Schizophrenia spectrum disorders are among the most debilitating mental disorders and has complex pathophysiological underpinnings. There is growing evidence that brain-derived neurotrophic factor (BDNF) can play a role in its pathogenesis. The present study investigated the longitudinal variation of serum BDNF levels in a 24-month observational prospective cohort study of Sardinian psychotic patients and its relationship with psychopathological and cognitive changes. Furthermore, we examined whether genetic variation within the BDNF gene could moderate these relationships.

Every 6 months, 105 patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and social measures. We performed a targeted analysis of four tag single nucleotide polymorphisms within the BDNF gene that were selected and analyzed using polymerase chain reaction. Longitudinal data were analyzed using mixed-effects linear regression models.

We observed a declining longitudinal trajectory of BDNF levels in psychotic patients in general, and in relation to the severity of depressive and negative symptoms. BDNF serum levels also declined in patients scoring lower in cognitive measures such as attention and speed of information processing and verbal fluency. The rs7934165 polymorphism moderated the significant association between verbal fluency and BDNF levels.

These findings in patients from real-world settings suggest a plausible role of peripheral BDNF levels as a marker of illness burden in schizophrenia spectrum disorders.

Alzheimer’s disease (AD) is a neurodegenerative pathology that develops mainly in elderly and senile people. Disruption of BDNF transport or suppression of its production appears to be typical for people of old age. Objective: To investigate the influence of Alzheimer’s disease on the secretion of brain factors and correlate with neuropsychological profiles.

12 men (2) and women (10) with Alzheimer’s disease were examined. The average age of the subjects was 76.25 + 4.89. Methods: MMSE, ADAS-COG, laboratory - BDNF was performed using the G7611 BDNF Emax (R) ImmunoAssaySystem 5 x 96 wells, BDNF Emax® Immunological test.

2 patients have mild dementia, 8 patients have moderate dementia, 2 patients have severe dementia. The average age of patients with mild dementia was 72.0 + 1.0. The average MMSE score is 16.7 + 3.4.

Correlation analysis showed a close relationship between a pronounced decrease in memory in memory tests (ADAS-COG) and a pronounced decrease in blood BDNF content (r = 0.676). A close statistically significant relationship was found between a low result of the recognition test and a low blood BDNF content (r = 0.598).

We assume that blood BDNF is a marker of pathologically accelerated aging of the central nervous system, since low test results for mnestic function are an indicator of severe degeneration in Alzheimer’s disease.

No significant relationships.

Schizophrenia spectrum disorders are among the most debilitating mental disorders and evidence on its pathophysiological underpinnings is scant. The brain-derived neurotrophic factor (BDNF) appears to be involved in the pathophysiology of these complex psychiatric disorders.

The present study investigates the longitudinal variation of serum BDNF levels in a 24-month observational cohort study of Sardinian psychotic patients (LABSP). This study assessed the variation in BDNF serum levels and its relationship with psychopathological and cognitive changes. Further, we also examined if genetic variations within the BDNF gene could moderate these relationships.

Every six months 105 LABSP patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and drug-related measures. Four tag single nucleotide polymorphisms (SNPs) within the BDNF gene were selected and analyzed using Polymerase Chain Reaction (PCR). Longitudinal data were analyzed using mixed-effects linear regression models (MLRM).

Analysis showed significantly lower peripheral BDNF levels in psychotic patients with depressive and negative symptoms. BDNF levels were also decreased in patients scoring lower in cognitive measures such as symbol coding and semantic fluency. In addition, Val66Met polymorphism within the BDNF gene significantly moderated the relationship between the severity of negative symptoms and BDNF levels.

Our findings are consistent with previous literature suggesting that peripheral BDNF levels are associated with some cognitive domains and mood disruption in major psychosis. The results also suggest the lack of association between most BDNF genetic variants, except Val66Met polymorphism, with the severity of negative symptoms.

No significant relationships.

Bipolar disorder (BD) is a complex mental disorder. Cognitive dysfunction represents a core feature, strongly related with patients’ functional outcome. Functional Remediation (FR), is an integrated neuropsychological and psychosocial rehabilitation treatment aimed at enhancing cognitive functions in order to achieve full functional recovery(Torrent et al., 2013). Evidence highlighted an association of neurotrophins and cognitive dysfunctions. Particularly, BDNF has been investigated a potential biomarker. Preliminary studies explored the effects induced through FR interventions on serum BDNF levels(Bonnin et al., 2019). Evidences suggest that high BDNF serum levels are related to good cognitive functioning(Mora et al., 2019). Results require further explorations. The present pilot study targets to identify the neurobiological correlates of response, investigating the potential neuroprotective role of the FR.

