Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis

Mojtabavi, Helia; Saghazadeh, Amene; Heuvel, Leigh van den; Bücker, Joana; Rezaei, Nima

doi:10.1371/journal.pone.0241928

Cited by 42 publications

(27 citation statements)

References 68 publications

(113 reference statements)

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“…Deficient or dysfunctional synthesis or secretion of BDNF has been implicated in the risk for several neuropsychiatric disorders, including major depression, anxiety disorders, and substance use disorders [55,68,69]. Notably, PTSD has been associated with elevated BDNF blood levels in at least 3 studies [70] while PTSD-like behavior in rats has been found to correlate with a reduction in Bdnf mRNA expression in the hippocampal CA1 region [71]. In humans, a polymorphism in the BDNF gene known to affect activity-dependent BDNF secretion [4] has been linked to increased risk for major depression [72], although the robustness of this association has recently been challenged [73].…”

Section: Clinical Implications and Directions For Future Researchmentioning

confidence: 99%

Robustly High Hippocampal BDNF levels under Acute Stress in Mice Lacking the Full-length p75 Neurotrophin Receptor

et al. 2021

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Background Brain-derived neurotrophic factor (BDNF) exerts its effects on neural plasticity via 2 distinct receptor types, the tyrosine kinase TrkB and the p75 neurotrophin receptor (p75NTR). The latter can promote inflammation and cell death while TrkB is critically involved in plasticity and memory, particularly in the hippocampus. Acute and chronic stress have been associated with suppression of hippocampal BDNF expression and impaired hippocampal plasticity. We hypothesized that p75NTR might be involved in the hippocampal stress response, in particular in stress-induced BDNF suppression, which might be accompanied by increased neuroinflammation. Method We assessed hippocampal BDNF protein concentrations in wild-type mice compared that in mice lacking the long form of the p75NTR (p75NTRExIII−/−) with or without prior exposure to a 1-hour restraint stress challenge. Hippocampal BDNF concentrations were measured using an optimized ELISA. Furthermore, whole-brain mRNA expression of pro-inflammatory interleukin-6 (Il6) was assessed with RT-PCR. Results Deletion of full-length p75NTR was associated with higher hippocampal BDNF protein concentration in the stress condition, suggesting persistently high hippocampal BDNF levels in p75NTR-deficient mice, even under stress. Stress elicited increased whole-brain Il6 mRNA expression irrespective of genotype; however, p75NTRExIII−/− mice showed elevated baseline Il6 expression and thus a lower relative increase. Conclusions Our results provide evidence for a role of p75NTR signaling in the regulation of hippocampal BDNF levels, particularly under stress. Furthermore, p75NTR signaling modulates baseline but not stress-related Il6 gene expression in mice. Our findings implicate p75NTR signaling as a potential pathomechanism in BDNF-dependent modulation of risk for neuropsychiatric disorders.

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Section: Clinical Implications and Directions For Future Researchmentioning

confidence: 99%

Robustly High Hippocampal BDNF levels under Acute Stress in Mice Lacking the Full-length p75 Neurotrophin Receptor

et al. 2021

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“…В исследованиях H. Mojtabavi и соавт. [66] было обнаружено повышение уровня нейротрофического фактора мозга (BDNF) в сыворотке крови у пациентов с ПТСР по сравнению со здоровым контролем. Авторы считают, что более высокие уровни BDNF у пациентов с ПТСР поддерживают гипотезу о том, что ПТСР является заболеванием, протекающим с нарушением процессов нейропластичности.…”

Section: биомаркеры птсрunclassified

Potential Biomarkers of Posttraumatic Stress Disorder

2021

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Background: although the search for biomarkers of mental disorders that is aimed at improving diagnosis, individualizing therapy based on knowledge of pathophysiological processes and preventing the development of mental illness is actively underway for endogenous mental disorders, the study of biological markers in non-endogenous mental disorders and posttraumatic stress disorder (PTSD) in particular has received much less attention. Aim: to analyze current state of research dedicated to genetic and biochemical biomarkers that can be used to identify high risk groups and clarify the diagnosis of PTSD. Material and method: keywords “biomarkers”, “post-traumatic stress disorder”, “pathogenesis” have been used to fi nd in PubMed articles published in 2010–2020. Conclusion: research methods for elucidating the mechanisms of PTSD are actively developing, however, the identifi cation of specifi c biomarkers (biochemical, molecular, genetic, epigenetic, neuroimaging, psychophysiological) is a complicated task. This complexity is associated with numerous pathogenic mechanisms of PTSD and frequent comorbidity with mental disorders (depression, anxiety) and somatic diseases, as well as lack of specifi city of detected biomarkers.

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“…Additionally, preclinical data show that chronic nicotine administration increases brain derived neurotrophic factor (BDNF) mRNA levels in the dentate gyrus, CA3, and CA1 subfields of the rat hippocampus [ 40 ]. Decreased levels of serum BDNF were found in PTSD [ 41 ], while a recent meta-analysis revealed higher plasma (not serum) BDNF levels in PTSD subjects [ 42 ] compared to controls. BDNF expressed in the limbic system highly moderates fear and stress responses [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

Moderating Effects of BDNF Genetic Variants and Smoking on Cognition in PTSD Veterans

et al. 2021

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Posttraumatic stress disorder (PTSD) is frequently associated with cognitive disturbances and high prevalence of smoking. This study evaluated cognition in war veterans with PTSD and control subjects, controlled for the effect of smoking and brain derived neurotrophic factor (BDNF) rs6265 and rs56164415 genotypes/alleles. Study included 643 male war veterans with combat related PTSD and 120 healthy controls. Genotyping was done by real time PCR. Cognitive disturbances were evaluated using the Positive and Negative Syndrome Scale (PANSS) cognition subscale and the Rey-Osterrieth Complex Figure (ROCF) test scores. Diagnosis (p < 0.001), BDNF rs56164415 (p = 0.011) and smoking (p = 0.028) were significant predictors of the cognitive decline in subjects with PTSD. BDNF rs56164415 T alleles were more frequently found in subjects with PTSD, smokers and non-smokers, with impaired cognition, i.e., with the higher PANSS cognition subscale scores and with the lower ROCF immediate recall test scores. Presence of one or two BDNF rs56164415 T alleles was related to cognitive decline in PTSD. The T allele carriers with PTSD had advanced cognitive deterioration in smokers and nonsmokers with PTSD, and worse short-term visual memory function. Our findings emphasize the role of the BDNF rs56164415 T allele and smoking in cognitive dysfunction in war veterans with PTSD.

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Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis

Cited by 42 publications

References 68 publications

Robustly High Hippocampal BDNF levels under Acute Stress in Mice Lacking the Full-length p75 Neurotrophin Receptor

Robustly High Hippocampal BDNF levels under Acute Stress in Mice Lacking the Full-length p75 Neurotrophin Receptor

Potential Biomarkers of Posttraumatic Stress Disorder

Moderating Effects of BDNF Genetic Variants and Smoking on Cognition in PTSD Veterans

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