Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE), but not S100B in major depressive disorder.

OBJECTIVES: Alterations in neuronal and glial integrity are considered to be of pathogenic impact on major depressive disorder (MDD). For MDD, data on cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) are lacking and scarce for glial protein S100B. METHODS: We measured CSF levels of NSE and S100B in 31 patients with MDD and 32 mentally healthy controls using electrochemiluminescence immunoassays (ECLIA). RESULTS: Adjusted means of NSE were significantly elevated in the MDD patients (11.73 ng/ml (9.95-13.52 95% CI) compared to the controls (6.17 ng/ml (4.55-7.78), F = 9.037, P = 0.004. Effect size for adjusted mean group difference of 5.57 ng/ml was found invariably high (Cohen's d = 1.23). Differentiating MDD from controls, a NSE cut-off of 7.94 ng/ml showed sensitivity of 81% (95% CI 63.7-90.8) and specificity of 75% (95% CI 57.9-86.7). Adjusted levels of S100B did not differ significantly between the two groups (1.12 ng/ml (0.77-1.48) in MDD, 0.97 ng/ml (0.64-1.30) in controls). CONCLUSIONS: Our results of elevated CSF-NSE levels support neuronal pathology in MDD and the potential use of CSF-NSE as marker in clinical diagnostics. Missing group differences in S100B do not promote a specific glial pathology in depressive disorders.

Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE) in Alzheimer's disease.

Neuron-specific enolase (NSE) is a neuronal glycolytic enzyme of which cerebrospinal fluid (CSF) levels are found altered following acute or prolonged neuronal damage. Investigations concerning the role of NSE in Alzheimer's disease (AD) are conflicting with both elevated and reduced levels. We measured CSF-levels of NSE in 32 patients with AD and 32 healthy subjects (HS) using an electrochemiluminescence immunoassay (ECLIA). Mean levels of adjusted NSE were significantly elevated in AD (18.12 ng/mL (95% CI 15.63-20.60), HS 8.46 ng/mL (95% CI 5.98-10.94), p=0.00002) and effect size for mean group differences high (1.84). NSE alone (cut-off score 15.80 ng/mL, 94% sensitivity, 97% specificity) and in combination with T-tau and P-Tau had high diagnostic accuracy to differentiate AD from HS. NSE correlated significantly with T-tau (r ≥ 0.87, p<0.000001) and P-tau (r ≥ 0.88, p<0.000001) in both AD and HS. Our results indicate elevated CSF-NSE levels to reflect altered neuronal metabolism in AD that may be used in supporting AD diagnostics.

No cross-sectional and longitudinal association of ferritin and symptoms of attention-deficit-/hyperactivity disorder in a large population-based sample of children: results from the GINIplus and LISAplus studies.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with alterations in iron metabolism, and low ferritin concentrations in peripheral blood have inconsistently been reported in clinically referred samples of children with ADHD. This study examined whether higher peripheral concentrations of ferritin, the major iron storage protein, are associated with decreased symptoms of ADHD in 2,805 children aged 10 years participating in two large population-based birth cohorts (GINIplus and LISAplus). Whether high ferritin concentrations at age 4 months predict lower ADHD symptoms at age 10 years was also investigated using a longitudinal approach in a subsample of 193 children. No indications for an association between peripheral ferritin concentrations and ADHD symptoms were found in this large population-based study. Re-evaluating iron substitution as a therapeutic measure for ADHD may be warranted.

FADS1 FADS2 gene cluster, PUFA intake and blood lipids in children: results from the GINIplus and LISAplus studies.

BACKGROUND: Elevated cholesterol levels in children can be a risk factor for cardiovascular diseases in later life. In adults, it has been shown that blood lipid levels are strongly influenced by polymorphisms in the fatty acid desaturase (FADS) gene cluster in addition to nutritional and other exogenous and endogenous determinants. Our aim was to investigate whether lipid levels are determined by the FADS genotype already in children and whether this association interacts with dietary intake of n-3 fatty acids. METHODS: The analysis was based on data of 2006 children from two German prospective birth cohort studies. Total cholesterol, HDL, LDL and triglycerides were measured at 10 years of age. Six single nucleotide polymorphisms (SNPs) of the FADS gene cluster were genotyped. Dietary n-3 fatty acid intake was assessed by food frequency questionnaire. Linear regression modeling was used to assess the association between lipid levels, n-3 fatty acid intake and FADS genotype. RESULTS: Individuals carrying the homozygous minor allele had lower levels of total cholesterol [means ratio (MR) ranging from 0.96 (p = 0.0093) to 0.98 (p = 0.2949), depending on SNPs] and LDL [MR between 0.94 (p = 0.0179) and 0.97 (p = 0.2963)] compared to homozygous major allele carriers. Carriers of the heterozygous allele showed lower HDL levels [ß between -0.04 (p = 0.0074) to -0.01 (p = 0.3318)] and higher triglyceride levels [MR ranging from 1.06 (p = 0.0065) to 1.07 (p = 0.0028)] compared to homozygous major allele carriers. A higher n-3 PUFA intake was associated with higher concentrations of total cholesterol, LDL, HDL and lower triglyceride levels, but these associations did not interact with the FADS1 FADS2 genotype. CONCLUSION: Total cholesterol, HDL, LDL and triglyceride concentrations may be influenced by the FADS1 FADS2 genotype already in 10 year old children. Genetically determined blood lipid levels during childhood might differentially predispose individuals to the development of cardiovascular diseases later in life.

