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3. Mir137 Polygenic Risk for Schizophrenia and Ephrin-Regulated Pathway: Role in Lateral Ventricles and Corpus Callosum Volume

Author

Blokland, Gabriëlla Antonina Maria, primary, Maleki, Nasim, additional, Jovicich, Jorge, additional, Mesholam-Gately, Raquelle, additional, DeLisi, Lynn E., additional, Turner, Jessica A., additional, Shenton, Martha E., additional, Voineskos, Aristotle, additional, Kahn, Rene S., additional, Roffman, Joshua L., additional, Holt, Daphne J., additional, Ehrlich, Stefan, additional, Kikinis, Zora, additional, Dazzan, Paola, additional, Murray, Robin, additional, Lee, Jimmy, additional, Sim, Kang, additional, Lam, Max, additional, de Zwarte, Sonja M. C., additional, Walton, Esther, additional, Kelly, Sinead, additional, Picchioni, Marco M., additional, Bramon, Elvira, additional, Makris, Nikos, additional, David, Anthony S., additional, Mondelli, Valeria, additional, Reinders, Antje ATS, additional, Oykhman, Efim, additional, Morris, Derek W., additional, Gill, Michael, additional, Corvin, Aiden, additional, Cahn, Wiepke, additional, Ho, New Fei, additional, Liu, Jianjun, additional, Gollub, Randy L., additional, Manoach, Dara S., additional, Calhoun, Vince D., additional, Sponheim, Scott R., additional, Buka, Stephen, additional, Cherkerzian, Sara, additional, Thermenos, Heidi W., additional, Dickie, Erin W., additional, Ciufolini, Simone, additional, Reis Marques, Tiago, additional, Crossley, Nicolas A., additional, Purcell, Shaun M., additional, Smoller, Jordan W., additional, van Haren, Neeltje E.M., additional, Toulopoulou, Timothea, additional, Donohoe, Gary, additional, Goldstein, Jill M., additional, Keshavan, Matcheri S., additional, Petryshen, Tracey L., additional, and del Re, Elisabetta Claudia, additional

Published
2024
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4. Alterations of lateral temporal cortical gray matter and facial memory as vulnerability indicators for schizophrenia: An MRI study in youth at familial high-risk for schizophrenia

Author

Brent, Benjamin K, Rosso, Isabelle M, Thermenos, Heidi W, Holt, Daphne J, Faraone, Stephen V, Makris, Nikos, Tsuang, Ming T, and Seidman, Larry J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pediatric, Neurosciences, Prevention, Mental Health, Clinical Research, Brain Disorders, Schizophrenia, Serious Mental Illness, 2.1 Biological and endogenous factors, Aetiology, 2.3 Psychological, social and economic factors, Mental health, Adolescent, Adult, Facial Recognition, Family, Female, Genetic Predisposition to Disease, Gray Matter, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Organ Size, Prognosis, Psychotic Disorders, Recognition, Psychology, Risk, Schizophrenic Psychology, Temporal Lobe, Young Adult, Familial high-risk, Lateral temporal cortex, Facial memory, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences
Abstract

BackgroundStructural alterations of the lateral temporal cortex (LTC) in association with memory impairments have been reported in schizophrenia. This study investigated whether alterations of LTC structure were linked with impaired facial and/or verbal memory in young first-degree relatives of people with schizophrenia and, thus, may be indicators of vulnerability to the illness.MethodsSubjects included 27 non-psychotic, first-degree relatives of schizophrenia patients, and 48 healthy controls, between the ages of 13 and 28. Participants underwent high-resolution magnetic resonance imaging (MRI) at 1.5Tesla. The LTC was parcellated into superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, and temporal pole. Total cerebral and LTC volumes were measured using semi-automated morphometry. The Wechsler Memory Scale - Third Edition and the Children's Memory Scale - Third Edition assessed facial and verbal memory. General linear models tested for associations among LTC subregion volumes, familial risk and memory.ResultsCompared with controls, relatives had significantly smaller bilateral middle temporal gyri. Moreover, right middle temporal gyral volume showed a significant positive association with delayed facial memory in relatives.ConclusionThese results support the hypothesis that smaller middle temporal gyri are related to the genetic liability to schizophrenia and may be linked with reduced facial memory in persons at genetic risk for the illness. The findings add to the growing evidence that children at risk for schizophrenia on the basis of positive family history have cortical and subcortical structural brain abnormalities well before psychotic illness occurs.

