Patterns of gene expression in developing embryos of Arabidopsis hybrids.

Hybrids between the Arabidopsis ecotypes C24 and Ler have high levels of hybrid vigour, or heterosis, in both biomass and seed yield. Heterosis can be detected throughout the development of the plant and in different tissues. We examined developing embryos and seeds of C24/Ler reciprocal hybrids with the aim of detecting the earliest time at which heterotic gene activity occurs. In the transcriptomes of 4-dap (days after pollination; dermatogen to globular) and 6-dap (heart) embryos from both parents and hybrids, 95% of expressed genes were at the mid parent value (MPV) and 95% of the genes with single nucleotide polymorphisms between C24 and Ler retained the same relative allelic expression levels in the hybrids as existed in the parents. This included loci that had equivalent levels of transcription in the two parents, together with loci which had different levels of expression in the parents. Amongst the genes which did not have MPV expression levels in the hybrids (non-additively expressed genes), approximately 40 in the globular embryo stage and 89 in the heart embryo stage had altered levels of transcription in both reciprocal hybrids; these genes could contribute to the heterotic phenotype of the hybrid embryo. Many of the non-additively expressed genes had expression levels that were shifted towards maternal levels of transcription, and these differed in the reciprocal hybrids. Allelic expression analysis indicated that most genes with altered allelic contributions in the hybrids had an increase in the expression level of the hybrid's maternal allele. Consistent with the maternal pattern of gene expression, embryo and seed also show maternally influenced phenotypes.

Changes in 24-nt siRNA levels in Arabidopsis hybrids suggest an epigenetic contribution to hybrid vigor.

Intraspecific hybrids between the Arabidopsis thaliana accessions C24 and Landsberg erecta have strong heterosis. The reciprocal hybrids show a decreased level of 24-nt small RNA (sRNA) relative to the parents with the decrease greatest for those loci where the parents had markedly different 24-nt sRNA levels. The genomic regions with reduced 24-nt sRNA levels were largely associated with genes and their flanking regions indicating a potential effect on gene expression. We identified several examples of genes with altered 24-nt sRNA levels that showed correlated changes in DNA methylation and expression levels. We suggest that such epigenetically generated differences in gene activity may contribute to hybrid vigor and that the epigenetic diversity between ecotypes provides increased allelic (epi-allelic) variability that could contribute to heterosis.

Increased risk of nursing home admission among middle aged and older adults with schizophrenia.

OBJECTIVE: Cross-sectional data indicate that persons with serious mental illness have increased risk of institution-based care, yet little is known about the long-term course of nursing home placement for persons with schizophrenia. This study describes nursing home entrance over a 10-year period among community residing Medicaid enrollees with schizophrenia compared with Medicaid enrollees with no mental illness. METHODS: The authors analyzed claims of 7,937 New Hampshire Medicaid beneficiaries aged 40 and older. Claims were followed annually from 1996 to 2005 to determine nursing home admission. Schizophrenia was identified from International Classification of Diseases: 9th Edition codes and used to model nursing home admission controlling for medical severity, physical disability, sex, and age. Cox proportional hazard models were run for the entire sample and then separately for middle-aged (40-64 years) and older-aged (65 years and older) subgroups. RESULTS: Persons with schizophrenia enter nursing homes earlier (median age 65) than persons with no mental illness (median age: 80). The greatest relative disparity occurs at middle age (40-64 years), where nursing home admission risk was 3.90 (95% confidence interval = 2.86-5.31) times greater for persons with schizophrenia than for persons with no mental illness. CONCLUSIONS: Middle-aged persons with schizophrenia have almost four times greater likelihood of early institutionalization in nursing homes compared with their same age peers with no mental illness. Efforts to prevent/reduce unwarranted nursing home admission among persons with schizophrenia should focus on health status in the fifth decade of life.

Recent trends in antipsychotic combination therapy of schizophrenia and schizoaffective disorder: implications for state mental health policy.

