Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function

Pippa A. Thomson, Barbara Duff, Douglas H.R. Blackwood, Liana Romaniuk, Andrew Watson, Heather C. Whalley, Xiang Li, Maria R. Dauvermann, T. William J. Moorhead, Catherine Bois, Niamh M. Ryan, Holly Redpath, Lynsey Hall, Stewart W. Morris, Edwin J.R. Van Beek, Neil Roberts, David J. Porteous, David St Clair, Brandon Whitcher, John Dunlop & 5 others Nicholas J. Brandon, Zoë A. Hughes, Jeremy Hall, Andrew McIntosh, Stephen M. Lawrie*

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain regions. The translocation showed significant linkage (LOD score 6.1) with a clinical phenotype that included schizophrenia, schizoaffective disorder, bipolar disorder, and recurrent major depressive disorder. Translocation carriers showed reduced cortical thickness in the left temporal lobe, which correlated with general psychopathology and positive psychotic symptom severity. They showed reduced gyrification in prefrontal cortex, which correlated with general psychopathology severity. Translocation carriers also showed significantly increased activation in the caudate nucleus on increasing verbal working memory load, as well as statistically significant reductions in the right dorsolateral prefrontal cortex glutamate concentrations. These findings confirm that the t(1;11) translocation is associated with a significantly increased risk of major psychiatric disorder and suggest a general vulnerability to psychopathology through altered cortical structure and function, and decreased glutamate levels.

Original languageEnglish
Article number16024
Journalnpj Schizophrenia
Volume2
DOIs
Publication statusPublished - 10 Aug 2016

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Psychopathology
Psychiatry
Glutamic Acid
Temporal Lobe
Prefrontal Cortex
Caudate Nucleus
Major Depressive Disorder
Brain Diseases
Bipolar Disorder
Short-Term Memory
Psychotic Disorders
Schizophrenia
Phenotype
Brain

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Thomson, P. A., Duff, B., Blackwood, D. H. R., Romaniuk, L., Watson, A., Whalley, H. C., ... Lawrie, S. M. (2016). Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function. npj Schizophrenia, 2, [16024]. https://doi.org/10.1038/npjschz.2016.24

Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function. / Thomson, Pippa A.; Duff, Barbara; Blackwood, Douglas H.R.; Romaniuk, Liana; Watson, Andrew; Whalley, Heather C.; Li, Xiang; Dauvermann, Maria R.; Moorhead, T. William J.; Bois, Catherine; Ryan, Niamh M.; Redpath, Holly; Hall, Lynsey; Morris, Stewart W.; Van Beek, Edwin J.R.; Roberts, Neil; Porteous, David J.; St Clair, David; Whitcher, Brandon; Dunlop, John; Brandon, Nicholas J.; Hughes, Zoë A.; Hall, Jeremy; McIntosh, Andrew; Lawrie, Stephen M.

In: npj Schizophrenia, Vol. 2, 16024, 10.08.2016.

Research output: Contribution to journalArticle

Thomson, PA, Duff, B, Blackwood, DHR, Romaniuk, L, Watson, A, Whalley, HC, Li, X, Dauvermann, MR, Moorhead, TWJ, Bois, C, Ryan, NM, Redpath, H, Hall, L, Morris, SW, Van Beek, EJR, Roberts, N, Porteous, DJ, St Clair, D, Whitcher, B, Dunlop, J, Brandon, NJ, Hughes, ZA, Hall, J, McIntosh, A & Lawrie, SM 2016, 'Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function', npj Schizophrenia, vol. 2, 16024. https://doi.org/10.1038/npjschz.2016.24
Thomson, Pippa A. ; Duff, Barbara ; Blackwood, Douglas H.R. ; Romaniuk, Liana ; Watson, Andrew ; Whalley, Heather C. ; Li, Xiang ; Dauvermann, Maria R. ; Moorhead, T. William J. ; Bois, Catherine ; Ryan, Niamh M. ; Redpath, Holly ; Hall, Lynsey ; Morris, Stewart W. ; Van Beek, Edwin J.R. ; Roberts, Neil ; Porteous, David J. ; St Clair, David ; Whitcher, Brandon ; Dunlop, John ; Brandon, Nicholas J. ; Hughes, Zoë A. ; Hall, Jeremy ; McIntosh, Andrew ; Lawrie, Stephen M. / Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function. In: npj Schizophrenia. 2016 ; Vol. 2.
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AU - Watson, Andrew

AU - Whalley, Heather C.

AU - Li, Xiang

AU - Dauvermann, Maria R.

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AU - Ryan, Niamh M.

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AU - Roberts, Neil

AU - Porteous, David J.

AU - St Clair, David

AU - Whitcher, Brandon

AU - Dunlop, John

AU - Brandon, Nicholas J.

AU - Hughes, Zoë A.

AU - Hall, Jeremy

AU - McIntosh, Andrew

AU - Lawrie, Stephen M.

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