Serum levels of adipocyte fatty acid-binding protein are decreased in chronic pancreatitis.

OBJECTIVE: Chronic pancreatitis (CP) is associated with an increased risk for diabetes mellitus and vascular disease. Adipocyte fatty acid-binding protein (AFABP) is a novel adipokine that is independently associated with the metabolic syndrome and cardiovascular disease. In the current study, we investigated serum AFABP levels in CP patients compared with sex- and body mass index-matched controls. METHODS: Adipocyte fatty acid-binding protein was determined with enzyme-linked immunosorbent assay in control subjects (n = 60) and diabetic as well as nondiabetic CP (n = 60) patients and correlated to clinical and biochemical measures of glucose and lipid metabolism, as well as renal function in both groups. RESULTS: Median serum AFABP levels were significantly lower in CP patients compared with controls (12.5 vs 20.9 µg/L, P = 0.003). Furthermore, body mass index, sex, and CP independently predicted circulating AFABP. In contrast, no significant difference in circulating AFABP could be demonstrated between diabetic and nondiabetic CP patients. CONCLUSIONS: Circulating AFABP is paradoxically lower in CP patients and does not depend on pancreatic diabetes. Our data do not support a role of circulating AFABP in metabolic and vascular risk in CP patients.

Diagnostic value of S100B and neuron-specific enolase in mild pediatric traumatic brain injury.

OBJECT: During recent years, several biomarkers have been introduced for use in the diagnosis of traumatic brain injury (TBI). The primary objective of this investigation was to determine if S100B (or S100 calcium-binding protein B) and neuron-specific enolase (NSE) serum concentrations can effectively be used to discriminate between symptomatic and asymptomatic children with minor head trauma. METHODS: The authors conducted a prospective clinical study that involved patients age 6 months to 15 years who had sustained minor head trauma. Children with concomitant extracranial injuries were excluded. Blood samples were obtained within 6 hours of injury to measure S100B and NSE levels in serum. The authors defined 2 diagnostic groups: a mild TBI group (patients with Glasgow Coma Scale [GCS] scores of 13-15) in whom there were clinical signs of concussion (short loss of consciousness, amnesia, nausea, vomiting, somnolence, headache, dizziness, or impaired vision) and a head contusion group (patients with a GCS score of 15) in whom symptoms were absent. Both S100B and NSE concentrations were compared between the 2 groups. Secondary end points were defined as follows: correlation of S100B/NSE and a) the presence of scalp lacerations, b) GCS score, c) age, and d) correlation between S100B and NSE. RESULTS: One hundred forty-eight patients were enrolled (53 in the contusion group, 95 in the mild TBI group). After adjusting for differences in age and time of injury to blood sample withdrawal, there was no significant difference in S100B or NSE between patients in the 2 groups. Scalp lacerations and GCS score had no affect on posttraumatic S100B or NSE concentrations. The correlation between S100B and NSE was significant. Both markers showed a significant negative correlation with age. CONCLUSIONS: The authors demonstrated that S100B and NSE do not discriminate between symptomatic and asymptomatic children with minor head injury. There seem to be limitations in marker sensitivity when investigating pediatric patients with mild TBI.

Validation of the phenylalanine/tyrosine ratio determined by tandem mass spectrometry: sensitive newborn screening for phenylketonuria.

The efficacy of the tandem mass spectrometry as a tool for the newborn screening of phenylketonuria, an inherited metabolic disorder, was investigated. Precision, reproducibility, selectivity and sensitivity were validated for phenylalanine and tyrosine measurements from dried blood spots. Bland-Altman plots were used to assess the agreement with conventional methods like fluorometry and ion exchange chromatography. The utility of the phenylalanine/tyrosine ratio for discrimination between mild hyperphenylalaninemia and classical types of phenylketonuria was investigated. Depending on concentration levels of phenylalanine and tyrosine the within-run and between-run assay variability ranged between 4.2% and 12.7%. Higher recoveries and a lower detection limit were found for the mass spectrometric method when compared to the fluorometric method. Pearson correlation coefficients of 0.91 for tandem mass spectrometry vs. fluorometric method, as well as 0.95 for tandem mass spectrometry vs. ion exchange chromatography were calculated. The closest agreement between methods was observed between tandem mass spectrometry and ion exchange chromatography. The results demonstrate a high efficacy of the tandem mass spectrometric method for quantitative determination of phenylalanine and tyrosine from dried blood spots. The phenylalanine/tyrosine ratio is crucial to improve the specificity and positive predictive value for the diagnosis of classical phenylketonuria.