Peripheral Brain-derived Neurotrophic Factor Research Articles

Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer’s disease: Possible role of BDNF and oxidative stress

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique which is increasingly used for cognitive impairment in Alzheimer’s Disease (AD). Although rTMS has been shown to modify Brain-Derived Neurotrophic Factor (BDNF) and oxidative stress levels in many neurological and psychiatric diseases, there is still no study evaluating the relationship between memory performance, BDNF, oxidative stress, and resting brain connectivity following rTMS in Alzheimer's patients. Furthermore, there are increasing clinical data showing that the stimulation of strategic brain regions may lead to more robust improvements in memory functions compared to conventional rTMS. In this study, we aimed to evaluate the possible disease-modifying effects of rTMS on the lateral parietal cortex in AD patients who have the highest connectivity with the hippocampus. To fill the mentioned research gaps, we have evaluated the relationships between resting-state Functional Magnetic Resonance Imaging (fMRI), cognitive scores, blood BDNF levels, and total oxidative/antioxidant status to explain the therapeutic and potential disease-modifying effects of rTMS which has been applied at 20 Hz frequencies for two weeks. Our results showed significantly increased visual recognition memory functions and clock drawing test scores which were associated with elevated peripheral BDNF levels, and decreased oxidant status after two weeks of left lateral parietal TMS stimulation. Clinically our findings suggest that the left parietal region targeted rTMS application leads to significant improvement in familiarity-based cognition associated with the network connections between the left parietal region and the hippocampus.

Peripheral BDNF correlated with miRNA in BD-II patients

ObjectivesWe have identified the association between peripheral levels of candidate miRNAs (miR-7-5p, miR-142-3p, miR-221-5p, and miR-370-3p) for BD-II in previous study. Most of these miRNAs are associated with regulation of expression of peripheral brain derived neurotrophic factor (BDNF) levels. In order to clarify the underlying mechanism of BDNF and miRNAs in the pathogenesis of BD-II, it is of interest to investigate the relation between the peripheral levels of miR-7-5p, miR-142-3p, miR-221-5p, miR-370-3p with BDNF levels. Because the BDNF Val66Met polymorphism influence the secretion of BDNF, we further stratified the above correlations by this polymorphism. MethodsWe have recruited 98 BD-II patients. Beside analyzing peripheral levels of miR-7-5p, miR-142-3p, miR-221-5p, miR-370-3p, and BDNF, the genetic distribution of the BDNF Val66Met polymorphism was also analyzed. ResultsWe found that the miR7-5p, miR221-5p, and miR370-3p significantly correlated with the BDNF levels for all patients. If stratified by the BDNF Val66Met polymorphism, the significant correlation between miR221-5p and miR370-3p with BDNF only remained in the Val/Met genotype. However, the correlation between miR7-5p and BDNF level is significant in all 3 genotypes. ConclusionOur result supported that these miRNAs may be involved in the pathomechanism of BD-II through relation with BDNF.

Effect of pedaling cadence on serum levels of brain-derived neurotrophic factor during ergometric exercise in healthy adults

Brain-derived neurotrophic factor (BDNF) is a known essential mediator responsible for the beneficial effects of physical activity on brain health. Exercise-induced lactate is a potential endogenous factor that may increase BDNF expression, and the selection of cadence in exercise prescription is thought to influence lactate concentrations. The aim of this study was to examine the effect of pedaling cadence on circulating BDNF levels through lactate production in healthy adult men. Seventeen healthy adult men participated in three experimental sessions: a 40-min session of cycle-ergometry exercise with a pedaling cadence of 60 rpm at a workload of 40% peak oxygen uptake (Ex.60), a 40-min cycling exercise with a pedaling cadence of 100 rpm at the same workload as the Ex.60 (Ex.100), and a session of complete rest for 40 min (CON). Serum BDNF levels were measured before and after each session, and heart rate (HR) and lactate concentrations were evaluated after each session. Ex.100 significantly increased serum BDNF and lactate levels (p 0.05). The relative change in BDNF levels had a significant strong correlation with relative change in lactate (p 0.05). High-cadence aerobic exercise can increase peripheral BDNF levels through an increase in lactate concentrations, whereas the workload is low to moderate. This study indicates that exercise regimen considering pedaling cadence may have the possibility of inducing better brain health.

