Daily and Intermittent Smoking Decrease Gray Matter Volume and Concentrations of Glutamate, Creatine, Myo-Inositol and<i>N</i>-acetylaspartate in the Prefrontal Cortex

Faulkner, Paul; Paioni, Susanna Lucini; Kozhuharova, Petya; Orlov, Natasza; Lythgoe, David J.; Daniju, Yusuf; Morgenroth, Elenor; Barker, Holly; Allen, Paul

doi:10.1101/2020.09.08.288050

Cited by 3 publications

(5 citation statements)

References 51 publications

(38 reference statements)

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“…While previous volumetric studies have also reported that tobacco use is associated with lower than normal GMV within PFC regions (e.g. Faulkner et al, 2020;Franklin et al, 2014;Fritz et al, 2014), this is the first study to report similarly low PFC volume in both cannabis users who also use tobacco, and non-cannabis-using tobacco smokers. This finding raises the possibility that the low GMV within the PFC is not entirely attributable to the neurotoxic effects of cannabis, but may be partly due to regular tobacco use.…”

Section: Discussionmentioning

confidence: 40%

“…‘Pack years’ (mean = 2.75, SD = 3.65, range = 0.2–144) was calculated as the average number of packs of cigarettes smoked per day multiplied by the number of years of smoking, as in previous research (e.g. Durazzo et al, 2016; Gallinat et al, 2006; Faulkner et al, 2020). Tobacco users had limited lifetime exposure to cannabis, with no self-report history of regular use and no use reported 6 months prior to MRI scanning.…”

Section: Methodsmentioning

confidence: 99%

“…Cousijn et al, 2012; Yücel et al, 2008). This is problematic as tobacco is often used with cannabis (Banbury et al, 2013; United States Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, 2012), and tobacco use is also associated with relatively lower GMV in PFC regions (Brody et al, 2004; Faulkner et al, 2020; Franklin et al, 2014; Fritz et al, 2014; Gallinat et al, 2006). Currently, only two studies have attempted to determine the contribution of co-occurring cannabis and tobacco use on brain volume (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Prefrontal cortex and putamen grey matter alterations in cannabis and tobacco users

et al. 2022

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Background: Previous magnetic resonance imaging studies in regular cannabis users report altered grey matter volume (GMV) in brain regions, including the prefrontal cortex (PFC), putamen and hippocampus. However, most studies have tended to recruit recreational users with high levels of cannabis use, and have not controlled for the possible confounding effects of tobacco use. We attempt to address these limitations in the present study. Methods: We acquired volumetric images in sex, age and IQ-matched groups of (1) regular Cannabis users who also smoke Tobacco cigarettes (‘CT’; n = 33), (2) non-cannabis-using Tobacco cigarette smokers (‘T’; n = 19) and (3) non-cannabis/tobacco-using Controls (‘C’; n = 35). GMV in bilateral PFC, putamen and hippocampal regions was compared across groups. We also examined the associations between GMV differences and levels of cannabis and tobacco use, measures of intellectual function, and of depression, anxiety and stress. Results: Relative to controls, both CT and T groups showed lower GMV in the left inferior frontal gyrus, and greater GMV in the putamen. In addition, lower GMV in the right frontal pole in the CT group (but not the T group) was associated with lifetime cannabis use, but not with cigarette use. Conclusions: Regular cannabis users who also smoked tobacco cigarettes showed altered GMV patterns relative to controls. However, a similar pattern of GMV differences was also seen between regular tobacco users that did not use cannabis. Further research is needed to disentangle the effects of cannabis and tobacco use on brain structure.

