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Objectives: Brain-derived neurotrophic factor (BDNF) plays an essential role in brain and metabolic health. The fact that higher concentrations are associated with improved cognitive performance has resulted in numerous intervention trials that aim at elevating BDNF levels. This systematic review provides an overview of the relation between various nutritional factors and BDNF concentrations in controlled human intervention studies. Methods: A systematic search in May 2020 identified 48 articles that examined the effects of dietary patterns or foods (n = 3), diets based on energy intake (n = 7), vitamins and minerals (n = 7), polyphenols (n = 11), long-chain omega-3 polyunsaturated fatty acids (n = 5), probiotics (n = 8), and miscellaneous food supplements (n = 7). Results: In particular, studies with dietary patterns or foods showed increased peripheral BDNF concentrations. There are also strong indications that polyphenols tend to have a positive effect on BDNF concentrations. Four of the 11 included studies with a polyphenol intervention showed a significant increase in BDNF concentrations, one study showed an increase but this was not statistically analyzed, and two studies showed a trend to an increase. Discussion: The two polyphenol classes, phenolic acids, and other phenolic compounds were responsible for the significant effects. No clear effect was found for the other dietary factors, which might also be related to whether serum or plasma was used for BDNF analysis. More work is needed to understand the relation between peripheral and central BDNF concentrations.

There is a growing literature on the impact of genetic variation on outcome in traumatic brain injury (TBI). Whereas a substantial proportion of these publications have focused on the apolipoprotein E (APOE) gene, several have explored the influence of other polymorphisms. We undertook a systematic review of the impact of single-nucleotide polymorphisms (SNPs) in non-apolipoprotein E (non-APOE) genes associated with patient outcomes in adult TBI). We searched EMBASE, MEDLINE, CINAHL, and gray literature from inception to the beginning of August 2017 for studies of genetic variance in relation to patient outcomes in adult TBI. Sixty-eight articles were deemed eligible for inclusion into the systematic review. The SNPs described were in the following categories: neurotransmitter (NT) in 23, cytokine in nine, brain-derived neurotrophic factor (BDNF) in 12, mitochondrial genes in three, and miscellaneous SNPs in 21. All studies were based on small patient cohorts and suffered from potential bias. A range of SNPs associated with genes coding for monoamine NTs, BDNF, cytokines, and mitochondrial proteins have been reported to be associated with variation in global, neuropsychiatric, and behavioral outcomes. An analysis of the tissue, cellular, and subcellular location of the genes that harbored the SNPs studied showed that they could be clustered into blood-brain barrier associated, neuroprotective/regulatory, and neuropsychiatric/degenerative groups. Several small studies report that various NT, cytokine, and BDNF-related SNPs are associated with variations in global outcome at 6-12 months post-TBI. The association of these SNPs with neuropsychiatric and behavioral outcomes is less clear. A definitive assessment of role and effect size of genetic variation in these genes on outcome remains uncertain, but could be clarified by an adequately powered genome-wide association study with appropriate recording of outcomes.

Objectives: Brain-derived neurotrophic factor (BDNF) plays an essential role in brain and metabolic health. The fact that higher concentrations are associated with improved cognitive performance has resulted in numerous intervention trials that aim at elevating BDNF levels. This systematic review provides an overview of the relation between various nutritional factors and BDNF concentrations in controlled human intervention studies. Methods: A systematic search in May 2020 identified 48 articles that examined the effects of dietary patterns or foods (n = 3), diets based on energy intake (n = 7), vitamins and minerals (n = 7), polyphenols (n = 11), long-chain omega-3 polyunsaturated fatty acids (n = 5), probiotics (n = 8), and miscellaneous food supplements (n = 7). Results: In particular, studies with dietary patterns or foods showed increased peripheral BDNF concentrations. There are also strong indications that polyphenols tend to have a positive effect on BDNF concentrations. Four of the 11 included studies with a polyphenol intervention showed a significant increase in BDNF concentrations, one study showed an increase but this was not statistically analyzed, and two studies showed a trend to an increase. Discussion: The two polyphenol classes, phenolic acids, and other phenolic compounds were responsible for the significant effects. No clear effect was found for the other dietary factors, which might also be related to whether serum or plasma was used for BDNF analysis. More work is needed to understand the relation between peripheral and central BDNF concentrations.