Upregulating Effect of Wheat on Brain-Derived Neurotrophic Factor in Human Lung Adenocarcinoma A549 Cells.

The neurotrophic hypothesis of depression, that is, a deficiency in hippocampal brain-derived neurotrophic factor (BDNF) leads to depression, has gained widespread acceptance. BDNF is synthesized in various peripheral tissues such as the lung, kidney, liver, heart and testis, besides the brain. Peripheral BDNF can traverse the blood-brain barrier and reach the hippocampus; accordingly, substances that upregulate BDNF production in peripheral tissues may be useful in the treatment of depression. The Mediterranean diet, containing high amounts of whole grains including unrefined wheat, vegetables, fruits, nuts, and olive oil, reportedly reduces the risk of depression. The association between the high consumption of unrefined wheat in the Mediterranean diet and BDNF production in peripheral tissues is unclear. In this study, we investigated the BDNF production capacity of human lung adenocarcinoma cell line A549 and the effect of wheat on BDNF production in the cells. Methanol extracts of whole-wheat flour and wheat bran, which are forms of unrefined wheat, increased the BDNF level in the culture medium of A549 cells. However, methanol extract of wheat endosperm had no effect on the BDNF level in these cells. Our findings suggest that wheat bran contains ingredients that upregulate BDNF production in peripheral tissues, and unrefined wheat potentially contributes to the elevation in peripheral BDNF level.

Does Aerobic and Resistance Exercise Influence Episodic Memory through Unique Mechanisms?

Aerobic and resistance exercise (acute and chronic) independently and collectively induce beneficial responses in the brain that may influence memory function, including an increase in cerebral blood flow, neurogenesis, neuroelectrical alterations, and protein production. However, whether aerobic and resistance exercise improve memory via similar or distinct mechanisms has yet to be fully explained. Here, we review the unique influence of aerobic and resistance exercise on neural modulation, proteins, receptors, and ultimately, episodic memory. Resistance training may optimize neural communication, information processing and memory encoding by affecting the allocation of attentional resources. Moreover, resistance exercise can reduce inflammatory markers associated with neural communication while increasing peripheral and central BDNF (brain-derived neurotrophic factor) production. Aerobic training increases hippocampal levels of BDNF and TrkB (Tropomyosin receptor kinase B), protein kinases and glutamatergic proteins. Likewise, both aerobic and anaerobic exercise can increase CREB (cAMP response element-binding protein) phosphorylation. Thus, we suggest that aerobic and resistance exercise may influence episodic memory via similar and, potentially, distinct mechanisms.

Acute Systemic Response Of BDNF, Lactate and Cortisol to Strenuous Exercise Modalities in Healthy Untrained Women.

Acute bouts of intense exercise increase lactate concentration, which in turn stimulates brain-derived neurotrophic factor (BDNF) production. Cortisol released during intense exercise might inhibit BDNF synthesis. This study examined the acute effects of 2 protocols of strenuous exercise on serum BDNF. Seventeen physically-active healthy females (Age = 20.0 ± 0.9 yr., BMI = 23.0 ± 2.6 kg/m2) performed a strenuous cycle-ergometer graded exercise test (GXT) and a high-intensity interval training session (HIIT). Serum BDNF, serum cortisol, cortisol: BDNF ratio and blood lactate (BLa) were recorded at baseline and immediately following exercise. Although non-statistically significant, the HIIT session elicited a higher magnitude of change from baseline for BDNF (d = 0.17) and cortisol (d = 1.18) than after the GXT (d = -0.26, and d = 0.82, respectively). An interaction was found between GXT and HIIT trials and measurements on BLa levels, with higher post-exertion values after HIIT than after GXT (p < 0.0001, η2 = 0.650, 95%CI = 2.2, 5.2). The higher BLa levels did not raise circulating BDNF. The elevated cortisol levels may have overcome the effects of lactate on BDNF. However, the higher BLa induced by HIIT suggest that interval exercise modality on the long-term could be a feasible intervention to increase circulating peripheral BDNF, at least in untrained healthy women.

Circulating Brain-Derived Neurotrophic Factor, Antioxidant Enzymes Activities, and Mitochondrial DNA in Bipolar Disorder: An Exploratory Report.

