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Regional Heterogeneity of Brain Morphometrical Changes in recreational Ketamine Use Individuals

Poster No:

558

Submission Type:

Abstract Submission

Authors:

YI-HSUAN LIU¹, Kun-Hsien Chou¹^,2, Pei-Lin Lee³, Chia-Chun Hung⁴^,5, Li-Hung Chang¹, Marc Potenza⁶^,7^,8^,9^,10, Chiang-Shan Li⁶, Tony Szu-Hsien Lee¹¹^,5^,12, Ching-Po Lin¹^,3^,13^,14

Institutions:

¹Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan, ²Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, ³Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan, ⁴Continuing Education Master's Program of Addiction Prevention and Treatment, National Taiwan Normal, Taipei, Taiwan, ⁵Center for Addiction Prevention and Policy Research, National Taiwan Normal University, Taipei, Taiwan, ⁶Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, ⁷The Child Study Center, School of Medicine, Yale University, New Haven, CT, ⁸Department of Neuroscience and the The Wu Tsai Institute, Yale University, New Haven, CT, ⁹The Connecticut Council on Problem Gambling, Wethersfield, CT, ¹⁰The Connecticut Mental Health Center, New Haven, CT, ¹¹Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan, ¹²Continuing Education Master's Program of Addiction Prevention and Treatment, National Taiwan Normal University, Taipei, Taiwan, ¹³Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, ¹⁴Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan

First Author:

YI-HSUAN LIU
Institute of Neuroscience, National Yang Ming Chiao Tung University
Taipei, Taiwan

Co-Author(s):

Kun-Hsien Chou
Institute of Neuroscience, National Yang Ming Chiao Tung University|Brain Research Center, National Yang Ming Chiao Tung University
Taipei, Taiwan|Taipei, Taiwan

Pei-Lin Lee
Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University
Taipei, Taiwan

Chia-Chun Hung
Continuing Education Master's Program of Addiction Prevention and Treatment, National Taiwan Normal|Center for Addiction Prevention and Policy Research, National Taiwan Normal University
Taipei, Taiwan|Taipei, Taiwan

Li-Hung Chang
Institute of Neuroscience, National Yang Ming Chiao Tung University
Taipei, Taiwan

Chiang-Shan Li
Department of Psychiatry, School of Medicine, Yale University
New Haven, CT

Tony Szu-Hsien Lee
Department of Health Promotion and Health Education, National Taiwan Normal University|Center for Addiction Prevention and Policy Research, National Taiwan Normal University|Continuing Education Master's Program of Addiction Prevention and Treatment, National Taiwan Normal University
Taipei, Taiwan|Taipei, Taiwan|Taipei, Taiwan

Ching-Po Lin
Institute of Neuroscience, National Yang Ming Chiao Tung University|Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University|Department of Education and Research, Taipei City Hospital|Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes
Taipei, Taiwan|Taipei, Taiwan|Taipei, Taiwan|Miaoli, Taiwan

Introduction:

The engagement in recreational substance use during youth can exert significant and enduring effects on brain development. Among the array of recreational substances in Taiwan, ketamine stands out as particularly prevalent among young individuals, due to its affordability, easy accessibility, and relatively minor legal consequences [1]. Although our comprehension of the neurobiological alterations associated with ketamine abuse has advanced considerably [2,3], there exists a notable gap in knowledge concerning brain changes resulting from early, non-medical exposure to ketamine. To address this gap, we recruited participants with early ketamine exposure from the community. Given the distinctive characteristics of these individuals, it is crucial to emphasize individual brain structure alterations to elucidate the impact of early-stage ketamine use. Hence, in this study, we employ a personalized analytical approach with structural T1-weighted MRI anatomical scans to pinpoint subtle yet significant changes in gray matter volume among a cohort of young adults with early exposure to recreational ketamine use.

Methods:

Participants consisted of 174 individuals from Taiwan, including 53 ketamine use (KU) and 121 healthy controls (HC) [Table 1]. T1-weighted MRI anatomical scans were preprocessed using the VBM pipeline [4]. We extract regional gray matter volume (GMV) from 1060 brain areas and map them into nine corresponded large-scale brain networks [5,6,7]. For individual-level analyses, we employed a w-score approach to identify extreme regional GMV changes for each participant [8]. A general linear model was constructed using healthy controls to obtain beta coefficient estimates of GMV for each ROI, incorporating covariates such as age, sex, and education. This model was applied to individuals with ketamine use further, wherein we calculated residuals for the 1060 brain regions per participant and transformed them into corresponding W-scores. To provide a summary of individual variation in KU, w-scores were summarized by counting how many subjects had an extreme deviation (extreme deviation defined as p< 0.001, |z| > 3.29) at a given ROI, and then dividing by the group size to show the frequency of individuals with extreme deviations at that brain area. For group-level analyses, we employed an ANCOVA model to identify brain regions with significant between-group difference in GMV using the same statistic threshold (p< 0.001) as in the individual analysis. Subsequently, to control for the varying number of regions within networks, we divided the number of significantly different areas to the total within each.

·Table 1: Demographics.

Results:

Upon examination of individual-level w-scores, our analysis uncovered that KU exhibits more extensive alterations in regional GMV, a phenomenon potentially obscured by conventional case-control group-level analysis (Fig 1. (a)). The most substantial impact is also observed in the frontoparietal, somatomotor, visual, dorsal attention, and default networks (Fig 1. (b)).

·Fig 1

Conclusions:

In our investigation, we have identified morphometric heterogeneity throughout the brains of individuals with early exposure to ketamine. Remarkably, the networks involved deviate from the conventional findings associated with addiction, particularly those related to reward networks. This discovery suggests that employing individual-level analysis might unveil subtle yet significant anatomical changes among a cohort of young adults with early exposure to recreational ketamine use. These initial findings provide a glimpse into the potential nuanced direct impact of ketamine or the possibility of serving as an early biomarker for the essential brain networks associated with addiction. Further research is indispensable to validate and gain deeper insights into the implications of these preliminary observations.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Emotion, Motivation and Social Neuroscience:

Social Neuroscience Other

Lifespan Development:

Early life, Adolescence, Aging

Modeling and Analysis Methods:

Methods Development ²

Keywords:

Addictions

Data analysis

Morphometrics

MRI

STRUCTURAL MRI

Other - ketamine

^1|2Indicates the priority used for review

Provide references using author date format

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