White matter alterations in chronic MDMA use: Evidence from diffusion tensor imaging and neurofilament light chain blood levels

Zimmermann, Josua; Friedli, Nicole; Bavato, Francesco; Stämpfli, Philipp; Coray, Rebecca; Baumgartner, Markus R.; Grandgirard, Denis; Leib, Stephen L.; Opitz, Antje; Seifritz, Erich; Stock, Ann‐Kathrin; Beste, Christian; Cole, David M.; Quednow, Boris B.

doi:10.1016/j.nicl.2022.103191

Cited by 11 publications

(3 citation statements)

References 90 publications

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“…Users of ketamine ( 37 ) and cocaine ( 38 ), psychoactive drugs associated with cognitive deficits and brain structure alterations, may have increased blood levels of NfL. In contrast, the use of ecstasy does not seem to affect NfL ( 39 ). In the present study, a substance use disorder diagnosis was present in 50 and 65% of the patients in the assessment and hospital groups, respectively.…”

Section: Discussionmentioning

confidence: 99%

Plasma neurofilament light chain protein is not increased in forensic psychiatric populations: a pilot study

et al. 2023

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IntroductionNeurofilament light chain protein (NfL) is a fluid biomarker of neural injury measurable in cerebrospinal fluid and blood. Patients with different neurodegenerative disorders and mild traumatic brain injury display elevated levels of NfL. However, so far, elevated levels of NfL have not been demonstrated in persons with psychiatric disorders. To our knowledge, the occurrence of NfL in the blood has not previously been studied in persons undergoing forensic psychiatric assessment or persons treated in forensic mental health services. Supposedly, these persons suffer from experiences and conditions with a higher risk of neural injury than other psychiatric patients.MethodsIn this pilot study, we investigated plasma levels of NfL in 20 persons undergoing forensic psychiatric assessment and 20 patients at a forensic psychiatric hospital. NfL values were compared with control groups of healthy individuals matched for age and sex.ResultsThe prevalence of increased NfL in both forensic groups was low and did not differ compared with the controls. However, some persons undergoing forensic psychiatric assessment showed slightly elevated values.DiscussionThe slightly elevated values were observed in the group investigated closer in time to the index crime, when elevated NfL levels could be expected to be more prevalent due to acute conditions from the time of the offense. This gives reason to look further into this group.

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Section: Discussionmentioning

confidence: 99%

Plasma neurofilament light chain protein is not increased in forensic psychiatric populations: a pilot study

et al. 2023

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“…In total, 49 chronic MDMA users and 47 MDMA‐naïve healthy controls (age: 18–45 years) were recruited for this cross‐sectional case–control study. Diffusion tensor imaging, quantitative susceptibility mapping, and substance use data from this sample have been published before (Zimmermann et al, 2022). The groups were matched regarding age, sex, verbal intelligence, years of education, and smoking status.…”

Section: Methodsmentioning

confidence: 99%

The functional connectome of 3,4‐methyldioxymethamphetamine‐related declarative memory impairments

Coray,

Zimmermann,

Haugg

et al. 2023

Human Brain Mapping

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The chronic intake of 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) bears a strong risk for sustained declarative memory impairments. Although such memory deficits have been repeatedly reported, their neurofunctional origin remains elusive. Therefore, we here investigate the neuronal basis of altered declarative memory in recurrent MDMA users at the level of brain connectivity. We examined a group of 44 chronic MDMA users and 41 demographically matched controls. Declarative memory performance was assessed by the Rey Auditory Verbal Learning Test and a visual associative learning test. To uncover alterations in the whole brain connectome between groups, we employed a data‐driven multi‐voxel pattern analysis (MVPA) approach on participants' resting‐state functional magnetic resonance imaging data. Recent MDMA use was confirmed by hair analyses. MDMA users showed lower performance in delayed recall across tasks compared to well‐matched controls with moderate‐to‐strong effect sizes. MVPA revealed a large cluster located in the left postcentral gyrus of global connectivity differences between groups. Post hoc seed‐based connectivity analyses with this cluster unraveled hypoconnectivity to temporal areas belonging to the auditory network and hyperconnectivity to dorsal parietal regions belonging to the dorsal attention network in MDMA users. Seed‐based connectivity strength was associated with verbal memory performance in the whole sample as well as with MDMA intake patterns in the user group. Our findings suggest that functional underpinnings of MDMA‐related memory impairments encompass altered patterns of multimodal sensory integration within auditory processing regions to a functional heteromodal connector hub, the left postcentral gyrus. In addition, hyperconnectivity in regions of a cognitive control network might indicate compensation for degraded sensory processing.

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“…Our recent work also reported elevated NfL levels in patients with chronic ketamine addiction, demonstrating its sensitivity to substance-related brain pathology [ 13 ]. However, NfL levels in chronic MDMA (“ecstasy”) users did not differ from levels in healthy participants [ 21 ]. The lack of white matter pathology in MDMA users from the same sample was also confirmed by diffusion tensor imaging measures.…”

Section: Introductionmentioning

confidence: 99%

A Longitudinal Investigation of Blood Neurofilament Light Chain Levels in Chronic Cocaine Users

et al. 2023

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The identification of a blood marker of brain pathology that is sensitive to substance-induced neurotoxicity and dynamically responds to longitudinal changes in substance intake would substantially improve clinical monitoring in the field of substance use and addiction. Here, we explored the hypothesis that plasma levels of neurofilament light chain (NfL), a promising marker of neuroaxonal pathology, are elevated in chronic cocaine users and longitudinally associated with changes in cocaine use. Plasma NfL levels were determined using single molecule array (SIMOA) technology at baseline and at a 4-month follow-up. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples. In a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in cocaine users (n=35) compared to stimulant-naïve healthy controls (n=35). A positive correlation between cocaine hair concentration and NfL levels was also found. Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up, indicating a rise in NfL with increased cocaine use and a reduction with decreased use. No associations between use or change of use of other substances (including the neurotoxic cocaine adulterant levamisole) and NfL levels were found. Our findings demonstrate that NfL is a sensitive marker for assessing cocaine-related neuroaxonal pathology, supporting the utility of blood NfL analysis in addiction research but also suggesting the detailed assessment of substance use in neurological studies and diagnostics.

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White matter alterations in chronic MDMA use: Evidence from diffusion tensor imaging and neurofilament light chain blood levels

Cited by 11 publications

References 90 publications

Plasma neurofilament light chain protein is not increased in forensic psychiatric populations: a pilot study

Plasma neurofilament light chain protein is not increased in forensic psychiatric populations: a pilot study

The functional connectome of 3,4‐methyldioxymethamphetamine‐related declarative memory impairments

A Longitudinal Investigation of Blood Neurofilament Light Chain Levels in Chronic Cocaine Users

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