Prefrontal cortex neural activity predicts reduction of non-suicidal self-injury in adolescents with major depressive disorder: An event related potential study

Liu, Huishan; Wen, Yujiao; Liang, Xinmiao; Xu, Yifan; Qiao, Dan; Yang, Chunxia; Han, Min; Li, Hong; Tian, Rong; Zhang, Xuemin; Li, Gaizhi; Liu, Zhifen

doi:10.3389/fnins.2022.972870

Cited by 2 publications

(2 citation statements)

References 46 publications

(51 reference statements)

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“…Activity dependent changes in myelin, including regulation of oligodendrocytes by BDNF and neurotransmitters, has also been described ( Monje, 2018 ; Xin and Chan, 2020 ). Increased myelination in the prefrontal cortex correlates with depression ( Liu et al, 2022 ). Most notably, a recent study in humans and animals found that increased myelin in the amygdala was associated with PTSD susceptibility and correlated with fear conditioning in animals ( Long et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA

Warner-Schmidt,

Stogniew,

Mandell

et al. 2024

Front. Neurosci.

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BackgroundPost-traumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. Available pharmacotherapies are limited, take weeks to show modest benefit and remain ineffective for up to 40% of patients. Methylone is currently in clinical development for the treatment of PTSD. Preclinical studies show rapid, robust and long-lasting antidepressant-like and anxiolytic effects. The mechanism of action underlying these effects is not yet fully understood. This study investigated the downstream gene expression changes and signaling pathways affected by methylone in key brain areas linked to PTSD and MDD. It also sought to determine whether neuroplasticity-related genes were involved. We compared effects of methylone with MDMA to explore similarities and differences in their brain effects because MDMA-assisted psychotherapy has recently shown benefit in clinical trials for PTSD and methylone is a structural analog of MDMA.MethodsMonoamine binding, uptake and release studies were performed and a high-throughput-screen evaluated agonist/antagonist activities at 168 GPCRs in vitro. We used RNA sequencing (RNA-seq) to probe drug-induced gene expression changes in the amygdala and frontal cortex, two brain areas responsible for emotional learning that are affected by PTSD and MDD. Rats were treated with methylone or MDMA (both 10 mg/kg, IP), and their responses were compared with controls. We performed functional enrichment analysis to identify which pathways were regulated by methylone and/or MDMA. We confirmed changes in gene expression using immunohistochemistry.ResultsMethylone, a monoamine uptake inhibitor and releaser, demonstrated no off-target effects at 168 GPCRs, unlike MDMA, which showed activity at 5HT2A and 5HT2C receptors. RNA-seq results revealed significant regulation of myelin-related genes in the amygdala, confirmed by immunohistochemistry. In the frontal cortex, methylone significantly upregulated genes implicated in neuroplasticity.ConclusionResults suggest that (1) methylone is a rapid-acting neuroplastogen that affects key brain substrates for PTSD and MDD and that (2) methylone appears to exhibit higher specificity and fewer off-target effects than MDMA. Together, these results are consistent with the reported clinical experiences of methylone and MDMA and bolster the potential use of methylone in the treatment of PTSD and, potentially, other neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA

Warner-Schmidt,

Stogniew,

Mandell

et al. 2024

Front. Neurosci.

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“…In recent years, there has been a growing interest in investigating the pathogenesis of adolescent depression using functional magnetic resonance imaging (fMRI). Previous studies showed that the prefrontal cortex may play a crucial role in regulating emotional responses ( 7 ), and abnormal functional connectivity (FC) in this brain region may be closely related to NSSI behavior ( 8 ). However, limited research has been conducted on the correlation between altered FC in the prefrontal cortex and NSSI among adolescents with depression.…”

Section: Introductionmentioning

confidence: 99%

A study on the association between prefrontal functional connectivity and non-suicidal self-injury in adolescents with depression

Guo,

Lu,

et al. 2024

Front. Neurol.

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ObjectiveAmong adolescents with depression, the occurrence of non-suicidal self-injury (NSSI) behavior is prevalent, constituting a high-risk factor for suicide. However, there has been limited research on the neuroimaging mechanisms underlying adolescent depression and NSSI behavior, and the potential association between the two remains unclear. Therefore, this study aims to investigate the alterations in functional connectivity (FC) of the regions in the prefrontal cortex with the whole brain, and elucidates the relationship between these alterations and NSSI behavior in adolescents with depression.MethodsA total of 68 participants were included in this study, including 35 adolescents with depression and 33 healthy controls. All participants underwent assessments using the 17-item Hamilton Depression Rating Scale (17-HAMD) and the Ottawa Self-Harm Inventory. In addition, functional magnetic resonance imaging (fMRI) data of the participants’ brains were collected. Subsequently, the FCs of the regions in the prefrontal cortex with the whole brain was calculated. The FCs showing significant differences were then subjected to correlation analyses with 17-HAMD scores and NSSI behavior scores.ResultCompared to the healthy control group, the adolescent depression group exhibited decreased FCs in several regions, including the right frontal eye field, left dorsolateral prefrontal cortex, right orbitofrontal cortex, left insula and right anterior cingulate coetex. The 17-HAMD score was positively correlated with the frequency of NSSI behavior within 1 year (rs = 0.461, p = 0.005). The FC between the right anterior cingulate cortex and the right precuneus showed a negative correlation with the 17-HAMD scores (rs = −0.401, p = 0.023). Additionally, the FC between the right orbitofrontal cortex and the right insula, demonstrated a negative correlation with the frequency of NSSI behavior within 1 year (rs = −0.438, p = 0.012, respectively).ConclusionAdolescents with depression showed decreased FCs of the prefrontal cortex with multiple brain regions, and some of these FCs were associated with the NSSI frequency within 1 year. This study provided neuroimaging evidence for the neurophysiological mechanisms underlying adolescent depression and its comorbidity with NSSI behavior.

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Prefrontal cortex neural activity predicts reduction of non-suicidal self-injury in adolescents with major depressive disorder: An event related potential study

Cited by 2 publications

References 46 publications

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA

A study on the association between prefrontal functional connectivity and non-suicidal self-injury in adolescents with depression

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