Published
2016

5. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project

Author

Blokland, Gabriëlla A.M., del Re, Elisabetta C., Mesholam-Gately, Raquelle I., Jovicich, Jorge, Trampush, Joey W., Keshavan, Matcheri S., DeLisi, Lynn E., Walters, James T.R., Turner, Jessica A., Malhotra, Anil K., Lencz, Todd, Shenton, Martha E., Voineskos, Aristotle N., Rujescu, Dan, Giegling, Ina, Kahn, René S., Roffman, Joshua L., Holt, Daphne J., Ehrlich, Stefan, Kikinis, Zora, Dazzan, Paola, Murray, Robin M., Di Forti, Marta, Lee, Jimmy, Sim, Kang, Lam, Max, Wolthusen, Rick P.F., de Zwarte, Sonja M.C., Walton, Esther, Cosgrove, Donna, Kelly, Sinead, Maleki, Nasim, Osiecki, Lisa, Picchioni, Marco M., Bramon, Elvira, Russo, Manuela, David, Anthony S., Mondelli, Valeria, Reinders, Antje A.T.S., Falcone, M. Aurora, Hartmann, Annette M., Konte, Bettina, Morris, Derek W., Gill, Michael, Corvin, Aiden P., Cahn, Wiepke, Ho, New Fei, Liu, Jian Jun, Keefe, Richard S.E., Gollub, Randy L., Manoach, Dara S., Calhoun, Vince D., Schulz, S. Charles, Sponheim, Scott R., Goff, Donald C., Buka, Stephen L., Cherkerzian, Sara, Thermenos, Heidi W., Kubicki, Marek, Nestor, Paul G., Dickie, Erin W., Vassos, Evangelos, Ciufolini, Simone, Reis Marques, Tiago, Crossley, Nicolas A., Purcell, Shaun M., Smoller, Jordan W., van Haren, Neeltje E.M., Toulopoulou, Timothea, Donohoe, Gary, Goldstein, Jill M., Seidman, Larry J., McCarley, Robert W., and Petryshen, Tracey L.

Published
2018
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6. Heritability of brain ventricle volume: Converging evidence from inconsistent results

Author

Kremen, William S, Panizzon, Matthew S, Neale, Michael C, Fennema-Notestine, Christine, Prom-Wormley, Elizabeth, Eyler, Lisa T, Stevens, Allison, Franz, Carol E, Lyons, Michael J, Grant, Michael D, Jak, Amy J, Jernigan, Terry L, Xian, Hong, Fischl, Bruce, Thermenos, Heidi W, Seidman, Larry J, Tsuang, Ming T, and Dale, Anders M

Subjects
Biological Psychology, Psychology, Aging, Neurosciences, Prevention, Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Ventricles, Child, Gene-Environment Interaction, Humans, Middle Aged, Organ Size, Sample Size, Twin Studies as Topic, Young Adult, Alzheimer's Disease, Endophenotype, Genetics, Lateral ventricles, Mild cognitive impairment, Structural MRI, Twins, Clinical Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Twin studies generally show great consistency for the heritability of brain structures. Ironically, the lateral ventricles--perhaps the most reliably measured brain regions of interest--are the most inconsistent when it comes to estimating genetic influences on their volume. Heritability estimates in twin studies have ranged from zero to almost 0.80. Here we aggregate heritability estimates from extant twin studies, and we review and reinterpret some of the findings. Based on our revised estimates, we conclude that lateral ventricular volume is indeed heritable. The weighted average heritability of the revised estimates was 0.54. Although accumulated environmental insults might seem most logical as the predominant cause of age-related ventricular expansion, the data strongly suggest that genetic influences on lateral ventricular volume are increasing with age. Genetic influences accounted for 32-35% of the variance in lateral ventricular volume in childhood, but about 75% of the variance in late middle and older age. These conclusions have implications for the basic understanding of the genetic and environmental underpinnings of normative and pathological brain aging.

