and never-married people (OR 1.32) had a higher risk for depression. Among elderly unmarried people, widowed people had a higher risk for depression than those who never married (OR 1.51). In conclusion, being unmarried was an important risk factor for depression in elderly people.

We have previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF(1) receptor. Moreover, the hydrophilic and weakly basic pyridine moiety increased the water solubility of some analogues. Compound 26 h exhibited good binding affinity at the human CRF(1) receptor with a K(i) value of 3.5 nM. As a functional antagonist, it dose-dependently inhibited CRF-stimulated cAMP production in cells expressing the CRF(1) receptor (IC(50) = 50 nM), and CRF-stimulated ACTH release from cultured rat pituitary cells (IC(50) = 20 nM). 26 h had a log P value of 4.9 and water solubility of greater than 10 mg/mL. Pharmacokinetic studies in rats showed that 26 h was orally bioavailable and able to penetrate into the brain. 26 h has been demonstrated in vivo efficacy in animal behavioral models that measure anxiolytic activity. These results suggest that analogues from this series were potent CRF(1) receptor antagonists with proper physicochemical properties and good pharmacokinetic profiles. 26 h was developed into a clinical compound and exhibited efficacy in patients with major depression.

Psychotherapy, including cognitive behavioural therapy (CBT), reminiscence and general psychotherapy (GPT), is viewed as effective treatment for depression, but its efficacy in older people is not well defined. This systematic review included 14 randomized controlled trials that assessed the efficacy of psychotherapy for treating depression in elderly people (> or = 55 years). The results of this meta-analysis showed that, compared with placebo, psychotherapy was more effective in reducing depression scores (standardized mean difference -0.92; 95% confidence interval -1.21, -0.36). Subgroup analysis showed that CBT, reminiscence and GPT were all more effective than placebo; psychotherapy as an adjunct to antidepressant medication did not increase effectiveness. There was no significant difference between CBT and reminiscence in improving depression. A higher drop-out rate was observed in studies that did not include psychotherapy versus those that did, although this difference was not statistically significant. Thus, various general formats of psychotherapy are effective for treating depression in older people, although psychotherapy does not significantly increase the effectiveness of anti-depressant medication.

ABSTRACT. In the present study, we examined whether the ARNTL (BMAL1) rs2278749 T/C polymorphism was associated with the susceptibility to Alzheimer disease (AD). This case-control study examined the genotypes of apolipoprotein E (APOE e4) and BMAL1 rs2278749 T/C using restriction fragment length polymorphism and the TaqMan assay, respectively. A total of 296 unrelated AD patients and 423 control subjects were included. Both in the entire sample and in APOE e4 non-carriers, the prevalence of T carriers in BMAL1 rs2278749 T/C in AD patients was significantly higher than that in control subjects (entire sample: χ 2 = 12.950, P < 0.0001; APOE e4 non-carriers: χ 2 = 13.094, P < 0.0001). Both in the entire sample and in APOE e4 non-carriers, the prevalence of TT genotypes 2278749 in AD patients was also significantly higher than that in control subjects (entire sample: χ 2 = 7.765, P = 0.024; APOE e4 non-carriers: χ 2 = 13.062, P < 0.0001). However, among APOE e4 carriers, the difference 18516 Q. Chen et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 18515-18522 (2015) in the prevalence of T carriers or TT genotypes in the BMAL1 rs2278749 T/C between patients and control subjects presents was not significant (T carriers: χ 2 = 0.078, P = 0.851 or TT genotypes: χ 2 = 2.576, P = 0.325). Among APOE e4 non-carriers, T carriers in the BMAL1 rs2278749 T/C were associated with a high susceptibility to AD, but among APOE e4 carriers, the association between AD and BMAL1 rs2278749 T/C was not significant.

Insulin resistance (IR),