6 results
Dentate gyrus volume deficit in schizophrenia
- Soichiro Nakahara, Jessica A. Turner, Vince D. Calhoun, Kelvin O. Lim, Bryon Mueller, Juan R. Bustillo, Daniel S. O'Leary, Sarah McEwen, James Voyvodic, Aysenil Belger, Daniel H. Mathalon, Judith M. Ford, Fabio Macciardi, Mitsuyuki Matsumoto, Steven G. Potkin, Theo G. M. van Erp
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- Journal:
- Psychological Medicine / Volume 50 / Issue 8 / June 2020
- Published online by Cambridge University Press:
- 03 June 2019, pp. 1267-1277
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Background
Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.
MethodsHippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.
ResultsThis study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = −0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = −0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10−8, 95% CI 7.0–14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.
ConclusionsThis study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.
Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms
- J. Ferri, J. M. Ford, B. J. Roach, J. A. Turner, T. G. van Erp, J. Voyvodic, A. Preda, A. Belger, J. Bustillo, D. O'Leary, B. A. Mueller, K. O. Lim, S. C. McEwen, V. D. Calhoun, M. Diaz, G. Glover, D. Greve, C. G. Wible, J. G. Vaidya, S. G. Potkin, D. H. Mathalon
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- Journal:
- Psychological Medicine / Volume 48 / Issue 15 / November 2018
- Published online by Cambridge University Press:
- 15 February 2018, pp. 2492-2499
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Background
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
MethodResting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
ResultsHC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
ConclusionsThalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium
- E. Walton, D. P. Hibar, T. G. M. van Erp, S. G. Potkin, R. Roiz-Santiañez, B. Crespo-Facorro, P. Suarez-Pinilla, N. E. M. van Haren, S. M. C. de Zwarte, R. S. Kahn, W. Cahn, N. T. Doan, K. N. Jørgensen, T. P. Gurholt, I. Agartz, O. A. Andreassen, L. T. Westlye, I. Melle, A. O. Berg, L. Morch-Johnsen, A. Færden, L. Flyckt, H. Fatouros-Bergman, Karolinska Schizophrenia Project Consortium (KaSP), E. G. Jönsson, R. Hashimoto, H. Yamamori, M. Fukunaga, N. Jahanshad, P. De Rossi, F. Piras, N. Banaj, G. Spalletta, R. E. Gur, R. C. Gur, D. H. Wolf, T. D. Satterthwaite, L. M. Beard, I. E. Sommer, S. Koops, O. Gruber, A. Richter, B. Krämer, S. Kelly, G. Donohoe, C. McDonald, D. M. Cannon, A. Corvin, M. Gill, A. Di Giorgio, A. Bertolino, S. Lawrie, T. Nickson, H. C. Whalley, E. Neilson, V. D. Calhoun, P. M. Thompson, J. A. Turner, S. Ehrlich
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- Journal:
- Psychological Medicine / Volume 48 / Issue 1 / January 2018
- Published online by Cambridge University Press:
- 26 May 2017, pp. 82-94
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Background
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
MethodsThis study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
ResultsMeta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
ConclusionsUsing an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Heritability of Multivariate Gray Matter Measures in Schizophrenia
- Jessica A. Turner, Vince D. Calhoun, Andrew Michael, Theo G. M. van Erp, Stefan Ehrlich, Judith M. Segall, Randy L. Gollub, John Csernansky, Steven G. Potkin, Beng-Choon Ho, Juan Bustillo, S. Charles Schulz, FBIRN, Lei Wang
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- Journal:
- Twin Research and Human Genetics / Volume 15 / Issue 3 / June 2012
- Published online by Cambridge University Press:
- 15 June 2012, pp. 324-335
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Structural brain measures are employed as endophenotypes in the search for schizophrenia susceptibility genes. We analyzed two independent structural imaging datasets with voxel-based morphometry and with source-based morphometry, a multivariate, independent components analysis, to determine the stability and heritability of regional gray matter concentration abnormalities in schizophrenia. The samples comprised 209 and 102 patients with schizophrenia and 208 and 96 healthy volunteers, respectively. The second sample additionally included non-ill siblings of participants with and without schizophrenia. A standard voxel-based analysis showed reproducible regional gray matter deficits in the affected participants compared with unrelated, unaffected controls in both datasets: patients showed significant gray matter concentration deficits in cortical frontal, temporal, and insular lobes. Source-based morphometry (SBM) was applied to the gray matter images of the entire sample to determine the effects of diagnosis on networks of covarying structures. The SBM analysis extracted 24 significant sets of covarying regions (components). Four of these components showed significantly lower gray matter concentrations in patients (p < .05). We determined the familiality of the observed SBM components based on 66 sibling pairs (25 discordant for schizophrenia). Two components, one including the medial frontal, insular, inferior frontal, and temporal lobes, and the other including the posterior occipital lobe, showed significant familiality (p < .05). We conclude that structural brain deficits in schizophrenia are replicable, and that SBM can extract unique familial and likely heritable components. SBM provides a useful data reduction technique that can provide measures that may serve as endophenotypes for schizophrenia.