Published
2012

7. Genetic and Environmental Contributions to Regional Cortical Surface Area in Humans: A Magnetic Resonance Imaging Twin Study

Author

Eyler, Lisa T, Prom-Wormley, Elizabeth, Panizzon, Matthew S, Kaup, Allison R, Fennema-Notestine, Christine, Neale, Michael C, Jernigan, Terry L, Fischl, Bruce, Franz, Carol E, Lyons, Michael J, Grant, Michael, Stevens, Allison, Pacheco, Jennifer, Perry, Michele E, Schmitt, J Eric, Seidman, Larry J, Thermenos, Heidi W, Tsuang, Ming T, Chen, Chi-Hua, Thompson, Wesley K, Jak, Amy, Dale, Anders M, and Kremen, William S

Subjects
Biological Psychology, Psychology, Clinical Research, Genetics, Animals, Brain Mapping, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Quantitative Trait, Heritable, Social Environment, cortex, cortical thickness, heritability, Neurosciences, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Cortical surface area measures appear to be functionally relevant and distinct in etiology, development, and behavioral correlates compared with other size characteristics, such as cortical thickness. Little is known about genetic and environmental influences on individual differences in regional surface area in humans. Using a large sample of adult twins, we determined relative contributions of genes and environment on variations in regional cortical surface area as measured by magnetic resonance imaging before and after adjustment for genetic and environmental influences shared with total cortical surface area. We found high heritability for total surface area and, before adjustment, moderate heritability for regional surface areas. Compared with other lobes, heritability was higher for frontal lobe and lower for medial temporal lobe. After adjustment for total surface area, regionally specific genetic influences were substantially reduced, although still significant in most regions. Unlike other lobes, left frontal heritability remained high after adjustment. Thus, global and regionally specific genetic factors both influence cortical surface areas. These findings are broadly consistent with results from animal studies regarding the evolution and development of cortical patterning and may guide future research into specific environmental and genetic determinants of variation among humans in the surface area of particular regions.

Published
2011

8. Genetic patterns of correlation among subcortical volumes in humans: Results from a magnetic resonance imaging twin study

Author

Eyler, Lisa T, Prom‐Wormley, Elizabeth, Fennema‐Notestine, Christine, Panizzon, Matthew S, Neale, Michael C, Jernigan, Terry L, Fischl, Bruce, Franz, Carol E, Lyons, Michael J, Stevens, Allison, Pacheco, Jennifer, Perry, Michele E, Schmitt, J Eric, Spitzer, Nicholas C, Seidman, Larry J, Thermenos, Heidi W, Tsuang, Ming T, Dale, Anders M, and Kremen, William S

Subjects
Biological Psychology, Psychology, Acquired Cognitive Impairment, Basic Behavioral and Social Science, Neurosciences, Brain Disorders, Behavioral and Social Science, Dementia, Mental Health, Genetics, Aging, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Cerebral Cortex, Gene Expression Regulation, Developmental, Genetic Variation, Humans, Individuality, Male, Middle Aged, Models, Genetic, Twins, behavioral genetics, hippocampus, amygdala, striatum, pallidum, caudate, putamen, thalamus, ventricles, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes. We then examined the patterns of genetic correlation through hierarchical cluster analysis and by principal components analysis. We found that a model with four genetic factors best fit the data: a Basal Ganglia/Thalamus factor; a Ventricular factor; a Limbic factor; and a Nucleus Accumbens factor. Homologous regions from each hemisphere loaded on the same factors. The observed patterns of genetic correlation suggest the influence of multiple genetic influences. There is a genetic organization among structures which distinguishes between brain and cerebrospinal fluid spaces and between different subcortical regions. Further study is needed to understand this genetic patterning and whether it reflects influences on early development, functionally dependent patterns of growth or pruning, or regionally specific losses due to genes involved in aging, stress response, or disease.

Published
2011

9. Salivary cortisol and prefrontal cortical thickness in middle-aged men: A twin study

Author

Kremen, William S, O'Brien, Robert C, Panizzon, Matthew S, Prom-Wormley, Elizabeth, Eaves, Lindon J, Eisen, Seth A, Eyler, Lisa T, Hauger, Richard L, Fennema-Notestine, Christine, Fischl, Bruce, Grant, Michael D, Hellhammer, Dirk H, Jak, Amy J, Jacobson, Kristen C, Jernigan, Terry L, Lupien, Sonia J, Lyons, Michael J, Mendoza, Sally P, Neale, Michael C, Seidman, Larry J, Thermenos, Heidi W, Tsuang, Ming T, Dale, Anders M, and Franz, Carol E