Цель исследования изучить по данным литературы особенности личностных свойств, расстройств аффективно-тревожного спектра и значение генетического полиморфизма в развитии обсессивно-компульсивного расстройства. Материалы и методы исследования. Был проведен обзор современной отечественной и зарубежной, преимущественно англоязычной, литературы, посвященной обсессивно-компульсивному расстройству. Результаты и их обсуждение. В представленном теоретическом обзоре обсессивно-компульсивное расстройство раскрывается как недостаточно изученная форма нозологии. В его формировании определяется значимая роль тревоги, которая может выступать в качестве общего знаменателя при привлечении к обсессивно-компульсивному расстройству сопутствующих расстройств аффективно-тревожного спектра. Отмечается, что коморбидность значительно утяжеляет течение обсессивно-компульсивного расстройства, что выступает важным критерием при составлении прогностического плана лечения и построения психотерапии. В завершение по данным литературы обсессивно-компульсивное расстройство определяется как генетически наследуемое заболевание, нейробиологической основой которого может выступать нейротрофический фактор головного мозга и его генетический полиморфизм. Заключение. Имеющаяся на данном этапе исследований информация подробно описывает разнообразие симптомов при обсессивно-компульсивном расстройстве, однако отсутствие четких представлений о его этиологии затрудняет подбор эффективных методов лечения и профилактики. Тревога при обсессивно-компульсивном расстройстве может выступать и в качестве фактора риска развития заболевания, и в качестве постоянного спутника для пациента, уже страдающего данным расстройством. При дефиците нейротрофического фактора, ответственного за нейропластичность головного мозга и, в частности, гиппокампа, возрастает вероятность формирования психических расстройств, и уже на данном этапе существуют исследования, благодаря которым можно предположить связь количества нейротрофина и, в качестве причины, полиморфизма его генов в организме, с появлением симптоматики обсессивно-компульсивного расстройства., The research purpose was to study, according to the literature, the features of personality traits, affective-anxiety spectrum disorders and the significance of genetic polymorphism in the development of obsessive-compulsive disorder. Materials and research methods. A review of modern domestic and foreign, mainly English-language, literature on obsessive-compulsive disorder was carried out. Results and its discussion. In the presented theoretical review, obsessive-compulsive disorder is revealed as an insufficiently studied form of nosology. In its formation, the significant role of anxiety is determined, which can act as a common denominator when concomitant disorders of the affective-anxiety spectrum are involved in obsessive-compulsive disorder. It is noted that comorbidity significantly aggravates the course of obsessive-compulsive disorder, which is an important criterion in the preparation of a prognostic treatment plan and the construction of psychotherapy. According to the literature, obsessive-compulsive disorder is defined as a genetically inherited disease, the neurobiological basis of which may be the brain-derived neurotrophic factor and its genetic polymorphism. Conclusion. The available information describes in detail the variety of symptoms in obsessive-compulsive disorder. However, the lack of clear ideas about its etiology makes it difficult to select effective methods of treatment and prevention. Anxiety in obsessive-compulsive disorder can act both as a risk factor for the development of the disease, and as a constant companion for a patient already suffering from this disorder. With a deficiency of the neurotrophic factor responsible for the neuroplasticity of the brain and, in particular, the hippocampus, the likelihood of developing mental disorders increases. Already at this stage, there are studies that can suggest a relationship between the amount of neurotrophin and, as a cause, the polymorphism of its genes in the body, with the appearance of symptoms of obsessive-compulsive disorder.