Assess the effectiveness of FR in ameliorate cognitive deficits measured with BAC-A and psychosocial functioning with FAST, in modifying BDNF levels in a sample of euthymic patients with BD, compared to standard treatment.

Two arms(1:1)randomized, rater-blinded, controlled study of 30out-patients with BD-I and BD-II, according to DSM-5 criteria. Patients between 18 and 55 years in euthymic phase. Neurocognitive and clinical assessments, at the same times, serum assessment of BDNF levels will be performed.

All patients will be assessed at baseline(T0), at the end of treatment(T1) and at the 3-month follow-up(T2).

After treatment, patients receiving FR show better cognitive and psychosocial performance than those receiving TAU.

Given the important role of neutrophins in the pathogenesis of BD, identifying BD-specific biomarkers would contribute to understand the underlying neuro-pathophysiological processes and to personalize treatments.

No significant relationships.

To evaluate the impact of genetic deletion of receptors of the counterregulatory arms of the renin–angiotensin system in depressive-like behaviours.

8–12 weeks-old male mice wild type (WT, C57BL/6J) and mice with genetic deletion of MrgD (MrgD KO) or Mas receptors (Mas KO) were subjected to the Forced Swim Test (FST) and the Tail Suspension Test (TST). Brain-derived neurotrophic factor (BDNF) levels were measured by enzyme-linked immunosorbent assay (ELISA). Blockade of Mas was performed by acute intracerebroventricular (icv) injection of its selective antagonist, A779.

No statistical difference in immobility time was observed between MrgD KO and WT male animals subjected to FST and TST. However, acute icv injection of A779 significantly increased the immobility time of MrgD KO male mice subjected to FST and TST, suggesting the involvement of Mas in preventing depressive-like behaviour. Indeed, Mas KO male animals showed increased immobility time in FST and TST, evidencing a depressive-like behaviour in these animals, in addition to a reduction in BDNF levels in the prefrontal cortex and hippocampus. No changes in BDNF levels were observed in MrgD KO male animals.

Our data showed that Mas plays an important role in the neurobiology of depression probably by modulating BDNF expression. On the contrary, lack of MrgD did not alter depressive-like behaviour, which was supported by the lack of alterations in BDNF levels.

According to the World Health Organization (WHO, 2017) depressive disorder continues to be the most widespread and growing mental illness in the world, also assumes that in 2020 depression will have a prevalence equal to one in six individuals. Studies of neuroanatomy have highlighted structural alterations in the hippocampus, striatal nuclei and prefrontal cortex in patients with mood disorders. This alteration in depressed patients is closely related to the secretion of neurotrophic factors, in particular there is a reduction in BDNF (Brain Derived Neurotrophic Factor).

The objective of this study is to demonstrate which treatments are effective in reducing depressive symptoms that allow the increase of BDNF and consequently the structural homostaticity of the brain.

We have selected data from the literature of the last decade, collected on major search engines such as: Google Scholar, Research Gate, PubMed, Ebsco. Articles collected by selecting the following Keyword: depression, BDNF (Brain Derived Neurotrophic Factor), neuroimaging cognitive behavior therapy.

The results show that in patients treated with a single drug treatment or vagus nerve stimulation, repetitive transcranial magnetic stimulation (Lang et al., 2008) or electroconvulsive therapy had improvements in BDNF levels, although compared to drug treatment there are problems of no responders, no compliance and lack of effectiveness in reducing vulnerability to relapse. In addition, the study has shown that patients treated with cognitive behavioral therapy have reported greater changes in the frontal and temporal cortex reducing both depressive symptoms and the risk of relapse.

Underlines the importance of an integrated approach

Alzheimer’s disease (AD) is a neurodegenerative pathology that develops mainly in elderly and senile people. Disruption of BDNF transport or suppression of its production appears to be typical for people of old age.

Objective: To investigate the influence of Alzheimer’s disease on the secretion of brain factors and correlate with neuropsychological profiles.