Subjects
Biomedical and Clinical Sciences, Health Sciences, Mental Health, Genetics, Prevention, Basic Behavioral and Social Science, Brain Disorders, Behavioral and Social Science, Neurosciences, Aging, 1.2 Psychological and socioeconomic processes, 1.1 Normal biological development and functioning, Underpinning research, 2.1 Biological and endogenous factors, Aetiology, Mental health, Brain Mapping, Humans, Hydrocortisone, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Phenotype, Prefrontal Cortex, Quantitative Trait, Heritable, Radioimmunoassay, Saliva, Twins, Heritability, Magnetic resonance imaging, Hippocampus, HPA axis structure, Genetic correlation, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract

Although glucocorticoid receptors are highly expressed in the prefrontal cortex, the hippocampus remains the predominant focus in the literature examining relationships between cortisol and brain. We examined phenotypic and genetic associations of cortisol levels with the thickness of prefrontal and anterior cingulate cortex regions, and with hippocampal volume in a sample of 388 middle-aged male twins who were 51-59 years old. Small but significant negative phenotypic associations were found between cortisol levels and the thickness of left dorsolateral (superior frontal gyrus, left rostral middle frontal gyrus) and ventrolateral (pars opercularis, pars triangularis, pars orbitalis) prefrontal regions, and right dorsolateral (superior frontal gyrus) and medial orbital frontal cortex. Most of the associations remained significant after adjusting for general cognitive ability, cardiovascular risk factors, and depression. Bivariate genetic analyses suggested that some of the associations were primarily accounted for by shared genetic influences; that is, some of the genes that tend to result in increased cortisol levels also tend to result in reduced prefrontal cortical thickness. Aging has been associated with reduced efficiency of hypothalamic-pituitary-adrenal function, frontal lobe shrinkage, and increases in health problems, but our present data do not allow us to determine the direction of effects. Moreover, the degree or the direction of the observed associations and the extent of their shared genetic underpinnings may well change as these individuals age. Longitudinal assessments are underway to elucidate the direction of the associations and the genetic underpinnings of longitudinal phenotypes for changes in cortisol and brain morphology.

Published
2010

10. Altered working memory-related brain activity in children at familial high risk for psychosis: A preliminary study

Author

Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, van Gool, Kevin CA, Collin, Guusje, Bauer, Clemens CC, Molokotos, Elena, Mesholam-Gately, Raquelle I, Thermenos, Heidi W, Seidman, Larry J, Gabrieli, John DE, Whitfield-Gabrieli, Susan, Keshavan, Matcheri S, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, van Gool, Kevin CA, Collin, Guusje, Bauer, Clemens CC, Molokotos, Elena, Mesholam-Gately, Raquelle I, Thermenos, Heidi W, Seidman, Larry J, Gabrieli, John DE, Whitfield-Gabrieli, Susan, and Keshavan, Matcheri S

Abstract

BACKGROUND: Schizophrenia spectrum disorders are heritable illnesses that usually manifest in early adulthood but are increasingly viewed as neurodevelopmental disorders. Functional magnetic resonance imaging (fMRI) studies show altered brain activity during performance of working memory (WM) tasks in both individuals with schizophrenia and their first-degree relatives as compared to healthy controls (HC). This study examined whether similar changes are already present in pre-adolescent children at familial high-risk (FHR) for psychosis. METHODS: 37 children (17 FHR, 20 HC) between 7 and 12 years old participated in this study. WM performance was assessed using the Wechsler Intelligence Scale for Children-IV (WISC-IV). To assess brain activation during WM performance, participants completed a visual block-designed n-back task with 2 conditions (2-back and 0-back) during scanning. fMRI data was preprocessed and analyzed using FSL Feat. RESULTS: Compared to HC, FHR children showed significantly lower WISC-IV WM scores. In addition, FHR children exhibited hypoactivation in the 2-back (versus 0-back) condition in a cluster encompassing bilateral precuneus and cuneus and right posterior cingulate cortex. There were no significant group-differences in n-back task performance and brain activation. The precuneus cluster was not correlated with n-back performance or WISC WM scores. CONCLUSIONS: The current results provide preliminary evidence of impaired WM function and altered brain activity during WM performance in children with a familial predisposition for psychosis. Longitudinal studies are needed to determine whether these findings are related to abnormal brain development and predictive of cognitive deficits and psychosis later in life.