AimAccumulated evidence indicates that neurotrophin deregulations, oxidative stress injury, and mitochondrial dysfunction have been involved in bipolar disorder (BD); however, their real roles in BD are unclear. Investing the possible interaction between three systems is worthwhile understanding this complex process.MethodsWe measured plasma brain-derived neurotrophic factor (BDNF) level, leukocytes mitochondrial DNA copy number (mtDNAcn), and activities of antioxidant enzymes in BD patients (n = 97) and healthy controls (n = 31). Analysis of variance and linear regression analyses were performed to explore the interaction between mtDNAcn, antioxidant enzymes, and BDNF.ResultsCompared with healthy controls, there were significant decreases of glutathione peroxidase activity, BDNF levels, and mtDNA content, significant increases of manganese superoxide dismutase (MnSOD) activity among BD patients (all p < 0.05). Regression analysis showed MnSOD activity had a moderate effect on BDNF (beta = 0.23, t = 8.5, p = 0.001). Copper zinc SOD and total SOD activity were significantly correlated with Hamilton Depression Scale scores in depressive patients (r = −0.38, p = 0.013; r = −0.35, p = 0.022). Unexpectedly, we observed no significant correlation between mtDNA content and BDNF in BD patients (p > 0.05).ConclusionThe findings coincide with our hypothesis that abnormal antioxidant enzymes, mtDNAcn, and peripheral BDNF may be involved in the course of BD. There were significant correlations between peripheral BDNF, antioxidant enzyme activities and mtDNAcn, suggesting that oxidative stress, mitochondrial function, and BDNF may influence each other in BD.

Plasma Exosomal Brain-Derived Neurotrophic Factor Correlated with the Postural Instability and Gait Disturbance-Related Motor Symptoms in Patients with Parkinson's Disease.

Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin, responsible for neuronal development, function, and survival. Assessments of peripheral blood BDNF in patients with Parkinson’s disease (PD) previously yielded inconsistent results. Plasma exosomes can carry BDNF, so this study investigated the role of plasma exosomal BDNF level as a biomarker of PD. A total of 114 patients with mild to moderate PD and 42 non-PD controls were recruited, and their clinical presentations were evaluated. Plasma exosomes were isolated with exoEasy Maxi Kits, and enzyme-linked immunosorbent assay was used to assess plasma exosomal BDNF levels. Statistical analysis was performed using SPSS version 19.0, and findings were considered significant at p < 0.05. The analysis revealed no significant differences in plasma exosomal BDNF levels between patients with PD and controls. Patients with PD with low plasma exosomal BDNF levels (in the lowest quartile) exhibited a significant association with daily activity dysfunction but not with cognition/mood or overall motor symptoms as assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Investigation of UPDRS part III subitems revealed that low plasma exosomal BDNF level was significantly associated with increased motor severity of postural instability and gait disturbance (PIGD)-associated symptoms (rising from a chair, gait, and postural stability) after adjustment for age and sex. In conclusion, although plasma exosomal BDNF level could not distinguish patients with PD from controls, the association with PIGD symptoms in patients with PD may indicate its potential role as a biomarker. Follow-up studies should investigate the association between plasma exosomal BDNF levels and changes in clinical symptoms.

Peripheral BDNF Response to Physical and Cognitive Exercise and Its Association With Cardiorespiratory Fitness in Healthy Older Adults.

