Lower and higher volumes of physical exercise build up brain reserves against memory deficits triggered by a head injury in mice.

Decreasing neurotrophic support and impaired mitochondrial bioenergetics are key mechanisms for long-term neurodegeneration and cognitive decline after traumatic brain injury (TBI). We hypothesize that preconditioning with lower and higher volumes of physical exercise upregulates the CREB-BDNF axis and bioenergetic capability, which might serve as neural reserves against cognitive impairment after severe TBI. Using a running wheel mounted in the home cage, mice were engaged in lower (LV, 48 h free access, and 48 h locked) and higher (HV, daily free access) exercise volumes for thirty days. Subsequently, LV and HV mice remained for additional thirty days in the home cage with the running wheel locked and were euthanized. The sedentary group had the running wheel always locked. For the same type of exercise stimulus in a given time, daily workout presents higher volume than alternate days workout. The total distance ran in the wheel was the reference parameter to confirm distinct exercise volumes. On average, LV exercise ran 27.522 m and HV exercise ran 52.076 m. Primarily, we investigate whether LV and HV protocols increase neurotrophic and bioenergetic support in the hippocampus thirty days after exercise ceased. Regardless of volume, exercise increased hippocampal pCREBSer133-CREB-proBDNF-BDNF signaling and mitochondrial coupling efficiency, excess capacity, and leak control, that may compose the neurobiological basis for neural reserves. Further, we challenge these neural reserves against secondary memory deficits triggered by a severe TBI. After thirty days of exercise LV and HV, and sedentary (SED) mice were submitted to the CCI model. Mice remained for additional thirty days in the home cage with the running wheel locked. The mortality after severe TBI was approximately 20% in LV and HV, while in the SED was 40%. Also, LV and HV exercise sustained hippocampal pCREBSer133-CREB-proBDNF-BDNF signaling, mitochondrial coupling efficiency, excess capacity, and leak control for thirty days after severe TBI. Corroborating these benefits, the mitochondrial H2O2 production linked to complexes I and II was attenuated by exercise regardless of the volume. These adaptations attenuated spatial learning and memory deficits caused by TBI. In summary, preconditioning with LV and HV exercise builds up long-lasting CREB-BDNF and bioenergetic neural reserves that preserve memory fitness after severe TBI.

l-Hypaphorine and d-hypaphorine: Specific antiacetylcholinesterase activity in rat brain tissue.

Acetylcholinesterase (AChEis) inhibitors are used to treat neurodegenerative diseases like Alzheimer's disease (AD). l-Hypaphorine (l-HYP) is a natural indole alkaloid that has been shown to have effects on the central nervous system (CNS). The goal of this research was to synthesize l-HYP and d-HYP and test their anticholinesterasic properties in rat brain regions. l-HYP suppressed acetylcholinesterase (AChE) activity only in the cerebellum, whereas d-HYP inhibited AChE activity in all CNS regions studied. No cytotoxic effect on normal human cells (HaCaT) was observed in the case of l-HYP and d-HYP although an increase in cell proliferation. Molecular modeling studies revealed that d-HYP and l-HYP have significant differences in their binding mode positions and interact stereospecifically with AChE's amino acid residues.

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy

Objective: Clinical and biological correlates of resilience in major depressive disorder are scarce. We aimed to investigate the effect of the Val66Met polymorphism in the BDNF gene on resilience scores in major depressive disorder patients and evaluate the polymorphism's moderation effect on resilience scores in response to cognitive therapy. Method: A total of 106 major depressive disorder patients were enrolled in this clinical randomized study. The Resilience Scale and the Hamilton Rating Scale for Depression were applied at baseline, post-treatment, and at six months of follow-up. Blood samples were obtained at baseline for molecular analysis. Results: The baseline resilience scores were higher in patients with the Met allele (114.6±17.6) than in those with the Val/Val genotype (104.04±21.05; p = 0.037). Cognitive therapy treatment increased resilience scores (p ≤ 0.001) and decreased depressive symptoms (p ≤ 0.001). In the mixed-effect model, the Val/Val genotype represented a decrease in resilience scores (t218 = -1.98; p = 0.048), and the Val66Met polymorphism interacted with sex to predict an increase in total resilience scores during cognitive treatment (t218 = 2.69; p = 0.008). Conclusion: Our results indicate that cognitive therapy intervention could improve resilience in follow-up, considering that gender and genetic susceptibility are predicted by the Val66Met polymorphism.

