Cortisol levels are positively correlated with hippocampal N-acetylaspartate.

BACKGROUND: This study examined the relationship of hypothalamic-pituitary-adrenal measures and hippocampal N-acetylaspartate (NAA) in posttraumatic stress disorder (PTSD) patients and control subjects. METHODS: Eleven patients with combat-related PTSD and 11 control subjects were evaluated with magnetic resonance spectroscopy as well as by morning salivary cortisol samples before and after administration of low-dose dexamethasone (.5 mg). RESULTS: Left hippocampal NAA was strongly associated with both pre-dexamethasone cortisol levels (n = 22, r =.53, p =.013) and post-dexamethasone cortisol levels (n = 22, r =.63, p =.002). After accounting for clinical symptom severity and hippocampal volume, cortisol levels accounted for 21.9% of the variance (F = 5.6, p =.004) in left hippocampal NAA and 12.6% of the variance (F = 3.2, p =.035) in right hippocampal NAA. CONCLUSIONS: This study shows a positive relationship between cortisol levels and hippocampal NAA in subjects without hypercortisolemia. Within the range of values seen in our subjects, cortisol may have a trophic effect on the hippocampus.     

The severity of cortical Alzheimer's type changes is positively correlated with increased amyloid-beta Levels: Resolubilization of amyloid-beta with transition metal ion chelators

The most consistent diagnostic neuropathological lesion in Alzheimer's disease (AD) is the senile plaque of which the 4 kD amyloid-beta (Abeta) peptide is the major proteinaceous component. In this study cortical Abeta levels were immunochemically measured in 70 post-mortem human brains and compared against their neuropathological grading as determined by the densities of amyloid plaques and neurofibrillary tangles. The mean concentration of cortical Abeta/mg protein increased with the severity of the cortical degenerative changes (AD0 < AD1 < AD2 < AD3). Brains with the severe degenerative changes (AD3), corresponded to definite AD cases and exhibited significantly increased concentrations of Abeta (11.1+/-3.08 ng/mg total protein, n=17) when compared with control brains without any degenerative changes (AD0; 0.06+/-0.06 ng/mg total protein, n=14,P=0.003). The extraction of Abeta from the cortex of AD3 brains was significantly enhanced in a dose dependent manner by the presence of the metal ion chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (5 mM TPEN, P < 0.0001). The chelator/antioxidant 1,2-dithiolane-3-pentanoic acid (lipoic acid), also resolubilized Abetain a dose-dependant manner. Both chelators also enhanced the extraction of Abeta from the frontal cortex of AbetaPP-transgenic mice suggesting this animal model of amyloidosis may be useful for evaluating the biochemical and therapeutic effects of chelators/antioxidants on Abeta deposition. In summary our results indicate that increased Abeta load is correlated with the severity of the cortical AD-type changes and that chelators/antioxidants may be useful in reducing neuronal amyloid burden.     

Serum high-sensitivity C-reactive protein levels are positively associated with cognitive impairments in patients with first-episode schizophrenia

BackgroundTo clarify the controversy regarding the relationship between serum high-sensitivity C-reactive protein (hs-CRP) levels and cognitive impairments in first-episode schizophrenic patients and examine whether hs-CRP is a potential objective biological indicator for evaluating cognitive impairment in first-episode schizophrenic patients.MethodsSerum hs-CRP levels were measured in 58 first-episode schizophrenic patients and 31 healthy controls using immunofluorescence. The Brief Psychiatric Rating Scale (BPRS) and the P300 event-related potential were assessed. The relationship between serum hs-CRP levels and both BPRS scores and P300 were analyzed.ResultsSerum hs-CRP levels and BPRS scores were significantly higher in the study group than in the control group. The incubation period of P3 was longer, and the amplitude of P3 was larger in the study group than in the control group. Correlation analysis showed that in the study group, serum hs-CRP levels were positively correlated with BPRS total scores. Serum hs-CRP levels were also positively correlated with the incubation period of P3 and negatively correlated with P3 amplitudes.ConclusionsSerum hs-CRP levels were positively associated with cognitive impairment in first-episode schizophrenic patients and potentially represent an objective biological indicator for the rapid evaluation of cognitive impairment in first-episode schizophrenic patients.     

