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Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
Method
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
Results
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Conclusions
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
A survey of ABO blood groups, secretor status and smoking habits among 389 students and staff of a school in which there was an outbreak of meningococcal disease found no difference in the distribution of the ABO blood groups but a significantly higher proportion of non-secretors (37·6%) in the population examined compared with that reported for previous surveys of the neighbouring population in Glasgow (26·2%) (P < 0·0005). There was also a significantly higher proportion of non-secretors among carriers of meningococci (47%) compared with non-carriers (32%). Increased carriage of meningococci among non-secretors might contribute to the increased susceptibility of individuals with this genetic characteristic to meningococcal disease observed in previous studies. Although passive exposure to cigarette smoke has been associated with meningococcal disease, there was no association between passive smoking and carriage. There was, however, a significant association between active smoking and carriage.
This report describes a clinical trial in which pericyazine and chlorpromazine were used with 45 disturbed patients resident in a hospital for the mentally subnormal. The patients, who comprised a clinically heterogeneous sample, were randomly allocated by the hospital pharmacist to two major groups; in one, half the patients were given pericyazine for a 12-week period and an inert preparation for a further 12-week period while the remaining patients had the inert preparation during the first period and pericyazine during the second. In the other group, which was given chlorpromazine, the same procedure was followed. Prior to the trial proper, there was a six-week period during which all drugs except anti-convulsants were tapered off. All preparations were in syrup form and were indistinguishable from each other by taste or smell. Only the pharmacist was aware of what syrup a given patient received.
Mr. President, Ladies and Gentlemen: as my contribution to this morning's topic, “Legislation and Mental Health,” I had hoped to be able to give you the outlines of the proposals contained in a new Mental Health Bill under way in Northern Ireland. Time has not been on my side, as it just happens the Bill is being presented to-day for its first reading in the Northern Ireland Parliament, and as only after that will it be available for publication, I am not able to make use of it as the basis of my paper this morning.
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