Physical exercise (PE) has been shown to improve brain function via multiple neurobiological mechanisms promoting neuroplasticity. Cognitive exercise (CE) combined with PE may show an even greater effect on cognitive function. Brain-derived neurotrophic factor (BDNF) is important for neuroplastic signaling, may reduce with increasing age, and is confounded by fitness. The source and physiological role of human peripheral blood BDNF in plasma (pBDNF) is thought to differ from that in serum (sBDNF), and it is not yet known how pBDNF and sBDNF respond to PE and CE. A training intervention study in healthy older adults investigated the effects of acute (35 min) and prolonged (12 weeks, 30 sessions) CE and PE, both alone and in combination, on pBDNF and sBDNF. Cross-sectional associations between baseline pBDNF, sBDNF and cardiorespiratory fitness (CRF) were also investigated. Participants (65–75 years) were randomly assigned to four groups and prescribed either CE plus 35 min of rest (n = 21, 52% female); PE [performed on a cycle ergometer at moderate intensity (65–75% of individual maximal heart rate)] plus 35 min of rest (n = 27, 56% female); CE plus PE (n = 24, 46% female), or PE plus CE (n = 25, 52% female). Groups were tested for CRF using a maximal treadmill ergometer test (VO2peak); BDNF levels (collected 48 h after CRF) during baseline, after first exercise (PE or CE) and after second exercise (PE, CE or rest); and cognitive ability pre and post 12-week training. At both pre and post, pBDNF increased after CE and PE (up to 222%), and rest (∼67%), whereas sBDNF increased only after PE (up to 18%) and returned to baseline after rest. Acute but not prolonged PE increased both pBDNF and sBDNF. CE induced acute changes in pBDNF only. Baseline pBDNF was positively associated with baseline sBDNF (n = 93, r = 0.407, p < 0.001). No changes in CRF were found in any of the groups. Baseline CRF did not correlate with baseline BDNF. Even though baseline pBDNF and sBDNF were associated, patterns of changes in pBDNF and sBDNF in response to exercise were explicitly different. Further experimental scrutiny is needed to clarify the biological mechanisms of these results.

The role of peripheral brain-derived neurotrophic factor in chronic osteoarthritic joint pain.

The role of peripheral brain-derived neurotrophic factor in chronic osteoarthritic joint pain.

Effect of vortioxetine vs. escitalopram on plasma BDNF and platelet serotonin in depressed patients

Escitalopram and vortioxetine are efficacious antidepressants. They directly target serotonin (5-HT) system, but vortioxetine mechanism of action is distinct from the one of selective serotonin reuptake inhibitors (SSRIs). Treatment with SSRIs decrease platelet 5-HT concentration and increase peripheral brain-derived neurotrophic factor (BDNF) levels. Since vortioxetine has a multimodal mechanism of action, it is expected to have a greater effect on circulatory BDNF concentration, compared to conventional antidepressants. This longitudinal study aimed to explore and compare the effects of 4-weeks of treatment with vortioxetine and escitalopram on plasma BDNF and platelet 5-HT concentration in patients with major depressive disorder (MDD). The results revealed that vortioxetine significantly increased plasma BDNF concentration (p = .018) and significantly decreased platelet 5-HT concentration (p < .001). Treatment with escitalopram significantly decreased platelet 5-HT concentration (p < .001), but it did not affect plasma BDNF concentration (p = .379). Response to vortioxetine was not predicted by baseline plasma BDNF or platelet 5-HT concentration, but response to escitalopram was predicted by baseline platelet 5-HT concentration. These effects might be due to vortioxetine unique mechanism of action, but the clinical implications are unclear. It remains to be determined whether this finding extends during long-term vortioxetine treatment, and which, if any, clinical effects emerge from BDNF increase.

Cannabis use influence on peripheral brain-derived neurotrophic factor levels in antipsychotic-naïve first-episode psychosis.

The objective of this study is to determine whether cannabis influences BDNF levels in patients with psychosis (FEP) and healthy volunteers (HV) to help understand the role of BDNF in psychosis. We assessed the association between BDNF and cannabis in a cohort of FEP antipsychotic-naïve patients and HV, whilst controlling for other potential confounding factors. 70 FEP drug-naive patients and 57 HV were recruited. A sociodemographic variable collection, structured clinical interview, weight and height measurement, substance use determination, and blood collection to determine BDNF levels by ELISA analysis were done. In FEP patients, cannabis use was associated with BDNF levels (high cannabis use was associated with lower BDNF levels). Moreover, cannabis use was statistically significantly associated with age (high use of cannabis was associated with younger age). In HV, no relationship between cannabis use and BDNF levels was observed. Otherwise, cannabis use was significantly associated with tobacco use, so that high cannabis users were also high tobacco users. This study showed a different association between cannabis use and BDNF levels in FEP patients compared with HV, particularly, with high doses of cannabis. These findings may help understand the deleterious effects of cannabis in some vulnerable individuals, as well as discrepancies in the literature.

