Neurotransmitter-related interhemispheric disconnectivity in depression with and without anxiety
Poster No:
577
Submission Type:
Abstract Submission
Authors:
Wen Zhu1, Huaijin Gao1, Rui Qian1, Chengjiaao Liao1, Dan Wu1, Zhiyong Zhao1
Institutions:
1Zhejiang University, Hangzhou, China
First Author:
Co-Author(s):
Introduction:
Anxiety exacerbates major depressive disorder (MDD), leading to adverse outcomes such as lower socioeconomic status and impaired adaptive functioning[1]. Prior studies have reported alterations in interhemispheric functional connectivity in MDD[2], but the impact of post-depression anxiety on this connectivity remains unexplored so far. Moreover, recent evidence indicates that neurotransmitters, such as serotonin (5-HT), norepinephrine (NE) and dopamine (DA), play a pivotal role in the neural mechanisms of depression[3], and show a close association with interhemispheric functional connectivity[4]. Consequently, the primary objective of this study is to examine how depression and anxiety impact interhemispheric functional connectivity and to explore their association with neurotransmitter receptors.
Methods:
We screened resting-state fMRI (rs-fMRI) data of MDD patients with anxiety (N = 334) and without anxiety (N = 145) and normal controls (NCs, N = 307) with matched age, sex, education and head motion from the Chinese REST-meta-MDD database. The rs-fMRI images were preprocessed at each site using a standardized DPARSF processing pipeline[5], including slice timing correction, realignment, segmentation, signal regression of white matter and CSF, normalization, smoothing, and filtering (0.01- 0.1Hz). We computed voxel-mirrored homotopic connectivity (VMHC) by calculating the Pearson correlation coefficient between each voxel's residual time series and its symmetrical interhemispheric counterpart, which were then Fisher z-transformed before group-level analysis. Inter-group comparisons used voxel-wise linear mixed models, followed by Gaussian random field (GRF) correction with voxel-wise p-value < 0.01 and cluster-wise p-value < 0.05.
Neurotransmitter receptor density data were obtained from a recent report[6] that collated data from a large number of PET studies involving over 1,200 healthy adults, and it provided the density of 19 unique neurotransmitter receptors and transporters in the Schaefer-100 atlas. Then, normalized density (z-scored) was derived for each of the 19 receptors and transporters across the 100 regions[4]. Finally, we assessed the relationship between VMHC alterations in MDD and neurotransmitter receptor density using Pearson correlation across the 100 regions (FDR correction).
Neurotransmitter receptor density data were obtained from a recent report[6] that collated data from a large number of PET studies involving over 1,200 healthy adults, and it provided the density of 19 unique neurotransmitter receptors and transporters in the Schaefer-100 atlas. Then, normalized density (z-scored) was derived for each of the 19 receptors and transporters across the 100 regions[4]. Finally, we assessed the relationship between VMHC alterations in MDD and neurotransmitter receptor density using Pearson correlation across the 100 regions (FDR correction).
Results:
Compared with NCs, non-anxious MDD showed lower VMHC values in posterior cingulate cortex (PCC), while anxious MDD displayed decreased VMHC values in PCC, inferior frontal gyrus (IFG), medial prefrontal cortex (mPFC), middle frontal gyrus (MFG) and parahippocampal gyrus (PHG) (Fig.1). The non-anxious and anxious MDD subgroups did not show significant alterations in the VMHC. Moreover, the VMHC difference between non-anxious MDD and NC group negatively correlated with densities of 5-HT4 receptor, while the VMHC difference between anxious MDD and NC positively correlated with densities of 5-HT2a, H3, M1 and mGluR5 receptors. (Fig.2)
·Fig.1 Voxel-wise inter-group comparisons of VMHC. (A) and (B) show regions with significantly lower VMHC values in patient group than normal controls, and the distribution of their VMHC values, respec
·Fig.2 Correlation between VMHC differences and two neurotransmitter receptors. The regions with white circles have higher/lower density than other regions, consistent with VMHC alterations in patient
Conclusions:
We found decreased VMHC in PCC in both non-anxious and anxious MDD compared with NC, indicating this alteration may be specific to depressive symptom[7,8]. Moreover, we observed anxious-specific decreases in the VMHC of mPFC, MFG, PHG and IFG, suggesting a more severe interhemispheric functional connectivity impairment in anxiety than depression[7]. Importantly, we found significant links between VMHC changes and neurotransmitter density. The depression-related receptor (5-HT4) is involved in serotonin release and further affects cognitive functions[9], while anxiety-related receptors (5-HT2a, H3, M1, and mGluR5) may influence the release of 5-HT, glutamate and GABA, related to emotional regulation[10]. In summary, our findings uncovered different patterns of interhemispheric disconnectivity in MDD with and without anxiety, which was associated with distinct neurotransmitter systems.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Transmitter Receptors 2
Novel Imaging Acquisition Methods:
BOLD fMRI
Keywords:
Anxiety
FUNCTIONAL MRI
Neurotransmitter
Psychiatric Disorders
1|2Indicates the priority used for review
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