Dataset Information

Increased hippocampal glutamate and volumetric deficits in unmedicated patients with schizophrenia.

ABSTRACT:

Importance

Alterations in glutamatergic neurotransmission have been postulated to be a key pathophysiologic mechanism in schizophrenia.

Objective

To evaluate hippocampal volumetric measures and neurometabolites in unmedicated patients with schizophrenia and the correlations between these markers. Our a priori hypothesis was that glutamate levels would negatively correlate with hippocampal volume in schizophrenia.

Design, setting, and participants

Combined 3-T structural magnetic resonance imaging and single-voxel proton magnetic resonance spectroscopy study at the Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, of 27 unmedicated patients with schizophrenia and 27 healthy controls.

Main outcomes and measures

Hippocampal volumetric measures and neurometabolites, and the correlations between volumetric measurements and neurometabolites.

Results

Hippocampal volumetric deficits, increased ratios of hippocampal glutamate and glutamine to creatine (Glx/Cr), and a loss of correlation between hippocampal N-acetylaspartate (NAA)/Cr and Glx/Cr in patients with schizophrenia were found. Significant correlations between hippocampal volumetric measures and Glx/Cr were also found in patients with schizophrenia but not healthy controls.

Conclusions and relevance

Our findings support the theory that alterations in hippocampal glutamate levels potentially account for structural deficits in the hippocampus observed in schizophrenia neuroimaging studies.

SUBMITTER: Kraguljac NV

PROVIDER: S-EPMC7891898 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Publications

Increased hippocampal glutamate and volumetric deficits in unmedicated patients with schizophrenia.

Kraguljac Nina V NV Kraguljac Nina V NV White David M DM Reid Meredith A MA Lahti Adrienne C AC

JAMA psychiatry 20131201 12

<h4>Importance</h4>Alterations in glutamatergic neurotransmission have been postulated to be a key pathophysiologic mechanism in schizophrenia.<h4>Objective</h4>To evaluate hippocampal volumetric measures and neurometabolites in unmedicated patients with schizophrenia and the correlations between these markers. Our a priori hypothesis was that glutamate levels would negatively correlate with hippocampal volume in schizophrenia.<h4>Design, setting, and participants</h4>Combined 3-T structural mag ...[more]

PMID: 24108440

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Project description:Despite the well-established role of striatal dopamine in psychosis, current views generally agree that cortical dysfunction is likely necessary for the emergence of psychotic symptoms. The topographic organization of striatal-cortical connections is central to gating and integration of higher-order information, so a disruption of such topography via dysregulated dopamine could lead to cortical dysfunction in schizophrenia. However, this hypothesis remains to be tested using multivariate methods ascertaining the global pattern of striatal connectivity and without the confounding effects of antidopaminergic medication.To examine whether the pattern of brain connectivity across striatal subregions is abnormal in unmedicated patients with schizophrenia and whether this abnormality relates to psychotic symptoms and extrastriatal dopaminergic transmission.In this multimodal, case-control study, we obtained resting-state functional magnetic resonance imaging data from 18 unmedicated patients with schizophrenia and 24 matched healthy controls from the New York State Psychiatric Institute. A subset of these (12 and 17, respectively) underwent positron emission tomography with the dopamine D2 receptor radiotracer carbon 11-labeled FLB457 before and after amphetamine administration. Data were acquired between June 16, 2011, and February 25, 2014. Data analysis was performed from September 1, 2014, to January 11, 2016.Group differences in the striatal connectivity pattern (assessed via multivariable logistic regression) across striatal subregions, the association between the multivariate striatal connectivity pattern and extrastriatal baseline D2 receptor binding potential and its change after amphetamine administration, and the association between the multivariate connectivity pattern and the severity of positive symptoms evaluated with the Positive and Negative Syndrome Scale.Of the patients with schizophrenia (mean [SEM] age, 35.6 [11.8] years), 9 (50%) were male and 9 (50%) were female. Of the controls (mean [SEM] age, 33.7 [8.8] years), 10 (42%) were male and 14 (58%) were female. Patients had an abnormal pattern of striatal connectivity, which included abnormal caudate connections with a distributed set of associative cortex regions (?229 = 53.55, P?=?.004). In patients, more deviation from the multivariate pattern of striatal connectivity found in controls correlated specifically with more severe positive symptoms (??=?-0.77, P?=?.002). Striatal connectivity also correlated with baseline binding potential across cortical and extrastriatal subcortical regions (t25?=?3.01, P?=?.01, Bonferroni corrected) but not with its change after amphetamine administration.Using a multimodal, circuit-level interrogation of striatal-cortical connections, it was demonstrated that the functional topography of these connections is globally disrupted in unmedicated patients with schizophrenia. These findings suggest that striatal-cortical dysconnectivity may underlie the effects of dopamine dysregulation on the pathophysiologic mechanism of psychotic symptoms.

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Dataset Information

Increased hippocampal glutamate and volumetric deficits in unmedicated patients with schizophrenia.

Importance

Objective

Design, setting, and participants

Main outcomes and measures

Results

Conclusions and relevance

Publications

Increased hippocampal glutamate and volumetric deficits in unmedicated patients with schizophrenia.

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