12 men (2) and women (10) with Alzheimer’s disease were examined. The average age of the subjects was 76.25 + 4.89. Methods: MMSE, ADAS-COG, laboratory - BDNF was performed using the G7611 BDNF Emax (R) ImmunoAssaySystem 5 x 96 wells, BDNF Emax® Immunological test.

2 patients have mild dementia, 8 patients have moderate dementia, 2 patients have severe dementia. The average age of patients with mild dementia was 72.0 + 1.0. The average MMSE score is 16.7 + 3.4. Correlation analysis showed a close relationship between a pronounced decrease in memory in memory tests (ADAS-COG) and a pronounced decrease in blood BDNF content (r = 0.676). A close statistically significant relationship was found between a low result of the recognition test and a low blood BDNF content (r = 0.598).

we assume that blood BDNF is a marker of pathologically accelerated aging of the central nervous system, since low test results for mnestic function are an indicator of severe degeneration in Alzheimer’s disease

No significant relationships.

Brain-derived neurotrophic factor (BDNF) plays an important role in depression and sleep disorders. It influences the inflammatory process and may affect the interactions between psychological state and gastrointestinal symptoms.

The study aimed to compare BDNF concentrations in the group of Crohn’s disease (CD), ulcerative colitis (UC) patients, and healthy control (HC), as well as to correlate it with the severity of depression and insomnia.

The study included 94 inflammatory bowel disease patients (IBD, 57 CD, and 37 UC) and 26 HC. Each participant completed the following questionnaires: Pittsburgh Sleep Quality Index (PSQI), Athens insomnia scale (AIS), and Beck Depression Inventory (BDI). BDNF protein concertation measurements were performed using ELISA. Funding: National Science Centre, Poland-2018/31/N/NZ5/03715.

CD patients had a higher serum level of BDNF (22.5 ng/mL, IQR:17.5-28.5) than UC patients (19.1 ng/mL, IQR:12.3-24.6; p=0.045). CD group had higher BDNF concentrations than HC (17.5 ng/mL, IQR:13.2-23.8; p=0.010), but no such differences were found between UC and HC groups (p=0.544). A positive correlation was found between AIS and BDNF among IBD (r=0.22, p=0.035). Additionally, patients, who obtained high BDI scores (>7 points) had lower BDNF concentrations than others (p=0.004). The patients with long sleep latency (>10 min) achieved a higher BDNF level than others (p=0.038). However. BDNF level did not correlate with PSQI results.

BDNF serum level is increased in CD, but not in UC patients. Overall, the severity of insomnia symptoms correlates positively with BDNF levels. Future research should focus on the further explanation of those observations.

Depression and coronary heart disease (CHD) are highly comorbid conditions. Brain-derived neurotrophic factor (BDNF) plays an important role in cardiovascular processes. Depressed patients typically show decreased BDNF concentrations. We analysed the relationship between BDNF and depression in a sample of patients with CHD and additionally distinguished between cognitive-affective and somatic depression symptoms. We also investigated whether BDNF was associated with somatic comorbidity burden, acute coronary syndrome (ACS) or congestive heart failure (CHF).

The following variables were assessed for 225 hospitalised patients with CHD: BDNF concentrations, depression [Patient Health Questionnaire-9 (PHQ-9)], somatic comorbidity (Charlson Comorbidity Index), CHF, ACS, platelet count, smoking status and antidepressant treatment.

Regression models revealed that BDNF was not associated with severity of depression. Although depressed patients (PHQ-9 score >7) had significantly lower BDNF concentrations compared to non-depressed patients (p = 0.04), this was not statistically significant after controlling for confounders (p = 0.15). Cognitive-affective symptoms and somatic comorbidity burden each closely missed a statistically significant association with BDNF concentrations (p = 0.08, p = 0.06, respectively). BDNF was reduced in patients with CHF (p = 0.02). There was no covariate-adjusted, significant association between BDNF and ACS.

Serum BDNF concentrations are associated with cardiovascular dysfunction. Somatic comorbidities should be considered when investigating the relationship between depression and BDNF.

Brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and in the protection against oxidative damage and neuronal apoptosis. After exercise, there is an increased expression of this myokine, especially in skeletal muscle and brain. Low BDNF levels have been described in neurodegenerative diseases. Alcoholics show both muscle atrophy and brain atrophy. Thus, this study was performed in order to analyze serum BDNF levels among alcoholics and their associations with brain atrophy and muscle strength.