Published
2023

12. Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis

Author

Thermenos, Heidi W., Juelich, Richard J., DiChiara, Samantha R., Mesholam-Gately, Raquelle I., Woodberry, Kristen A., Wojcik, Joanne, Makris, Nikos, Keshavan, Matcheri S., Whitfield-Gabrieli, Susan, Woo, Tsung-Ung W., Petryshen, Tracey L., Goldstein, Jill M., Shenton, Martha E., McCarley, Robert W., and Seidman, Larry J.

Published
2016
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20. Genetic and environmental influences on the size of specific brain regions in midlife: The VETSA MRI study

Author

Kremen, William S., Prom-Wormley, Elizabeth, Panizzon, Matthew S., Eyler, Lisa T., Fischl, Bruce, Neale, Michael C., Franz, Carol E., Lyons, Michael J., Pacheco, Jennifer, Perry, Michele E., Stevens, Allison, Schmitt, J. Eric, Grant, Michael D., Seidman, Larry J., Thermenos, Heidi W., Tsuang, Ming T., Eisen, Seth A., Dale, Anders M., and Fennema-Notestine, Christine

Published
2010
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22. Altered resting-state functional connectivity in young children at familial high risk for psychotic illness: A preliminary study

Author

Anteraper, Sheeba Arnold, Collin, Guusje, Guell, Xavier, Scheinert, Timothy, Molokotos, Elena, Henriksen, Maria Toft, Mesholam-Gately, Raquelle, Thermenos, Heidi W, Seidman, Larry J, Keshavan, Matcheri S, Gabrieli, John DE, Whitfield-Gabrieli, Susan, Anteraper, Sheeba Arnold, Collin, Guusje, Guell, Xavier, Scheinert, Timothy, Molokotos, Elena, Henriksen, Maria Toft, Mesholam-Gately, Raquelle, Thermenos, Heidi W, Seidman, Larry J, Keshavan, Matcheri S, Gabrieli, John DE, and Whitfield-Gabrieli, Susan

Abstract

© 2019 Elsevier B.V. Multiple lines of evidence suggest that illness development in schizophrenia and other psychotic disorders predates the first psychotic episode by many years. In this study, we examined a sample of 15 pre-adolescent children, ages 7 through 12 years, who are at familial high-risk (FHR) because they have a parent or sibling with a history of schizophrenia or related psychotic disorder. Using multi-voxel pattern analysis (MVPA), a data-driven fMRI analysis, we assessed whole-brain differences in functional connectivity in the FHR sample as compared to an age- and sex-matched control (CON) group of 15 children without a family history of psychosis. MVPA analysis yielded a single cluster in right posterior superior temporal gyrus (pSTG/BA 22) showing significant group-differences in functional connectivity. Post-hoc characterization of this cluster through seed-to-voxel analysis revealed mostly reduced functional connectivity of the pSTG seed to a set of language and default mode network (DMN) associated brain regions including Heschl's gyrus, inferior temporal gyrus extending into fusiform gyrus, (para)hippocampus, thalamus, and a cerebellar cluster encompassing mainly Crus I/II. A height-threshold of whole-brain p < .001 (two-sided), and FDR-corrected cluster-threshold of p < .05 (non-parametric statistics) was used for post-hoc characterization. These findings suggest that abnormalities in functional communication in a network encompassing right STG and associated brain regions are present before adolescence in at-risk children and may be a risk marker for psychosis. Subsequent changes in this functional network across development may contribute to either disease manifestation or resilience in children with a familial vulnerability for psychosis.

Published
2021

23. Altered resting-state functional connectivity in young children at familial high risk for psychotic illness: A preliminary study

Author

McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Anteraper, Sheeba Rani Arnold, Collin, Guusje, Guell Paradis, Xavier, Scheinert, Timothy, Molokotos, Elena, Henriksen, Maria Toft, Mesholam-Gately, Raquelle, Thermenos, Heidi W, Seidman, Larry J, Keshavan, Matcheri S, Gabrieli, John D. E., Whitfield-Gabrieli, Susan, McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Anteraper, Sheeba Rani Arnold, Collin, Guusje, Guell Paradis, Xavier, Scheinert, Timothy, Molokotos, Elena, Henriksen, Maria Toft, Mesholam-Gately, Raquelle, Thermenos, Heidi W, Seidman, Larry J, Keshavan, Matcheri S, Gabrieli, John D. E., and Whitfield-Gabrieli, Susan

