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Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms
- J. Ferri, J. M. Ford, B. J. Roach, J. A. Turner, T. G. van Erp, J. Voyvodic, A. Preda, A. Belger, J. Bustillo, D. O'Leary, B. A. Mueller, K. O. Lim, S. C. McEwen, V. D. Calhoun, M. Diaz, G. Glover, D. Greve, C. G. Wible, J. G. Vaidya, S. G. Potkin, D. H. Mathalon
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- Journal:
- Psychological Medicine / Volume 48 / Issue 15 / November 2018
- Published online by Cambridge University Press:
- 15 February 2018, pp. 2492-2499
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Background
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
MethodResting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
ResultsHC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
ConclusionsThalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium
- E. Walton, D. P. Hibar, T. G. M. van Erp, S. G. Potkin, R. Roiz-Santiañez, B. Crespo-Facorro, P. Suarez-Pinilla, N. E. M. van Haren, S. M. C. de Zwarte, R. S. Kahn, W. Cahn, N. T. Doan, K. N. Jørgensen, T. P. Gurholt, I. Agartz, O. A. Andreassen, L. T. Westlye, I. Melle, A. O. Berg, L. Morch-Johnsen, A. Færden, L. Flyckt, H. Fatouros-Bergman, Karolinska Schizophrenia Project Consortium (KaSP), E. G. Jönsson, R. Hashimoto, H. Yamamori, M. Fukunaga, N. Jahanshad, P. De Rossi, F. Piras, N. Banaj, G. Spalletta, R. E. Gur, R. C. Gur, D. H. Wolf, T. D. Satterthwaite, L. M. Beard, I. E. Sommer, S. Koops, O. Gruber, A. Richter, B. Krämer, S. Kelly, G. Donohoe, C. McDonald, D. M. Cannon, A. Corvin, M. Gill, A. Di Giorgio, A. Bertolino, S. Lawrie, T. Nickson, H. C. Whalley, E. Neilson, V. D. Calhoun, P. M. Thompson, J. A. Turner, S. Ehrlich
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- Journal:
- Psychological Medicine / Volume 48 / Issue 1 / January 2018
- Published online by Cambridge University Press:
- 26 May 2017, pp. 82-94
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Background
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
MethodsThis study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
ResultsMeta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
ConclusionsUsing an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
The impact of parent socio-economic status on executive functioning and cortical morphology in individuals with schizophrenia and healthy controls
- R. A. Yeo, D. Martinez, J. Pommy, S. Ehrlich, S. C. Schulz, B.-C. Ho, J. R. Bustillo, V. D. Calhoun
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- Journal:
- Psychological Medicine / Volume 44 / Issue 6 / April 2014
- Published online by Cambridge University Press:
- 19 July 2013, pp. 1257-1265
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Background
Relatively lower executive functioning is characteristic of individuals with schizophrenia. As low socio-economic status (SES) early in life (i.e. parent SES) has been linked with lower executive skills in healthy children, we hypothesized that parental SES (pSES) would be more strongly related to executive functioning in individuals with schizophrenia than in controls and have a greater impact on prefrontal cortical morphology.
MethodHealthy controls (n = 125) and individuals with schizophrenia (n = 102) completed tests assessing executive functioning and intelligence. The groups were matched on pSES, which was evaluated with the Hollingshead–Redlich scale. A principal components analysis (PCA) was conducted on 10 variables from six executive tests, yielding three specific components (fluency, planning and response inhibition). Voxel-based morphometry (VBM) was used to evaluate effects of pSES on gray matter (GM) concentration.
ResultsLower pSES was associated with lower scores across the three executive functioning components, and a significant group by pSES interaction was observed such that low pSES, in particular, affected individuals with schizophrenia. These effects remained significant when intellectual ability, education and self-SES (sSES) were added as covariates. VBM revealed that lower pSES was associated with reduced GM volume in several anterior brain regions, especially the superior frontal gyrus, in patients but not in controls.
ConclusionsThese findings suggest that individuals with schizophrenia may be particularly vulnerable to the adverse impact of low pSES, in terms of both lower executive skills and reduced anterior GM volumes.