Qi-training enhances neutrophil function by increasing growth hormone levels in elderly men

This article investigated the effects of Qi-training on the neuroendocrine response and superoxide generation by neutrophils in healthy elderly men. One hour of Qi-training significantly reduced the plasma concentration of cortisol, and increased plasma concentrations of growth hormone and melatonin. Generation of superoxide by neutrophils increased significantly immediately after Qi-training (p < .01). The change in neutrophil superoxide generation was significantly correlated with the change in growth hormone concentration after Qi-training (p < .01). These data indicate that, in elderly men, Qi-training enhances superoxide generation by neutrophils, possibly via the changes in plasma growth hormone concentration.     

Irisin levels are correlated with inflammatory markers in frontotemporal dementia

Irisin is a recently discovered adipomyokine involved in the regulation of glucose and lipid, which also exhibits anti-inflammatory and neuroprotective properties. Here we aimed to compare irisin peripheral levels between individuals with behavioral variant frontotemporal dementia (bvFTD) and cognitively healthy matched controls, in addition to investigating whether there is a correlation between irisin and pro-inflammatory cytokines (IL-6 and TNF) concentrations. Twenty-nine individuals participated in this study, being 18 patients with probable bvFTD and 11 controls. Irisin, IL-6 and TNF levels were measured in EDTA plasma through ELISA. There was no difference of the levels of irisin between the groups (p = 0.964). However, in the bvFTD, but not in control group, the levels of irisin were positively correlated with the concentration of IL-6 (r = 0.637, p = 0.006) and TNF (r = 0.517, p = 0.034). The results suggest that the production of irisin in bvFTD could be related to chronic inflammatory and neurodegenerative states in these patients.     

Low testosterone levels in elderly men with dysthymic disorder

OBJECTIVE: A decline in hypothalamic-pituitary-gonadal (HPG) axis function is often seen in elderly men, and dysthymic disorder is common. Symptoms of both HPG axis hypofunction and dysthymic disorder include dysphoria, fatigue, and low libido. The authors compared total testosterone levels in three groups of elderly men. METHOD: Total testosterone levels were measured in subjects who met DSM-IV criteria for major depressive disorder (N=13) or dysthymic disorder (N=32) and a comparison group (N=175) who had participated in an epidemiological study of male aging and had scored below the median on the Center for Epidemiologic Studies Depression Scale, a well-validated, self-report depression symptom inventory. RESULTS: There were no differences among the three groups in measured demographic variables, including age and weight. Median testosterone levels varied for those with dysthymic disorder (295 ng/dl), major depressive disorder (425 ng/dl), and no depression (423 ng/dl). A test for differences in central tendency showed a statistically significant difference among the three groups. Post hoc pairwise comparisons revealed statistically significant differences between those with dysthymic disorder and those with major depressive disorder and no depression. CONCLUSIONS: Total testosterone levels were lower in elderly men with dysthymic disorder than in men with major depressive disorder and men without depressive symptoms. Dysthymic disorder in elderly men may be related to HPG axis hypofunction.     

Comorbid behavioural problems in Tourette's syndrome are positively correlated with the severity of tic symptoms

OBJECTIVE: We studied the comorbid behavioural and mood problems in children with non-psychiatric Tourette's syndrome (TS) and their relationship with severity of tic disorder. METHOD: Sixty-nine TS children and 69 healthy controls were assessed by Child Behavior Checklist (CBCL) and Yale Global Tic Severity Scale (YGTSS). The relationships between behavioural problems and severity of tic symptoms were analysed statistically by comparison, correlation and multiple linear regression. RESULTS: Tourette's syndrome patients scored significantly lower (p<0.01) on the CBCL competency subscales and total score, and higher on all behavioural problem subscales and total score (p<0.01). Expectedly, the TS children had lower social competence than normal children. Among the TS children, the severity of tic symptoms is positively correlated with the severity of overall impairment in school and social competence. When the behavioural and mood problems commonly associated with TS were studied in detail, we found that delinquent behaviour, thought problems, attention problems, aggressive behaviour and externalizing are positively correlated with severity of tic symptoms. CONCLUSION: The findings indicated that children with TS-only also had a broad range of behavioural problems, and some of these were related to the severity of tic symptoms.     