Acute increases in brain-derived neurotrophic factor in plasma following physical exercise relates to subsequent learning in older adults

Multidomain lifestyle interventions represents a promising strategy to counteract cognitive decline in older age. Brain-derived neurotrophic factor (BDNF) is essential for experience-dependent plasticity and increases following physical exercise, suggesting that physical exercise may facilitate subsequent learning. In a randomized-controlled trial, healthy older adults (65–75 years) completed a 12-week behavioral intervention that involved either physical exercise immediately before cognitive training (n = 25; 13 females), physical exercise immediately after cognitive training (n = 24; 11 females), physical exercise only (n = 27; 15 females), or cognitive training only (n = 21; 12 females). We hypothesized that cognition would benefit more from cognitive training when preceded as opposed to followed by physical exercise and that the relationship between exercise-induced increases in peripheral BDNF and cognitive training outcome would be greater when cognitive training is preceded by physical exercise. Greater increases of plasma BDNF were associated with greater cognitive training gains on trained task paradigms, but only when such increases preceded cognitive training (ß = 0.14, 95% CI [0.04, 0.25]). Average cognitive training outcome did not differ depending on intervention order (ß = 0.05, 95% CI [−0.10, 0.20]). The study provides the first empirical support for a time-critical but advantageous role for post-exercise increases in peripheral BDNF for learning at an interindividual level in older adults, with implications for future multidomain lifestyle interventions.

Low brain-derived neurotrophic factor protein levels and single-nucleotide polymorphism Val66Met are associated with peripheral neuropathy in type II diabetic patients.

Studies by our group demonstrated brain-derived neurotrophic factor (BDNF) levels in blood and BDNF-Val66met-SNP as potential biomarkers in chemotherapy-induced peripheral neuropathy. Here, we evaluate symptoms of peripheral neuropathy (PN) and depression in patients with type II diabetes mellitus in search of an association with serum BDNF levels and the Val66Met-SNP. In total, 90 patients enrolled in the study; 23 (25.6%) had known PN, as determined by nerve conduction studies (NCS-PN), and 67 (74.4%) were not diagnosed with PN (U-PN). PN symptoms were assessed and graded in these groups using the total neuropathy score (TNSr) and DN4 scales. Small nerve fiber testing of sensitivity thresholds to cold, warm and hot pain signals was performed using the Q-sense device. Depression was assessed using the PHQ9 questionnaire. BDNF protein levels and Val66Met-SNP were determined with ELISA and Sanger sequencing, respectively. NCS-PN patients showed lower serum BDNF levels alongside significantly higher TNSr, DN4 and PHQ9 scores and lower hot pain sensitivity thresholds as compared to U-PN patients. Patients with Met-BDNF-SNP showed increased TNSr scores and lower hot pain sensitivity thresholds as compared to patients with Val-BDNF-SNP. Depression showed a weaker correlation with sensitivity thresholds to hot pain signals as compared to TNSr and DN4 scores. Diminished peripheral BDNF resources and Met-BDNF-SNP genotype are associated with augmented symptoms of PN in patients with type II diabetes mellitus. Sensitivity thresholds to hot pain signals may be less influenced by depression and possibly more accurately detect PN symptoms in diabetic patients.

Evaluation of Biochemical and Epigenetic Measures of Peripheral Brain-Derived Neurotrophic Factor (BDNF) as a Biomarker in Huntington's Disease Patients.

Huntington’s disease (HD) is an autosomal-dominant neurodegenerative movement disorder that presents with prominent cognitive and psychiatric dysfunction. Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of HD, as well as other neurodegenerative and psychiatric disorders, and epigenetic alterations in the complex BDNF promoter have been associated with its deregulation in pathological conditions. BDNF has gained increased attention as a potential biomarker of disease; but currently, the conflicting results from measurements of BDNF in different biofluids difficult the assessment of its utility as a biomarker for HD. Here, we measured BDNF protein levels in plasma (n = 85) and saliva (n = 81) samples from premanifest and manifest HD patients and normal controls using ELISA assays. We further examined DNA methylation levels of BDNF promoter IV using DNA derived from whole blood of HD patients and healthy controls (n = 40) using pyrosequencing. BDNF protein levels were not significantly different in plasma samples across diagnostic groups. Plasma BDNF was significantly correlated with age in control subjects but not in HD patients, nor were significant gender effects observed. Similar to plasma, salivary BDNF was correlated with age only in control subjects, with no gender effects observed. Importantly, we detected significantly lower levels of salivary BDNF in premanifest and manifest HD patients compared to control subjects, with lower BDNF levels being observed in premanifest patients within a predicted 10 years to disease onset. Salivary and plasma BDNF levels were not significantly correlated with one another, suggesting different origins. DNA methylation at four out of the 12 CpG sites studied in promoter IV were significantly altered in HD patients in comparison to controls. Interestingly, methylation at three of these CpG sites was inversely correlated to the Hospital Anxiety and Depression Scale (HADS) scores. BDNF promoter methylation was not correlated with motor or cognitive scores in HD patients, and was not associated with sex or age in neither disease nor control groups. Conclusion: Our studies show that BDNF protein levels are decreased in saliva; and BDNF promoter methylation increased in blood in HD subjects when compared to controls. These findings suggest that salivary BDNF measures may represent an early marker of disease onset and DNA methylation at the BDNF promoter IV, could represent a biomarker of psychiatric symptoms in HD patients.

