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Frontiers in Psychiatry 2021Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce...
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies ( = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.
PubMed: 34566723
DOI: 10.3389/fpsyt.2021.724606 -
Frontiers in Neurology 2021Through a systematic review and meta-analysis of the literature we aimed to compare the levels of BDNF, NGF, NT-3, NT-4, and GDNF between human term and preterm...
Through a systematic review and meta-analysis of the literature we aimed to compare the levels of BDNF, NGF, NT-3, NT-4, and GDNF between human term and preterm infants, and investigate factors implicated in the variability of effect size estimates. The analysis was performed in three online databases, MEDLINE Complete, PsycINFO, and CINAHL. A random effects model was used to calculate the standardized mean difference (SMD) of neurotrophic factor levels in preterm infants vs. term within a 95% confidence interval (CI). To explore sources of heterogeneity meta-regression models were implemented. Sixteen studies were included in this meta-analysis. A combined sample of 1,379 preterm and 1,286 term newborns were evaluated. We identified significant lower BDNF (SMD = -0.32; 95% CI: -0.59, -0.06; = 0.014) and NT-3 (SMD = -0.31; 95% CI: -0.52, -0.09; = 0.004) levels in preterm compared to term infants. No significant difference was observed in NGF and NT-4 levels between groups. Given that only two effect sizes were generated for GDNF levels, no meta-analytical model was performed. Meta-regression models revealed sample type (placental tissue, cerebrospinal fluid, peripheral blood, and umbilical cord blood) as a significant moderator of heterogeneity for BDNF meta-analysis. No significant associations were found for gestational week, birth weight, and clinical comorbidity of newborns with effect sizes. Our findings indicated that lower BDNF and NT-3 levels may be associated with preterm birth. Future studies with larger samples sizes should investigate neurodevelopmental manifestations resulting from neurotrophic factor dysregulation among preterm infants.
PubMed: 33868149
DOI: 10.3389/fneur.2021.643576 -
Neuroscience and Biobehavioral Reviews Apr 2023Epigenomic modifications of the brain-derived neurotrophic factor (BDNF) gene have been postulated to underlie the pathogenesis of neurodevelopmental, psychiatric, and... (Review)
Review
Epigenomic modifications of the brain-derived neurotrophic factor (BDNF) gene have been postulated to underlie the pathogenesis of neurodevelopmental, psychiatric, and neurological conditions. This systematic review summarizes current evidence investigating the association of BDNF epigenomic modifications (DNA methylation, non-coding RNA, histone modifications) with brain-related phenotypes in humans. A novel contribution is our creation of an open access web-based application, the BDNF DNA Methylation Map, to interactively visualize specific positions of CpG sites investigated across all studies for which relevant data were available. Our literature search of four databases through September 27, 2021 returned 1701 articles, of which 153 met inclusion criteria. Our review revealed exceptional heterogeneity in methodological approaches, hindering the identification of clear patterns of robust and/or replicated results. We summarize key findings and provide recommendations for future epigenomic research. The existing literature appears to remain in its infancy and requires additional rigorous research to fulfill its potential to explain BDNF-linked risk for brain-related conditions and improve our understanding of the molecular mechanisms underlying their pathogenesis.
Topics: Humans; Brain; Brain-Derived Neurotrophic Factor; DNA Methylation; Epigenomics; Phenotype
PubMed: 36764636
DOI: 10.1016/j.neubiorev.2023.105078 -
PloS One 2023Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor expressed in several tissues, including the brain, gut, and pancreas. Activation of the BDNF/TrkB/CREB... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor expressed in several tissues, including the brain, gut, and pancreas. Activation of the BDNF/TrkB/CREB reduces hepatic gluconeogenesis, induces hepatic insulin signal transduction, and protects against pancreatic beta-cell loss in diabetes mellitus (DM). Several studies have investigated the possible association between BDNF and DM and its complications, but the results have been conflicting.
AIM
In the present study, we aimed at systematically reviewing the literature on the serum and plasma levels of BDNF in DM and its subgroups such as T2DM, DM patients with depression, and patients with retinopathy.
METHODS
A comprehensive search was conducted in PubMed, Scopus, and Web of Science. We identified 28 eligible studies and calculated the standardized mean difference (SMD) of outcomes as an effect measure.
RESULTS
The meta-analysis included 2734 patients with DM and 6004 controls. Serum BDNF levels were significantly lower in patients with DM vs. controls (SMD = -1.00, P<0.001). Plasma BDNF levels were not different in patients with DM compared with controls. When conducting subgroup analysis, serum BDNF levels were lower among patients with T2DM (SMD = -1.26, P<0.001), DM and depression (SMD = -1.69, P<0.001), and patients with diabetic retinopathy (DR) vs. controls (SMD = -1.03, P = 0.01).
