Comorbidity of ketamine dependence with major depressive disorder increases the vulnerability to neuroaxonal pathology

Huang, Ming‐Chyi; Chen, Chun-Hsin; Liu, Tung‐Hsia; Chung, Albert E.; Liu, Yuli; Quednow, Boris B.; Bavato, Francesco

doi:10.1016/j.jpsychires.2023.01.009

Cited by 12 publications

(6 citation statements)

References 33 publications

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“…Higher NfL levels have previously been described in patients with MDD, in patients with bipolar disorder, and in a sample of treatmentseeking ketamine users with a history of MDD [13,14,40]. An interaction between affective disorders and substance use in increasing the vulnerability to brain pathology has also been described, and disturbed activity of neurotrophic factors has been postulated as shared mechanism [41,42]. However, in the present study, we specifically excluded subjects with history of bipolar disorder or current major depressive episodes.…”

Section: Discussionmentioning

confidence: 96%

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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Section: Discussionmentioning

confidence: 96%

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

et al. 2023

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“…The evidence was constrained by the quality and heterogeneity of included studies. Controls were not consistently age- and sex-matched (6,18), and some studies lacked control subjects (41,42,51). The limited number of studies and data precluded adequate adjustment for known covariates of NfL and GFAP, such as age, sex, weight/BMI, and renal function (2).…”

Section: Discussionmentioning

confidence: 99%

“…Those with major depression exhibited significantly higher concentrations of baseline CSF NfL compared to the rest of the group (major depression mean: 427 ± 186 vs control mean: 277 ± 186 ng/L), whilst there was no difference in the GFAP concentrations (major depression mean: 946 ± 196 vs control: 887 ± 308 ng/L). Subsequent studies comparing blood NfL and GFAP in mood disorders to healthy controls have yielded mixed findings, either finding elevated concentrations in mood disorders (15–17), or no difference (6,18).…”

Section: Introductionmentioning

confidence: 99%

Neurofilament light and glial fibrillary acidic protein in mood and anxiety disorders: A systematic review and meta-analysis

Kang,

Grewal,

Eratne

et al. 2024

Preprint

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BackgroundNeurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal injury measurable in cerebrospinal fluid (CSF) and blood. Despite their potential as diagnostic tests for neurodegenerative disorders, it is unclear how they behave in mood and anxiety disorders. We conducted a systematic review and meta-analysis to investigate whether NfL and GFAP concentrations were altered in adults with mood and anxiety disorders compared to healthy controls.MethodsThe study was prospectively registered on PROSPERO (CRD42023434617). We followed the PRISMA guidelines, searched PubMed, Web of Science, PsycINFO, MEDLINE and Embase up to the 31/05/2023, and assessed relevant studies and their risk of bias. The primary outcome was the standardised mean difference (SMD) and 95% confidence interval (95% CI) of NfL and GFAP concentrations, which was pooled using a random-effects model adopting the restricted maximum likelihood estimator.ResultsTwenty-one studies met inclusion criteria, comprising of 2327 individuals (695 major depression, 502 bipolar disorder, and 1130 controls). When we compared people with major depression and controls, there was no difference in NfL (SMD = 0.29; 95% CI: -0.10, 0.68) nor GFAP (SMD = 0.47; 95% CI: -0.74, 1.68). In people with bipolar disorder, NfL was significantly elevated compared to controls (SMD = 0.58; 95% CI: 0.16, 0.99). However, the subgroup analysis including more sensitive assay kits (blood Simoa and CSF ELISA), found no significant difference (SMD = 0.40; 95% CI: -0.04, 0.85). Only one study studied GFAP in bipolar disorder. No studies explored NfL nor GFAP concentrations in anxiety disorders.DiscussionWe found that NfL and GFAP concentrations were not elevated in depression. In bipolar disorder, NfL concentration was elevated, though not in the sensitivity analysis. Our study informs clinicians about how to interpret these emerging biomarkers in determining whether a person’s symptoms are caused by a neurodegenerative or mood disorder.

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“…Previous studies about NfL levels in MDD patients have revealed inconsistent findings. Some of them have shown increased peripheral NfL concentration in patients with MDD compared with health control; however, others did not find the difference, especially in cognitively unimpaired MDD sample [ 36 – 38 ]. Two studies have further reported the association of NfL levels with executive function and processing speed in MDD patients [ 37 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association with neurofilament light chain

Chen,

Chiu,

Huang

et al. 2024

BMC Geriatr

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Background Cognitive impairment is a growing problem with increasing burden in global aging. Older adults with major depressive disorder (MDD) have higher risk of dementia. Neurofilament light chain (NfL) has been proven as a potential biomarker in neurodegenerative disease, including dementia. We aimed to investigate the association between cognitive deficits and NfL levels in older adults with MDD. Methods In this cross-sectional study, we enrolled 39 MDD patients and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer’s type, as controls, from a tertiary psychiatric hospital. Both groups were over age 65 and with matched Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and each cognitive domain. Results In the MDD group, participants had higher rate of family psychiatry history and current alcohol use habit compared with controls. Control group of neurocognitive disorders showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits clustered with that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster. Conclusions We noted the negative correlation between NfL levels and cognition in MDD patients clustered with neurodegenerative disorder, Alzheimer’s type. NfL could be a promising candidate as a biomarker to predict subtype of patients in MDD to develop cognitive decline. Further longitudinal studies and within MDD cluster analysis are required to validate our findings for clinical implications.

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Comorbidity of ketamine dependence with major depressive disorder increases the vulnerability to neuroaxonal pathology

Cited by 12 publications

References 33 publications

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

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

Neurofilament light and glial fibrillary acidic protein in mood and anxiety disorders: A systematic review and meta-analysis

Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association with neurofilament light chain

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