Background and Objectives: To investigate the clinical characteristics of adolescents with early-onset full psychotic disorders either with Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) or DRD2/ANKK1 Taq1A (rs1800497) polymorphisms. Method: 101 cases with early-onset schizophrenia (EOS) or other psychotic spectrum disorders (SSD) and 150 healthy controls were included in the current study. Using the Positive and Negative Symptom Scale (PANSS), patient subgroups were compared for their psychotic symptoms, age-onset, duration of untreated illness, and family history of psychiatric disorders. The real-time polymerase chain reaction (RT-PCR) was implemented for genotyping procedures. Results: Study groups and patient subgroups were similar regarding their sociodemographic characteristics (16.4 +/- 2.6 years, 62.2% male for all participants). Results did not reveal any difference between patients and healthy controls for DRD2/ANKK1 Taq1A and BDNF Val66Met genotypes. Patients with A1A2 (Gly/Lys) allele reported higher rates of substance use compared to A2A2 (Glu/Glu) counterparts. Other clinical variables were found similar. EOS/SSD group with Val66Met heterozygote allele revealed lower levels of negative symptoms than Val/Val homozygotes. Conversely, the age onset of full psychotic disorder, total positive symptom score, and total general psychopathology score of PANSS were found comparable between Val/Met and Val/Val groups. In the logistic regression model, Glu/Lys genotypes remained significant for the presence of substance use. Conclusion: The interaction between substance use and the DRD2 gene should be investigated for the development of early-onset psychotic disorders. BDNF Val66Met polymorphism also could be a disease-modifying factor for the presence of negative symptoms. (C) 2021 Asociacion Universitaria de Zaragoza para el Progreso de la Psiquiatria y la Salud Mental. Published by Elsevier Espana, S.L.U. All rights reserved., 42496, This study was funded by the Scientific Research ProjectsCoordination Unit of Istanbul University-Cerrahpasa. Projectnumbers: 42496, 54033.

