Depression in the first year of stay for elderly long-term nursing home residents in the USA.

BACKGROUND: Understanding the prevalence, incidence and cofactors of depression among long-term elderly nursing home (LTNH) residents domiciled for eight months or more may help optimize depression treatment in this vulnerable group. We quantified first year depression in American LTNH residents and the associations between depression and resident/facility characteristics. METHODS: Data were obtained from the Minimum Data Set and Online Survey Certification and Reporting for 634,060 LTNH residents admitted from 1999 to 2005 in 4,216 facilities. Depression first diagnosed at admission and at subsequent quarterly intervals through the first year of stay was examined. Logistic regressions modeled correlates of newly identified depression in each time-period. RESULTS: Recorded depression at admission and during the first year increased from 1999 to 2005. By 2005, 54.4% of LTNH residents had depression diagnosed over the first year; 32.8% at admission and a further 21.6% later during the first year. Antidepressant use was reported prior to depression diagnosis for 48% of those first identified depressed after admission. Men, non-Hispanic blacks, never married, and severely-cognitively impaired LTNH residents were less often identified with depression, particularly at admission. Pain and physical comorbidity were positively associated with depression identified throughout the first year. Prior institutionalization was associated with depression at admission, but not new depression after admission. Facility characteristics had weaker associations with depression. CONCLUSIONS: High depression rates at admission and during the first year indicate a need to monitor and treat large numbers of American LTNH residents for depression. Reduced associations between demographics and depression as stays progress suggest other factors have increased roles in depression etiology.

Variation of CNV distribution in five different ethnic populations.

Recent studies have revealed a new type of variation in the human genome encompassing relatively large genomic segments ( approximately 100 kb-2.5 Mb), commonly referred to as copy number variation (CNV). The full nature and extent of CNV and its frequency in different ethnic populations is still largely unknown. In this study we surveyed a set of 12 CNVs previously detected by array-CGH. More than 300 individuals from five different ethnic populations, including three distinct European, one Asian and one African population, were tested for the occurrence of CNV using multiplex ligation-dependent probe amplification (MLPA). Seven of these loci indeed showed CNV, i.e., showed copy numbers that deviated from the population median. More precise estimations of the actual genomic copy numbers for (part of) the NSF gene locus, revealed copy numbers ranging from two to at least seven. Additionally, significant inter-population differences in the distribution of these copy numbers were observed. These data suggest that insight into absolute DNA copy numbers for loci exhibiting CNV is required to determine their potential contribution to normal phenotypic variation and, in addition, disease susceptibility.

A novel locus for autosomal recessive nonsyndromic hearing impairment, DFNB63, maps to chromosome 11q13.2-q13.4.

Hereditary hearing impairment is a genetically heterogeneous disorder. To date, 49 autosomal recessive nonsyndromic hearing impairment (ARNSHI) loci have been described, and there are more than 16 additional loci announced. In 25 of the known loci, causative genes have been identified. A genome scan and fine mapping revealed a novel locus for ARNSHI (DFNB63) on chromosome 11q13.2-q13.4 in a five-generation Turkish family (TR57). The homozygous linkage interval is flanked by the markers D11S1337 and D11S2371 and spans a 5.3-Mb interval. A maximum two-point log of odds score of 6.27 at a recombination fraction of theta = 0.0 was calculated for the marker D11S4139. DFNB63 represents the eighth ARNSHI locus mapped to chromosome 11, and about 3.33 Mb separate the DFNB63 region from MYO7A (DFNB2/DFNB11). Sequencing of coding regions and exon-intron boundaries of 13 candidate genes, namely SHANK2, CTTN, TPCN2, FGF3, FGF4, FGF19, FCHSD2, PHR1, TMEM16A, RAB6A, MYEOV, P2RY2 and KIAA0280, in genomic DNA from an affected individual of family TR57 revealed no disease-causing mutations.

A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome.

Homozygosity mapping and linkage analysis in a Turkish family with autosomal recessive prelingual sensorineural hearing loss revealed a 15-cM critical region at 17q25.1-25.3 flanked by the polymorphic markers D17S1807 and D17S1806. The maximum two-point lod score was 4.07 at theta=0.0 for the marker D17S801. The linkage interval contains the Usher syndrome 1G gene (USH1G) that is mutated in patients with Usher syndrome (USH) type 1g and encodes the SANS protein. Mutation analysis of USH1G led to the identification of a homozygous missense mutation D458V at the -3 position of the PDZ binding motif of SANS. This mutation was also present homozygously in one out of 64 additional families from Turkey with autosomal recessive nonsyndromic hearing loss and heterozygously in one out of 498 control chromosomes. By molecular modeling, we provide evidence that this mutation impairs the interaction of SANS with harmonin. Ophthalmologic examination and vestibular evaluation of patients from both families revealed mild retinitis pigmentosa and normal vestibular function. These results suggest that these patients suffer from atypical USH.

Four novel TMC1 (DFNB7/DFNB11) mutations in Turkish patients with congenital autosomal recessive nonsyndromic hearing loss.

Mutations in the transmembrane channel-like gene 1 (TMC1) cause prelingual autosomal recessive (DFNB7/11) and postlingual progressive autosomal dominant (DFNA36) nonsyndromic hearing loss. To determine the genetic causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) in the northeast and east of Turkey, 65 unrelated families without mutations in the protein coding region of the GJB2 (GJB2-negative) were analyzed. A genomewide scan for homozygosity and linkage analysis in one of these families revealed a 13.2 cM critical region between D9S273 and D9S153 at chromosome 9p13.2-q21.31 with a maximum two-point lod score of 4.00 at theta=0.0 for marker D9S175. TMC1 is in this critical region. Homozygosity screening with intragenic markers for TMC1 in the remaining 64 families suggested involvement of this gene in three additional families. Subsequent sequencing of TMC1 in these four families revealed four novel homozygous mutations, c.776A>G [p.Tyr259Cys], c.821C>T [p.Pro274Leu], c.1334G>A [p.Arg445His], and c.1083_1087delCAGAT [p.Arg362ProfrX6]. Our results indicate that TMC1 mutations account for at least 6% (4/65) of ARNSHL in GJB2-negative Turkish families from the northeast and east of Turkey.

HLA alleles and haplotypes in the east Black Sea Turkish population.

HLA class I and class II alleles were studied for the first time in 234 unrelated individuals inhabiting the East Black Sea region in Turkey. This region is on the historic silk road and close to Georgia. HLA class I (A* and B*) and class II DRB1* typing was done by the PCR-SSP method. A total of 17 HLA-A* alleles, 34 HLA-B* alleles, and 15 HLA-DRB1* alleles were detected. HLA-A*-B*, A*-DRB1*, and B*-DRB1* two-loci linkage disequilibrium data show that two specific combinations (A2-B35, A2-DRB1*11, and B35-DRB1*13) had the highest frequency (more than three or four times) compared with the other two-loci combinations, possibly reflecting an ancient founder effect. A*24 B*18 DRB1*13 and A*32 B*27 DRB1*11 were the most common haplotypes in the east Black sea Turkish population. HLA-B* showed the highest heterozygosity (94%) among the samples. The observed diversity in the HLA-A* and HLA-DRB1* loci was quite similar, ranging from 79% to 84%. We suggest that the east Black Sea Turkish population is characterized by the features of the Turkish anthropological type with some influence of other groups, such as Caucasians, Asians, and Mediterraneans.