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Role of Nuclei-Specific Fronto-Amygdala Pathway in Antidepressant Selection

Poster No:

391

Submission Type:

Abstract Submission

Authors:

Li Xue¹, Ting Wang², Junneng Shao¹, Qian Liao¹, Lingling Hua³, Hao Sun³, Zhijian Yao³, Qing Lu²

Institutions:

¹School of Biological Sciences & Medical Engineering, Southeast University, NanJing, Jiangsu, ²School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, Jiangsu, ³Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu

First Author:

Li Xue
School of Biological Sciences & Medical Engineering, Southeast University
NanJing, Jiangsu

Co-Author(s):

Ting Wang
School of Biological Sciences & Medical Engineering, Southeast University
Nanjing, Jiangsu

Junneng Shao
School of Biological Sciences & Medical Engineering, Southeast University
NanJing, Jiangsu

Qian Liao
School of Biological Sciences & Medical Engineering, Southeast University
NanJing, Jiangsu

Lingling Hua
Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University
Nanjing, Jiangsu

Hao Sun
Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University
Nanjing, Jiangsu

Zhijian Yao
Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University
Nanjing, Jiangsu

Qing Lu
School of Biological Sciences & Medical Engineering, Southeast University
Nanjing, Jiangsu

Introduction:

The amygdala and its cortical circuits play important roles in both pathophysiology and therapeutic alleviation of major depressive disorder (MDD)¹. Selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI), two common antidepressants, modulate the connectivity and neurotransmission within cortico-amygdala circuit². However, further investigations are required to understand the individual differences at amygdala level among patients who response to these two different antidepressants, which could lead to more personalized treatments for MDD. The aim of this study was to investigate the cortico-amygdala white matter (WM) connections and their association with antidepressant treatment and to clarify whether specific nuclei-level amygdala connection is sensitive in distinguishing SSRI and SNRI.

Methods:

The flowchart of whole work was shown in Figure 1. From diffusion tensor imaging (DTI) of 106 patients with major depressive disorder (MDD) who response to SSRI (SSRI-Responders) or SNRI (SNRI-Responders), the cortico-amygdala WM connectivity was estimated using probabilistic tractography. 'Winner takes all' algorithm³ was used to label the amygdala voxels and then create a connectome labelling matrix according to its cortical WM connections. K-modes clustering method based on Hamming distance was used to cluster the amygdala into subdivisions. For the segmented subdivisions, we measured the fractional anisotropy (FA) values of each cortico-subdivision WM connection and compared between SSRI-Responders and SNRI-Responders. Finally, we decoded the neural circuit with discriminative significance using microscale transcriptomic and chemo-architecture analysis.

Results:

Significant difference was detected in the WM connections between left amygdala and frontal lobe. The left amygdala was subdivided into three nuclei according its cortical connections, named as superficial amygdala nucleus (supAMY), medial amygdala nucleus (medialAMY) and lateral amygdala nucleus (lateralAMY), as shown in Figure 2. Group difference was also detected in FA of fronto-medialAMY WM tracts, which we referred to a pharmacological propensity pattern. Furthermore, this pattern was colocalized with gene expression involved in "synaptic transmission" and aligned with the distribution of serotonin (5-HT) and noradrenaline (NAT) neurotransmitter system with different degree across two groups, as 5-HT is the strongest contributor (43.85%) to SSRI-Responders and NAT is the strongest contributor (42.74%) to SNRI-Responders.

Conclusions:

We reveal a pharmacological propensity pattern, fronto-medialAMY circuit, in distinguishing patients treated with SSRIs and SNRIs. The mapping between macroscale pharmacological propensity connectome and microscale molecular chemoarchitecture may provide new testable evidence to inform decision-making in antidepressant treatment of MDD.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Genetics:

Genetic Association Studies ²

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural)

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Transmitter Receptors

Novel Imaging Acquisition Methods:

Diffusion MRI

Keywords:

Computational Neuroscience

Machine Learning

Neurotransmitter

Phenotype-Genotype

Psychiatric Disorders

Sub-Cortical

Tractography

White Matter

^1|2Indicates the priority used for review

·Figure 1

·Figure 2

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Resting state

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Patients

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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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Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Please indicate which methods were used in your research:

Diffusion MRI

For human MRI, what field strength scanner do you use?

3.0T

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FSL

Free Surfer

Provide references using APA citation style.

[1] Nelson, J.C., L. Portera, and A.C. Leon, Are there differences in the symptoms that respond to a selective serotonin or norepinephrine reuptake inhibitor? Biol Psychiatry, 2005. 57(12): p. 1535-42.
[2]

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