Abstract

© 2019 Elsevier B.V. Multiple lines of evidence suggest that illness development in schizophrenia and other psychotic disorders predates the first psychotic episode by many years. In this study, we examined a sample of 15 pre-adolescent children, ages 7 through 12 years, who are at familial high-risk (FHR) because they have a parent or sibling with a history of schizophrenia or related psychotic disorder. Using multi-voxel pattern analysis (MVPA), a data-driven fMRI analysis, we assessed whole-brain differences in functional connectivity in the FHR sample as compared to an age- and sex-matched control (CON) group of 15 children without a family history of psychosis. MVPA analysis yielded a single cluster in right posterior superior temporal gyrus (pSTG/BA 22) showing significant group-differences in functional connectivity. Post-hoc characterization of this cluster through seed-to-voxel analysis revealed mostly reduced functional connectivity of the pSTG seed to a set of language and default mode network (DMN) associated brain regions including Heschl's gyrus, inferior temporal gyrus extending into fusiform gyrus, (para)hippocampus, thalamus, and a cerebellar cluster encompassing mainly Crus I/II. A height-threshold of whole-brain p < .001 (two-sided), and FDR-corrected cluster-threshold of p < .05 (non-parametric statistics) was used for post-hoc characterization. These findings suggest that abnormalities in functional communication in a network encompassing right STG and associated brain regions are present before adolescence in at-risk children and may be a risk marker for psychosis. Subsequent changes in this functional network across development may contribute to either disease manifestation or resilience in children with a familial vulnerability for psychosis., NIMH (Grant R21-MH092840)

Published
2021

24. Hyperactivation of Posterior Default Mode Network During Self-Referential Processing in Children at Familial High-Risk for Psychosis

Author

Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research at MIT, Collin, Guusje, Bauer, Clemens CC, Anteraper, Sheeba Arnold, Gabrieli, John DE, Molokotos, Elena, Mesholam-Gately, Raquelle, Thermenos, Heidi W, Seidman, Larry J, Keshavan, Matcheri S, Shenton, Martha E, Whitfield-Gabrieli, Susan, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research at MIT, Collin, Guusje, Bauer, Clemens CC, Anteraper, Sheeba Arnold, Gabrieli, John DE, Molokotos, Elena, Mesholam-Gately, Raquelle, Thermenos, Heidi W, Seidman, Larry J, Keshavan, Matcheri S, Shenton, Martha E, and Whitfield-Gabrieli, Susan

Abstract

Patients with schizophrenia spectrum disorders show disturbances in self-referential processing and associated neural circuits including the default mode network (DMN). These disturbances may precede the onset of psychosis and may underlie early social and emotional problems. In this study, we examined self-referential processing in a group of children (7–12 years) at familial high risk (FHR) for psychosis (N = 17), compared to an age and sex-matched group of healthy control (HC) children (N = 20). The participants were presented with a list of adjectives and asked to indicate whether or not the adjectives described them (self-reference condition) and whether the adjectives described a good or bad trait (semantic condition). Three participants were excluded due to chance-level performance on the semantic task, leaving N = 15 FHR and N = 19 HC for final analysis. Functional MRI (fMRI) was used to measure brain activation during self-referential vs. semantic processing. Internalizing and externalizing problems were assessed with the Child Behavior Checklist (CBCL). Evaluating main effects of task (self > semantic) showed activation of medial prefrontal cortex in HC and precuneus/posterior cingulate cortex (PCC) in FHR. Group-comparison yielded significant results for the FHR > HC contrast, showing two clusters of hyperactivation in precuneus/ PCC (p = 0.004) and anterior cerebellum / temporo-occipital cortex (p = 0.009). Greater precuneus/PCC activation was found to correlate with greater CBCL internalizing (r = 0.60, p = 0.032) and total (r = 0.69, p = 0.009) problems. In all, this study shows hyperactivity of posterior DMN during self-referential processing in pre-adolescent FHR children. This finding posits DMN-related disturbances in self-processing as a developmental brain abnormality associated with familial risk factors that predates not just psychosis, but also the prodromal stage. Moreover, our results suggest that early disturbances in self-referential proce

Published
2021

25. Reliability of functional magnetic resonance imaging activation during working memory in a multi-site study: Analysis from the North American Prodrome Longitudinal Study

