Macrophage migration inhibitory factor (MIF) gene is associated with adolescents’ cortisol reactivity and anxiety

Lipschutz, Rebecca; Bick, Johanna; Nguyen, Victoria; Lee, Maria; Leng, Lin; Grigorenko, Elena L.; Bucala, Richard; Mayes, Linda C.; Crowley, Michael J.

doi:10.1016/j.psyneuen.2018.05.033

Cited by 7 publications

(3 citation statements)

References 45 publications

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“…In addition, camphor, α-pinene, linalool, and methyl eugenol have high a nity for EP300, MIF, and leucine rich repeat kinase 2 (LRRK2) targets. Furthermore, EP300 [38], MIF [39], and LRRK2 [40] have been con rmed to be associated with anxiety (Fig. S1), thus indicating that the above components and targets are signi cantly related to anxiety and are worthy of further investigation.…”

Section: Discussionmentioning

confidence: 93%

Mechanism Underlying the Anxiolytic Effect of Cinnamomum Camphora Chvar. Borneol Essential Oil Revealed by Network Pharmacology

Xiao

Xie

et al. 2021

Preprint

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Background: Anxiety disorder, the most common mental health issue, can cause palpitations, fear, and compulsive behavior, and can severely endanger human health. Most drugs to treat anxiety disorder can cause a variety of side effects, therefore, it is important to seek natural and safe complementary and alternative therapies.Methods: The open field (OF), elevated plus maze (EPM), and light-dark box (LDB) tests were used to confirm the anxiolytic effect of BEO in mice. Further, we constructed a component-target-signaling pathway network and a protein-protein interaction (PPI) network for the regulation of anxiety by BEO through pharmacological network analyses, and performed Gene Ontology (GO) enrichment analyses of BEO targets, and analyzed the active components and targets of BEO through molecular docking.Results: In the OF test, BEO significantly prolonged the time spent by the mice in the central area (p < 0.05), in a dose dependent manner (r = 0.9992), and also significantly increased the number of central area entries (p < 0.01). In the EPM test, BEO significantly increased the time spent in the open arms (p < 0.01) and the number of entries into the open arms (p < 0.01) in a dose-dependent manner (r = 0.9733, r = 0.9669). In the LDB tests, BEO significantly increased the light area duration (p < 0.05) and the transition number (p < 0.01) in a dose-dependent manner (r = 0.9166, r = 0.9572), thus confirming its anxiolytic effect. Network pharmacology results showed that 33 active components in BEO acted on 54 targets, mainly through modulation of neuroactive ligand-receptor interactions, G-protein coupled receptor signaling pathways, and RNA polymerase II transcription factor activity. PPI network analysis identified 48 key proteins, including estrogen receptor 1 (ESR1), androgen receptor (AR), and mitogen-activated protein kinase 8 (MAPK8). Molecular docking results showed that the main active components of BEO are borneol, β-caryophyllene, α-cadinol, limonene, and α- selinene, which act on the key targets CNR2, ADRA2B, and ADORA2A.Conclusion: Our results indicated that BEO has multi-component, multi-target, and multi-pathway characteristics, thus providing a theoretical basis for further research on the mechanism of action of BEO as a potential anxiolytic agent.

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Section: Discussionmentioning

confidence: 93%

Mechanism Underlying the Anxiolytic Effect of Cinnamomum Camphora Chvar. Borneol Essential Oil Revealed by Network Pharmacology

Xiao

Xie

et al. 2021

Preprint

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“…No differences in the expression of MIF mRNA in drug-free MDD were found [ 54 ]. A genetic study in the adolescent group revealed the association of MIF polymorphisms with anxiety and attenuated cortisol reactivity [ 55 ]. Patients from a randomized controlled trial compared mindfulness-based therapy with treatment as usual, with different psychiatric diagnoses: depression, anxiety, or stress and adjustment disorders were included.…”

Section: Discussionmentioning

confidence: 99%

Elevated Epidermal Growth Factor (EGF) as Candidate Biomarker of Mood Disorders—Longitudinal Study in Adolescent and Young Adult Patients

Skibińska

Kapelski

Dmitrzak‐Węglarz

et al. 2021

JCM

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Bipolar disorder (BD) is a chronic mental disorder that affects more than 1% of the population worldwide. Over 65% of patients experience early onset of the disease. Most cases of juvenile bipolar disorder begin with a depressed mood episode, and up to 50% of youth initially diagnosed with major depression go onto developing a BD. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a two-year follow-up study on 79 adolescent patients diagnosed with MDD or BD, with a detailed clinical assessment at five visits. We monitored diagnosis change from MDD to BD. The control group consisted of 31 healthy youths. According to the neurodevelopmental and neuroimmunological hypotheses of mood disorders, we analyzed serum levels of brain-derived neurotrophic factor (BDNF), proBDNF, epidermal growth factor (EGF), migration inhibitory factor (MIF), stem cell factor (SCF), and correlations with clinical factors. We detected a significant disease-dependent increase in EGF level in MDD and BP patients at baseline exacerbation of depressive or hypomanic/manic episodes as well as in euthymic state compared to healthy controls. No potential biological predictors of disease conversion were found. Replication studies on a larger cohort of patients are needed.

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“…Recently, a macrophage-specific cytokine has been linked to anxiety. The macrophage migration inhibitory factor (MIF) is a pro-inflammatory macrophage-specific cytokine that is active in the HPA axis and characterized haplotype variants of that gene were linked to diminished expression and lowered adolescent anxiety disorder [8]. MIF has been linked to the recruitment of natural killer T cells via an IFN-γ gradient in skin lesions, thus suggesting a similar role in causing the migration and stimulation of inflammatory leucocytes in the HPA axis [9].…”

Section: Diaeventological Sources Of Gadmentioning

confidence: 99%

The Diaeventology of Anxiety Disorders

Guerra¹

2019

Anxiety Disorders - From Childhood to Adulthood

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Anxiety is a crippling neuropsychiatric condition that encompasses a complex endophenotypic network of genetic, immunological, epigenetic, and metabolic mechanisms, interacting with the environment. A new approach to complex biological systems, including mental states and their neurological correlates, is diaeventology, a paradigm that exposes the event ontologies of these biomolecular/cellular mechanisms. General anxiety disorder has been studied in subclinical and clinical research settings where evidence is obtained for a longitudinal patterning of chronic and episodic and often increasingly stressful life events that provide the etiology and development of the pathology. Early events that involve brain oxygen deprivation coupled with carbon dioxide abundance are linked to biochemical and epigenetic processes associated with anxiety instantiation. A verified analysis of the current evidence suggests a neuroimmune mechanism that aligns with stress pathophysiology and epigenetic re-tailoring of key genomic loci that inappropriately compensate and misdirect biological defense mechanisms toward central nervous system dysfunction presenting as anxiety disorders.

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Macrophage migration inhibitory factor (MIF) gene is associated with adolescents’ cortisol reactivity and anxiety

Cited by 7 publications

References 45 publications

Mechanism Underlying the Anxiolytic Effect of Cinnamomum Camphora Chvar. Borneol Essential Oil Revealed by Network Pharmacology

Mechanism Underlying the Anxiolytic Effect of Cinnamomum Camphora Chvar. Borneol Essential Oil Revealed by Network Pharmacology

Elevated Epidermal Growth Factor (EGF) as Candidate Biomarker of Mood Disorders—Longitudinal Study in Adolescent and Young Adult Patients

The Diaeventology of Anxiety Disorders

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