Looking Backward, Looking Forward: MLA Members Speak
- April Alliston, Elizabeth Ammons, Jean Arnold, Nina Baym, Sandra L. Beckett, Peter G. Beidler, Roger A. Berger, Sandra Bermann, J.J. Wilson, Troy Boone, Alison Booth, Wayne C. Booth, James Phelan, Marie Borroff, Ihab Hassan, Ulrich Weisstein, Zack Bowen, Jill Campbell, Dan Campion, Jay Caplan, Maurice Charney, Beverly Lyon Clark, Robert A. Colby, Thomas C. Coleman III, Nicole Cooley, Richard Dellamora, Morris Dickstein, Terrell Dixon, Emory Elliott, Caryl Emerson, Ann W. Engar, Lars Engle, Kai Hammermeister, N. N. Feltes, Mary Anne Ferguson, Annie Finch, Shelley Fisher Fishkin, Jerry Aline Flieger, Norman Friedman, Rosemarie Garland-Thomson, Sandra M. Gilbert, Laurie Grobman, George Guida, Liselotte Gumpel, R. K. Gupta, Florence Howe, Cathy L. Jrade, Richard A. Kaye, Calhoun Winton, Murray Krieger, Robert Langbaum, Richard A. Lanham, Marilee Lindemann, Paul Michael Lützeler, Thomas J. Lynn, Juliet Flower MacCannell, Michelle A. Massé, Irving Massey, Georges May, Christian W. Hallstein, Gita May, Lucy McDiarmid, Ellen Messer-Davidow, Koritha Mitchell, Robin Smiles, Kenyatta Albeny, George Monteiro, Joel Myerson, Alan Nadel, Ashton Nichols, Jeffrey Nishimura, Neal Oxenhandler, David Palumbo-Liu, Vincent P. Pecora, David Porter, Nancy Potter, Ronald C. Rosbottom, Elias L. Rivers, Gerhard F. Strasser, J. L. Styan, Marianna De Marco Torgovnick, Gary Totten, David van Leer, Asha Varadharajan, Orrin N. C. Wang, Sharon Willis, Louise E. Wright, Donald A. Yates, Takayuki Yokota-Murakami, Richard E. Zeikowitz, Angelika Bammer, Dale Bauer, Karl Beckson, Betsy A. Bowen, Stacey Donohue, Sheila Emerson, Gwendolyn Audrey Foster, Jay L. Halio, Karl Kroeber, Terence Hawkes, William B. Hunter, Mary Jambus, Willard F. King, Nancy K. Miller, Jody Norton, Ann Pellegrini, S. P. Rosenbaum, Lorie Roth, Robert Scholes, Joanne Shattock, Rosemary T. VanArsdel, Alfred Bendixen, Alarma Kathleen Brown, Michael J. Kiskis, Debra A. Castillo, Rey Chow, John F. Crossen, Robert F. Fleissner, Regenia Gagnier, Nicholas Howe, M. Thomas Inge, Frank Mehring, Hyungji Park, Jahan Ramazani, Kenneth M. Roemer, Deborah D. Rogers, A. LaVonne Brown Ruoff, Regina M. Schwartz, John T. Shawcross, Brenda R. Silver, Andrew von Hendy, Virginia Wright Wexman, Britta Zangen, A. Owen Aldridge, Paula R. Backscheider, Roland Bartel, E. M. Forster, Milton Birnbaum, Jonathan Bishop, Crystal Downing, Frank H. Ellis, Roberto Forns-Broggi, James R. Giles, Mary E. Giles, Susan Blair Green, Madelyn Gutwirth, Constance B. Hieatt, Titi Adepitan, Edgar C. Knowlton, Jr., Emanuel Mussman, Sally Todd Nelson, Robert O. Preyer, David Diego Rodriguez, Guy Stern, James Thorpe, Robert J. Wilson, Rebecca S. Beal, Joyce Simutis, Betsy Bowden, Sara Cooper, Wheeler Winston Dixon, Tarek el Ariss, Richard Jewell, John W. Kronik, Wendy Martin, Stuart Y. McDougal, Hugo Méndez-Ramírez, Ivy Schweitzer, Armand E. Singer, G. Thomas Tanselle, Tom Bishop, Mary Ann Caws, Marcel Gutwirth, Christophe Ippolito, Lawrence D. Kritzman, James Longenbach, Tim McCracken, Wolfe S. Molitor, Diane Quantic, Gregory Rabassa, Ellen M. Tsagaris, Anthony C. Yu, Betty Jean Craige, Wendell V. Harris, J. Hillis Miller, Jesse G. Swan, Helene Zimmer-Loew, Peter Berek, James Chandler, Hanna K. Charney, Philip Cohen, Judith Fetterley, Herbert Lindenberger, Julia Reinhard Lupton, Maximillian E. Novak, Richard Ohmann, Marjorie Perloff, Mark Reynolds, James Sledd, Harriet Turner, Marie Umeh, Flavia Aloya, Regina Barreca, Konrad Bieber, Ellis Hanson, William J. Hyde, Holly A. Laird, David Leverenz, Allen Michie, J. Wesley Miller, Marvin Rosenberg, Daniel R. Schwarz, Elizabeth Welt Trahan, Jean Fagan Yellin
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- Journal:
- PMLA / Publications of the Modern Language Association of America / Volume 115 / Issue 7 / December 2000
- Published online by Cambridge University Press:
- 23 October 2020, pp. 1986-2078
- Print publication:
- December 2000
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