High insulin levels are positively associated with peripheral nervous system function

Objective – The aim of this study was to analyze peripheral nervous system (PNS) function in overweight and obese individuals. Materials and Methods – Forty‐four adult non‐diabetic overweight individuals were recruited. Peroneal motor nerve conduction and radial, sural, and medial plantar sensory nerve conduction were studied. Insulin and glucose levels were determined twice (over a 2‐ to 3‐year period) with an oral glucose tolerance test (OGTT). Multiple stepwise linear regression models adjusted for age, height, weight, and skin temperature were used to analyze the data. Results – Analysis revealed that baseline insulin levels measured 120 min after an OGTT explained 18% of the variation in peroneal F‐wave minimum latency, 8% of peroneal F‐wave maximum latency variation, 15% of sural sensory latency variation, 13% of sural sensory nerve conduction velocity (NCV) variation, and 10% of the variation in medial plantar sensory NCV. Discussion and Conclusion – Our study shows that serum insulin levels measured 120 min after an OGGT are positively associated with PNS function. High insulin levels without notably high glucose levels appear to be beneficial for the function of the PNS.     

Low protein Z plasma levels are independently associated with acute coronary syndromes

Protein Z (PZ) is a single chain vitamin-K-dependent glycoprotein synthesized by the liver. Studies in vivo and in vitro suggest that PZ plays an important role in inhibiting coagulation as it serves as cofactor for the inactivation of factor Xa by forming a complex with the plasma PZ-dependent protease inhibitor. Recently, conflicting findings on plasma PZ levels in patients with ischemic stroke have been published. Aim of our study was to investigate the role of PZ in acute coronary syndromes (ACS). PZ plasma levels were determined in 223 (189 M; 34 F) patients with ACS referring to the Coronary Intensive Therapy Unit of University of Florence and in 265 (219 M; 46 F) healthy subjects. Patients under oral anticoagulation treatment as well as subjects with positivity for antiphospholipid antibodies were excluded. None had liver or kidney dysfunction. The mean PZ plasma level was lower in patients (1508 +/- 730 ng/mL) than in controls (1728 +/- 594 ng/mL) (p < 0.0001). PZ levels below the 5th percentile (565 ng/mL) of normal values distribution in control subjects were found in 15.7% of patients and in 4.9% of controls (p <0.0001). At multivariate analysis, PZ levels below 565 ng/mL were associated with ACS (OR=3.3; 99%CI 1.1-9.7; p = 0.004). The contemporary presence of low PZ levels and smoking habit leads to an increased risk of ACS (OR=9.5; 99%CI 2.4-37.2; p < 0.0001). In conclusion, our results suggest a possible role of PZ in the occurrence of arterial thrombosis.     

Distinct effects of testosterone on plasma and cerebrospinal fluid amyloid-beta levels

The effect of testosterone on the levels of the Alzheimer's disease amyloid-beta peptide (Abeta) was investigated in guinea pigs. Castrated guinea pigs (GPX) were administered testosterone at two different dosages, following which plasma and cerebrospinal fluid (CSF) Abeta_{40} levels were measured. Plasma Abeta_{40} levels were reduced in GPX in the early stages of low-dose testosterone treatment, whereas CSF Abeta_{40} levels were only reduced by the time circulating testosterone had returned to untreated GPX levels. The supraphysiological testosterone dose did not reduce CSF Abeta_{40} levels significantly until circulating testosterone was back to uncastrated levels, whereas plasma Abeta_{40} levels significantly increased over time in these animals. These results indicate that the extent of testosterone-induced changes to Abeta_{40} levels and their response rates depend on both the tissue examined and testosterone dosage.     

Serum VEGF levels in acute ischaemic strokes are correlated with long-term prognosis

Background and purpose:  We investigated whether serum vascular endothelial growth factor (VEGF) levels in acute-stage ischaemic stroke patients with small vessel disease (SVD) or large vessel disease (LVD) are correlated with long-term prognoses, based on the difference in NIH Stroke Scale (NIHSS) scores between acute and chronic stages.
Methods:  From March 2007 to May 2008, we evaluated patients who experienced an ischaemic stroke for the first time, defined as SVD ( n  = 89) or LVD ( n  = 91) using the TOAST classification. Serum samples were taken immediately after admission (within 24 h of stroke onset) to evaluate VEGF levels. After 3 months, follow-up NIHSS scores were collected for all patients.
Results:  Serum VEGF levels in the acute stage (within 24 h of stroke onset) were higher in the LVD group than in the SVD group and were correlated with infarction volume. The increase in serum VEGF levels in the acute stage was proportional to an improved NIHSS score after 3 months. After adjustment for covariates, serum VEGF levels in the acute stage were still significantly correlated with the long-term prognosis of ischaemic stroke.
Conclusion:  Serum VEGF levels are correlated with long-term prognoses in acute ischaemic stroke patients.     

