PURPOSE: The hippocampus is central to the pathophysiology of schizophrenia. Histology shows abnormalities in the dentate granule cell layer (DGCL), but its small size (~100 μm thickness) has precluded in vivo human studies. We used ultra high field magnetic resonance imaging (MRI) to compare DGCL morphology of schizophrenic patients to matched controls. METHOD: Bilateral hippocampi of 16 schizophrenia patients (10 male) 40.7 ± 10.6 years old (mean ± standard deviation) were imaged at 7 Tesla MRI with heavily T₂*-weighted gradient-echo sequence at 232 μm in-plane resolution (0.08 μL image voxels). Fifteen matched controls (8 male, 35.6 ± 9.4 years old) and one ex vivo post mortem hippocampus (that also underwent histopathology) were scanned with same protocol. Three blinded neuroradiologists rated each DGCL on a qualitative scale of 1 to 6 (from "not discernible" to "easily visible, appearing dark gray or black") and mean left and right DGCL scores were compared using a non-parametric Mann-Whitney test. RESULTS: MRI identification of the DGCL was validated with histopathology. Mean right and left DGCL ratings in patients (3.2 ± 1.0 and 3.5 ± 1.2) were not statistically different from those of controls (3.9 ± 1.1 and 3.8 ± 0.8), but patients had a trend for lower right DGCL score (p = 0.07), which was significantly associated with patient diagnosis (p = 0.05). The optimal 48% sensitivity and 80% specificity for schizophrenia were achieved with a DGCL rating of ≤2. CONCLUSION: Decreased contrast in the right DGCL in schizophrenia was predictive of schizophrenia diagnosis. Better utility of this metric as a schizophrenia biomarker may be achieved in future studies of patients with homogeneous disease subtypes and progression rates.
PURPOSE: The hippocampus is central to the pathophysiology of schizophrenia. Histology shows abnormalities in the dentate granule cell layer (DGCL), but its small size (~100 μm thickness) has precluded in vivo human studies. We used ultra high field magnetic resonance imaging (MRI) to compare DGCL morphology of schizophrenicpatients to matched controls. METHOD: Bilateral hippocampi of 16 schizophreniapatients (10 male) 40.7 ± 10.6 years old (mean ± standard deviation) were imaged at 7 Tesla MRI with heavily T₂*-weighted gradient-echo sequence at 232 μm in-plane resolution (0.08 μL image voxels). Fifteen matched controls (8 male, 35.6 ± 9.4 years old) and one ex vivo post mortem hippocampus (that also underwent histopathology) were scanned with same protocol. Three blinded neuroradiologists rated each DGCL on a qualitative scale of 1 to 6 (from "not discernible" to "easily visible, appearing dark gray or black") and mean left and right DGCL scores were compared using a non-parametric Mann-Whitney test. RESULTS: MRI identification of the DGCL was validated with histopathology. Mean right and left DGCL ratings in patients (3.2 ± 1.0 and 3.5 ± 1.2) were not statistically different from those of controls (3.9 ± 1.1 and 3.8 ± 0.8), but patients had a trend for lower right DGCL score (p = 0.07), which was significantly associated with patient diagnosis (p = 0.05). The optimal 48% sensitivity and 80% specificity for schizophrenia were achieved with a DGCL rating of ≤2. CONCLUSION: Decreased contrast in the right DGCL in schizophrenia was predictive of schizophrenia diagnosis. Better utility of this metric as a schizophrenia biomarker may be achieved in future studies of patients with homogeneous disease subtypes and progression rates.
Authors: D Velakoulis; C Pantelis; P D McGorry; P Dudgeon; W Brewer; M Cook; P Desmond; N Bridle; P Tierney; V Murrie; B Singh; D Copolov Journal: Arch Gen Psychiatry Date: 1999-02
Authors: J I Nurnberger; M C Blehar; C A Kaufmann; C York-Cooler; S G Simpson; J Harkavy-Friedman; J B Severe; D Malaspina; T Reich Journal: Arch Gen Psychiatry Date: 1994-11
Authors: Paul A Yushkevich; John B Pluta; Hongzhi Wang; Long Xie; Song-Lin Ding; Eske C Gertje; Lauren Mancuso; Daria Kliot; Sandhitsu R Das; David A Wolk Journal: Hum Brain Mapp Date: 2014-09-02 Impact factor: 5.038
Authors: Shan Cong; Shannon L Risacher; John D West; Yu-Chien Wu; Liana G Apostolova; Eileen Tallman; Maher Rizkalla; Paul Salama; Andrew J Saykin; Li Shen Journal: Brain Imaging Behav Date: 2018-12 Impact factor: 3.978
Authors: Paul A Yushkevich; Robert S C Amaral; Jean C Augustinack; Andrew R Bender; Jeffrey D Bernstein; Marina Boccardi; Martina Bocchetta; Alison C Burggren; Valerie A Carr; M Mallar Chakravarty; Gaël Chételat; Ana M Daugherty; Lila Davachi; Song-Lin Ding; Arne Ekstrom; Mirjam I Geerlings; Abdul Hassan; Yushan Huang; J Eugenio Iglesias; Renaud La Joie; Geoffrey A Kerchner; Karen F LaRocque; Laura A Libby; Nikolai Malykhin; Susanne G Mueller; Rosanna K Olsen; Daniela J Palombo; Mansi B Parekh; John B Pluta; Alison R Preston; Jens C Pruessner; Charan Ranganath; Naftali Raz; Margaret L Schlichting; Dorothee Schoemaker; Sachi Singh; Craig E L Stark; Nanthia Suthana; Alexa Tompary; Marta M Turowski; Koen Van Leemput; Anthony D Wagner; Lei Wang; Julie L Winterburn; Laura E M Wisse; Michael A Yassa; Michael M Zeineh Journal: Neuroimage Date: 2015-01-14 Impact factor: 6.556
Authors: E J Meyer; I I Kirov; A Tal; M S Davitz; J S Babb; M Lazar; D Malaspina; O Gonen Journal: AJNR Am J Neuroradiol Date: 2016-07-21 Impact factor: 3.825
Authors: Nina Vanessa Kraguljac; Matthew Carle; Michael A Frölich; Steve Tran; Michael A Yassa; David Matthew White; Abhishek Reddy; Adrienne Carol Lahti Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2017-02-28