Данная работа посвящена исследованию генетической базы для Ð¿ÑÐ¸Ñ Ð¾Ð»Ð¾Ð³Ð¸Ñ‡ÐµÑÐºÐ¾Ð¹ адаптации человека экстремальным климатическим условиям. Для исследования были выбраны две группы практически Ð·Ð´Ð¾Ñ€Ð¾Ð²Ñ‹Ñ Ð»ÑŽÐ´ÐµÐ¹, Ð²Ñ‹Ð¿Ð¾Ð»Ð½ÑÑŽÑ‰Ð¸Ñ Ð¾Ð¿ÐµÑ€Ð°Ñ‚Ð¾Ñ€ÑÐºÑƒÑŽ деятельность. Целевая группа состоит из лиц, Ð¿Ñ€Ð¾Ð¶Ð¸Ð²Ð°ÑŽÑ‰Ð¸Ñ Ð² ÑÐºÑÑ‚Ñ€ÐµÐ¼Ð°Ð»ÑŒÐ½Ñ‹Ñ ÑƒÑÐ»Ð¾Ð²Ð¸ÑÑ ÐÑ€ÐºÑ‚Ð¸ÐºÐ¸. Контрольная группа состоит из лиц, Ð¿Ñ€Ð¾Ð¶Ð¸Ð²Ð°ÑŽÑ‰Ð¸Ñ Ð² ÑƒÑÐ»Ð¾Ð²Ð¸ÑÑ ÑÑ€ÐµÐ´Ð½ÐµÐ¹ полосы России. Для определения уровня адаптации использовался набор Ð¿ÑÐ¸Ñ Ð¾Ð»Ð¾Ð³Ð¸Ñ‡ÐµÑÐºÐ¸Ñ Ñ‚ÐµÑÑ‚Ð¾Ð², Ð¿Ñ€Ð¸Ð½Ð°Ð´Ð»ÐµÐ¶Ð°Ñ‰Ð¸Ñ ÑÑ‚Ð°Ð½Ð´Ð°Ñ€Ñ‚Ð½Ð¾Ð¼Ñƒ инструментарию современной Ð¿ÑÐ¸Ñ Ð¾Ð´Ð¸Ð°Ð³Ð½Ð¾ÑÑ‚Ð¸ÐºÐ¸. Для проведения генетического обследования у Ð¾Ð±ÑÐ»ÐµÐ´ÑƒÐµÐ¼Ñ‹Ñ Ð±Ñ‹Ð»Ð° взята цельная кровь из вены, из которой выделялась ДНК с последующим исследованием полиморфизмов ACE Ins/Del (rs4646994), ACTN3 R577X (rs1815739), BDNF Val66Met (rs6265) и HTR2A T102C (rs6313) методом ПЦРв реальном времени. Были получены данные, согласно которым прослеживается связь между вариантами Ð´Ð°Ð½Ð½Ñ‹Ñ Ð¿Ð¾Ð»Ð¸Ð¼Ð¾Ñ€Ñ„Ð¸Ð·Ð¼Ð¾Ð² и социально-Ð¿ÑÐ¸Ñ Ð¾Ð»Ð¾Ð³Ð¸Ñ‡ÐµÑÐºÐ¾Ð¹ адаптацией к экстремальным условиям Ð²Ñ‹ÑÐ¾ÐºÐ¸Ñ ÑˆÐ¸Ñ€Ð¾Ñ‚. Согласно этим данным, полиморфизмы генов BDNF и ACE оказывают значимое влияние на адаптацию. Полученные результаты могут быть использованы для проведения генетического тестирования с целью предсказания возможной способности адаптации людей к экстремальным условиям Ð²Ñ‹ÑÐ¾ÐºÐ¸Ñ ÑˆÐ¸Ñ€Ð¾Ñ‚., The given work is devoted to the study of the genetic basis for the psychological adaptation of a person to extreme climatic conditions. Two groups of practically healthy people performing operator activities were selected for the study. The target group consists of people living in the extreme conditions of the Arctic. The control group consists of people living in the conditions of the central part of Russia. To determine the level of adaptation, a set of psychological tests belonging to the standard tools of modern psychodiagnostics was used. To conduct a genetic examination, whole blood was taken from a vein from which DNA was isolated, followed by a real-time PCR study of ACE Ins/Del (rs4646994), ACTN3 R577X (rs1815739), BDNF Val66Met (rs6265) and HTR2A T102C (rs6313) polymorphisms. Data were obtained, according to which there is a connection between the variants of these polymorphisms and socio-psychological adaptation to extreme conditions of high latitudes. According to these data, polymorphisms of the BDNF and ACE genes have a significant effect on adaptation. The results obtained can be used for genetic testing in order to predict the possible ability of people to adapt to extreme conditions of high latitudes.

Alongside their function in primary haemostasis and thrombo-inflammation, platelets are increasingly considered a bridge between mental, immunological and coagulation-related disorders. This review focuses on the link between platelets and the pathophysiology of major depressive disorder (MDD) and its most frequent comorbidities. Platelet- and neuron-shared proteins involved in MDD are functionally described. Platelet-related studies performed in the context of MDD, cardiovascular disease, and major neurodegenerative, neuropsychiatric and neurodevelopmental disorders are transversally presented from an epidemiological, genetic and functional point of view. To provide a complete scenario, we report the analysis of original data on the epidemiological link between platelets and depression symptoms suggesting moderating and interactive effects of sex on this association. Epidemiological and genetic studies discussed suggest that blood platelets might also be relevant biomarkers of MDD prediction and occurrence in the context of MDD comorbidities. Finally, this review has the ambition to formulate some directives and perspectives for future research on this topic ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:21 issue:22 pages:1-31 ispartof: location:Switzerland status: published