Serum cystatin C levels are negatively correlated with post-stroke cognitive dysfunction

Stroke is the leading cause of death and long-term disability worldwide,and cognitive impairment and dementia are major complications of ischemic stroke.Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies.However,the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results.This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months.Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke.According to the MMSE score,308 patients (52.9%) had post-stroke cognitive dysfunction.After adjusting for potential confounding factors,the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30–0.98),compared with the lowest quartile.The correlation between serum CysC and cognitive dysfunction was modified by renal function status.We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044),but not in those with abnormal renal function.Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke,especially in those with normal renal function.The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction,and could be used to treat post-stroke cognitive dysfunction.The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No.2012-02) on December 30,2012,and was registered at ClinicalTrials.gov (identifier No.NCT01840072) on April 25,2013.     

Enlarged perivascular spaces are associated with cognitive function in healthy elderly men

OBJECTIVES: Increased white matter (WM) lesions on magnetic resonance imaging (MRI) are associated with worse cognitive function in older people. Enlarged perivascular spaces (EPVS) commonly coexist with and share some risk factors for WM lesions but are not quantified in published scales. It is not known whether the extent of EPVS is also associated with cognitive function. We tested the hypothesis that more EPVS would be associated with worse cognitive function. METHODS: Ninety seven healthy men (65-70 years), not on medications, underwent MRI scanning and comprehensive cognitive testing. EPVS were quantified in both the basal ganglia/centrum semiovale and the hippocampus, and WM lesions were measured. RESULTS: Scores on published WM lesion rating scales intercorrelated highly significantly and positively (rho = 0.61 to 0.91, p<0.0001). A summary (WML) factor derived from principal components analysis of the WM scales correlated with EPVS in the basal ganglia/centrum semiovale (rho = 0.48, p<0.0001) but not in the hippocampus. EPVS scores in the basal ganglia/centrum semiovale correlated significantly and negatively with non-verbal reasoning (rho = -0.21, p = 0.038) and general visuospatial ability (rho = -0.22, p = 0.032), adjusted for prior intelligence. The WML factor correlated significantly and negatively with visuospatial ability, as previously reported, and showed an unexpected positive correlation with one test of verbal memory (list-learning). CONCLUSIONS: These findings suggest that increased EPVS are correlated with worse cognitive function. Future studies examining changes in WM with ageing should consider incorporating measures of EPVS and examine the sequence of EPVS and WM lesion development over time. More work is needed to develop valid and reliable measures of EPVS.     

Uric formaldehyde levels are negatively correlated with cognitive abilities in healthy older adults

Recent studies have shown that the abnormal accumulation of endogenous formaldehyde could be a critical factor in age-related cognitive decline. The aim of this study was to estimate the correlation between uric formaldehyde and general cognitive abilities in a community-based elderly population, and to measure the extent and direction in which the correlation varied with demographic characteristics. Using a double-blind design, formaldehyde in human urine was analyzed by high-performance liquid chromatography (n = 604), and general cognitive abilities were measured using the Montreal Cognitive Assessment (MoCA). Demographic characteristics, in terms of age, gender, residential region, and education were taken into consideration. We found that uric formaldehyde levels were inversely correlated with the MoCA score, and the concentration varied with demographic features: higher odds of a high formaldehyde level occurred among the less educated and those living in old urban or rural areas. In cytological experiments, the level of cellular formaldehyde released into the medium increased as SH-SY5Y and BV2 cells were incubated for three days. Formaldehyde in excess impaired the processes of N2a cells and neurites of primary cultured rat hippocampal cells. However, removal of formaldehyde markedly rescued and regenerated the processes of N2a cells. These results demonstrated a negative correlation between the endogenous formaldehyde and general cognitive abilities. High formaldehyde levels could be a risk factor for cognitive impairment in older adults, and could be developed as a non-invasive marker for detection and monitoring of age-related cognitive impairment.     

