Serum cytokines and anxiety in adolescent depression patients: Gender effect.

The present study compares the serum cytokine levels between adolescent depression patients and healthy controls and assesses correlation between depression, anxiety scores and serum levels of eight cytokines. Study also checked the variation in serum levels with medication status (medication free/naïve vs. patients on medication). Following clinical and psychometric assessment of 77 adolescent (aged 13-18 years) depression patients (49 males and 28 females; 56 medication free/naïve) and 54 healthy controls (25 males, 29 females), eight cytokines (IL-1ß, IL-2, IL-6, IL-10, TNF-α, IFN-γ, TGF-ß1 and IL-17A {denoted IL-17 throughout}) were measured in serum using ELISA. Depressed adolescents had significantly high levels of IL-2 (p<0.001) and IL-6 (p=0.03) as compared to controls. The female population skewed the result of one cytokine (IL-6) in patients. Anxiety scores showed positive correlation (only in female patients) with IL-1ß, IL-10 and negative correlation with TGF-ß1 and IL-17. The gender effect in relationship between anxiety and cytokines was not straightforward. On comparing study groups on the medication/naïve status, IL-2 and TGF-ß1 showed significant difference between the groups (p<0.001, p=0.007 higher in medicated). Depression in adolescents was associated with elevation of proinflammatory serum cytokines with a gender bias for females. Anxiety scores correlated negatively with TGF-ß1 and IL-17.

A cross-sectional study of tumor markers during normal and high-risk pregnancies.

OBJECTIVE: To determine tumor marker concentrations during normal and high-risk pregnancies. METHODS: The present cross-sectional study included women attending the gynecology outpatient department at All India Institute of Medical Sciences, New Delhi, India, between November 1, 2012 and March 31, 2013. Their serum was assayed for carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 15-3 (CA15-3). RESULTS: A total of 251 pregnant women and 31 nonpregnant women were included. Median CEA value was lower among pregnant women than among nonpregnant women (1.2µg/L vs 1.4µg/L; P=0.006), whereas that of CA15-3 was higher (16.7U/mL vs 12.3U/mL; P=0.03). CA19-9 concentration was higher among pregnant women aged 25-29years (7.0U/mL) or 30-34years (7.2U/mL) than among those aged 20-24years (4.2U/mL; P=0.01 for both). The CA15-3 level was increased during the second (13.0U/mL) and third (60.5U/mL) trimesters compared with the first trimester (9.5U/mL) (P≤0.01 for both comparisons). It was also raised in high-risk pregnancies (33.7U/mL), specifically pregnancies complicated by gestational diabetes mellitus (39.7U/mL), intrahepatic cholestasis of pregnancy (64.3U/mL), or heart disease (54.0U/mL) (P<0.05 for all). CONCLUSION: CA15-3 concentrations rise during pregnancy, but whether this increase can be attributed to physiological changes in breast tissue needs to be investigated further.

Synergistic epistasis of paraoxonase 1 (rs662 and rs85460) and apolipoprotein E4 genes in pathogenesis of Alzheimer's disease and vascular dementia.

Genetic polymorphism and epistasis play a role in etiopathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). In this case-control study, a total of 241 patients were included in the study to see the effect of paraoxonase 1 (PON1; rs662 and rs85460) and apolipoprotein E (ApoE) genes in altering the odds of having AD and VaD along with serum PON and lipid profile. The presence of at least 1 variant allele of rs662, but not rs85460, increased the risk of having AD by 1.8-fold (95% confidence interval [CI]: 0.97-3.40) and VaD by 3.09-fold (95% CI: 1.4-6.9). The interaction between PON1 genes (rs662 and rs85460) and ApoE genes showed synergistic epistasis in altering the odds of significantly having both AD and VaD. On the other hand, low serum level of high-density lipoprotein and low level of serum PON activity were found associated significantly (P ≤ .001 in both cases) only in patients with VaD as compared to healthy control.

Serum folic acid and RFC A80G polymorphism in Alzheimer's disease and vascular dementia.

Low level of vitamin B12 and folic acid has been reported to play an important role in the pathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). Serum folic acid and vitamin B12 were assayed in 80 AD and 50 VaD cases and in 120 healthy controls. The reduced folate carrier (RFC1) gene, rs1051266, which encodes the RFC 1, protein was analyzed for polymorphism by polymerase chain reaction-restriction fragment length polymorphism. It was observed that the patients having folic acid <8.45 ng/mL had 2.4 (95% confidence interval [CI]: 1.4-4.5) times higher odds of having AD and 2.1 (95% CI: 1.1-4.2) times higher odds of having VaD than patients having folic acid ≥8.45 ng/mL. Serum vitamin B12 level did not show any such statistically significant effect in altering the odds. No direct association was found between variant (G) allele or genotype of rs1051266 with AD and VaD cases. On serum folate level no association was observed with gene polymorphism.

Coagulopathy as prognostic marker in acute traumatic brain injury.

