Eric A Nelson1, Nina V Kraguljac2, Jose O Maximo2, Frederic Briend2, William Armstrong2, Lawrence W Ver Hoef3, Victoria Johnson2, Adrienne C Lahti4. 1. Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama. 2. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama. 3. Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama. 4. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: alahti@uabmc.edu.
Abstract
BACKGROUND: Converging lines of evidence point to hippocampal dysfunction in schizophrenia. It is thought that hippocampal dysfunction spreads across hippocampal subfields and to cortical regions by way of long-range efferent projections. Importantly, abnormalities in the excitation/inhibition balance could impair the long-range modulation of neural networks. The goal of this project was twofold. First, we sought to identify replicable patterns of hippocampal dysconnectivity in patients with a psychosis spectrum disorder. Second, we aimed to investigate a putative link between glutamatergic metabolism and hippocampal connectivity alterations. METHODS: We evaluated resting-state hippocampal functional connectivity alterations in two cohorts of patients with a psychosis spectrum disorder. The first cohort consisted of 55 medication-naïve patients with first-episode psychosis and 41 matched healthy control subjects, and the second cohort consisted of 42 unmedicated patients with schizophrenia and 41 matched control subjects. We also acquired measurements of glutamate + glutamine in the left hippocampus using magnetic resonance spectroscopy for 42 patients with first-episode psychosis and 37 healthy control subjects from our first cohort. RESULTS: We observed a pattern of hippocampal functional hypoconnectivity to regions of the default mode network and hyperconnectivity to the lateral occipital cortex in both cohorts. We also show that in healthy control subjects, greater hippocampal glutamate + glutamine levels predicted greater hippocampal functional connectivity to the anterior default mode network. Furthermore, this relationship was reversed in medication-naïve subjects with first-episode psychosis. CONCLUSIONS: These results suggest that an alteration in the relationship between glutamate and functional connectivity may disrupt the dynamic of major neural networks.
BACKGROUND: Converging lines of evidence point to hippocampal dysfunction in schizophrenia. It is thought that hippocampal dysfunction spreads across hippocampal subfields and to cortical regions by way of long-range efferent projections. Importantly, abnormalities in the excitation/inhibition balance could impair the long-range modulation of neural networks. The goal of this project was twofold. First, we sought to identify replicable patterns of hippocampal dysconnectivity in patients with a psychosis spectrum disorder. Second, we aimed to investigate a putative link between glutamatergic metabolism and hippocampal connectivity alterations. METHODS: We evaluated resting-state hippocampal functional connectivity alterations in two cohorts of patients with a psychosis spectrum disorder. The first cohort consisted of 55 medication-naïve patients with first-episode psychosis and 41 matched healthy control subjects, and the second cohort consisted of 42 unmedicated patients with schizophrenia and 41 matched control subjects. We also acquired measurements of glutamate + glutamine in the left hippocampus using magnetic resonance spectroscopy for 42 patients with first-episode psychosis and 37 healthy control subjects from our first cohort. RESULTS: We observed a pattern of hippocampal functional hypoconnectivity to regions of the default mode network and hyperconnectivity to the lateral occipital cortex in both cohorts. We also show that in healthy control subjects, greater hippocampal glutamate + glutamine levels predicted greater hippocampal functional connectivity to the anterior default mode network. Furthermore, this relationship was reversed in medication-naïve subjects with first-episode psychosis. CONCLUSIONS: These results suggest that an alteration in the relationship between glutamate and functional connectivity may disrupt the dynamic of major neural networks.
Authors: Andrea Schmitt; Corinna Steyskal; Hans-Gert Bernstein; Thomas Schneider-Axmann; Eleni Parlapani; Evelin L Schaeffer; Wagner F Gattaz; Bernhard Bogerts; Christoph Schmitz; Peter Falkai Journal: Acta Neuropathol Date: 2008-09-06 Impact factor: 17.088
Authors: John E Lisman; Joseph T Coyle; Robert W Green; Daniel C Javitt; Francine M Benes; Stephan Heckers; Anthony A Grace Journal: Trends Neurosci Date: 2008-04-07 Impact factor: 13.837
Authors: Martin Wilson; Ovidiu Andronesi; Peter B Barker; Robert Bartha; Alberto Bizzi; Patrick J Bolan; Kevin M Brindle; In-Young Choi; Cristina Cudalbu; Ulrike Dydak; Uzay E Emir; Ramon G Gonzalez; Stephan Gruber; Rolf Gruetter; Rakesh K Gupta; Arend Heerschap; Anke Henning; Hoby P Hetherington; Petra S Huppi; Ralph E Hurd; Kejal Kantarci; Risto A Kauppinen; Dennis W J Klomp; Roland Kreis; Marijn J Kruiskamp; Martin O Leach; Alexander P Lin; Peter R Luijten; Małgorzata Marjańska; Andrew A Maudsley; Dieter J Meyerhoff; Carolyn E Mountford; Paul G Mullins; James B Murdoch; Sarah J Nelson; Ralph Noeske; Gülin Öz; Julie W Pan; Andrew C Peet; Harish Poptani; Stefan Posse; Eva-Maria Ratai; Nouha Salibi; Tom W J Scheenen; Ian C P Smith; Brian J Soher; Ivan Tkáč; Daniel B Vigneron; Franklyn A Howe Journal: Magn Reson Med Date: 2019-03-28 Impact factor: 4.668
Authors: Dost Ongür; Thomas J Cullen; Daniel H Wolf; Michael Rohan; Paul Barreira; Martin Zalesak; Stephan Heckers Journal: Arch Gen Psychiatry Date: 2006-04
Authors: Nathan L Hutcheson; Meredith A Reid; David M White; Nina V Kraguljac; Kathy B Avsar; Mark S Bolding; Robert C Knowlton; Jan A den Hollander; Adrienne C Lahti Journal: Schizophr Res Date: 2012-07-23 Impact factor: 4.939
Authors: Matthew F Glasser; Stamatios N Sotiropoulos; J Anthony Wilson; Timothy S Coalson; Bruce Fischl; Jesper L Andersson; Junqian Xu; Saad Jbabdi; Matthew Webster; Jonathan R Polimeni; David C Van Essen; Mark Jenkinson Journal: Neuroimage Date: 2013-05-11 Impact factor: 6.556