizophrenia complications, Schizophrenia genetics, Siblings
- Abstract
Despite clear evidence of important genetic influences on schizophrenia, identifying the genes involved has been difficult because of the genetic complexity of the phenotype. The use of additional phenotypic measures that are more sensitive to the genetic liability than is the clinical diagnosis should enhance the power to detect small individual genetic effects. The present study assessed the neuropsychological performance of 30 male schizophrenia probands, 30 of their unaffected male siblings, and 20 well controls matched on age, sex, and education in order to identify measures that may be particularly sensitive to the genetic liability to schizophrenia and thus may be useful in gene mapping studies. Siblings showed impaired neuropsychological performance compared to controls on four out of the five measures used. Additional results suggested that Trails B was especially effective at discriminating index siblings from controls, thus supporting its potential utility as a candidate quantitative phenotype to aid in gene mapping studies of the disorder.
- Published
- 2005
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31. Developmental pathology, dopamine, and stress: a model for the age of onset of schizophrenia symptoms.
- Author
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Thompson JL, Pogue-Geile MF, and Grace AA
- Subjects
- Adolescent, Age of Onset, Child, Dopamine metabolism, Glutamic Acid metabolism, Humans, Hypothalamo-Hypophyseal System physiopathology, Interpersonal Relations, Pituitary-Adrenal System physiopathology, Social Behavior, Stress, Psychological psychology, Brain physiopathology, Developmental Disabilities epidemiology, Developmental Disabilities physiopathology, Schizophrenia epidemiology, Schizophrenia metabolism, Schizophrenia physiopathology, Stress, Psychological epidemiology
- Abstract
It is unknown why the onset of schizophrenia is typically during late adolescence or early adulthood. The fact that numerous brain maturational processes normally occur during this age period has led researchers to postulate how such processes may be related to the onset of symptoms. To help elucidate the question of age of onset, we selectively review schizophrenia-associated abnormalities of dopamine and related systems, including glutamate and hypothalamic-pituitary-adrenal systems; relevant models of pathophysiology; and the systems' developmental aspects. Based on current findings and conceptualizations, a model is then proposed in which, during adolescence, interactive pathological and normal adolescence-associated processes trigger a positive feedback system that results in a rapid increase in pathology that is proposed to underlie the development of active psychotic symptoms during late adolescence or early adulthood.
- Published
- 2004
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32. A specific deficit in context processing in the unaffected siblings of patients with schizophrenia.
- Author
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MacDonald AW 3rd, Pogue-Geile MF, Johnson MK, and Carter CS
- Subjects
- Adult, Cognition Disorders genetics, Female, Genetic Predisposition to Disease, Humans, Male, Neuropsychological Tests, Prefrontal Cortex physiopathology, Psychiatric Status Rating Scales, Psychomotor Performance, Psychotic Disorders diagnosis, Psychotic Disorders genetics, Psychotic Disorders physiopathology, Reaction Time, Schizophrenia physiopathology, Schizophrenic Psychology, Cognition Disorders diagnosis, Schizophrenia diagnosis, Schizophrenia genetics, Siblings
- Abstract
Background: Understanding the biological basis of complex, heritable illnesses such as schizophrenia is facilitated by sensitive and functionally specific measures of intermediate processes. Context processing is a theoretically motivated construct associated with executive function. Impairments in this process have been associated with dysfunction of the prefrontal cortex. In the present study, we evaluated whether a specific deficit in context processing could be associated with the unexpressed genetic liability to schizophrenia., Methods: Twenty-four patients with schizophrenia, 24 unaffected siblings and 36 control subjects completed a version of the AX task with (1) a condition that required context processing and (2) an expectancy condition in which intact context processing could lead to errors., Results: Patients and unaffected siblings performed relatively worse in the context processing condition, whereas controls performed relatively worse in the expectancy condition. A double dissociation between siblings and controls (F = 9.5, P<.005) constituted strong evidence of a specific deficit in context processing associated with a familial or genetic liability to schizophrenia. Preliminary evidence of high diagnostic efficiency was also noted (specificity, 38%; and sensitivity, 100%)., Conclusions: Context processing deficits have been associated with dorsolateral prefrontal cortex dysfunctions in schizophrenia. Such a dysfunction may occur even when genetic liability to schizophrenia is unexpressed clinically. The present method of demonstrating a double dissociation may be a useful approach to exploring endophenotypes related to specific cognitive and neural processes that can be measured in ways sensitive to subtle group differences.