Author

Forsyth, Jennifer K., McEwen, Sarah C., Gee, Dylan G., Bearden, Carrie E., Addington, Jean, Goodyear, Brad, Cadenhead, Kristin S., Mirzakhanian, Heline, Cornblatt, Barbara A., Olvet, Doreen M., Mathalon, Daniel H., McGlashan, Thomas H., Perkins, Diana O., Belger, Aysenil, Seidman, Larry J., Thermenos, Heidi W., Tsuang, Ming T., van Erp, Theo G.M., Walker, Elaine F., Hamann, Stephan, Woods, Scott W., Qiu, Maolin, and Cannon, Tyrone D.

Published
2014
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26. White Matter Microstructure in Individuals at Clinical High Risk of Psychosis: A Whole-Brain Diffusion Tensor Imaging Study

Author

Clemm von Hohenberg, Christian, Pasternak, Ofer, Kubicki, Marek, Ballinger, Thomas, Vu, Mai-Anh, Swisher, Tali, Green, Katie, Giwerc, Michelle, Dahlben, Brian, Goldstein, Jill M., Woo, Tsung-Ung W., Petryshen, Tracey L., Mesholam-Gately, Raquelle I., Woodberry, Kristen A., Thermenos, Heidi W., Mulert, Christoph, McCarley, Robert W., Seidman, Larry J., and Shenton, Martha E.

Published
2014
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27. Reliability of neuroanatomical measurements in a multisite longitudinal study of youth at risk for psychosis

Author

Cannon, Tyrone D., Sun, Frank, McEwen, Sarah Jacobson, Papademetris, Xenophon, He, George, van Erp, Theo G.M., Jacobson, Aron, Bearden, Carrie E., Walker, Elaine, Hu, Xiaoping, Zhou, Lei, Seidman, Larry J., Thermenos, Heidi W., Cornblatt, Barbara, Olvet, Doreen M., Perkins, Diana, Belger, Aysenil, Cadenhead, Kristin, Tsuang, Ming, Mirzakhanian, Heline, Addington, Jean, Frayne, Richard, Woods, Scott W., McGlashan, Thomas H., Constable, Todd R., Qiu, Maolin, Mathalon, Daniel H., Thompson, Paul, and Toga, Arthur W.

Published
2014
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28. Hyperactivation of Posterior Default Mode Network During Self-Referential Processing in Children at Familial High-Risk for Psychosis

Author

Collin, Guusje, primary, Bauer, Clemens C. C., additional, Anteraper, Sheeba Arnold, additional, Gabrieli, John D. E., additional, Molokotos, Elena, additional, Mesholam-Gately, Raquelle, additional, Thermenos, Heidi W., additional, Seidman, Larry J., additional, Keshavan, Matcheri S., additional, Shenton, Martha E., additional, and Whitfield-Gabrieli, Susan, additional

Published
2021
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38. Auditory Vigilance and Working Memory in Youth at Familial Risk for Schizophrenia or Affective Psychosis in the Harvard Adolescent Family High Risk Study

Author

Seidman, Larry J., primary, Pousada-Casal, Andrea, additional, Scala, Silvia, additional, Meyer, Eric C., additional, Stone, William S., additional, Thermenos, Heidi W., additional, Molokotos, Elena, additional, Agnew-Blais, Jessica, additional, Tsuang, Ming T., additional, and Faraone, Stephen V., additional

Published
2016
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40. Corrigendum to “Genetic and environmental influences on the size of specific brain regions in midlife: The VETSA MRI study”: [NeuroImage 49 (2010) 1213–1223]

Author

Kremen, William S., Prom-Wormley, Elizabeth, Panizzon, Matthew S., Eyler, Lisa T., Fischl, Bruce, Neale, Michael C., Franz, Carol E., Lyons, Michael J., Pacheco, Jennifer, Perry, Michele E., Stevens, Allison, Schmitt, J. Eric, Grant, Michael D., Seidman, Larry J., Thermenos, Heidi W., Tsuang, Ming T., Eisen, Seth A., Dale, Anders M., and Fennema-Notestine, Christine

Published
2010
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41. Reliability of neuroanatomical measurements in a multisite longitudinal study of youth at risk for psychosis

