Evaluation of neurometabolites in the amygdala of the adolescents

Poster No:

539 

Submission Type:

Abstract Submission 

Authors:

Yan Li1, Xin Mu1, Angela Jakary1, Tara Samson1, Tracy Luks1, Tony Yang1

Institutions:

1University of California San Francisco, San Francisco, CA

First Author:

Yan Li  
University of California San Francisco
San Francisco, CA

Co-Author(s):

Xin Mu  
University of California San Francisco
San Francisco, CA
Angela Jakary  
University of California San Francisco
San Francisco, CA
Tara Samson  
University of California San Francisco
San Francisco, CA
Tracy Luks  
University of California San Francisco
San Francisco, CA
Tony Yang  
University of California San Francisco
San Francisco, CA

Introduction:

While the amygdala has garnered attention for examining brain metabolism in the context of depressive symptoms, its small size and location make this challenging. In our study, we employed an atlas-based automatic spectral prescription (Bian, 2018; Li, 2017) to automatically obtain proton MR spectroscopy (MRS) data within the amygdala. The participant group is comprised of individuals from an ongoing clinical trial assessing the changes resulting from a neuroscience-based mindfulness intervention, Training for Awareness, Resilience, and Action (TARA) (Blom, 2014; Tymofiyeva, 2024). The goal of this study was to evaluate brain metabolism in the amygdala and its association with depression scores and the intervention's outcomes.

Methods:

43 healthy adolescents (average age 15.8±1.2 years [14-18]; 30 females/13 males) who exhibited elevated depressive symptoms, defined as a Reynolds Adolescent Depression Scale -2 (RADS-2) t-score of 50 or higher, were studied before and after participating in either a TARA or an active psychological education intervention, which were delievered via Zoom. A total of 89 1H MRS spectra from the left amygdala (53 spectra from 41 subjects) or the right amygdala (36 spectra from 27 subjects) using sLASER MRS (TE/TR=35/2000 ms) (Fig 1). The voxel location was preselected in the standard space and then automatically transferred to the subject space with the volume adjusted based on the head size. MRS data underwent processing that included eddy current correction, frequency alignment, and phase correction, followed by quantification in LcModel using a simulated basis set. Additionally, T1-weighted images were segmented at the voxel location for tissue correction. Each participant's depressive symptoms were evaluated using the RADS-2, the Beck Depression Inventory-II (BDI-II), the Quick Inventory of Depressive Symptomatology Adolescent (17 items; QIDS-A17), and the Insomnia Severity Index (ISI) before or after the MR visit. We performed a paired t-test to compare the difference in metabolism between the left and right amygdala. Multivariable linear regression models were utilized to examine the association between metabolite concentrations or ratios and clinical measures or intervention, with age and sex adjusted. Given the exploratory nature of the study, we did not apply multiple corrections.
Supporting Image: Abstract3326_Figure1.png
   ·Figure 1. An example of an automatically prescribed MRS is in the left amygdala. Top row: voxel location; middle row: tissue segmentation; bottom left: processed spectra data; bottom right: quantified
 

Results:

One example of MRS data is demonstrated in Fig 1. No significant differences in metabolites were observed between the right and left amygdala (N=25). Additionally, there were no significant correlations found between metabolites and RADS-2 scores. In the right amygdala, total NAA/total creatinine (tNAA/tCr) showed a negative association with BDI-II scores (p = 0.036; Fig 2a). In the left amygdala, both myo-inositol+glycine (mIG) (p = 0.005; Fig 2b) and mIG/tCr (p = 0.013) displayed significant negative associations with QIDS-A17 scores. mIG/tCr in the left amygdala is also negatively associated with BDI-II (p = 0.032). Furthermore, Glutathione/tCr in the left amygdala is associated with ISI (p=0.039).
A total of 15 patients were assessed both before and after the intervention, with 8 participants in the active psychological education group and 7 in the TARA mindfulness group.
All assessments indicated a notable reduction in depression symptoms, as demonstrated by the BDI-II (p=0.045; Fig 2c) and QIDS-A17 (p=0.002), with no differences observed between groups. The improvement in BDI-II correlated with an increase in total choline/tCr in the left amygdala (p=0.015; Fig 2e) or an increase in mI/tCr in the right amygdala (p=0.020). Consistent with earlier findings, the ISI also had a tendency toward a difference between the two interventions on ISI (p = 0.086) within this group (Fig 2d). The enhancement in ISI was linked to an increase in glutamine (p = 0.041; Fig 2f) or glutamine/tCr (p = 0.035) in the left amygdala.
Supporting Image: Abstract3326_Figure2.png
   ·Figure 2. Significant metabolite variables associated with BDI-II, QIDS-A17, and ISI.
 

Conclusions:

This study demonstrated the metabolite differences that are associated with depression symptoms.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1

Lifespan Development:

Early life, Adolescence, Aging

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Anatomy and Functional Systems

Novel Imaging Acquisition Methods:

MR Spectroscopy 2

Physiology, Metabolism and Neurotransmission:

Physiology, Metabolism and Neurotransmission Other

Keywords:

Magnetic Resonance Spectroscopy (MRS)
MR SPECTROSCOPY
PEDIATRIC
Pediatric Disorders
Psychiatric
Psychiatric Disorders

1|2Indicates the priority used for review

Abstract Information

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

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

Healthy subjects

Was this research conducted in the United States?

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Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.

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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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Not applicable

Please indicate which methods were used in your research:

Functional MRI
Other, Please specify  -   MR Spectroscopy

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

3.0T

Which processing packages did you use for your study?

Other, Please list

Provide references using APA citation style.

Bian W, et al. (2018). Fully automated atlas-based method for prescribing 3D PRESS MR spectroscopic imaging: Toward robust and reproducible metabolite measurements in human brain. Magn Reson Med. 79(2):636-642.
Li Y, et al. (2017). Reliable and Reproducible GABA Measurements Using Automated Spectral Prescription at Ultra-High Field. Front Human Neurosci. Oct25:11:506

Tymofiyeva O, et al. (2024). Interoceptive brain network mechanisms of mindfulness-based training in healthy adolescents. Frontier in Psychology. Aug 13:15:1410319.

Blom EH, et al. (2014). The development of an RDoC-based treatment program for adolescent depression: “Training for Awareness, Resilience, and Action” (TARA). Frontiers in Human Neuroscience. Aug 19; 8:630.

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