- Published
- 2003
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33. Variability within alpha- and beta-adrenoreceptor genes as a predictor of cardiovascular function at rest and in response to mental challenge.
- Author
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McCaffery JM, Pogue-Geile MF, Ferrell RE, Petro N, and Manuck SB
- Subjects
- Adult, Blood Pressure physiology, Diastole, Female, Forecasting, Genotype, Heart Rate physiology, Humans, Male, Models, Cardiovascular, Rest physiology, Systole, Cardiovascular System physiopathology, Genetic Variation, Receptors, Adrenergic, alpha genetics, Receptors, Adrenergic, beta genetics, Stress, Psychological genetics, Stress, Psychological physiopathology
- Abstract
Objectives: To investigate the association between polymorphic variation in alpha- and beta-adrenoreceptor genes and cardiovascular activity at rest and in response to psychological challenge in a sample in which the heritability of these cardiovascular phenotypes may be established., Methods: Several common polymorphisms were characterized within ADRA1B (alpha1B), ADRA2A (alpha2A), ADRB1 (beta1) and ADRB2 (beta2) and examined in relation to heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressure, both at rest and in response to stress. Participants were 309 European-American, young adult men and women (including 101 monozygotic and 44 dizygotic twin pairs)., Results: In the full sample, participants carrying any G allele at base pair (bp) 1165 in ADRB1 exhibited elevated resting SBP and DBP and a larger DBP response to mental challenge compared to homozygotes for the C allele (P < 0.04). An AA genotype at bp 145 in ADRB1 was also associated with higher resting SBP and DBP than AG or GG genotypes (P < 0.03). At bp 46 in ADRB2, GG homozygotes had higher resting DBP than subjects possessing any A allele (P < 0.05). For the same polymorphism, however, AG heterozygotes showed lower SBP than both AA and GG homozygotes (P < 0.05). In a subsample of genetically unrelated individuals, ADRB1 (1165) continued to predict resting SBP, DBP and DBP response to stress (P < 0.03), while ADRB2 (46) was associated with resting SBP (P < 0.04) but not DBP. Finally, the degree of allele sharing at ADRB1 (1165) also predicted variability in SBP and DBP at rest among dizygotic twin pairs (P < 0.04)., Conclusions: These results indicate that some polymorphic variation within adrenoreceptor genes contributes to interindividual variability in resting SBP and DBP and in DBP response to mental challenge.
- Published
- 2002
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34. Covariation of psychosocial characteristics associated with cardiovascular disease: genetic and environmental influences.
- Author
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Raynor DA, Pogue-Geile MF, Kamarck TW, McCaffery JM, and Manuck SB
- Subjects
- Adult, Analysis of Variance, Cardiovascular Diseases diagnosis, Cardiovascular Diseases psychology, Depressive Disorder diagnosis, Depressive Disorder psychology, Female, Humans, Male, Personality Inventory, Phenotype, Risk Factors, Twins, Dizygotic, Twins, Monozygotic, Cardiovascular Diseases genetics, Depressive Disorder genetics, Diseases in Twins, Hostility, Social Environment, Social Support
- Abstract
Objective: Three psychosocial characteristics associated with cardiovascular disease (CVD)-depression, hostility, and social support-tend to correlate with one another. However, the causes of each characteristic and why they tend to co-occur are not completely understood. Therefore, the current study used a twin design to examine the relative contributions of genetic and environmental influences to the variation and covariation of these three psychosocial characteristics., Methods: The sources of variation and covariation among the Beck Depression Inventory, the Cook-Medley Hostility Scale, and the Interpersonal Support Evaluation List were examined in a young adult community sample of 157 monozygotic and 75 dizygotic twin pairs., Results: Phenotypic confirmatory factor analysis indicated that a single latent factor could account for their moderate intercorrelations. Twin analyses indicated that the Beck Depression Inventory and Interpersonal Support Evaluation List were each influenced by genetic and nonshared environmental factors, whereas the Cook-Medley Hostility Scale was influenced by familial (genetic and/or shared environmental) and nonshared environmental factors. Bivariate associations between these scales were largely determined by common genetic effects and, to a lesser degree, common nonshared environmental effects. Covariation among the three scales could be explained by a single common genetic factor and a common nonshared environmental factor. Environmental factors shared within families did not contribute to covariation among the psychosocial characteristics., Conclusions: The results challenge the conventional approach of examining these psychosocial variables as independent risk factors for cardiovascular disease and argue for the importance of investigating specific causes for their covariation.
