Cannabis-related hippocampal volumetric abnormalities specific to subregions in dependent users

Chye, Yann; Suo, Chao; Yücel, Murat; Ouden, Lauren Den; Solowij, Nadia; Lorenzetti, Valentina

doi:10.1007/s00213-017-4620-y

Cited by 28 publications

(22 citation statements)

References 81 publications

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“…; Chye et al . ). Future investigative efforts should thus be mindful in assessing and discriminating between cannabis use and dependence when evaluating the harms and vulnerabilities associated with chronic cannabis use.…”

Section: Discussionmentioning

confidence: 97%

“…)] and in dependent users [i.e., reduced CA3 and CA4/DG volume (Chye et al . )]. Deflation confined to the CA3 and CA4/DG hippocampal subregions is noteworthy as these are the major sites for adult neurogenesis and subsequent innervation of new neurons, a process crucial for learning and memory, as well as affective and stress regulation (Canales ; Chambers ).…”

Section: Discussionmentioning

confidence: 99%

“…; Chye et al . )] and brain function [i.e. functional connectivity across amygdala, anterior cingulate, orbitofrontal cortex, hippocampus and nucleus accumbens (Filbey & Dunlop )].…”

Section: Introductionmentioning

confidence: 97%

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Alteration to hippocampal volume and shape confined to cannabis dependence: a multi‐site study

et al. 2018

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Cannabis use is highly prevalent and often considered to be relatively harmless. Nonetheless, a subset of regular cannabis users may develop dependence, experiencing poorer quality of life and greater mental health problems relative to non-dependent users. The neuroanatomy characterizing cannabis use versus dependence is poorly understood. We aimed to delineate the contributing role of cannabis use and dependence on morphology of the hippocampus, one of the most consistently altered brain regions in cannabis users, in a large multi-site dataset aggregated across four research sites. We compared hippocampal volume and vertex-level hippocampal shape differences (1) between 121 non-using controls and 140 cannabis users; (2) between 106 controls, 50 non-dependent users and 70 dependent users; and (3) between a subset of 41 controls, 41 non-dependent users and 41 dependent users, matched on sample characteristics and cannabis use pattern (onset age and dosage). Cannabis users did not differ from controls in hippocampal volume or shape. However, cannabis-dependent users had significantly smaller right and left hippocampi relative to controls and non-dependent users, irrespective of cannabis dosage. Shape analysis indicated localized deflations in the superior-medial body of the hippocampus. Our findings support neuroscientific theories postulating dependence-specific neuroadaptations in cannabis users. Future efforts should uncover the neurobiological risk and liabilities separating dependent and non-dependent use of cannabis.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Alteration to hippocampal volume and shape confined to cannabis dependence: a multi‐site study

et al. 2018

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“…Generally, studies have focused on brain regions with a high density of CB1 receptors [9], including subcortical structures such as the basal ganglia, hippocampus, and amygdala, as well as the cerebellum, cingulate cortex, and prefrontal cortex. Several studies have reported associations between frequent cannabis use in adolescents and young adults and reductions in hippocampal volumes [10][11][12]. However, other studies do not replicate these reductions [13][14][15][16][17], including one longitudinal study [18].…”

