Association between DRD2/ANKK1 rs1800497 C &gt; T polymorphism and post-traumatic stress disorder susceptibility: a multivariate meta-analysis

Niu, Yu‐Ming; Zhang, Jie; Tang, Hong; Cao, L.; Jiang, Tian; Hu, Yuanyuan

doi:10.3389/fnins.2023.1102573

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…Our results also revealed that the most highly significantly downregulated gene by methylone was Ankyrin Repeat and Kinase Domain Containing 1 (Ankk1), which regulates dopamine synthesis and has been associated with PTSD susceptibility ( Niu et al, 2023 ).…”

Section: Resultsmentioning

confidence: 68%

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: Resultsmentioning

confidence: 68%

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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“…This polymorphism has been associated with the regulation of dopamine synthesis and reduced D2 receptor expression in the brain, which forms the pathophysiological basis for various PTSD symptoms. The rs1800497 polymorphism has been shown to contribute to the severity of PTSD symptoms, and individuals with the A1 allele are more likely to develop PTSD following trauma exposure [ 42 ].…”

Section: Catalytic Factors Associated With Ptsdmentioning

confidence: 99%

Assessing and Modelling of Post-Traumatic Stress Disorder Using Molecular and Functional Biomarkers

Skolariki

Vrahatis

Krokidis

et al. 2023

Biology

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Post-traumatic stress disorder (PTSD) is a complex psychological disorder that develops following exposure to traumatic events. PTSD is influenced by catalytic factors such as dysregulated hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter imbalances, and oxidative stress. Genetic variations may act as important catalysts, impacting neurochemical signaling, synaptic plasticity, and stress response systems. Understanding the intricate gene networks and their interactions is vital for comprehending the underlying mechanisms of PTSD. Focusing on the catalytic factors of PTSD is essential because they provide valuable insights into the underlying mechanisms of the disorder. By understanding these factors and their interplay, researchers may uncover potential targets for interventions and therapies, leading to more effective and personalized treatments for individuals with PTSD. The aforementioned gene networks, composed of specific genes associated with the disorder, provide a comprehensive view of the molecular pathways and regulatory mechanisms involved in PTSD. Through this study valuable insights into the disorder’s underlying mechanisms and opening avenues for effective treatments, personalized interventions, and the development of biomarkers for early detection and monitoring are provided.

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“…It has been demonstrated that rs1800497 influences striatal D2 receptor availability [30] and DRD2 expression [31], but ANKK1 itself may function in dopaminergic pathways [32]. Rs1800497 T is reported to be a risk allele for mood disorders, addictions, and post-traumatic stress disorder (PTSD) [33,34].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis

Mikhailova,

Ivanoshchuk,

Orlov

et al. 2023

Genes

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Background: A socioeconomic crisis in Russia lasted from 1991 to 1998 and was accompanied by a sharp drop in the birth rate. The main factor that influenced the refusal to have children during this period is thought to be prolonged social stress. Methods: comparing frequencies of common gene variants associated with stress-induced diseases among generations born before, after, and during this crisis may show which genes may be preferred under the pressure of natural selection during periods of increased social stress in urban populations. Results: In the “crisis” group, a statistically significant difference from the other two groups was found in rs6557168 frequency (p = 0.001); rs4522666 was not in the Hardy–Weinberg equilibrium in this group, although its frequency did not show a significant difference from the other groups (p = 0.118). Frequencies of VNTRs in SLC6A3 and MAOA as well as common variants rs17689918 in CRHR1, rs1360780 in FKBP5, rs53576 in OXTR, rs12720071 and rs806377 in CNR1, rs4311 in ACE, rs1800497 in ANKK1, and rs7412 and rs429358 in APOE did not differ among the groups. Conclusions: a generation born during a period of prolonged destructive events may differ from the rest of the gene pool of the population in some variants associated with personality traits or stress-related disorders.

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Association between DRD2/ANKK1 rs1800497 C > T polymorphism and post-traumatic stress disorder susceptibility: a multivariate meta-analysis

Cited by 5 publications

References 42 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

Assessing and Modelling of Post-Traumatic Stress Disorder Using Molecular and Functional Biomarkers

Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis

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