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy.

OBJECTIVE: Clinical and biological correlates of resilience in major depressive disorder are scarce. We aimed to investigate the effect of the Val66Met polymorphism in the BDNF gene on resilience scores in major depressive disorder patients and evaluate the polymorphism's moderation effect on resilience scores in response to cognitive therapy. METHOD: A total of 106 major depressive disorder patients were enrolled in this clinical randomized study. The Resilience Scale and the Hamilton Rating Scale for Depression were applied at baseline, post-treatment, and at six months of follow-up. Blood samples were obtained at baseline for molecular analysis. RESULTS: The baseline resilience scores were higher in patients with the Met allele (114.6±17.6) than in those with the Val/Val genotype (104.04±21.05; p = 0.037). Cognitive therapy treatment increased resilience scores (p ≤ 0.001) and decreased depressive symptoms (p ≤ 0.001). In the mixed-effect model, the Val/Val genotype represented a decrease in resilience scores (t218 = -1.98; p = 0.048), and the Val66Met polymorphism interacted with sex to predict an increase in total resilience scores during cognitive treatment (t218 = 2.69; p = 0.008). CONCLUSION: Our results indicate that cognitive therapy intervention could improve resilience in follow-up, considering that gender and genetic susceptibility are predicted by the Val66Met polymorphism.

S100B protein and neuron-specific enolase as predictors of postoperative cognitive dysfunction in aged dogs: a case-control study.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) may be related to brain injury. S100B protein and neuron-specific enolase (NSE) have been investigated as potential biochemical markers of neural cell injury in animals and humans. This study aimed to investigate the association between POCD, brain injury and serum concentrations of S100B and NSE after periodontal surgery in aged dogs. STUDY DESIGN: Prospective observational animal study. ANIMALS: A total of 24 male and female dogs undergoing periodontal surgery. METHODS: Dogs were separated into two groups based on age: control group, 10 dogs ≤ 8 years and aged group, 14 dogs > 8 years. Cognitive function was measured preoperatively and on the seventh postoperative day using the Canine Cognitive Dysfunction Rating scale and the Age-Related Cognitive and Affective Disorders scale. S100B protein and NSE serum concentrations were measured before and immediately after the surgery. RESULTS: POCD was not observed after surgery in the present study. Serum concentrations of S100B and NSE were increased postoperatively in the control group but not in the aged group (p = 0.04 and 0.03, respectively). Preoperative S100B serum concentrations were significantly higher in the aged group (p = 0.01). CONCLUSIONS: There was no association between POCD and high concentrations of S100B and NSE in dogs. However, increased postoperative serum concentrations of S100B and NSE were found in the control group after surgery, an effect that may indicate neural damage. CLINICAL RELEVANCE: The results suggest that anesthesia and oral surgery are associated with higher postoperative serum concentrations of S100B and NSE in dogs ≤ 8 years old, which may indicate neural damage. Serum concentrations of S100B were elevated in aged dogs before anesthesia, a finding that might be related to chronic preoperative brain damage.

Probucol Protects Neuronal Cells Against Peroxide-Induced Damage and Directly Activates Glutathione Peroxidase-1.

Experimental evidence has shown that probucol, a hypocholesterolemic agent, is also able to increase glutathione peroxidase (GPx) activity. However, there is a lack of knowledge about the mechanism(s) involved in this event. In this study, in vitro experiments with purified GPx1 from bovine erythrocytes and cultured SH-SY5Y neuroblastoma cells, as well as in silico studies with GPx1, were performed in order to elucidate mechanisms mediating the stimulatory effect of probucol on GPx activity and to investigate the relevance of this event in terms of susceptibility against peroxide-induced cytotoxicity. In vitro experiments with purified GPx1 showed a direct stimulatory effect of probucol on the activity of GPx1, which was related to an increase in Vmax with no changes in KM. Probucol also increased GPx activity in cultured SH-SY5Y neuroblastoma cells, while the levels of GPx1 expression were not changed, corroborating the results found with the purified enzyme. In addition, probucol rendered SH-SY5Y cells more resistant to hydroperoxide-induced cytotoxicity, and this event was abolished in GPx1 knocked-down cells. In silico studies with GPx1 pointed to a potential binding site for probucol at the close vicinity of the GSH pocket. Collectively, the results presented herein indicate that GPx1 plays a central role in the probucol-induced protective effects against peroxide toxicity. This highlights a novel target (GPx1) and a new mechanism of action (direct activation) for an "old drug." The relevance of such results for in vivo conditions deserves further investigation.