Section: Introductionmentioning

confidence: 99%

Cannabis Use in Youth is Associated with Limited Alterations in Brain Structure

Scott

Rosen

Moore

et al. 2018

Preprint

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Frequent cannabis use during adolescence has been associated with alterations in brain structure. However, studies have featured relatively inconsistent results, predominantly from small samples, and few studies have examined less frequent users to shed light on potential brain structure differences across levels of cannabis use. In this study, high-resolution T1weighted MRIs were obtained from 781 youth aged 14-21 years who were studied as part of the Philadelphia Neurodevelopmental Cohort. This sample included 147 cannabis users (109 Occasional [≤1-2 times per week] and 38 Frequent [≥ 3 times per week] Users) and 634cannabis Non-Users. Several structural neuroimaging measures were examined in whole brain analyses, including gray and white matter volumes, cortical thickness, and gray matter density.Established procedures for stringent quality control were conducted, and two automated neuroimaging software processing packages were used to ensure robustness of results. There were no significant differences by cannabis group in global or regional brain volumes, cortical thickness, or gray matter density, and no significant group by age interactions were found.Follow-up analyses indicated that values of structural neuroimaging measures by cannabis group were similar across regions, and any differences among groups were likely of a small magnitude. In sum, structural brain metrics were similar among adolescent and young adult cannabis users and non-users. Our data converge with prior large-scale studies suggesting small or limited associations between cannabis use and structural brain measures in youth.Detailed studies of vulnerability to structural brain alterations and longitudinal studies examining long-term risk are indicated.Note. K-W = Kruskall-Wallis; FCU = Frequent Cannabis User; NU = Non-User; OCU = Occasional Cannabis User.

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“…The hippocampal subfields have been shown to fulfill different roles in the memory processes conducted in the hippocampus; for example, the dentate gyrus and third section of the cornu ammonis (CA3) having been found to be involved in memory encoding 13 and early retrieval, while the first section of the cornu ammonis (CA1) has been linked with episodic memory 14 , memory consolidation, late retrieval, and recognition [15][16][17][18][19] . In the first study to examine the association of cannabis with hippocampal subfields, Chye et al 20 used Freesurfer's automated segmentation software (https://surfer.nmr.mgh.harvard.edu) to find many subfields of the hippocampus differentiated 39 cannabis dependent individuals from 35 non-users: CA1, CA2, CA3, CA4 and the dentate gyrus (DG). This study also found the CA2, CA3, CA4, and DG to be associated with lifetime amount of cannabis used.…”

Section: Introductionmentioning

confidence: 99%

Cannabis Use is Associated with Lower Hippocampus and Amygdala Volume: High-Resolution Segmentation of Structural Subfields in a Large Non-clinical Sample

Mm¹,

MacKillop²,

Sweet³

2019

Preprint

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There is mixed evidence that individuals who use cannabis have reduced hippocampal and amygdalar gray matter volume, potentially because of small sample sizes and imprecise morphological characterization. New automated segmentation procedures have improved the measurement of these structures and allow better examination of their subfields, which have been linked to distinct aspects of memory and emotion. The current study applies this new segmentation procedure to the Human Connectome Project Young Adult dataset (N = 1081) to investigate associations of cannabis use with gray matter volume in the hippocampus and amygdala. Results revealed significant bilateral inverse associations of hippocampal volume with recent cannabis use (positive THC urine drug screen) and total lifetime consumption (ps<.001), as well as association of the left amygdala total lifetime consumption (p<.001). Hippocampal subfield analyses indicated these associations were primarily driven by the head of the hippocampus, the first section of the cornu amonis (CA1), and the subicular complex, which have been linked to verbal working memory, episodic memory, and spatial memory respectively. In the amygdala, the association was driven by subfields in the basolateral complex, which links the amygdala to the cortex and is critical in emotion regulation. No associations were detected for age of cannabis initiation or lifetime presence of cannabis use disorder. In one of the largest studies to date, these results support the hypothesis that cannabis use is linked with hippocampal and amygdalar volume and clarify both the specific subfields and the specific aspects of cannabis use that are responsible for these links.

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Cannabis-related hippocampal volumetric abnormalities specific to subregions in dependent users

Abstract: Our results suggest a regionally and dependence-specific influence of cannabis use on the hippocampus. Hippocampal alteration in cannabis users was specific to the CA and DG regions and confined to dependent users.

Cited by 28 publications

References 81 publications

Alteration to hippocampal volume and shape confined to cannabis dependence: a multi‐site study

Alteration to hippocampal volume and shape confined to cannabis dependence: a multi‐site study

Cannabis Use in Youth is Associated with Limited Alterations in Brain Structure

Cannabis Use is Associated with Lower Hippocampus and Amygdala Volume: High-Resolution Segmentation of Structural Subfields in a Large Non-clinical Sample

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