Hippocampal subfield differences in people with and without recreational ketamine use: Insights from multi-modal neuroimaging.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Hippocampal subfield differences in people with and without recreational ketamine use: Insights from multi-modal neuroimaging.
Συγγραφείς:	Liu YH; Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Department of Neurology, Columbia University, New York, NY, USA., Hung CC; Center for Addiction Prevention and Policy Research, National Taiwan Normal University, Taipei, Taiwan.; Continuing Education Master's Program of Addiction Prevention and Treatment, National Taiwan Normal University, Taipei, Taiwan., Potenza MN; Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA.; The Child Study Center, School of Medicine, Yale University, New Haven, CT, USA.; Department of Neuroscience and the Wu Tsai Institute, Yale University, New Haven, CT, USA.; The Connecticut Council on Problem Gambling, Wethersfield, CT, USA.; The Connecticut Mental Health Center, New Haven, CT, USA., Chou KH; Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan., Lee PL; Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan., Huang CC; School of Psychology and Cognitive Science, East China Normal University, Shanghai, China., Li CR; Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA.; Department of Neuroscience and the Wu Tsai Institute, Yale University, New Haven, CT, USA., Lee TS; Center for Addiction Prevention and Policy Research, National Taiwan Normal University, Taipei, Taiwan.; Continuing Education Master's Program of Addiction Prevention and Treatment, National Taiwan Normal University, Taipei, Taiwan.; Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan., Lin CP; Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
Πηγή:	Addiction (Abingdon, England) [Addiction] 2026 Jun; Vol. 121 (6), pp. 1541-1556. Date of Electronic Publication: 2026 Jan 29.
Τύπος έκδοσης:	Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 9304118 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1360-0443 (Electronic) Linking ISSN: 09652140 NLM ISO Abbreviation: Addiction Subsets: MEDLINE
Imprint Name(s):	Publication: Oxford : Wiley-Blackwell Original Publication: Abingdon, Oxfordshire, UK : Carfax Pub. Co., c1993-
Ιατρικοί όροι (MeSH):	Neuroimaging/methods , Ketamine/adverse effects , Substance-Related Disorders/diagnostic imaging , Substance-Related Disorders/epidemiology , Substance-Related Disorders/pathology , Substance-Related Disorders/psychology , Anesthetics, Dissociative/adverse effects , Hippocampus/diagnostic imaging , Hippocampus/drug effects , Hippocampus/pathology, Taiwan/epidemiology ; Recreational Drug Use/psychology ; Punishment/psychology ; Receptors, N-Methyl-D-Aspartate/drug effects ; Receptors, N-Methyl-D-Aspartate/metabolism ; Tobacco Smoking/epidemiology ; Tobacco Smoking/pathology ; Tobacco Smoking/psychology ; Cross-Sectional Studies ; Case-Control Studies ; Neuropsychological Tests ; Multimodal Imaging ; Psychological Distress ; Reward ; Memory, Short-Term ; Dose-Response Relationship, Drug ; Organ Size ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult
Περίληψη:	Background and Aims: Recreational ketamine use has increased globally and is associated with psychiatric and cognitive concerns. The hippocampus in preclinical models shows damage and working-memory disruption with repeated dosing. However, whether specific hippocampal subregions may differ in people with chronic ketamine use remains unclear. In Taiwan, ketamine is predominantly consumed by smoking ketamine mixed with tobacco, producing smoking-related behavioral profiles like non-ketamine tobacco use participants (TUs). We therefore examined individuals with urine-confirmed ketamine as the only detected substance who reported predominantly smoking-administered recreational use (KUs) and used TUs as controls. This study aimed to: (1) characterize ketamine-use patterns and psychiatric symptoms; (2) compare working-memory and affective-behavioral measures between KUs and TUs; (3) quantify group differences in hippocampal subregion volumes; and (4) assess group differences in functional connectivity (FC) of identified subregions and relationships with neurotransmitter receptor distributions. Design: Cross-sectional case-control study with cognitive testing and neuroimaging. Setting: Community-based recruitment in Taiwan. Participants: 58 KUs (44 males; mean age = 21.00 ± 4.57) and 73 TUs (52 males; mean age = 24.34 ± 5.86). Measurements: Ketamine-use patterns (Addiction Severity Index), psychiatric symptoms [Symptom Checklist-90-Revised (SCL-90-R)], working-memory (N-back), affective-behavioral measures [Barratt Impulsiveness Scale (BIS-11), Buss and Perry Aggression Questionnaire (BPAQ), Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ)], hippocampal subfield volumes (FreeSurfer) and functional connectivity (FC) of identified subregions (seed-based analysis). Spatial correspondence with N-methyl-D-aspartate (NMDA) receptor density was evaluated using JuSpace. Findings: Heavier ketamine use was associated with greater psychological distress [Global Severity Index (GSI) r = 0.343, P = 0.011], particularly anxiety (r = 0.457, P < 0.001) and hostility (r = 0.442, P < 0.001). Although self-reported impulsivity, aggression and reward/punishment sensitivity did not differ between groups, KUs showed reduced accuracy under higher working-memory load [2-back: F(1, 124) = 4.16, P = 0.04, partial η² = 0.03; 1-back: F(1, 124) = 8.10, P = 0.005, η2 = 0.06]. KUs displayed reduced left hippocampal volume [F(1, 119) = 4.23, P = 0.04, η2 = 0.03], most marked in the hippocampal-amygdaloid-transition-area [HATA; F(1, 119) = 10.52, P = 0.002, η2 = 0.08]. KUs also showed increased FC between left HATA and frontal, cingulate, temporal, subcortical, insular and cerebellar regions (P < 0.05, AlphaSim corrected), which correlated with NMDA-receptor distributions (z = 0.30, P = 0.005, false discovery rate corrected). Conclusions: Recreational smoking-administered ketamine use appears to be associated with dose-dependent psychiatric symptoms, load-dependent working memory impairment, selective hippocampal subregion volumetric differences and altered network connectivity aligned with N-methyl-D-aspartate- (NMDA) receptor distribution. (© 2026 The Author(s). Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)
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Grant Information:	114-2321-B-A49-015 National Science and Technology Council, Taiwan; 113-2321-B-A49-015 National Science and Technology Council, Taiwan; 112-2321-B-A49-008 National Science and Technology Council, Taiwan; 114-2926-I-A49A-501-G National Science and Technology Council, Taiwan; 114-2221-E-A49-104-MY3 National Science and Technology Council, Taiwan; 107-2410-H-003-038-Y2 National Science and Technology Council, Taiwan; 106-2410-H-003-028 National Science and Technology Council, Taiwan; 105-2410-H-003-013 National Science and Technology Council, Taiwan; 109-2410-H-003-017-SS3 National Science and Technology Council, Taiwan; 112-2410-H-003-081-SS2 National Science and Technology Council, Taiwan; 109-2917-I-010-002 National Science and Technology Council, Taiwan; 113-2314-B-A49-070 National Science and Technology Council, Taiwan; 112-2314-B-A49-056 National Science and Technology Council, Taiwan; 114-2314-B-A49-041-MY3 National Science and Technology Council, Taiwan; Tri-Service General Hospital: Advanced National Defense Technology & Research Program; Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University; Brain Research Center, National Yang Ming Chiao Tung University; Ministry of Education (MOE)
Contributed Indexing:	Keywords: N‐methyl‐D‐aspartate receptors; functional neuroimaging; hippocampus; ketamine; magnetic resonance imaging; recreational substance use; substance‐related disorders; working memory
Substance Nomenclature:	690G0D6V8H (Ketamine) 0 (Anesthetics, Dissociative) 0 (Receptors, N-Methyl-D-Aspartate)
Entry Date(s):	Date Created: 20260130 Date Completed: 20260511 Latest Revision: 20260610
Update Code:	20260611
PubMed Central ID:	PMC13155325
DOI:	10.1111/add.70331
PMID:	41612591
Βάση Δεδομένων:	MEDLINE

Περιγραφή
ISSN:	1360-0443
DOI:	10.1111/add.70331