Linking glutamate and ACC connectivity and their relationship to symptom domains in schizophrenia
Poster No:
507
Submission Type:
Abstract Submission
Authors:
Jonatan Gustavsson1, Robert Bodén1, Simon Cervenka1, Linda Steinholtz1, Jan Weis2, Jonas Persson1
Institutions:
1Department of Medical Sciences, Uppsala University, Uppsala, Uppland, 2Department of Medical Physics, Uppsala University Hospital, Uppsala, Uppland
First Author:
Co-Author(s):
Introduction:
Schizophrenia (SZ) is marked by structural and functional brain abnormalities, including cortical thinning and disrupted functional connectivity within networks such as the salience network (Wang, Y. et al., 2024). Concurrent aberrations among patients are found in the major neurotransmitter systems glutamate and Gamma-aminobutyric acid (GABA) within the anterior cingulate cortex (ACC) – a core node in the salience network (Nakahara, T. et al., 2022). While dysfunctional glutaminergic signalling has been proposed as a central pathology in SZ (Kim et al., 1980), the relationship between the functional connectivity of ACC in patients and these two neurotransmitters and their implications for symptomatology remain understudied. In this study, we investigated the relationship between ACC connectivity and co-located glutamate and GABA in SZ patients and healthy controls (HC), and whether this has links to symptomatology.
Methods:
We included 65 participants of which 27 were long-term SZ patients (mean age 33 ± 7.4, 10 females) and 38 were HC (mean age 29 ± 11, 23 females). All participants underwent structural and resting-state functional MRI. Nine individuals were excluded from statistical analyses due to substandard quality of the functional connectivity maps. Glutamate and GABA concentrations were measured using 1H MR MEGA-PRESS spectroscopy in the ACC and ratios were calculated relative to total creatin. Symptom ratings were assessed based on the Brief Psychiatric Rating Scale, entailing positive (items 9,10, & 11), negative (items 16,17 & 18), and affective symptoms (items 3,4, & 5). Functional images were first pre-processed using fMRIPrep and then denoised and scrubbed using the Conn toolbox for seed-based analysis. Differences in the neurotransmitter levels between SZ and HC were assessed using independent t-tests, and links between neurotransmitters and ACC-connectivity were assessed using voxel-wise general linear models in Conn toolbox. Lastly, Spearman correlations between ACC-connectivity and symptom ratings were performed.
Results:
We found that glutamate and GABA levels within the ACC did not differ between SZ and HC. In contrast, we observed that SZ showed reduced connectivity bilaterally in core salience processing regions, the ACC and insula (Figure 1A). Furthermore, across the full sample, glutamate-related connectivity in dorsal ACC was linked to insular and cerebellum. However, GABA was not related to connectivity across all participants (Figure 1B). Lastly, average glutamate-related connectivity positively correlated with negative symptoms only (r = .52, p = .006).
·Figure 1
Conclusions:
In our study, we cross-sectionally corroborate the link between prefrontal glutamate levels and connectivity among salience processing networks and further extend it by demonstrating a relationship with negative symptoms. Our results connect the underlying mechanistic brain processes and subsequent debilitating set of symptoms in patients with schizophrenia.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling
Task-Independent and Resting-State Analysis 2
Novel Imaging Acquisition Methods:
MR Spectroscopy
Keywords:
FUNCTIONAL MRI
GABA
Glutamate
MR SPECTROSCOPY
Psychiatric
Psychiatric Disorders
Schizophrenia
1|2Indicates the priority used for review
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Nakahara, T. et al. Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis of 1H-magnetic resonance spectroscopy studies. Mol Psychiatry 27, 744–757 (2022) doi:10.1038/s41380-021-01297-6.
Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller B. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett. 1980;20:379–82.