Intradialytic exercise with blood flow restriction: Something to add to hemodialysis adequacy? Findings from a crossover study.

INTRODUCTION: Hemodialysis (HD) increases the lifespan of chronic kidney disease (CKD) patients. However, HD is only partially effective in replacing renal function. The aim of this study is to compare HD adequacy between sessions with intradialytic exercise with or without blood flow restriction (BFR) with sessions without exercise. METHODS: A crossover study including 22 adult CKD patients on HD. The patients were assigned to BFR (n = 11) or exercise alone group (n = 11). Each patient was submitted to four HD sessions (two with exercise and two control sessions). HD adequacy was assessed by equilibrated Kt/V-urea (eKT/V), single-pool Kt/V-urea (sp-Kt/V), urea and phosphorus rebound, urea reduction ratio (URR) and removal of urea and phosphorus in dialysate. FINDINGS: BFR exercise improved eKt/V and sp-Kt/V (1.32 ± 0.21 vs. 1.10 ± 0.16 for control, P < 0.001; 1.53 ± 0.26 vs. 1.27 ± 0.19 for control, P < 0.001, respectively) and URR (72.5 ± 5.4% vs. 66.1 ± 7.7% for control, P < 0.001). No difference in eKt/V, sp-Kt/V or URR could be detected between exercise alone and control HD sessions. Urea rebound was lower in BFR exercise vs. control sessions (-8.9 ± 9.1% vs. 30.7 ± 12.8%, P < 0.01) and exercise alone vs. control sessions (13.3 ± 29.0% vs. 42.4 ± 15.3%, P < 0.01). Phosphorus rebound was marginally lower in exercise vs. control sessions (14.4 ± 19.1% vs. 28.4 ± 22.1%, P = 0.18). Urea and phosphorus mass removal in dialysate were marginally higher in exercise vs. control sessions (42.2 ± 19.4 g vs. 35.7 ± 12.5 g, P = 0.24; 912.1 ± 360.9 mg vs. 778.6 ± 245.1 mg, P = 0.28). CONCLUSIONS: Intradialytic exercise with BFR was more effective than standard exercise in increasing HD adequacy.

Serum level of nerve growth factor is a potential biomarker of conversion to bipolar disorder in women with major depressive disorder.

AIM: The aim of this study was to identify biomarkers associated with major depressive disorder (MDD) and conversion from MDD to bipolar disorder (BD) in an outpatient sample of women. METHODS: This was a longitudinal study including women diagnosed with MDD and aged 18 to 60 years. The follow-up was 3 years. The diagnosis was performed using the Mini International Neuropsychiatric Interview Plus. Blood collection was just performed in the first phase. Serum interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and nerve growth factor (NGF) levels were measured using a commercial immunoassay kit. RESULTS: We included 156 women. The conversion rate from MDD to BD was 15.4% (n = 24). NGF serum levels were increased in patients who converted to BD compared to the remitted MDD group and current MDD group (P = 0.013). The Bonferroni post-hoc test for multiple comparisons revealed significant differences for higher NGF levels in patients who converted to BD compared to patients with current MDD (P = 0.037). Interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor serum levels did not differ among the groups. CONCLUSION: Our results suggest that NGF might be a useful biomarker associated with early detection of conversion to BD, helping clinicians in the clinical diagnosis.

Effects of cognitive-behavioral therapy on neurotrophic factors in patients with major depressive disorder

Objective: To correlate neurotrophic factors - brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) - and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT). Methods: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed. Results: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. Conclusion: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.

Effects of cognitive-behavioral therapy on neurotrophic factors in patients with major depressive disorder.

OBJECTIVE: To correlate neurotrophic factors - brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) - and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT). METHODS: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed. RESULTS: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. CONCLUSION: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.