Serum BDNF values were determined to 82 male alcoholics and 27 age-matched controls, and compared with handgrip strength, with the presence of brain atrophy, assessed by computed tomography, and with the intensity of alcoholism and liver function derangement.

BDNF levels and handgrip strength were significantly lower among patients. Handgrip strength was correlated with BDNF values, both in the whole population and in alcoholics, especially in patients over 59 years of age. BDNF was poorly related to liver dysfunction but showed no relationship with brain atrophy or age.

Chronic alcoholics show decreased BDNF serum levels that are related to muscle function impairment rather than to age, brain atrophy, liver dysfunction, or the amount of ethanol consumed.

Recent research suggests that the brain-derived neurotrophic factor (BDNF) may play a role in extinction learning. The goal of this study was to test whether variation in the BDNF Val66Met polymorphism is related to treatment response to exposure-based cognitive-behavior therapy (CBT), a form of extinction learning, in obsessive-compulsive disorder (OCD).

One hundred and six OCD patients from a specialized clinic, who underwent a standardized CBT treatment after partial or non-response to a 12-week pharmacological trial, were genotyped for the BDNF Val66Met and the relationship between genotype and treatment response was analyzed.

Among 98 CBT completers, 36% of those carrying the BDNF Met allele were rated as CBT responders compared to 60% of nonMet allele carriers (P = 0.027). When analyzing the different obsessive-compulsive symptom dimensions, in patients with contamination/cleaning symptoms, the Met allele was associated with a significantly worse CBT response (P<0.0001) and a lower obsessions severity decrease from pre- to posttreatment (P = 0.046).

Genetic variation in BDNF may be associated with treatment response in exposure-based CBT in OCD, especially in those patients exhibiting contamination/cleaning symptoms.

Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence.

Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder.

Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers.

No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

Schizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Brain-derived neurotrophic factor (BDNF) and C-reactive protein (CRP) are among the most commonly investigated peripheral markers of cognition in schizophrenia.

A systematic review in PubMed and Scopus databases was performed until 31 January 2019 to assess the relationship between cognitive impairment, CRP and BDNF levels in schizophrenia. A random-effects meta-analysis was conducted.

Current meta-analysis included 21 studies including 2449 patients with schizophrenia-spectrum disorders. Overall, both BDNF [r = 0.12, confidence interval (CI) 0.04–0.19] and CRP (r = −0.13, CI 0.08–0.18) levels were very modestly but significantly related to cognitive functioning in schizophrenia (r = 0.12, CI 0.04–0.19). In meta-analyses of cognitive domains, BDNF levels were significantly associated with verbal memory (r = 0.16, CI 0.09–0.23), working memory (r = 0.14, CI 0.06–0.22), processing speed (r = 0.18, CI 0.10–0.26) and verbal fluency (r = 0.09, CI 0–0.18) performances. Elevated CRP levels were related to all cognitive domains (r = −0.09 to −0.13) except for fluency. Subgroup analyses suggested that the relationship between cognitive and BDNF levels were more pronounced in chronic samples.

Current findings suggest that cognitive impairment in schizophrenia is significantly related to elevated CRP and reduced BDNF levels in schizophrenia, particularly in chronic samples. However, small effect sizes of these correlations suggest that inflammation and decreased BDNF levels do not play a major role in cognitive dysfunction in most patients with schizophrenia. Further studies are needed to investigate the potential intermediating and confounding factors which can influence the level of relationship between inflammation, neurotrophic factors and cognition in schizophrenia.

Nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects in animal models sensitive to acute drug treatment such as the forced swimming test. However, it is not yet clear if repeated treatment with these drugs is required to induce antidepressant-like effects in preclinical models.

The aim of this study was to test the effect induced by acute or repeated (7 days) treatment with 7-nitroindazole (7-NI), a preferential inhibitor of neuronal NOS, in rats submitted to the learned helplessness (LH) model. In addition, we aimed at investigating if 7-NI treatment would increase brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus, similarly to the effect of prototype antidepressants.

Animals were submitted to a pre-test (PT) session with inescapable footshocks or habituation (no shocks) to the experimental shuttle box. Six days later they were exposed to a test with escapable footshocks. Independent groups received acute (a single injection after PT or before test) or repeated (once a day for 7 days) treatment with vehicle or 7-NI (30 mg/kg).

