Dataset Information

In vivo brain endocannabinoid metabolism is related to hippocampus glutamate and structure - a multimodal imaging study with PET, ¹H-MRS, and MRI.

ABSTRACT: Dysregulation of hippocampus glutamatergic neurotransmission and reductions in hippocampal volume have been associated with psychiatric disorders. The endocannabinoid system modulates glutamate neurotransmission and brain development, including hippocampal remodeling. In humans, elevated levels of anandamide and lower activity of its catabolic enzyme fatty acid amide hydrolase (FAAH) are associated with schizophrenia diagnosis and psychotic symptom severity, respectively (Neuropsychopharmacol, 29(11), 2108-2114; Biol. Psychiatry 88 (9), 727-735). Although preclinical studies provide strong evidence linking anandamide and FAAH to hippocampus neurotransmission and structure, these relationships remain poorly understood in humans. We recruited young adults with and without psychotic disorders and measured FAAH activity, hippocampal glutamate and glutamine (Glx), and hippocampal volume using [¹¹C]CURB positron emission tomography (PET), proton magnetic resonance spectroscopy (¹H-MRS) and T1-weighted structural MRI, respectively. We hypothesized that higher FAAH activity would be associated with greater hippocampus Glx and lower hippocampus volume, and that these effects would differ in patients with psychotic disorders relative to healthy control participants. After attrition and quality control, a total of 37 participants (62% male) completed [¹¹C]CURB PET and ¹H-MRS of the left hippocampus, and 45 (69% male) completed [¹¹C]CURB PET and hippocampal volumetry. Higher FAAH activity was associated with greater concentration of hippocampal Glx (F_1,36.36 = 9.17, p = 0.0045; Cohen's f = 0.30, medium effect size) and smaller hippocampal volume (F_1,44.70 = 5.94, p = 0.019, Cohen's f = 0.26, medium effect size). These effects did not differ between psychosis and healthy control groups (no group interaction). This multimodal imaging study provides the first in vivo evidence linking hippocampal Glx and hippocampus volume with endocannabinoid metabolism in the human brain.

SUBMITTER: Watts JJ

PROVIDER: S-EPMC9485131 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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In vivo brain endocannabinoid metabolism is related to hippocampus glutamate and structure - a multimodal imaging study with PET, <sup>1</sup>H-MRS, and MRI.

Watts Jeremy J JJ Guma Elisa E Chavez Sofia S Tyndale Rachel F RF Ross Ruth A RA Houle Sylvain S Wilson Alan A AA Chakravarty Mallar M Rusjan Pablo M PM Mizrahi Romina R

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20220729 11

Dysregulation of hippocampus glutamatergic neurotransmission and reductions in hippocampal volume have been associated with psychiatric disorders. The endocannabinoid system modulates glutamate neurotransmission and brain development, including hippocampal remodeling. In humans, elevated levels of anandamide and lower activity of its catabolic enzyme fatty acid amide hydrolase (FAAH) are associated with schizophrenia diagnosis and psychotic symptom severity, respectively (Neuropsychopharmacol, 2 ...[more]

PMID: 35906490

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Project description:Multimodal neuroimaging studies combining proton magnetic resonance spectroscopy (1H-MRS) to quantify GABA and/or glutamate concentrations and functional magnetic resonance imaging (fMRI) to measure brain activity non-invasively have advanced understanding of how neurochemistry and neurophysiology may be related at a macroscopic level. The present study aimed to perform a systematic review and meta-analysis of available studies examining the relationship between 1H-MRS glutamate and/or GABA levels and task-related fMRI signal in the healthy brain. Ovid (Medline, Embase, and PsycINFO) and Pubmed databases were systematically searched to identify articles published until December 2019. The primary outcome of interest was the association between resting levels of glutamate or GABA and task-related fMRI. Fifty-five papers were identified for inclusion in the systematic review. A further 22 studies were entered into four separate meta-analyses. These meta-analyses found evidence of significant negative associations between local GABA levels and (a) fMRI activation to visual tasks in the occipital lobe, and (b) activation to emotion processing in the medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC). However, there was no significant association between mPFC/ACC glutamate levels and fMRI activation to cognitive control tasks or to emotional processing, with the relationship to emotion processing related neural activity narrowly missing significance. Moreover, our systematic review also found converging evidence of negative associations between GABA levels and local brain activity, and positive associations between glutamate levels and distal brain activity, outside of the 1H-MRS sampling region. Albeit less consistently, additional relationships between GABA levels and distal brain activity and between glutamate levels and local brain activity were found. It remains unclear if the absence of effects for other brain regions and other cognitive-emotional domains reflects study heterogeneity or potential confounding effects of age, sex, or other unknown factors. Advances in 1H-MRS methodology as well as in the integration of 1H-MRS readouts with other imaging modalities for indexing neural activity hold great potential to reveal key aspects of the pathophysiology of mental health disorders involving aberrant interactions between neurochemistry and neurophysiology such as schizophrenia.

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Dataset Information

In vivo brain endocannabinoid metabolism is related to hippocampus glutamate and structure - a multimodal imaging study with PET, ¹H-MRS, and MRI.

Publications

In vivo brain endocannabinoid metabolism is related to hippocampus glutamate and structure - a multimodal imaging study with PET, <sup>1</sup>H-MRS, and MRI.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

In vivo brain endocannabinoid metabolism is related to hippocampus glutamate and structure - a multimodal imaging study with PET, 1H-MRS, and MRI.

Publications

In vivo brain endocannabinoid metabolism is related to hippocampus glutamate and structure - a multimodal imaging study with PET, <sup>1</sup>H-MRS, and MRI.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

In vivo brain endocannabinoid metabolism is related to hippocampus glutamate and structure - a multimodal imaging study with PET, ¹H-MRS, and MRI.