Enhanced cholinergic-tone during the stress induce a depressive-like state in mice.

Major depressive disorder has a heterogeneous etiology, since it arises from the interaction of multiple factors and different pathophysiological mechanisms are involved in the symptomatology. This study aimed to investigate the role of the cholinergic system in the susceptibility to stress and, consequently, in the depression-like behavior. C57BL/6 mice were treated with Physostigmine (PHYS), an acetylcholinesterase (AChE) inhibitor, and were submitted to the social defeat stress. For the behavioral evaluation of the locomotor activity, anxiety-like and depression-like behaviors the open field, elevated plus maze, sucrose preference, social interaction and forced swim were used. Hippocampus and prefrontal cortex samples were collected for evaluation of AChE activity, as well as blood samples for analysis of serum cortisol levels. Our results showed that 15 min after the injection of PHYS there was a significant inhibition of AChE activity in the hippocampus and in the prefrontal cortex. On the other hand, in the end of the experimental design, day 12, there was no difference in AChE activity levels. Inhibition of AChE and exposure to the stress led to an increase in cortisol levels. Animals that received PHYS and were exposed to stress showed less social interaction and greater learned helplessness, anhedonia and anxious-like behavior. Taken together, our findings suggest that increasing the cholinergic tone shortly before stress induction impacts on the ability to cope with upcoming stressful situations, leading to a depressive-like state.

Mood disorder, anxiety, and suicide risk among subjects with alcohol abuse and/or dependence: a population-based study

Objective: To evaluate the prevalence of alcohol abuse and/or dependence in a population-based sample of young adults and assess the prevalence of comorbid mood disorders, anxiety, and suicide risk in this population. Methods: This cross-sectional, population-based study enrolled 1,953 young adults aged 18-35 years. The CAGE questionnaire was used to screen for alcohol abuse and/or dependence, with CAGE scores ≥ 2 considered positive. Psychiatric disorders were investigated through the structured Mini International Neuropsychiatric Interview (MINI). Results: Alcohol abuse and/or dependence was identified in 187 (9.60%) individuals (5.10% among women and 15.20% among men). Alcohol abuse and/or dependence were more prevalent among men than women, as well as among those who used tobacco, illicit drugs or presented with anxiety disorder, mood disorder, and suicide risk. Conclusion: These findings suggest that alcohol abuse and/or dependence are consistently associated with a higher prevalence of psychiatric comorbidities, could be considered important predictors of other psychiatric disorders, and deserve greater public heath attention, pointing to the need for alcohol abuse prevention programs.

Mood disorder, anxiety, and suicide risk among subjects with alcohol abuse and/or dependence: a population-based study.

OBJECTIVE: To evaluate the prevalence of alcohol abuse and/or dependence in a population-based sample of young adults and assess the prevalence of comorbid mood disorders, anxiety, and suicide risk in this population. METHODS: This cross-sectional, population-based study enrolled 1,953 young adults aged 18-35 years. The CAGE questionnaire was used to screen for alcohol abuse and/or dependence, with CAGE scores ≥ 2 considered positive. Psychiatric disorders were investigated through the structured Mini International Neuropsychiatric Interview (MINI). RESULTS: Alcohol abuse and/or dependence was identified in 187 (9.60%) individuals (5.10% among women and 15.20% among men). Alcohol abuse and/or dependence were more prevalent among men than women, as well as among those who used tobacco, illicit drugs or presented with anxiety disorder, mood disorder, and suicide risk. CONCLUSION: These findings suggest that alcohol abuse and/or dependence are consistently associated with a higher prevalence of psychiatric comorbidities, could be considered important predictors of other psychiatric disorders, and deserve greater public heath attention, pointing to the need for alcohol abuse prevention programs.

Polymorphism in CRHR1 gene affects the IL-1ß levels in suicidal attempters.