Little is known about antipsychotic combination therapy, although this practice is becoming increasingly common in the treatment of schizophrenia. Medicaid pharmaceutical claims for a cohort of 836 New Hampshire beneficiaries with schizophrenia or schizoaffective disorder were followed from 1995 through 1999. Use of traditional and atypical antipsychotic medications, antidepressants, anxiolytic hypnotics, and mood stabilizers was tracked monthly. The number of medications, frequency of coprescription, and Medicaid pharmaceutical costs are described. The proportion of individuals with schizophrenia and schizoaffective disorder treated with atypical antipsychotics grew from 43 percent in 1995 to 70 percent in 1999. At the same time, concurrent use of two or more antipsychotic medications quadrupled, increasing from 5.7 percent to 24.3 percent. Persons with schizophrenia were also prescribed more antidepressants (increased from 18.5% in 1995 to 35.6% in 1999), anxiolytics (increased from 19.9% to 33.5%), and mood stabilizers (increased from 17.7% to 30.0%). The increase in multiple agent therapy appears to be broad-based. Data are needed on the effectiveness and cost-effectiveness of these practices to inform clinical decision making and health policy.

Prescribing patterns for patients with posttraumatic stress disorder.

OBJECTIVE: The little information available about prescribing patterns for persons with posttraumatic stress disorder comes from male combat-veteran populations treated through programs of the Department of Veterans Affairs. The objective of this study was to comprehensively evaluate prescribing patterns for persons with a diagnosis of posttraumatic stress disorder (PTSD) in a community-based nonveteran sample in which women were well represented. METHODS: Prescription claims paid in December 1999 for New Hampshire Medicaid recipients with diagnostic codes for PTSD were analyzed. Frequencies of prescriptions for categories of medication were compared between patients with PTSD (N=165) and patients with major depression alone (N=2,208) and those with major depression co-occurring with PTSD (N=171). RESULTS: The patients with PTSD were predominantly women who were receiving services at community mental health centers. Selective serotonin reuptake inhibitors were more frequently prescribed for major depression (32 percent of cases) than for PTSD (23 percent). Other novel antidepressants were more frequently prescribed for major depression co-occurring with PTSD (25 percent of cases) than for major depression alone (18 percent). Atypical antipsychotic medications were more frequently prescribed for PTSD (17 percent of cases) and for major depression co-occurring with PTSD (20 percent) than for major depression alone (9 percent). Benzodiazepines and related hypnotics, trazodone, and mood stabilizers were more frequently prescribed for major depression co-occurring with PTSD than for major depression alone. CONCLUSIONS: The findings suggest that many outpatients who have PTSD are treated aggressively with medication, particularly when PTSD co-occurs with major depression, and that there are discrepancies between actual prescribing patterns and prescribing guidelines. These findings overlap trends observed in veteran populations.

Medicare and medicaid costs for schizophrenia patients by age cohort compared with costs for depression, dementia, and medically ill patients.

OBJECTIVE: The authors describe per-capita Medicaid and Medicare expenditures across age cohorts for individuals with schizophrenia and compare expenditures for patients with schizophrenia and those with depression, dementia, and non-psychiatric medical disorders. METHODS: Medicaid and Medicare claims were identified for dually-eligible beneficiaries ages 19+ in New Hampshire during 1999 (schizophrenia: N=1,423; depression: N=2,219; dementia: N=1,942; medical disorders alone: N=4,260). Annual per-capita weighted average expenditures were calculated for inpatient, outpatient, home-health, nursing home, pharmacy, physician, and other services. RESULTS: The greatest per-capita expenditures for individuals with schizophrenia were among older beneficiaries ($39,154 for ages 65-74 and $43,461 for ages 75+), versus younger beneficiaries ($25,633 for ages 19-44 and $31,529 for ages 45-64). Outpatient services were the highest expenditure among younger adults (ages 19-64), whereas nursing home services were the highest expenditure for ages 65+. Total expenditures for individuals with schizophrenia exceeded those for individuals with depression, dementia, or medical disorders across all age cohorts except age 45-64, where dementia expenditures were highest. Among individuals age 65-74, per-capita expenditures for schizophrenia were $11,304 higher than for depression and $28,256 higher than for medical disorders. CONCLUSION: Schizophrenia is one of the most expensive disorders across the adult lifespan, and expenditures increase across age cohorts. Effective interventions are needed that improve independent functioning in older age, in conjunction with innovative models of home- and community-based services that decrease high use of and expenditures for nursing homes.