Author

Cannon, Tyrone D., primary, Sun, Frank, additional, McEwen, Sarah Jacobson, additional, Papademetris, Xenophon, additional, He, George, additional, van Erp, Theo G.M., additional, Jacobson, Aron, additional, Bearden, Carrie E., additional, Walker, Elaine, additional, Hu, Xiaoping, additional, Zhou, Lei, additional, Seidman, Larry J., additional, Thermenos, Heidi W., additional, Cornblatt, Barbara, additional, Olvet, Doreen M., additional, Perkins, Diana, additional, Belger, Aysenil, additional, Cadenhead, Kristin, additional, Tsuang, Ming, additional, Mirzakhanian, Heline, additional, Addington, Jean, additional, Frayne, Richard, additional, Woods, Scott W., additional, McGlashan, Thomas H., additional, Constable, R. Todd, additional, Qiu, Maolin, additional, Mathalon, Daniel H., additional, Thompson, Paul, additional, and Toga, Arthur W., additional

Published
2013
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42. White Matter Microstructure in Individuals at Clinical High Risk of Psychosis: A Whole-Brain Diffusion Tensor Imaging Study

Author

Clemm von Hohenberg, Christian, primary, Pasternak, Ofer, additional, Kubicki, Marek, additional, Ballinger, Thomas, additional, Vu, Mai-Anh, additional, Swisher, Tali, additional, Green, Katie, additional, Giwerc, Michelle, additional, Dahlben, Brian, additional, Goldstein, Jill M., additional, Woo, Tsung-Ung W., additional, Petryshen, Tracey L., additional, Mesholam-Gately, Raquelle I., additional, Woodberry, Kristen A., additional, Thermenos, Heidi W., additional, Mulert, Christoph, additional, McCarley, Robert W., additional, Seidman, Larry J., additional, and Shenton, Martha E., additional

Published
2013
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43. Poster #108 ALTERED LANGUAGE NETWORK ACTIVITY IN YOUNG PEOPLE AT GENETIC RISK FOR SCHIZOPHRENIA

Author

Pelisi, Lynn E., primary, Thermenos, Heidi W., additional, Seidman, Larry J., additional, Whitfielf-Gabrieli, Susan, additional, Juelich, Richard, additional, Jabbar, Gul A., additional, Salwen, K.K., additional, Shenton, Martha, additional, Kubicki, Marek, additional, Gabrieli, John D.E., additional, Manschreck, Theo, additional, Francis, Alan, additional, and Keshavan, Matcheri, additional

Published
2012
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48. DEFAULT NETWORK AND MEDIAL PREFRONTAL CORTEX DYSFUNCTION IN SCHIZOPHRENIA AND IN FIRST DEGREE RELATIVES OF PERSONS WITH SCHIZOPHRENIA

Author

Seidman, Larry J., primary, Whitfield-Gabrieli, Susan, additional, Thermenos, Heidi W., additional, Rosso, Isabelle, additional, Makris, Nikos, additional, Milanovic, Snezana, additional, Goldstein, Jill M., additional, Gabrieli, John D.E., additional, Faraone, Stephen V., additional, and Tsuang, Ming T., additional

Published
2010
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49. Cortical Thickness Is Influenced by Regionally Specific Genetic Factors

Author

Rimol, Lars M., primary, Panizzon, Matthew S., additional, Fennema-Notestine, Christine, additional, Eyler, Lisa T., additional, Fischl, Bruce, additional, Franz, Carol E., additional, Hagler, Donald J., additional, Lyons, Michael J., additional, Neale, Michael C., additional, Pacheco, Jennifer, additional, Perry, Michele E., additional, Schmitt, J. Eric, additional, Grant, Michael D., additional, Seidman, Larry J., additional, Thermenos, Heidi W., additional, Tsuang, Ming T., additional, Eisen, Seth A., additional, Kremen, William S., additional, and Dale, Anders M., additional

Published
2010
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50. An fMRI study of working memory in persons with bipolar disorder or at genetic risk for bipolar disorder

Author

Thermenos, Heidi W., primary, Goldstein, Jill M., additional, Milanovic, Snezana M., additional, Whitfield-Gabrieli, Susan, additional, Makris, Nikos, additional, LaViolette, Peter, additional, Koch, Jennifer K., additional, Faraone, Stephen V., additional, Tsuang, Ming T., additional, Buka, Stephen L., additional, and Seidman, Larry J., additional

Published
2009
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