Is Peripheral BDNF Promoter Methylation a Preclinical Biomarker of Dementia?

Brain-derived neurotrophic factor (BDNF) has been implicated in dementia. Preliminary evidence suggests that BDNF DNA methylation may be a diagnostic biomarker of dementia, but the potential pre-clinical utility remains unclear. Participants in the ESPRIT study were assessed for cognitive function and dementia (DSM-IV criteria) over 14 years. BDNF exon 1 promoter methylation was measured in blood at baseline (n = 769) and buccal samples during follow-up (n = 1062). Genotyping was carried out for several common BDNF SNPs, including Val66Met (rs6265) and APOE ɛ4. Multivariable logistic regression analyses determined the association between BDNF methylation and both prevalent and incident dementia. Adjustment for gender, age, education, APOEɛ4 genotype, body mass index, depression, and type 2 diabetes, as well as possible effect modification by gender and genetic variation were also investigated. Weak evidence of an association between lower blood methylation and dementia was observed at one of 11 sites investigated (Δ-0.5%, 95% CI:-0.9,-0.04, p = 0.03, p = 0.22 adjusted for multiple comparisons). Buccal methylation at two other sites was associated with 14-year incident dementia cases prior to adjustment for multiple comparisons only, and the effect sizes were small (Δ+0.3%, OR:1.57, SE:0.30, p = 0.02, p = 0.14 adjusted and Δ-1.5%, OR:0.85, SE:0.06, p = 0.03, p = 0.14 adjusted). Genetic variation in the BDNF gene did not modify these associations, and no gender-specific effects were observed. There was only a weak correlation between blood and buccal BDNF log-methylation at two sites (both r=-0.11). There was no strong evidence that blood or buccal BDNF exon 1 promoter DNA methylation is associated with prevalent or incident dementia, and reported associations would not remain after adjustment for multiple testing.

A review of peripheral brain-derived neurotrophic factor levels in alcohol-dependent patients: Current understanding.

Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroplasticity of the brain, and its role in alcohol dependence has been explored in the recent past. Animal studies suggest that BDNF may function as a protective factor in transition from social drinking to an alcohol use disorder. However, clinical studies have not been able to establish similar findings and have shown mixed results. In order to obtain a comprehensive understanding, the current review aims to evaluate the existing literature on the role of BDNF in alcohol dependence. Articles were retrieved using search engines PubMed and Google Scholar. Original research studies focusing on human participants, published in English till October 2018 were reviewed. Studies which measured BDNF levels in serum or plasma or both were included in this study. A total of 13 studies were found which compared BDNF levels in alcohol-dependent patients with control population. The studies have mixed findings. Seven studies measured BDNF levels across the abstinence period, and most of the studies show improving BDNF levels across the abstinence. The current review supports the notion that BDNF plays an important role in the neuroplasticity of alcohol dependence. However, it is premature at this stage to draw conclusions that BDNF may be used as a biomarker, as there have been inconclusive findings when compared with control population. Future studies with longer follow-ups, larger sample size, comparing early and late periods of alcohol abstinence are required for better understanding of the role BDNF in alcohol dependence.

Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study

BackgroundHypothalamic pathology is a well-documented feature of Huntington's disease (HD) and is believed to contribute to circadian rhythm and habitual sleep disturbances. Currently, no therapies exist to combat hypothalamic changes, nor circadian rhythm and habitual sleep disturbances in HD. ObjectiveTo evaluate the effects of multidisciplinary rehabilitation on hypothalamic volume, brain-derived neurotrophic factor (BDNF), circadian rhythm and habitual sleep in individuals with preclinical HD. MethodsEighteen individuals with HD (ten premanifest and eight prodromal) undertook a nine-month multidisciplinary rehabilitation intervention (intervention group), which included exercise, cognitive and dual task training and social events, and were compared to a community sample of eleven individuals with premanifest HD receiving no intervention (control group). Hypothalamic volume, serum BDNF, salivary cortisol and melatonin concentrations, subjective sleep quality, daytime somnolence, habitual sleep-wake patterns, stress and anxiety and depression symptomatology were evaluated. ResultsHypothalamus grey matter volume loss was significantly attenuated in the intervention group compared to the control group after controlling for age, gender, Unified Huntington's Disease Rating Scale-Total Motor Score and number of cytosine-adenine-guanine repeats. Serum BDNF levels were maintained in the intervention group, but decreased in the control group following the study period. Both groups exhibited decreases in cortisol and melatonin concentrations. No changes were observed in sleep or mood outcomes. ConclusionsThis exploratory study provides evidence that multidisciplinary rehabilitation can reduce hypothalamic volume loss and maintain peripheral BDNF levels in individuals with preclinical HD but may not impact on circadian rhythm. Larger, randomised controlled trials are required to confirm these findings.

CHALLENGES AND OPPORTUNITIES WITH POLYGENIC RISK SCORES IN PSYCHIATRY

The main aim of this study is to evaluate the impact of functional remediation (FR) in serum brain derived neurotrophic factor (BDNF) levels in euthymic adult patients with Bipolar Disorder (BD). A total of 128 participants were recruited at the Hospital Clinic of Barcelona. They were assessed at baseline and at the end of follow-up by the means of Hamilton Depression Scale (HAM-D), Young Mania Rating Scale (YMRS) and Functioning Assessment Short Test (FAST), as well as a clinical structured interview to collect clinical and demographic variables of interest. Blood samples were also collected to assess BDNF levels. After baseline assessment, patients received FR, Psychoeducation or treatment as usual (TAU).One hundred and two out of 126 participants finished the study distributed as follows: FR group (n = 39); Psychoeducation group (n = 47) and TAU group (n = 16). Longitudinal repeated-measures analyses addressing the treatment effect on BDNF levels showed non-significant differences between the three groups (Pillai's trace = 0.06; F(2,97)= 0.28; p = 0.75), suggesting no interaction between treatment allocation and time on BDNF levels. The results of this study suggest that FR has no effect on peripheral BDNF levels in euthymic patients with BD, despite the improvement in psychosocial functioning.

Predicting stress resilience and vulnerability: brain-derived neurotrophic factor and rapid eye movement sleep as potential biomarkers of individual stress responses.

To examine the rapid eye movement sleep (REM) response to mild stress as a predictor of the REM response to intense stress and brain-derived neurotrophic factor (BDNF) as a potential biomarker of stress resilience and vulnerability. Outbred Wistar rats were surgically implanted with electrodes for recording electroencephalography (EEG) and electromyogram (EMG) and intraperitoneal Data loggers to record body temperature. Blood was also obtained to measure circulating BDNF. After recovery, rats were exposed to mild stress (novel chamber, NC) and later intense stress (shock training, ST), followed by sleep recording. Subsequently, rats were separated into resilient (Res; n=27) or vulnerable (Vul; n = 15) based on whether or not there was a 50% or greater decrease in REM after ST compared to baseline. We then compared sleep, freezing, and the stress response (stress-induced hyperthermia, SIH) across groups to determine the effects of mild and intense stress to determine if BDNF was predictive of the REM response. REM totals in the first 4 hours of sleep after exposure to NC predicted REM responses following ST with resilient animals having higher REM and vulnerable animals having lower REM. Resilient rats had significantly higher baseline peripheral BDNF compared to vulnerable rats. These results show that outbred rats display significant differences in post-stress sleep and peripheral BDNF identifying these factors as potential markers of resilience and vulnerability prior to traumatic stress.