The role of mBDNF on the beneficial effects of cognitive stimulation on the brain remains controversial, as well as the potential of peripheral mBDNF as a biomarker of environmental effects on its central status. We investigated the effect of different environmental conditions on recognition memory, proBDNF, mBDNF and synaptophysin levels in the hippocampus, and on mBDNF levels in blood. Male Wistar rats (6 and 17 months-old) were assigned to cognitively enriched (EE), standard (SE) and impoverished (IE) environmental conditions for twelve weeks. Novel object recognition was performed at week 10. When the animals were 9 and 20-months old, hippocampus was collected for mBDNF, proBDNF and synaptophysin analysis; serum was analyzed for mBDNF levels. The cognitively EE improved recognition memory, resulted in a trend to increased hippocampal mBDNF and augmented synaptophysin levels. Accordingly, hippocampal mBDNF, proBDNF and synaptophysin were significantly higher in EE than IE animals. Hippocampal mBDNF was positively correlated to proBDNF, cellular and behavioral plasticity markers. No effect of age was seen on the studied variables. Moreover, no significant effects of EE or IE on serum mBDNF were observed. Serum mBDNF also failed to correlate with hippocampal mBDNF, proBDNF and with the cellular and behavioral plasticity markers. These findings indicate that mBDNF is involved in neuronal and behavioral plasticity mechanisms induced by cognitively enriched environments, and that peripheral mBDNF may not always be a reliable biomarker of the effects of environmental settings on central mBDNF and plasticity, which is of special interest from a translational research perspective.

Despite moderate heritability estimates, the molecular architecture of aggressive behavior remains poorly characterized. This study compared gene expression profiles from a genetic mouse model of aggression with Zebrafish, an animal model traditionally used to study aggression. A meta-analytic, cross-species approach was used to identify genomic variants associated with aggressive behavior. The Rankprod algorithm was used to evaluated mRNA differences from prefrontal cortex tissues of three sets of mouse lines (N = 18) selectively bred for low and high aggressive behavior (SAL/LAL, TA/TNA, and NC900/NC100). The same approach was used to evaluate mRNA differences in Zebrafish (N = 12) exposed to aggressive or non-aggressive social encounters. Results were compared to uncover genes consistently implicated in aggression across both studies. Seventy-six genes were differentially expressed (PFP

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion. © 2015, The Author(s). Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Present study aims to investigate the role of AGEs, TGF-β1, BDNF and their receptors on diabetes-induced colon remodeling. Diabetes was induced by a single tail vein injection 40 mg/kg of STZ. The parameters of morphometric and biomechanical properties of colonic segments were obtained from diabetic and normal rats. The expressions of AGE, RAGE, TGF- β1, TGF- β1 receptor, BDNF and TrkB were immunohistochemically detected in different layers of the colon. The expressions of AGE, RAGE, TGF-β1 and TGF- β1 receptor were increased whereas BDNF and TrkB were decreased in the diabetic colon (P

Meta-analyses, published in 2008-2010, have confirmed abnormally low serum brain-derived neurotrophic factor (BDNF) concentrations in depressed patients and normalization of this by antidepressant treatment. These findings are believed to reflect peripheral manifestations of the neurotrophin hypothesis, which states that depression is secondary to an altered expression of BDNF in the brain. Since the publication of these meta-analyses, the field has seen a huge increase in studies on these topics. This motivated us to update the evidence on the aforementioned associations and, in addition, to compile the data on serum BDNF concentrations in relation to the symptom severity of depression. Using a manifold of data as compared with earlier meta-analyses, we find low serum BDNF concentrations in 2384 antidepressant-free depressed patients relative to 2982 healthy controls and to 1249 antidepressant-treated depressed patients (Cohen's d = -0.71 and -0.56, P-values