Approximately one million people commit suicide every year, being suicide attempts and ideation even more common. Changes in stress response and activation of the immune system have been associated with suicide risk. Here we investigated the interaction between immune system and HPA axis alterations in the suicide risk, looking for the influence of rs110402 CRHR1 SNP in the IL-1ß levels according to suicide ideation and attempt. This study evaluated 171 subjects of which 15 had suicidal ideation, 20 had suicide attempt and 136 were controls. Genotyping was performed by real-time PCR and IL-1ß levels were measured by ELISA. Our data showed that for each point increase in IL-1ß levels the risk of suicide attempt increased 5% [relative risk = 1.05 (95% CI: 1.0-1.10)]. After sample stratification by rs110402 SNP genotypes, we observed that in subjects carrying the A allele the risk raised to 15% [relative risk = 1.15 (95% CI: 1.03-1.28)], suggesting an apparent effect modification. Thus, this study showed that alterations in CRHR1 gene were associated with higher levels of IL-1ß, and increased risk for suicide, reinforcing the importance of multifactorial interactions of biological markers for psychiatric disorders.

Effects of Single Low Dose of Dexamethasone before Noncardiac and Nonneurologic Surgery and General Anesthesia on Postoperative Cognitive Dysfunction-A Phase III Double Blind, Randomized Clinical Trial.

UNLABELLED: Postoperative cognitive dysfunction (POCD) is a multifactorial adverse event most frequently in elderly patients. This study evaluated the effect of dexamethasone on POCD incidence after noncardiac and nonneurologic surgery. METHODS: One hundred and forty patients (ASA I-II; age 60-87 years) took part in a prospective phase III, double blind, randomized study involving the administration or not of 8 mg of IV dexamethasone before general anesthesia under bispectral index (BIS) between 35-45 or 46-55. Neuropsychological tests were applied preoperatively and on the 3rd, 7th, 21st, 90th and 180th days after surgery and compared with normative data. S100ß was evaluated before and 12 hours after induction of anesthesia. The generalized estimating equations (GEE) method was applied, followed by the posthoc Bonferroni test considering P<0.05 as significant. RESULTS: On the 3rd postoperative day, POCD was diagnosed in 25.2% and 15.3% of patients receiving dexamethasone, BIS 35-45, and BIS 46-55 groups, respectively. Meanwhile, POCD was present in 68.2% and 27.2% of patients without dexamethasone, BIS 35-45 and BIS 46-55 groups (p<0.0001). Neuropsychological tests showed that dexamethasone associated to BIS 46-55 decreased the incidence of POCD, especially memory and executive function. The administration of dexamethasone might have prevented the postoperative increase in S100ß serum levels. CONCLUSION: Dexamethasone can reduce the incidence of POCD in elderly patients undergoing surgery, especially when associated with BIS 46-55. The effect of dexamethasone on S100ß might be related with some degree of neuroprotection. TRIAL REGISTRATION: www.clinicaltrials.gov NCT01332812.

Mechanisms involved in the antinociception induced by spinal administration of inosine or guanine in mice.

It is well known that adenine-based purines exert multiple effects on pain transmission. Recently, we have demonstrated that guanine-based purines may produce some antinociceptive effects against chemical and thermal pain in mice. The present study was designed to investigate the antinociceptive effects of intrathecal (i.t.) administration of inosine or guanine in mice. Additionally, investigation into the mechanisms of action of these purines, their general toxicity and measurements of CSF purine levels were performed. Animals received an i.t. injection of vehicle (30mN NaOH), inosine or guanine (up to 600nmol) and submitted to several pain models and behavioural paradigms. Guanine and inosine produced dose-dependent antinociceptive effects in the tail-flick, hot-plate, intraplantar (i.pl.) glutamate, i.pl. capsaicin and acetic acid pain models. Additionally, i.t. inosine inhibited the biting behaviour induced by spinal injection of capsaicin and i.t. guanine reduced the biting behaviour induced by spinal injection of glutamate or AMPA. Intrathecal administration of inosine (200nmol) induced an approximately 115-fold increase on CSF inosine levels. This study provides new evidence on the mechanism of action of extracellular guanine and inosine presenting antinociceptive effects following spinal administration. These effects seem to be related, at least partially, to the modulation of A1 adenosine receptors.

Brain Insulin Administration Triggers Distinct Cognitive and Neurotrophic Responses in Young and Aged Rats.

Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24 months) and young (4 months) male Wistar rats were intracerebroventricularly injected with insulin (20 mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze. Insulin increased memory performance in young rats, but not in aged rats. Thus, we searched for cellular and molecular mechanisms that might account for this distinct memory response. In contrast with our expectation, insulin treatment increased the proliferative activity in aged rats, but not in young rats, implying that neurogenesis-related effects do not explain the lack of insulin effects on memory in aged rats. Furthermore, the expression levels of the IR and downstream signaling proteins such as GSK3-ß, mTOR, and presynaptic protein synaptophysin were increased in aged rats in response to insulin. Interestingly, insulin treatment increased the expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptors in the hippocampus of young rats, but not of aged rats. Our data therefore indicate that aged rats can have normal IR downstream protein expression but failed to mount a BDNF response after challenge in a spatial memory test. In contrast, young rats showed insulin-mediated TrkB/BDNF response, which paralleled with improved memory performance.

Association of interleukin-10 levels with age of onset and duration of illness in patients with major depressive disorder

Objective: To investigate peripheral levels of interleukin-10 (IL-10) in patients with major depressive disorder (MDD) and bipolar disorder (BD) and evaluate the relationship between IL-10, age of disease onset, and duration of illness. Methods: Case-control study nested in a population-based cohort of 231 individuals (age 18-24 years) living in Pelotas, state of Rio Grande do Sul, Brazil. Participants were screened for psychopathology using the Mini-International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV (SCID-I). Serum IL-10 was measured using commercially available immunoassay kits. Results: Peripheral levels of IL-10 were not significantly different in individuals with MDD or BD as compared to controls. However, higher IL-10 levels were found in MDD patients with a later disease onset as compared with controls or early-onset patients. In addition, IL-10 levels correlated negatively with illness duration in the MDD group. In the BD group, age of onset and duration of illness did not correlate with IL-10 levels. Conclusion: Higher levels of IL-10 are correlated with late onset of MDD symptoms. Moreover, levels of this cytokine might decrease with disease progression, suggesting that an anti-inflammatory balance may be involved in the onset of depressive symptoms and disease progression in susceptible individuals.

Association of interleukin-10 levels with age of onset and duration of illness in patients with major depressive disorder.

OBJECTIVE: To investigate peripheral levels of interleukin-10 (IL-10) in patients with major depressive disorder (MDD) and bipolar disorder (BD) and evaluate the relationship between IL-10, age of disease onset, and duration of illness. METHODS: Case-control study nested in a population-based cohort of 231 individuals (age 18-24 years) living in Pelotas, state of Rio Grande do Sul, Brazil. Participants were screened for psychopathology using the Mini-International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV (SCID-I). Serum IL-10 was measured using commercially available immunoassay kits. RESULTS: Peripheral levels of IL-10 were not significantly different in individuals with MDD or BD as compared to controls. However, higher IL-10 levels were found in MDD patients with a later disease onset as compared with controls or early-onset patients. In addition, IL-10 levels correlated negatively with illness duration in the MDD group. In the BD group, age of onset and duration of illness did not correlate with IL-10 levels. CONCLUSION: Higher levels of IL-10 are correlated with late onset of MDD symptoms. Moreover, levels of this cytokine might decrease with disease progression, suggesting that an anti-inflammatory balance may be involved in the onset of depressive symptoms and disease progression in susceptible individuals.

Changes in Purines Concentration in the Cerebrospinal Fluid of Pregnant Women Experiencing Pain During Active Labor.

Labor pain has been reported as a severe pain and can be considered as a model of acute visceral pain. It is well known that extracellular purines have an important role in pain signaling in the central nervous system. This study analyzes the relationship between extracellular purines and pain perception during active labor. A prospective observational study was performed. Cerebrospinal fluid (CSF) levels of the purines and their metabolites were compared between women at term pregnancy with labor pain (n = 49) and without labor pain (Caesarian section; n = 47). Control groups (healthy men and women without chronic or acute pain-n = 40 and 32, respectively) were also investigated. The CSF levels of adenosine were significantly lower in the labor pain group (P = 0.026) and negatively correlated with pain intensity measured by a visual analogue scale (r = -0.48, P = 0.0005). Interestingly, CSF levels of uric acid were significantly higher in healthy men as compared to women. Additionally, pregnant women showed increased CSF levels of ADP, GDP, adenosine and guanosine and reduced CSF levels of AMP, GTP, and uric acid as compared to non-pregnant women (P < 0.05). These findings suggest that purines, in special the nucleoside adenosine, are associated with pregnancy and labor pain.