- Published
- 2002
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35. Genetic and environmental influences on schizotypy: a community-based twin study.
- Author
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MacDonald AW 3rd, Pogue-Geile MF, Debski TT, and Manuck S
- Subjects
- Adolescent, Adult, Environment, Family Relations, Female, Humans, Male, Psychiatric Status Rating Scales, Risk Factors, Social Behavior, Surveys and Questionnaires standards, Twins, Dizygotic, Twins, Monozygotic, Schizophrenia genetics, Schizotypal Personality Disorder genetics
- Abstract
This study investigated the factor structure and etiology of four self-report schizotypy questionnaires during young adulthood (age 18-27) in 98 monozygotic and 59 same-sex dizygotic twin pairs from the community. A single phenotypic factor was identified that was primarily associated with Perceptual Aberration, Magical Ideation, and the Rust Inventory of Schizotypal Cognitions scales, and less so with Social Anhedonia. Univariate etiologic models suggested that in addition to nonshared environmental influences, Perceptual Aberration and Social Anhedonia were significantly influenced by either genes or shared family environment, whereas Magical Ideation and the Rust Inventory were influenced by shared family environment, but not genes. Multivariate twin analyses detected a common schizotypy factor, primarily defined by Perceptual Aberration, Magical Ideation, and the Rust Inventory scales, that was influenced by genes or shared environment as well as nonshared environment. Contrary to expectations, these results suggest that, at least in community-based samples, these "positive" schizotypy questionnaires are not strongly genetically influenced.
- Published
- 2001
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36. Familial liability to schizophrenia: a sibling study of negative symptoms.
- Author
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Craver JC and Pogue-Geile MF
- Subjects
- Adult, Female, Humans, Male, Mood Disorders complications, Reproducibility of Results, Schizophrenia complications, Schizophrenia diagnosis, Severity of Illness Index, Mood Disorders diagnosis, Schizophrenia genetics, Sibling Relations
- Abstract
Negative symptoms are important features in schizophrenia, so in milder form they might also serve as indicators of "unexpressed" liability to schizophrenia among patients' adult relatives without schizophrenia. To address this question, we assessed negative symptoms in 39 stable schizophrenia or schizoaffective outpatients, 39 of their siblings, 38 well control probands, and 38 of their siblings. Negative symptom measures included standard behavior ratings of the core negative symptoms of affective flattening and alogia, as well as a self-report measure of social anhedonia. As expected, even stable outpatients with schizophrenia exhibited significantly more negative symptoms than control probands and control siblings. However, negative behavioral symptoms of affective flattening, alogia, and anhedonia did not significantly differentiate the siblings of the schizophrenia patients from the control probands or their siblings, although there were some trends for anhedonia. The findings suggest that core negative symptoms of observed affective flattening and poverty of speech are not likely to be useful as strong indicators of "unexpressed" liability to schizophrenia.
- Published
- 1999
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37. The nature of environmental influences on weight and obesity: a behavior genetic analysis.
- Author
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Grilo CM and Pogue-Geile MF
- Subjects
- Humans, Risk Factors, Body Weight genetics, Individuality, Obesity genetics, Obesity psychology, Social Environment
- Abstract
The nature of environmental influences on individual differences in weight and obesity is presently unclear. To resolve this issue, behavior genetic studies are reviewed for their relevance to environmental influences on weight and obesity. Results are consistent in suggesting that environmental experiences are important for weight and obesity, although they account for much less variation than do the effects of genes. Furthermore, only environmental experiences that are not shared among family members appear to be important. In contrast, experiences that are shared among family members appear largely irrelevant in determining individual differences in weight and obesity. These conclusions are consistent with a growing body of evidence on the relative unimportance of such shared experiences for many psychological characteristics.
- Published
- 1991
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38. Hospitalization and the cognitive deficits of schizophrenia. The influences of age and education.
- Author
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Goldstein G, Zubin J, and Pogue-Geile MF
- Subjects
- Adult, Aging psychology, Educational Status, Humans, Length of Stay, Male, Perceptual Disorders diagnosis, Regression Analysis, Wechsler Scales, Hospitalization, Neuropsychological Tests, Schizophrenia diagnosis, Schizophrenic Psychology
- Abstract
The study investigated the relationship between length of hospitalization and increasing cognitive deficit in schizophrenics. Using Halstead-Reitan Battery data obtained from 245 schizophrenic patients, multiple regression analyses were performed using age, education, and length of hospitalization as independent variables and various summary test indices as dependent variables. These analyses showed that there was not a statistically significant change in percentage of explained variance when length of hospitalization was entered into the multiple regression equations. On the basis of these analyses, it was concluded that the association between increasing deficit and length of hospitalization experienced by schizophrenic patients is no greater than what would be anticipated on the basis of aging.