International audience; Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has emerged as an active mediator in many essential functions in the central nervous system of mammals. BDNF plays significant roles in neurogenesis, neuronal maturation and/or synaptic plasticity and is involved in cognitive functions such as learning and memory. Despite the vast literature present in mammals, studies devoted to BDNF in the brain of other animal models are scarse. Zebrafish is a teleost fish widely known for developmental genetic studies and is emerging as model for translational neuroscience research. In addition, its brain shows many sites of adult neurogenesis allowing higher regenerative properties after traumatic injuries. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the distribution of bdnf mRNAs in the larval and adult zebrafish brain and to characterize the phenotype of cells expressing bdnf mRNAs by means of double staining studies. Our results showed that bdnf mRNAs were widely expressed in the brain of 7 days old larvae and throughout the whole brain of mature female and male zebrafish. In adults, bdnf mRNAs were mainly observed in the dorsal telencephalon, preoptic area, dorsal thalamus, posterior tuberculum, hypothalamus, synencephalon, optic tectum and medulla oblongata. By combining immunohistochemistry with in situ hybridization, we showed that bdnf mRNAs were never expressed by radial glial cells or proliferating cells. By contrast, bdnf transcripts were expressed in cells with neuronal phenotype in all brain regions investigated. Our results provide the first demonstration that the brain of zebrafish expresses bdnf mRNAs in neurons and open new fields of research on the role of the BDNF factor in brain mechanisms in normal and brain repairs situations.

International audience; The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels.

Introduction: Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers, and current smokers-with and without nicotine dependence-and to examine the interaction of the polymorphism and smoking status with serum BDNF.Methods: We used baseline serum and gene data of BDNF on 2,088 participants from the Netherlands Study of Depression and Anxiety (NESDA) to investigate smoking-BDNF association while controlling for potential confounding variables. Nicotine dependence was assessed with the Fagerstrom Test for Nicotine Dependence (FTND).Results: Smokers with and without nicotine dependence had higher levels of serum BDNF than former and never-smokers. Nicotine dependence and number of cigarettes smoked per day did not add to the prediction of serum BDNF; however, total number of smoking years was a significant predictor of serum BDNF. There was no association of BDNF Val66Met, nor an interaction of this polymorphism and smoking status, with serum BDNF.Conclusions: Current smoking and higher number of smoking years are associated with higher levels of serum BDNF, and this is independent of the BDNF genotype. Nicotine dependence itself is not associated with a further increase or decrease of serum BDNF. Longitudinal investigations that address changes in serum BDNF in incident smokers and/or in quitters may be useful to understand the association of smoking with BDNF.

Meta-analyses, published in 2008-2010, have confirmed abnormally low serum brain-derived neurotrophic factor (BDNF) concentrations in depressed patients and normalization of this by antidepressant treatment. These findings are believed to reflect peripheral manifestations of the neurotrophin hypothesis, which states that depression is secondary to an altered expression of BDNF in the brain. Since the publication of these meta-analyses, the field has seen a huge increase in studies on these topics. This motivated us to update the evidence on the aforementioned associations and, in addition, to compile the data on serum BDNF concentrations in relation to the symptom severity of depression. Using a manifold of data as compared with earlier meta-analyses, we find low serum BDNF concentrations in 2384 antidepressant-free depressed patients relative to 2982 healthy controls and to 1249 antidepressant-treated depressed patients (Cohen's d=-0.71 and -0.56, P-values