CONTEXT: Coagulopathy frequently occurs following traumatic brain injury (TBI) and usually occurs 6-72 hour post-trauma. The incidence and the probable risk factors for development of coagulopathy and poor outcome following TBI are largely unknown and vary considerably. AIMS: To assess the incidence and probable risk factors for development of coagulopathy and to identify the risk factors for poor outcome in terms of median survival time following TBI. MATERIALS AND METHODS: In this prospective study over two years, patients of isolated moderate and severe traumatic brain injury (GCS≤12) admitted to trauma center had coagulation profile (PT, APTT, thrombin time, fibrinogen and D-dimer), arterial lactate and ABG analysis done on day of admission and on day three. Coagulopathy was defined as prothrombin time (PT) or/and activated partial thromboplastin time (APTT) more than 1.5 times the normal control. Incidence of in-hospital mortality was assessed in all cases. STATISTICAL ANALYSIS: A stepwise logistic regression analysis was performed to identify risk factors for coagulopathy and mortality in these patients. RESULTS: A total of 208 patients were enrolled in the study. The mean age was 32 ± 12 years and mean GCS was 7.1 ± 2.8. Coagulopathy was present in 46% (n = 96) of patients. Risk factors for development of coagulopathy were found out to be severity of head injury (OR: 2.81), elevated D-dimer (OR: 3.43), low hemoglobin (OR: 3.13), and effaced cisterns in the CT scan (OR: 2.72). Presence of coagulopathy (OR: 2.97) and severity of head injury (OR: 5.70) strongly predicted poor outcome, and were associated with a decreased median survival time. CONCLUSIONS: There is a high incidence of coagulopathy following TBI. The presence of coagulopathy as well as of severity of TBI are strong predictors of in-hospital mortality in these patients.

Serum neurotrophic factors in adolescent depression: gender difference and correlation with clinical severity.

BACKGROUND: Brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3) and glial cell line derived neurotrophic factor (GDNF) play critical role in growth, differentiation, maintenance and synaptic plasticity in neuronal systems which is more relevant in adolescence. The present study was undertaken to verify the 'neurotrophin hypothesis' in adolescent depression by (i) comparing serum concentrations of neurotrophic factors in depression patients and healthy control, and (ii) analyzing correlations between clinical severity and serum neurotrophin levels. METHODS: Eighty four adolescent (aged 13-18 years) depressed patients (56 males; 60 medication free/naive) and 64 healthy controls (39 males) were recruited. Severity of depression was measured by Beck's depression inventory, and anxiety by state-trait anxiety inventory. Measurement of serum neurotrophins was done by ELISA. RESULTS: Adolescents with depression had significantly lower levels of BDNF: mean diff. (95% C.I.): 2093.9 (1074.0, 3113.9), NGF: 813.3 (343.1, 1283.6) and GDNF: 158.8 (77.2, 240.4) compared to controls. On gender based analysis female controls had significantly increased trait anxiety scores [-1.1 (-1.8, -0.1)], as compared to control males. In the patient group, female patients had far lower level of NGF: 919.6 (210.9, 1628.3) and NT-3: 1288.8 (145.4, 2432.3) compared to male. BDI-II score showed a statistically significant (p<0.01) negative correlation with all four neurotrophins in male patients while in female patients such negative correlation was observed only with NGF and GDNF (p<0.01). LIMITATIONS: The study is cross-sectional from a tertiary care hospital. CONCLUSION: The novelty of the study lies in its large number of exclusively adolescent depression patients showing significant reduction of BDNF, NGF and GDNF serum levels as compared to controls. A gender bias with much reduction in female has also been recorded.

MTHFR (677 and 1298) and IL-6-174 G/C genes in pathogenesis of Alzheimer's and vascular dementia and their epistatic interaction.

Genetic risk factors play an important role in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VaD). In this case-control study, we examined C677T and A1298C (rs1801133 and rs1801131) polymorphism in the methylenetetrahydrofolate reductase (MTHFR) genes and their correlation with plasma levels of homocysteine (Hcy) in AD and VaD cases and evaluated the gene-gene interaction (epistasis) with IL-6-174 G/C (rs1800795). CC genotype was associated with elevated levels of plasma homocysteine (p = 0.004) as compared with genotype AA of rs1801131. In AD, we observed a significant (p = 0.04) association with C alleles of rs1801131. Regression analysis revealed that the presence of both rs1801133 T and rs1800795 C alleles increased the odds of developing AD by 2.5 and VaD by 3.7-fold. While rs1800795 (CC or GC) genotypes alone increased the odds of developing VaD by 2.2-fold, the presence of CC genotype of rs1801131 nullified this effect. The findings support the hypothesis that multiple genes are involved to alter the odds of developing AD and VaD.

IL-6-174 G/C and ApoE gene polymorphisms in Alzheimer's and vascular dementia patients attending the cognitive disorder clinic of the All India Institute of Medical Sciences, New Delhi.

BACKGROUND: Remarkable improvement in the life expectancy of the Indian population is expected to commensurate with the increase in number of dementia cases. Among various types of dementia, Alzheimer's disease (AD) and vascular dementia (VaD) are common and widely studied. We evaluated the role of apolipoprotein E (ApoE) and interleukin-6 (IL-6)-174 G/C gene polymorphism along with serum IL-6 levels in AD and VaD patients. METHODS: The polymorphisms in ApoE and IL-6-174 G/C genes were assessed using RFLP. Serum IL-6 level was measured by ELISA. RESULTS: The allele ε4 of the ApoE gene was found to be associated with AD and VaD patients (p < 0.05). No association of IL-6-174 G/C polymorphism was observed in AD patients, while the IL-6-174 C allele increased the odds of having VaD twofold. Regression analysis to assess possible interaction between ApoE and the IL-6-174 G/C genes revealed that presence of both the ε4 and C alleles increased the odds of having AD 13.75-fold and VaD 14.7-fold. Serum IL-6 levels did not correlate with either presence or severity of disease among AD or VaD patients. CONCLUSION: The ApoE ε4 allele is an important genetic marker for AD and VaD. Presence of both ApoE ε4 and IL-6 C genes increases the OR of having AD and VaD markedly.