Eleni Ι. Kalogirou

IMPORTANCE: Estrogens have neuroprotective and antidepressive effects; however, associations between indices of reduced endogenous estrogens and risk for postmenopausal depression have not been systematically explored. OBJECTIVE: To investigate the association of age at menopause and the duration of the reproductive period with the risk for depression among postmenopausal women with naturally occurring menopause. DATA SOURCES: A search strategy for use of MEDLINE was developed (through January 1, 2015) using the key terms menopause, climacteric, reproductive period, depression, and mood disorders. References of included studies and reviews were also screened; authors were contacted to maximize synthesized evidence. STUDY SELECTION: A total of 12,323 articles, without language restriction, were screened by pairs of reviewers to identify observational studies related to the study hypothesis; 14 studies were eligible for meta-analysis. DATA EXTRACTION AND SYNTHESIS: Pairs of reviewers independently extracted information on study design and type of analysis by participants' characteristics and methods of depression ascertainment. Study quality was assessed using the Newcastle-Ottawa Scale, and fixed- or random-effects models were implemented. MAIN OUTCOMES AND MEASURES: Pooled-effect estimates for depression, defined by psychiatric evaluation or validated instruments, by age at menopause and duration of the reproductive period. RESULTS: The 14 studies included in the meta-analysis represented 67,714 women. An inverse association (reported as odds ratio [OR]; 95% CI of 2-year increments) with depression in postmenopausal women was shown for increasing age at menopause (0.98; 0.96-0.99 [67,434 unique participants; 13 studies]) and duration of the reproductive period (0.98; 0.96-0.99 [54,715 unique participants; 5 studies]). Menopause at age 40 or more years compared with premature menopause was associated with a 50% decreased risk for depression (3033 unique participants; 4 studies). Pooling of studies examining severe depression showed a 5% decrease in risk of severe depression with increasing (2-year increment) age at menopause (52,736 unique participants; 3 studies); sensitivity analysis of studies controlling for past depression revealed similar results for age at menopause (0.98; 0.96-1.00 [48,894 unique participants; 3 studies). No heterogeneity or publication bias was evident in the main analyses. CONCLUSIONS AND RELEVANCE: Longer exposure to endogenous estrogens, expressed as older age at menopause and longer reproductive period, is associated with a lower risk of depression in later life. Identifying women at higher risk for depression due to early menopause who could benefit from psychiatric intervention or estrogen-based therapies could be useful in the clinical setting.

OBJECTIVE: To investigate the association of cognitive impairment (COGI) and depression with all-cause mortality and cardiovascular-specific mortality among community-dwelling elderly individuals in rural Greece. METHODS: Cognition and depressive symptomatology of 676 Velestino town residents aged ≥60 years were assessed using Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS), respectively. Eight-year all-cause mortality and cardiovascular mortality were explored by multivariate Cox regression models controlling for major confounders. RESULTS: Two hundred and one patients died during follow-up. Cognitive impairment (MMSE ≤ 23) was independently associated with all-cause mortality (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.13-2.18) and cardiovascular mortality (HR: 1.57, 95%CI: 1.03-2.41). Moderate to severe depression (GDS > 10) was significantly associated only with a 51% increase in all-cause mortality. A male-specific association was noted for moderate to severe depression, whereas the effect of COGI was limited to females. Noteworthy, COGI and depression comorbidity, rather than their sole presence, increased all-cause mortality and cardiovascular mortality by 66% and 72%, respectively. The mortality effect of COGI was augmented among patients with depression and of depression among patients with COGI. CONCLUSION: COGI and depression, 2 entities often coexisting among elderly individuals, appear to increase all-cause mortality and cardiovascular mortality. Gender-specific modes may prevail but their comorbidity should be carefully assessed, as it seems to represent an independent index of increased frailty, which eventually shortens life expectancy.

We have determined the alpha-thalassaemia (alpha-thal) determinants in 78 patients with Hb H disease from Cyprus; 25 were Turkish Cypriots and 53 were Greek Cypriots. Four deletional and three non-deletional alpha-thal alleles were present; the -alpha(3.7 kb) alpha-thal-2 and the --MED-I alpha-thal-1 were most frequently seen; --MED-II and -(alpha)20.5 deletions occurred at considerably lower frequencies. About 15% of all chromosomes carried a non-deletional alpha-thal-2 allele; of these the 5 nucleotide (nt) deletion at the first intervening sequence (IVS-I) donor splice site was present in approximately 8% of all chromosomes. Two types of polyadenylation signal (poly A) mutations were observed. No striking frequency differences were seen between Greek and Turkish Cypriot patients. Combinations of the various types of alpha-thal resulted in eight different forms of Hb H disease. The phenotypes were comparable except for great variations in the level of Hb H which was highest (average approximately 22%) in the 12 patients with the alpha 5nt alpha/--MED-I combination. One patient with the same form of Hb H disease but with an additional beta-thal (IVS-I-110,G-->A) heterozygosity had a most severe microcytosis and hypochromia with < 1% Hb H. Variations in the level of Hb H might correlate with the severity of the disease, although this was not evident from the haematological data.