The neuropeptide VGF (non-acronymic), which has antidepressant-like effects, enhances adult hippocampal neurogenesis as well as synaptic activity and plasticity in the hippocampus, however the interaction between these processes and the mechanism underlying this regulation remain unclear. In this study, we demonstrate that VGF-derived peptide TLQP-62 specifically enhances the generation of early progenitor cells in nestin-GFP mice. Specifically, TLQP-62 significantly increases the number of Type 2a neural progenitor cells (NPCs) while reducing the number of more differentiated Type 3 cells. The effect of TLQP-62 on proliferation rather than differentiation was confirmed using NPCs in vitro; TLQP-62 but not scrambled peptide PEHN-62 increases proliferation in a cell line as well as in primary progenitors from adult hippocampus. Moreover, TLQP-62 but not scrambled peptide increases Cyclin D mRNA expression. The proliferation of NPCs induced by TLQP-62 requires synaptic activity, in particular through NMDA and metabotropic glutamate receptors. The activation of glutamate receptors by TLQP-62 activation induces phosphorylation of CaMKII through NMDA receptors and protein kinase D through metabotropic glutamate receptor 5 (mGluR5). Furthermore, pharmacological antagonists to CaMKII and PKD inhibit TLQP-62-induced proliferation of NPCs indicating that these signaling molecules downstream of glutamate receptors are essential for the actions of TLQP-62 on neurogenesis. We also show that TLQP-62 gradually activates Brain-Derived Neurotrophic Factor (BDNF)-receptor TrkB in vitro and that Trk signaling is required for TLQP-62-induced proliferation of NPCs. Understanding the precise molecular mechanism of how TLQP-62 influences neurogenesis may reveal mechanisms by which VGF-derived peptides act as antidepressant-like agents.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that modifies cortical excitability according to the stimulation parameters. Preclinical and clinical studies in healthy volunteers suggest that tDCS induces neuroplastic alterations of cortical excitability, which might explain its clinical effects in major depressive disorder (MDD). We therefore examined whether tDCS, as compared to the antidepressant sertraline, increases plasma brain-derived neurotrophic factor (BDNF) levels, a neurotrophin associated with neuroplasticity. Patients (n=73) with major depressive disorder were randomized to active/sham tDCS and sertraline/placebo (four groups) in this 6-week, double-blind, placebo-controlled trial. We measured BDNF plasma levels at baseline and endpoint, observing no significant changes of BDNF levels after treatment. In addition, no significant changes were observed in responders and non-responders as well as no relationships between BDNF levels and clinical and psychopathological variables related to depression. Thus, in one of the few placebo-controlled trials evaluating BDNF changes over an antidepressant treatment course, we did not observe BDNF increase regardless of clinical improvement in depressed patients. Regarding tDCS, BDNF plasma levels might not be a good candidate biomarker to evaluate depression improvement or be a predictor of response in patients treated with tDCS, as our results showed that BDNF increase was not necessary to induce clinical response. Finally, our findings do not support a relationship between BDNF and improvement of depression.

Tourette syndrome (TS) is a heritable disorder characterized by tics that are decreased in some patients by treatment with alpha adrenergic agonists and dopamine receptor blockers. Thus, this study examines the relationship between catecholamine gene expression in blood and tic severity. TS diagnosis was confirmed using Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and tic severity measured using the Yale Global Tic Severity Scale (YGTSS) for 26 un-medicated subjects with TS. Whole blood was collected and Ribonucleic acid (RNA) processed on Affymetrix Human Exon 1.0 ST arrays. An Analysis of Covariance (ANCOVA) identified 3627 genes correlated with tic severity (p

Brain-derived neurotrophic factor (BDNF) is a key mediator of the activity-dependent processes in the brain that have a major impact on neuronal development and plasticity. Impaired control of neuronal activity-induced BDNF expression mediates the pathogenesis of various neurological and psychiatric disorders. Different environmental stimuli, such as the use of pharmacological compounds, physical and learning exercises or stress exposure, lead to activation of specific neuronal networks. These processes entail tight temporal and spatial transcriptional control of numerous BDNF splice variants through epigenetic mechanisms. The present review highlights recent findings on the dynamic and long-term epigenetic programming of BDNF gene expression by the DNA methylation, histone-modifying and microRNA machineries. The review also summarizes the current knowledge on the activity-dependent BDNF mRNA trafficking critical for rapid local regulation of BDNF levels and synaptic plasticity. Current data open novel directions for discovery of new promising therapeutic targets for treatment of neuropsychiatric disorders.This article is part of the Special Issue entitled ‘BDNF Regulation of Synaptic Structure, Function, and Plasticity’.