Patterns of cortical activity in schizophrenia
- J. Schroeder, M. S. Buchsbaum, B. V. Siegel, F. J. Geider, R. J. Haier, J. Lohr, J. Wu, S. G. Potkin
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- Journal:
- Psychological Medicine / Volume 24 / Issue 4 / November 1994
- Published online by Cambridge University Press:
- 09 July 2009, pp. 947-955
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Eighty-three patients with schizophrenia and 47 healthy controls received positron emission tomography (PET) with 18F-2-deoxyglucose uptake while they were executing the Continuous Performance Test (CPT). The entire cortex was divided into 16 regions of interest in each hemisphere, four in each lobe of the brain, and data from corresponding right and left hemispheric regions were averaged. Data from the schizophrenic patients were subjected to a factor analysis, which revealed five factors that explained 80% of the common variance. According to their content, the factors were identified and labelled ‘parietal cortex and motor strip’, ‘associative areas’, ‘temporal cortex’, ‘hypofrontality’ (which included midfrontal and occipital areas) and ‘frontal cortex’. Hemispheric asymmetry was only confirmed for the temporal cortex. Factor weights obtained in the schizophrenic group were applied to the metabolic data of the healthy controls and factor scales computed. Schizophrenics were significantly more hypofrontal than the controls, with higher values on the ‘parietal cortex and motor strip’ factor and a trend towards higher values in the temporal cortex. A canonical discriminant analysis confirmed that the ‘hypofrontality’ and ‘parietal cortex and motor strip’ factors accurately separated the schizophrenic group from the healthy controls. Hemispheric asymmetry was only confirmed for the temporal lobe. Significantly higher factor scores for the left temporal lobe in schizophrenics than in normals were obtained when calculated for the right and left hemisphere separately. Taken together, our results confirm the importance of hypofrontality as a pattern of cortical metabolic rate and point to the potential importance of parietal and motor strip function in schizophrenia.
19 - Brain imaging and pharmacogenetics in Alzheimer's disease and schizophrenia
- from Part VI - Pharmacogenetics and brain imaging
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- By Steven G. Potkin, Department of Psychiatry and Human Behavior, University of California, Irvine, USA, James L. Kennedy, Clarke Institute of Psychiatry, University of Toronto, Canada, Vincenzo S. Basile, Clarke Institute of Psychiatry, University of Toronto, Canada
- Edited by Bernard Lerer, Hadassah-Hebrew Medical Center, Jerusalem
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- Book:
- Pharmacogenetics of Psychotropic Drugs
- Published online:
- 20 August 2009
- Print publication:
- 29 August 2002, pp 391-400
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Summary
Brain imaging techniques combined with genetics contribute to developing an understanding of the pathophysiological mechanism of disease and treatment response. Psychiatric genetics identifies associations between allelic variation in genes and the risk for the development of psychiatric illness. Although the genetic association of apoE4 with the development of Alzheimer's disease is well established, there is a need to devise strategies that can fill in the missing links between apoE gene variation and the pathophysiological mechanism of Alzheimer's disease. Brain imaging addresses and bridges this gap. The combination of imaging, allelic characterization, and clinical response synergistically contributes to understanding the role apoE4 plays in the development of Alzheimer's disease and its response to treatment. An analogous argument is made for combining brain imaging with allelic subtyping to understand clinical antipsychotic response in schizophrenia. This chapter establishes the efficacy of new pharmacological treatments for groups of patients with schizophrenia and Alzheimer's disease.