Nocturnal plasma levels of cytokines in healthy men

Summary Nocturnal cytokine levels were measured serially in 12 healthy male volunteers for 12 h, including 8 h of polygraphically monitored nocturnal sleep. Plasma concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor- (TNF-) were determined in 30-min intervals by enzyme-linked immunoadsorbant assays. In some subjects cytokines were not detectable at all. In the remaining volunteers (27% for IL-1, 58% for IL-6 and TNF-, respectively) occasional values near to the detection limits (DL) of the assays could be measured. With respect to IL-1 and IL-6, plasma levels above the DL were significantly more frequent during sleep than during the preceding time of wakefulness. No temporal association with NREM or REM episodes could be shown. TNF- values above the DL were randomly distributed across the 12-h period investigated. It is concluded that in a considerable percentage of healthy subjects small amounts of cytokines are released at night. Release of IL-1 and IL-6 is temporally associated with sleep, whereas the release of TNF- is not. It remains to be established whether nocturnal cytokine release reflects either an interaction between sleep and host defense mechanisms or a sleep-independent circadian rhythmicity.     

Age-sensitive cognitive function, growth hormone and insulin-like growth factor 1 plasma levels in healthy older men

Circulating levels of growth hormone (GH) change during the process of aging. Decline of cognitive functioning with aging is also well established. In this study, we investigated whether insulin-like growth factor 1 (IGF-1) and the GH response to a challenge of GH-releasing hormone and GH-releasing peptide 6 were associated with age-sensitive cognitive functions, but not with functions that do not decline with aging, in 17 healthy male subjects aged between 66 and 76 years. In addition, relations with anthropometric measures were examined. Neuropsychological performance was scored on tests of variables not sensitive to aging (general knowledge, vocabulary, basic visual perception and reading ability), and of variables sensitive to aging (visuoconstructive ability, perceptual motor and mental processing speed, and verbal long-term memory). After correcting for education, the serum GH response was significantly associated with two age-sensitive cognitive tests (measures of mental processing speed), but with none of the tests not sensitive to aging. However, the direction of the association was opposite to the relation between IGF-1 and these cognitive tests: higher levels of GH response were associated with poorer cognitive performance, whereas higher levels of IGF-1 were associated with better performance. GH response, but not IGF-1, was inversely correlated with body mass index. The results are in accordance with previous research suggesting a disruption of the relation between IGF-1 and GH secretion in older age.     

Behavioral flexibility positively correlated with relative brain volume in predatory bats

We investigated the potential relationships between foraging strategies and relative brain and brain region volumes in predatory (animal-eating) echolocating bats. The species we considered represent the ancestral state for the order and approximately 70% of living bat species. The two dominant foraging strategies used by echolocating predatory bats are substrate-gleaning (taking prey from surfaces) and aerial hawking (taking airborne prey). We used species-specific behavioral, morphological, and ecological data to classify each of 59 predatory species as one of the following: (1) ground gleaning, (2) behaviorally flexible (i.e., known to both glean and hawk prey), (3) clutter tolerant aerial hawking, or (4) open-space aerial hawking. In analyses using both species level data and phylogenetically independent contrasts, relative brain size was larger in behaviorally flexible species. Further, relative neocortex volume was significantly reduced in bats that aerially hawk prey primarily in open spaces. Conversely, our foraging behavior index did not account for variability in hippocampus and inferior colliculus volume and we discuss these results in the context of past research.     

Homocysteine plasma levels are elevated in females with anorexia nervosa

Summary. In the present pilot study significantly (T = 2.46, P = 0.018) higher levels of homocysteine were found in female anorectic patients (14.07, SD 7.3µmol/l; n = 18) when compared with bulimic patients (10.25, SD 2.82; n = 27) or healthy controls (8.10, SD 1.79; n = 25). Since homocysteine can induce neuronal cell death leading to brain atrophy in different diseases and since it has been linked to depressive disorders these findings may have important implications for understanding common symptoms in patients suffering from anorexia.Present address: Department of Psychiatry and Psychotherapy, University of Basel, Switzerland