Convergent Evidence from Multimodal Imaging Reveals Amygdala Abnormalities in Schizophrenic Patients and Their First-Degree Relatives

Abstract

BackgroundShared neuropathological features between schizophrenic patients and their first-degree relatives have potential as indicators of genetic vulnerability to schizophrenia. We sought to explore genetic influences on brain morphology and function in schizophrenic patients and their relatives.MethodsUsing a multimodal imaging strategy, we studied 33 schizophrenic patients, 55 of their unaffected parents, 30 healthy controls for patients, and 29 healthy controls for parents with voxel-based morphometry of structural MRI scans and functional connectivity analysis of resting-state functional MRI data.ResultsSchizophrenic patients showed widespread gray matter reductions in the bilateral frontal cortices, bilateral insulae, bilateral occipital cortices, left amygdala and right thalamus, whereas their parents showed more localized reductions in the left amygdala, left thalamus and right orbitofrontal cortex. Patients and their parents shared gray matter loss in the left amygdala. Further investigation of the resting-state functional connectivity of the amygdala in the patients showed abnormal functional connectivity with the bilateral orbitofrontal cortices, bilateral precunei, bilateral dorsolateral frontal cortices and right insula. Their parents showed slightly less, but similar changes in the pattern in the amygdala connectivity. Co-occurrences of abnormal connectivity of the left amygdala with the left orbitofrontal cortex, right dorsolateral frontal cortex and right precuneus were observed in schizophrenic patients and their parents.ConclusionsOur findings suggest a potential genetic influence on structural and functional abnormalities of the amygdala in schizophrenia. Such information could help future efforts to identify the endophenotypes that characterize the complex disorder of schizophrenia.

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

“…We therefore performed a voxel-based morphometry (VBM) analysis on a large group of siblings and controls (n = 170) -a larger group than in most grey matter studies reporting significant differences between relatives and controls (for example, see the studies by Hu and colleagues, 21 Tian and colleagues 22 and Oertel-Knöchel and colleagues 23 ). Based on previous large VBM studies [12][13][14] we did not expect to find grey matter differences between the general group of siblings and controls.…”

Does neuroanatomy account for superior temporal dysfunction in early psychosis? A multimodal MRI investigation

“…1,2 Based on a subset of studies that used a multimodal approach, it has been sug gested that an intrinsic relationship exists in established psych osis between brain structure and function. [3][4][5] More recently, qualitatively similar changes have been reported in the earliest stages of the disorder -both in those at ultrahigh risk (UHR) for psychosis and in those who have experienced a first epi sode of the disorder (FEP). [6][7][8][9][10][11][12][13][14][15][16] Compared with more estab lished psychosis, 3,17 however, little is known about the associa tion between the functional and structural alterations observed in the UHR and FEP states.…”

“…[3][4][5] More recently, qualitatively similar changes have been reported in the earliest stages of the disorder -both in those at ultrahigh risk (UHR) for psychosis and in those who have experienced a first epi sode of the disorder (FEP). [6][7][8][9][10][11][12][13][14][15][16] Compared with more estab lished psychosis, 3,17 however, little is known about the associa tion between the functional and structural alterations observed in the UHR and FEP states. [18][19][20] In support of a similar relation ship existing to that seen in established psychosis, Rasser and colleagues 19 reported a correlated reduction between neuro function during performance of the Tower of London task and cortical thickness in the left frontoparietal regions of 10 pa tients with FEP versus 10 controls.…”

“…A fast diffeomorphic image registration algorithm 39 was used to warp the grey matter partitions into a new studyspecific reference space with an isotropic spatial resolution of 1.5 mm 3 . The warped grey mat ter partitions were then affinetransformed into MNI space.…”

“…The cognitive paradigm we used was a voice recognition task, which we chose because it had been shown to be effective in detecting widespread and robust neurofunctional alterations in early and established psycho sis. 22,23 Based on the limited literature available to date, we hypothesized that in terms of neurofunction, the FEP group would present with significantly less activation in frontal and temporal regions than the control group, with inter medi ate changes in the UHR group; 12,13 that any regions showing functional reduction in the FEP and/or UHR groups versus the control group would show a correspond ing alteration in grey matter volume; 3,4 and that a significant correlation between regional activation and grey matter vol ume would be observed in regions showing both functional and structural alteration, suggesting an intrinsic association between the 2 types of deficit. 19,20,24,25 …”