CONCLUSIONS
Serum BDNF levels were lower in patients with DM, T2DM, DM with depression, and DM and DR than the controls. Our findings are in line with the hypothesis that decreased BDNF levels might impair glucose metabolism and contribute to the pathogenesis of DM and its complications.
Topics: Humans; Brain-Derived Neurotrophic Factor; Diabetic Retinopathy; Transforming Growth Factor beta; Diabetes Mellitus, Type 2
PubMed: 36787304
DOI: 10.1371/journal.pone.0268816 -
BMC Geriatrics Jul 2022Multicomponent physical exercise is the most recommended type of physical intervention in older adults. Experimental data suggest the relevance of the muscle-brain axis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multicomponent physical exercise is the most recommended type of physical intervention in older adults. Experimental data suggest the relevance of the muscle-brain axis and the relationship between muscle contraction and release of brain-derived neurotrophic factor, however, the impact of this relationship on cognition remains unclear, especially in people with diagnosis of cognitive impairment. This study assesses the effect of multicomponent physical exercise on global cognition in people with mild cognitive impairment or dementia.
METHODS
Randomized controlled trials published until January 2021 were searched across three electronic databases (PubMed, Scopus, and Cochrane Database). Data about exercises included in the multicomponent intervention (endurance, strength, balance, or flexibility), the inclusion of aerobic exercise, and the change in global cognition were extracted. The effect size was represented as a standardized mean difference. Risk of bias was assessed by the RoB2 tool.
RESULTS
A total of 8 studies were included. The overall effect size suggested an effect of multicomponent exercise on global cognition. However, the subgroup analysis showed an effect only when aerobic exercise was included in the intervention. No effect when mild cognitive impairment and dementia were assessed separately was found.
CONCLUSION
This study suggests that multicomponent physical exercise could have an effect on global cognition in people with mild cognitive impairment or dementia only when aerobic exercise is included in the intervention. Our results support the inclusion of structured physical exercise programs in the management of people with cognitive impairment.
Topics: Aged; Cognition; Cognitive Dysfunction; Dementia; Exercise; Exercise Therapy; Humans
PubMed: 35879665
DOI: 10.1186/s12877-022-03302-1 -
Journal of Sport and Health Science Mar 2023This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription. (Meta-Analysis)
Meta-Analysis Review
Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.
METHODS
A systematic search for relevant studies was performed in 3 databases. Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included: adiponectin, apelin, brain-derived neurotrophic factor, fetuin-A, fibroblast growth factor-21, follistatin, ghrelin, interleukin (IL)-6, IL-8, IL-10, IL-15, IL-18, leptin, myostatin, omentin, resistin, retinol-binding protein 4, tumor necrosis factor-α, and visfatin.
RESULTS
Forty randomized controlled trials were selected for data extraction (n = 2160). Exercise training induces changes in adiponectin, fetuin-A, fibroblast growth factor-21, IL-6, IL-10, leptin, resistin, and tumor necrosis factor-α levels but has no significant effects on apelin, IL-18, and ghrelin compared to controls. Physical exercise training favored large and positive changes in pooled exerkines (i.e., an overall effect size calculated from several exerkines) (Hedge's g = 1.02, 95% confidence interval (95%CI): 0.76-1.28), which in turn were related to changes in glycated hemoglobin (mean difference (MD) = -0.81%, 95%CI: -0.95% to -0.67%), fasting glucose (MD = -23.43 mg/dL, 95%CI: -30.07 mg/dL to -16.80 mg/dL), waist circumference (MD = -3.04 cm, 95%CI: -4.02 cm to -2.07 cm), and body mass (MD = -1.93 kg, 95%CI: -2.00 kg to -1.86 kg). Slightly stronger effects were observed with aerobic, resistance, or high-intensity interval protocols at moderate- to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.
CONCLUSION
Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.
Topics: Humans; Diabetes Mellitus, Type 2; Resistin; Apelin; Leptin; Ghrelin; Interleukin-10; Interleukin-18; Adiponectin; alpha-2-HS-Glycoprotein; Tumor Necrosis Factor-alpha; Randomized Controlled Trials as Topic; Exercise; Fibroblast Growth Factors
PubMed: 36351545
DOI: 10.1016/j.jshs.2022.11.003 -
PloS One 2023Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM.
METHODS
A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant studies assessing BDNF levels or gene polymorphism in patients with FM and comparing them with controls were included. Case reports, reviews, and non-English studies were excluded. We conducted the random-effect meta-analysis to estimate the pooled standardized mean difference (SMD) or odds ratio (OR) and 95% confidence interval (CI).
RESULTS
Twenty studies were found to be included composed of 1,206 FM patients and 1,027 controls. The meta-analysis of 15 studies indicated that the circulating BDNF levels were significantly higher in FM (SMD 0.72, 95% CI 0.12 to 1.31; p-value = 0.02). However, no difference between the rate of Val/Met carrier status at the rs6265 site was found (p-value = 0.43). Using meta-regression, the sample size and age variables accounted for 4.69% and 6.90% of the observed heterogeneity of BDNF level analysis, respectively.
