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In memory of Professor Iain Wilkinson: cognitive and neuroimaging endophenotypes in a consanguineous schizophrenia multiplex family
- Iain D. Wilkinson, Tariq Mahmood, Sophia Faye Yasmin, Anneka Tomlinson, Jamshid Nazari, Hamid Alhaj, Soumaya Nasser el din, Joanna Neill, Chhaya Pandit, Shahzad Ashraf, Alastair G. Cardno, Steven J. Clapcote, Chris F. Inglehearn, Peter W. Woodruff
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- Journal:
- Psychological Medicine / Volume 53 / Issue 7 / May 2023
- Published online by Cambridge University Press:
- 07 February 2022, pp. 3178-3186
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Background
Schizophrenia endophenotypes may help elucidate functional effects of genetic risk variants in multiply affected consanguineous families that segregate recessive risk alleles of large effect size. We studied the association between a schizophrenia risk locus involving a 6.1Mb homozygous region on chromosome 13q22–31 in a consanguineous multiplex family and cognitive functioning, haemodynamic response and white matter integrity using neuroimaging.
MethodsWe performed CANTAB neuropsychological testing on four affected family members (all homozygous for the risk locus), ten unaffected family members (seven homozygous and three heterozygous) and ten healthy volunteers, and tested neuronal responses on fMRI during an n-back working memory task, and white matter integrity on diffusion tensor imaging (DTI) on four affected and six unaffected family members (four homozygous and two heterozygous) and three healthy volunteers. For cognitive comparisons we used a linear mixed model (Kruskal–Wallis) test, followed by posthoc Dunn's pairwise tests with a Bonferroni adjustment. For fMRI analysis, we counted voxels exceeding the p < 0.05 corrected threshold. DTI analysis was observational.
ResultsFamily members with schizophrenia and unaffected family members homozygous for the risk haplotype showed attention (p < 0.01) and working memory deficits (p < 0.01) compared with healthy controls; a neural activation laterality bias towards the right prefrontal cortex (voxels reaching p < 0.05, corrected) and observed lower fractional anisotropy in the anterior cingulate cortex and left dorsolateral prefrontal cortex.
ConclusionsIn this family, homozygosity at the 13q risk locus was associated with impaired cognition, white matter integrity, and altered laterality of neural activation.
‘Munchausen's syndrome by proxy’ or a ‘miscarriage of justice’? An initial application of functional neuroimaging to the question of guilt versus innocence
- Sean A. Spence, Catherine J. Kaylor-Hughes, Martin L. Brook, Sudheer T. Lankappa, Iain D. Wilkinson
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- Journal:
- European Psychiatry / Volume 23 / Issue 4 / June 2008
- Published online by Cambridge University Press:
- 16 April 2020, pp. 309-314
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‘Munchausen's syndrome by proxy’ characteristically describes women alleged to have fabricated or induced illnesses in children under their care, purportedly to attract attention. Where conclusive evidence exists the condition's aetiology remains speculative, where such evidence is lacking diagnosis hinges upon denial of wrong-doing (conduct also compatible with innocence). How might investigators obtain objective evidence of guilt or innocence? Here, we examine the case of a woman convicted of poisoning a child. She served a prison sentence but continues to profess her innocence. Using a modified fMRI protocol (previously published in 2001) we scanned the subject while she affirmed her account of events and that of her accusers. We hypothesized that she would exhibit longer response times in association with greater activation of ventrolateral prefrontal and anterior cingulate cortices when endorsing those statements she believed to be false (i.e., when she ‘lied’). The subject was scanned 4 times at 3 Tesla. Results revealed significantly longer response times and relatively greater activation of ventrolateral prefrontal and anterior cingulate cortices when she endorsed her accusers' version of events. Hence, while we have not ‘proven’ that this subject is innocent, we demonstrate that her behavioural and functional anatomical parameters behave as if she were.
Contributors
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. 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Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- The Cambridge Dictionary of Christianity
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- 05 August 2012
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- 20 September 2010, pp xi-xliv
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Chapter 19 - Perfusion and diffusion imaging in chronic carotid disease
- from Section 2 - Cerebrovascular disease
- Edited by Jonathan H. Gillard, University of Cambridge, Adam D. Waldman, Imperial College London, Peter B. Barker, The Johns Hopkins University School of Medicine
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- Clinical MR Neuroimaging
- Published online:
- 05 March 2013
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- 26 November 2009, pp 258-272
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Summary
Introduction
Diseases affecting the arterial supply to and distribution within the brain often interfere with central nervous system (CNS) metabolism. Such interference, which frequently results from internal carotid artery (ICA) pathology, can lead to the onset of clinical symptoms, signaling the need for investigation of the brain via an appropriate imaging modality. Imaging has historically been used to exclude the presence of pathology such as hemorrhage, neoplasm, or infection and latterly to investigate hemodynamic cause and status. The nature of metabolic change and the onset of associated symptoms can be broadly classified as being either acute or chronic. In the acute case (“brain attack”), an abrupt alteration in brain function resulting from changes in vascular supply, which are non-transient, is termed stroke. The ability of a healthcare system to respond quickly and effectively to the presentation of acute stroke may well depend heavily on the provision of imaging technology: the applications of diffusion and perfusion MR imaging (MRI) in this context are detailed elsewhere (Ch. 15). This chapter will concentrate on the utility of perfusion and diffusion in the context of chronic ICA disease. The majority of carotid disease is atherosclerotic, and so emphasis will be placed on this pathology.