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Section: Discussionmentioning

confidence: 40%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prefrontal cortex and putamen grey matter alterations in cannabis and tobacco users

et al. 2022

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“…Spectra were analysed using LCModel 6.3-1L, with a basis set consisting of 19 simulated spectra, as in Morgenroth et al (2019) and Faulkner et al (2020a) (for the full basis set, see Supplementary Materials). This basis set was simulated using FID-A (Simpson et al, 2017) for TE = 8.5ms, magnetic field strength = ∼3T and assuming ideal RF pulses.…”

Section: Methodsmentioning

confidence: 99%

“…Kumar et al, 2002), on the basis that creatine was considered to be stable within regions of interest and across individuals (Li et al, 2003). However, prefrontal creatine is influenced by cigarette smoking (Durazzo et al, 2016; Faulkner et al, 2020a), cocaine use (Chang et al, 1997), cannabis use (Prescot et al, 2011), anxiety (Yue et al, 2012) and schizophrenia (Öngür et al, 2009). Moreover, the relationship between brain creatine and depression is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Relationship Between Depression, Prefrontal Creatine and Gray Matter Volume

Faulkner

Paioni

Kozhuharova

et al. 2021

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Background: Depression and low mood are leading contributors to disability worldwide. Research indicates that clinical depression may be associated with low creatine concentrations in the brain and low prefrontal gray matter volume. Because sub-clinical depression also contributes to difficulties in day-to-day life, understanding the neural mechanisms of depressive symptoms in all individuals, even at a sub-clinical level, may aid public health. Methods: Eighty-four young adult participants completed the Depression, Anxiety and Stress Scale (DASS) to quantify severity of depression, anxiety and stress, and underwent 1H-Magnetic Resonance Spectroscopy of the medial prefrontal cortex and structural MRI to determine whole-brain gray matter volume. Results/Outcomes: DASS depression scores were negatively associated with A) concentrations of creatine (but not other metabolites) in the prefrontal cortex, and B) with gray matter volume in the right superior medial frontal gyrus. Medial prefrontal creatine concentrations and right superior medial frontal gray matter volume were positively correlated. DASS anxiety and DASS stress scores were not related to prefrontal metabolite concentrations or whole-brain gray matter volume. Conclusions/Interpretations: This study provides preliminary evidence from a representative group of individuals who exhibit a range of depression levels, that prefrontal creatine and gray matter volume are negatively associated with depression. While future research is needed to fully understand this relationship, these results provide support for previous findings which indicate that increasing creatine concentrations in the prefrontal cortex may improve mood and wellbeing.

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The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study

et al. 2021

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Glutamatergic excitotoxicity is hypothesised to underlie synaptic loss in schizophrenia pathogenesis, but it is unknown whether synaptic markers are related to glutamatergic function in vivo. Additionally, it has been proposed that N-acetyl aspartate (NAA) levels reflect neuronal integrity. Here, we investigated whether synaptic vesicle glycoprotein 2 A (SV2A) levels are related to glutamatergic markers and NAA in healthy volunteers (HV) and schizophrenia patients (SCZ). Forty volunteers (SCZ n = 18, HV n = 22) underwent [11C]UCB-J positron emission tomography and proton magnetic resonance spectroscopy (1H-MRS) imaging in the left hippocampus and anterior cingulate cortex (ACC) to index [11C]UCB-J distribution volume ratio (DVR), and creatine-scaled glutamate (Glu/Cr), glutamate and glutamine (Glx/Cr) and NAA (NAA/Cr). In healthy volunteers, but not patients, [11C]UCB-J DVR was significantly positively correlated with Glu/Cr, in both the hippocampus and ACC. Furthermore, in healthy volunteers, but not patients, [11C]UCB-J DVR was significantly positively correlated with Glx/Cr, in both the hippocampus and ACC. There were no significant relationships between [11C]UCB-J DVR and NAA/Cr in the hippocampus or ACC in healthy volunteers or patients. Therefore, an appreciable proportion of the brain 1H-MRS glutamatergic signal is related to synaptic density in healthy volunteers. This relationship is not seen in schizophrenia, which, taken with lower synaptic marker levels, is consistent with lower levels of glutamatergic terminals and/or a lower proportion of glutamatergic relative to GABAergic terminals in the ACC in schizophrenia.

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Daily and Intermittent Smoking Decrease Gray Matter Volume and Concentrations of Glutamate, Creatine, Myo-Inositol andN-acetylaspartate in the Prefrontal Cortex

Cited by 3 publications

References 51 publications

Prefrontal cortex and putamen grey matter alterations in cannabis and tobacco users

Prefrontal cortex and putamen grey matter alterations in cannabis and tobacco users

Relationship Between Depression, Prefrontal Creatine and Gray Matter Volume

The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study

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