CONCLUSION
Our meta-analysis demonstrated that FM is correlated with increased peripheral BDNF levels. This biomarker's diagnostic and prognostic value should be further investigated in future studies.
Topics: Humans; Biomarkers; Brain-Derived Neurotrophic Factor; Cognitive Dysfunction; Fibromyalgia; Polymorphism, Genetic
PubMed: 38127937
DOI: 10.1371/journal.pone.0296103 -
Cureus Sep 2023The prevalence of cannabis use disorders has become a noteworthy global public health issue. Understanding the neurobiological factors associated with cannabis use... (Review)
Review
The prevalence of cannabis use disorders has become a noteworthy global public health issue. Understanding the neurobiological factors associated with cannabis use disorder (CUD) is crucial for creating effective interventions. One such factor, the brain-derived neurotrophic factor (BDNF), has been linked to the onset and persistence of addictive behaviors. This systematic review aims to summarize the existing literature on BDNF levels in individuals with CUD to provide a comprehensive overview of the current evidence. A systematic search was conducted using electronic databases (PubMed, Scopus) for relevant studies. The search approach yielded a total of 785 articles, with 559 located in the PubMed database and 226 in Scopus. Studies reporting BDNF levels in individuals with CUD compared to healthy controls were included in this study. Ultimately, eight articles were included in this systematic review. The primary emphasis of these studies was on individuals who were cannabis users or had a dependency on cannabis. There is considerable variation in the estimated effect size among included studies due to heterogeneity; hence, a random effect model was used for meta-analysis. The findings of our study suggest that the effect size of BDNF levels was 0.25 with 95% CI (-0.55; 1.05) in cannabis users, which was not statistically significant (p-value=0.54). Therefore, it is important to interpret the results with caution, and additional research is warranted to investigate the potential factors contributing to this heterogeneity.
PubMed: 37900486
DOI: 10.7759/cureus.45960 -
Life (Basel, Switzerland) Sep 2023Several studies have been conducted to prove the bidirectional relationship between cardiovascular disease (CVD) and depression. These two major illnesses share several... (Review)
Review
BACKGROUND
Several studies have been conducted to prove the bidirectional relationship between cardiovascular disease (CVD) and depression. These two major illnesses share several common risk factors such that the development of either condition may increase the risk of the occurrence of the other. Brain-derived neurotrophic factor (BDNF) has been suggested as a reliable biomarker for depression and a strong predictor of CVD because it plays an important role in neuron survival and growth, serves as a neurotransmitter modulator, and promotes neuronal plasticity. The aim of this systematic review was to examine the bidirectional relationship between CVD and depression, focusing on the potential role of low serum BDNF levels in the development of either disease in the presence of the other.
METHODS
A systematic search strategy was developed using PRISMA guidelines.
RESULTS
Six studies (comprising 1251 patients) were identified, all of which examined the association between CVD and depression.
CONCLUSIONS
It was found that there may be a strong association between low serum BDNF levels and the risk of post-stroke depression. However, the studies on the role of altered serum BDNF levels and other types of CVD are few. Therefore, the inverse association between depression and CVD cannot be proven.
PubMed: 37895349
DOI: 10.3390/life13101967 -
Frontiers in Psychiatry 2022There were conflicting results on the comparison of brain-derived neurotrophic factor (BDNF) levels between poststroke depression (PSD) patients and stroke patients...
BACKGROUNDS
There were conflicting results on the comparison of brain-derived neurotrophic factor (BDNF) levels between poststroke depression (PSD) patients and stroke patients without PSD among previous studies. Thus, we conducted this systemic review and meta-analysis to explore the alteration of serum BDNF levels in PSD.
METHODS
This study included articles from the Web of Science and PubMed databases that were published before December 2021. STATA 12.0 software was used to compute the standardized mean difference (SMD) and 95% confidence interval (CI) regarding the comparison of serum BDNF in PSD and stroke patients without PSD.
RESULTS
We collected the mean value and standard deviation (SD) of serum BDNF in PSD and stroke patients without PSD from six studies (PSD: = 268, stroke patients without PSD: = 425). The present meta-analysis showed decreased serum BDNF level in patients with PSD, compared to stroke patients without PSD with a random-effects model (mean value of BDNF level [PSD vs. stroke patients without PSD]: 14.106 vs. 17.995 ng/ml; SMD = -1.578; 95% CI: -2.820, -0.337; = 97.8%, -value for Q test < 0.001).
CONCLUSION
Brain-derived neurotrophic factor may work as a potential biomarker to predict the risk of PSD among stroke survivors. More large-sample clinical trials exploring the alteration of serum BDNF levels in PSD among stroke patients need to be conducted to verify this result.
PubMed: 35664480
DOI: 10.3389/fpsyt.2022.876557