Alterations to the brain’s vascular supply, hemodynamic failure, and the search for clinically relevant physiological indicators
Patients with chronic cerebrovascular blood supply deficits often present with a history of symptoms such as those associated with transient ischemic attacks (TIAs), amaurosis fugax, or having experienced an episode of minor or non-disabling stroke. Sometimes they have experienced more than one such ischemic event. They may be at high risk of having a significant disabling stroke and although previous symptoms may have had sudden onset, for the purposes of this chapter, their speedy resolution classifies their overall disease state as being chronic. In the clinical setting, the overall aim of imaging in this patient group is to aid the prevention of recurrent ischemia, thereby reducing the risk of disabling stroke.
¿Síndrome de Munchausen por poderes o “error de la justicia”? Aplicación preliminar de la neuroimagen funcional para diferenciar entre culpabilidad e inocencia
- Sean A. Spence, Catherine J. Kaylor-Hughes, Martin L. Brook, Sudheer T. Lankappa, Iain D. Wilkinson
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- European Psychiatry (Ed.Española) / Volume 15 / Issue 7 / October 2008
- Published online by Cambridge University Press:
- 12 May 2020, pp. 347-353
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- October 2008
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El “síndrome de Munchausen por poderes” se refiere, en general, a mujeres acusadas de haber inventado o producido enfermedades en niños bajo su cuidado, destinadas a atraer la atención sobre sí misma. Cuando hay pruebas concluyentes, hay dudas sobre la etiología de la enfermedad, pero cuando no hay pruebas, el diagnóstico depende de la negación de la intencionalidad (conducta también compatible con la inocencia). ¿Cómo podrían los investigadores conseguir pruebas objetivas sobre culpabilidad o inocencia? En este artículo analizamos el caso de una mujer condenada por envenenar a su hija. Cumplió la condena en la cárcel, pero sigue reclamando su inocencia. Usando un protocolo modificado de RMf (publicado ya en 2001) realizamos la prueba de neuroimagen mientras ella confirmaba su versión de los acontecimientos y mientras aceptaba la de sus acusadores. Sugerimos la hipótesis de que los tiempos de respuesta serían más largos y se asociaran con mayor activación de la corteza cingular anterior y prefrontal ventrolateral cuando hacía declaraciones falsas (es decir, cuando “mentía”). La mujer fue sometida 4 veces a RM de 3 teslas. Los resultados revelaron tiempos de respuesta considerablemente más largos y un activación relativamente mayor de la corteza cingular anterior y prefrontal ventrolateral cuando aceptaba la versión de los acontecimientos de sus acusadores. Es decir que aunque no hemos “probado” que esta mujer es inocente, demostramos que sus parámetros conductuales y funcionales anatómicos se comportan como si lo fuera.
Structural brain correlates of unconstrained motor activity in people with schizophrenia
- Tom F. D. Farrow, Michael D. Hunter, Iain D. Wilkinson, Russell D. J. Green, Sean A. Spence
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- Journal:
- The British Journal of Psychiatry / Volume 187 / Issue 5 / November 2005
- Published online by Cambridge University Press:
- 02 January 2018, pp. 481-482
- Print publication:
- November 2005
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Avolition affects quality of life in chronic schizophrenia. We investigated the relationship between unconstrained motor activity and the volume of key executive brain regions in 16 male patients with schizophrenia. Wrist-worn actigraphy monitors were used to record motor activity over a 20 h period. Structural magnetic resonance imaging brain scans were parcellated and individual volumes for anterior cingulate cortex and dorsolateral prefrontal cortex extracted. Patients' total activity was positively correlated with volume of left anterior cingulate cortex. These data suggest that the volume of specific executive structures may affect (quantifiable) motor behaviours, having further implications for models of the ‘will’ and avolition.
Modafinil modulates anterior cingulate function in chronic schizophrenia
- Sean A. Spence, Russell D. Green, Iain D. Wilkinson, Mike D. Hunter
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- Journal:
- The British Journal of Psychiatry / Volume 187 / Issue 1 / July 2005
- Published online by Cambridge University Press:
- 02 January 2018, pp. 55-61
- Print publication:
- July 2005
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Background
Schizophrenia is associated with widespread cognitive deficits that have an impact on social function. Modafinil promotes wakefulness and is reported to enhance cognition.
AimsTo study the acute effects of modafinil administration upon brain activity and cognitive performance in people with chronic schizophrenia.
MethodIn a randomised double-blind placebo-controlled crossover design, 19 patients received either modafinil (100 mg) or placebo prior to undertaking a working memory task with functional magnetic resonance imaging.
ResultsSeventeen patients completed the study and another underwent acute relapse 4 days post-drug. Modafinil administration was associated with significantly greater activation in the anterior cingulate cortex during the working memory task. The anterior cingulate cortex signal correlated with cognitive performance, although only a subset of patients exhibited ‘enhancement’.
ConclusionsModafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation.
16 - Perfusion and diffusion imaging in chronic carotid disease
- from SECTION 2 - CEREBROVASCULAR DISEASE
- Edited by Jonathan H. Gillard, University of Cambridge, Adam D. Waldman, Charing Cross Hospital, London, Peter B. Barker, The Johns Hopkins University
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- Clinical MR Neuroimaging
- Published online:
- 07 December 2009
- Print publication:
- 02 December 2004, pp 246-262
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