- Published
- 1991
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39. Negative and positive symptoms in schizophrenia and depression: a followup.
- Author
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Pogue-Geile MF and Harrow M
- Subjects
- Adolescent, Adult, Affect, Cognition Disorders psychology, Delusions psychology, Female, Follow-Up Studies, Hallucinations psychology, Hospitalization, Humans, Male, Psychomotor Performance, Role, Social Adjustment, Speech, Thinking, Depressive Disorder psychology, Schizophrenic Psychology
- Abstract
Negative and positive symptoms were investigated in a sample of 72 young schizophrenic and depressed patients at followup approximately 1 1/2 years after hospital discharge. Flat affect, poverty of speech, and psychomotor retardation were included as negative symptoms, and delusions, hallucinations, and florid thought disorder as positive symptoms. Marked negative symptoms were found to occur in a subgroup of schizophrenic subjects at followup, but were infrequent in depressed subjects. Educational difficulties and poor social functioning before initial hospitalization were associated with later negative symptoms at followup for schizophrenic subjects. Negative symptoms were also related to concurrent outcome measures of instrumental and social functioning at followup. Contrary to some hypotheses, negative and positive symptoms, when assessed concurrently, were not at opposite ends of a bipolar continuum. Rather, they appeared to be independent phenomena in schizophrenia during the early posthospital phase. Overall, these results suggest that negative symptoms are important for a subgroup of schizophrenic patients during the early course of their disorder and that they have important correlates with specific aspects of role functioning.
- Published
- 1984
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40. Twin-family studies of common fears and phobias.
- Author
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Rose RJ, Miller JZ, Pogue-Geile MF, and Cardwell GF
- Subjects
- Adolescent, Adult, Female, Genetic Variation, Genetics, Behavioral, Humans, Male, Pregnancy, Phobic Disorders genetics, Twins psychology, Twins, Dizygotic psychology, Twins, Monozygotic psychology
- Published
- 1981
41. Sentence perception and distractibility in schizophrenic, manic, and depressed patients.
- Author
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Pogue-Geile MF and Oltmanns TF
- Subjects
- Adolescent, Adult, Humans, Middle Aged, Attention, Bipolar Disorder psychology, Depression psychology, Schizophrenic Psychology, Speech Perception
- Published
- 1980
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42. The prognostic significance of negative symptoms in schizophrenia.
- Author
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Pogue-Geile MF
- Subjects
- Acute Disease, Humans, Prognosis, Psychiatric Status Rating Scales, Schizophrenia diagnosis, Schizophrenic Psychology
- Published
- 1989
43. Negative symptoms in schizophrenia: their longitudinal course and prognostic importance.
- Author
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Pogue-Geile MF and Harrow M
- Subjects
- Adolescent, Adult, Delusions psychology, Female, Hallucinations psychology, Humans, Longitudinal Studies, Male, Mood Disorders psychology, Prognosis, Psychiatric Status Rating Scales, Psychomotor Disorders psychology, Schizophrenic Language, Social Adjustment, Verbal Behavior, Schizophrenia diagnosis, Schizophrenic Psychology
- Abstract
Negative and positive symptoms were investigated longitudinally in 39 young schizophrenic patients at two followup assessments approximately 2.5 and 5 years after hospital discharge. Negative symptoms, such as flat affect and poverty of speech, which were assessed at the first followup, were found to be effective prognostic signs in schizophrenic patients for predicting later poor role functioning at the second followup. The prognostic importance of negative symptoms was predominantly due to their tendency to occur in patients who were already functioning poorly in social and instrumental areas at the first followup, and who tended to continue doing poorly at the second followup. Contrary to some current hypotheses, positive symptoms, such as delusions and hallucinations, were also found to be prognostic of later deficits in role functioning at the second followup. Negative symptoms appeared to be generally persistent over time, although there was some tendency toward remission. Potential models of the etiology of negative symptoms and their role in schizophrenia are proposed.
- Published
- 1985
- Full Text
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