Repeated, but not acute, treatment with 7-NI attenuated LH development. The effect was similar to repeated imipramine treatment. Moreover, in an independent experimental group, only repeated treatment with 7-NI and imipramine increased BDNF protein levels in the hippocampus.

The results suggest the nitrergic system could be a target for the treatment of depressive-like conditions. They also indicate that, similar to the positive control imipramine, the antidepressant-like effects of NOS inhibition could involve an increase in hippocampal BDNF levels.

Bipolar Disorder (BD) is a severe psychiatric condition characterized by grey matter (GM) volumes reduction. Neurotrophic factors have been suggested to play a role in the neuroprogressive changes during the illness course. In particular peripheral brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in BD. The aim of our study was to investigate if serum levels of BDNF are associated with GM volumes in BD patients and healthy controls (HC).

We studied 36 inpatients affected by a major depressive episode in course of BD type I and 17 HC. Analysis of variance was performed to investigate the effect of diagnosis on GM volumes in the whole brain. Threshold for significance was P < 0.05, Family Wise Error (FWE) corrected for multiple comparisons. All the analyses were controlled for the effect of nuisance covariates known to influence GM volumes, such as age, gender and lithium treatment.

BD patients showed significantly higher serum BDNF levels compared with HC. Reduced GM volumes in BD patients compared to HC were observed in several brain areas, encompassing the caudate head, superior temporal gyrus, insula, fusiform gyrus, parahippocampal gyrus, and anterior cingulate cortex. The interaction analysis between BDNF levels and diagnosis showed a significant effect in the middle frontal gyrus. HC reported higher BDNF levels associated with higher GM volumes, whereas no association between BDNF and GM volumes was observed in BD.

Our study seems to suggest that although the production of BDNF is increased in BD possibly to prevent and repair neural damage, its effects could be hampered by underlying neuroinflammatory processes interfering with the neurodevelopmental role of BDNF.

Evidences suggest that GAB2 and BDNF genes may be associated with Alzheimer's disease (AD). We aimed to investigate the GAB2 rs2373115 and BDNF rs6265 polymorphisms and the risk of AD in a Brazilian sample.

269 AD patients and 114 controls were genotyped with Real-time PCR. Multifactor dimensionality reduction (MDR) was employed to explore the effects of gene–gene interactions.

GAB2 and BDNF were not associated with AD in our sample. Nevertheless BDNF Val allele (rs6265) presented a synergic association with the APOE ε4 allele. A multiple logistic regression demonstrated that the APOE ε4 allele and years of education were the best predictors for AD. In ε4 non-carriers sex, education and hypertension were independently correlated with AD, while in ε4 carriers we did not observe any association. The findings were further confirmed by bootstrapping method.

Our data suggest that the interaction of BDNF and APOE has significant effect on AD. Moreover in absence of ε4, female sex, low level of education and hypertension are independently associated with AD. Interventions aimed to prevent AD should focus on these factors and also taking into account the APOE alleles.

Depression and cognitive decline are highly prevalent in older persons and both are associated with low serum brain derived neurotrophic factor (BDNF). Mutual pathways of depression and cognitive decline in older persons may explain the overlap in symptoms and low serum BDNF. We hypothesized that serum BDNF levels are lower in depressed elderly with poor cognitive performance (global or specifically in working memory, speed of information processing, and episodic memory) compared to depressed elderly without cognitive impairment or non-depressed controls.

BDNF Serum levels and cognitive functioning were examined in 378 depressed persons and 132 non-depressed controls from a large prospective study on late-life depression. The association between BDNF levels and each cognitive domain among the depressed patients was tested by four separate linear regression models adjusted for relevant covariates. An analysis of covariance (ANCOVA) was performed to compare BDNF serum levels in three groups (depression with cognitive impairment, depression without cognitive impairment, and non-depressed controls), when adjusted for potential confounders.

No significant linear association was found between BDNF and any of the four cognitive domains tested. There are no differences in BDNF levels between controls and depressed patients with or without cognitive impairment global or in specific domains after controlling for confounders.

BDNF serum levels in this cohort of older depressed patients and controls are not related to cognitive functioning. As BDNF is essential for the survival and functioning of neurons, its levels may remain normal in stages of disease where remission is achievable.