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Some Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans experience serious mental health (MH) problems. As OEF/OIF soldiers leave active military duty, their growing numbers pose a challenge to the Department of Veterans Affairs (VA) in delivering high-quality mental health/substance-use disorder (MH/SUD) care.To determine whether the quality of MH/SUD care provided by the VA differs by OEF/OIF veteran status.Veterans with selected MH/SUDs were identified from administrative records using diagnostic codes. OEF/OIF service was determined based on Defense Manpower Data Center separation files. Eleven processes of care and 7 utilization performance indicators were examined. Regression analyses were adjusted for veteran demographic and clinical characteristics to test for differences in care by OEF/OIF status.Of the 836,699 veterans with selected diagnoses who received MH/SUD treatment in FY2007, 52,870 (6.3%) were OEF/OIF veterans. In unadjusted analyses, OEF/OIF veterans were more likely to receive evidence-based care processes captured by 6 of the 11 dichotomous performance indicators examined; however, among those receiving psychotherapy encounters, OEF/OIF veterans received significantly fewer visits (6.9 vs. 9.7, P0.0001). In adjusted analyses, only postdischarge follow-up remained meaningfully higher for OEF/OIF veterans.Efforts to maintain and/or increase OEF/OIF veteran participation in VA MH/SUD services should be informed by their characteristics, such as younger age and better physical health relative to other veterans.

In 2006 the Department of Veterans Affairs commissioned the Altarum Institute and the RAND Corporation to do an evaluation of its mental health treatment system. We found that veterans with mental illness and substance use disorders represented 15.4 percent of all veterans using Veterans' Health Administration (VHA) services in 2007 and that they accounted for 32.9 percent ($12 billion) of VHA costs, of which the majority was for non-mental health conditions. The average cost for a veteran with mental illness and substance use in our study was $12,337, or 2.7 times the cost for an average veteran without these conditions. The quality of care for the veterans in our study, although similar to or better than the care given to comparable privately insured patients or those enrolled in Medicare or Medicaid, varied by as much as twenty-three percentage points among regional service networks. Performance on some indicators, such as whether those with alcohol dependence received pharmacotherapy, was low. There is a need for substantial improvement in the care of these veterans, particularly with respect to ensuring the delivery of evidence-based treatments.

To elucidate the genetic architecture of familial schizophrenia we combine linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa. We demonstrate that individually rare inherited copy number variants (CNVs) are more frequent in cases with familial schizophrenia as compared to unaffected controls and affect almost exclusively genic regions. Interestingly, we find that while the prevalence of rare structural variants is similar in familial and sporadic cases, the type of variants is markedly different. In addition, using a high-density linkage scan with a panel of nearly 2,000 markers, we identify a region on chromosome 13q34 that shows genome-wide significant linkage to schizophrenia and show that in the families not linked to this locus, there is evidence for linkage to chromosome 1p36. No causative CNVs were identified in either locus. Overall, our results from approaches designed to detect risk variants with relatively low frequency and high penetrance in a well-defined and relatively homogeneous population, provide strong empirical evidence supporting the notion that multiple genetic variants, including individually rare ones, that affect many different genes contribute to the genetic risk of familial schizophrenia. They also highlight differences in the genetic architecture of the familial and sporadic forms of the disease.

The quality of mental health care provided by the U.S. Department of Veterans Affairs (VA) was compared with care provided to a comparable population treated in the private sector.Two cohorts of individuals with mental disorders (schizophrenia, bipolar disorder, posttraumatic stress disorder, major depression, and substance use disorders) were created with VA administrative data (N=836,519) and MarketScan data (N=545,484). The authors computed VA and MarketScan national means for seven process-based quality measures related to medication evaluation and management and estimated national-level performance by age and gender.In every case, VA performance was superior to that of the private sector by more than 30%. Compared with individuals in private plans, veterans with schizophrenia or major depression were more than twice as likely to receive appropriate initial medication treatment, and veterans with depression were more than twice as likely to receive appropriate long-term treatment.Findings demonstrate the significant advantages that accrue from an organized, nationwide system of care. The much higher performance of the VA has important clinical and policy implications.

The quality of mental health care delivered by the U.S. Department of Veterans Affairs (VA) is generally as good or better than care delivered by private health plans, although it falls short of the high standards set in VA guidelines.

Background NOGO Receptor 1 (RTN4R) regulates axonal growth, as well as axon regeneration after injury. The gene maps to the 22q11.2 schizophrenia susceptibility locus and is thus a strong functional and positional candidate gene. Methodology/Principal Findings We evaluate evidence for genetic association between common RTN4R polymorphisms and schizophrenia in a large family sample of Afrikaner origin and screen the exonic sequence of RTN4R for rare variants in an independent sample from the U.S. We also employ animal model studies to assay a panel of schizophrenia-related behavioral tasks in an Rtn4r-deficient mouse model. We found weak sex-specific evidence for association between common RTN4R polymorphisms and schizophrenia in the Afrikaner patients. In the U.S. sample, we identified two novel non-conservative RTN4R coding variants in two patients with schizophrenia that were absent in 600 control chromosomes. In our complementary mouse model studies, we identified a haploinsufficient effect of Rtn4r on locomotor activity, but normal performance in schizophrenia-related behavioral tasks. We also provide evidence that Rtn4r deficiency can modulate the long-term behavioral effects of transient postnatal N-methyl-D-aspartate (NMDA) receptor hypofunction. Conclusions Our results do not support a major role of RTN4R in susceptibility to schizophrenia or the cognitive and behavioral deficits observed in individuals with 22q11 microdeletions. However, they suggest that RTN4R may modulate the genetic risk or clinical expression of schizophrenia in a subset of patients and identify additional studies that will be necessary to clarify the role of RTN4R in psychiatric phenotypes. In addition, our results raise interesting issues about evaluating the significance of rare genetic variants in disease and their role in causation.

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view about chromatin structure has emerged, including its interrelationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded novel mechanistic and evolutionary insights about the functional landscape of the human genome. Together, these studies are defining a path forward to pursue a more-comprehensive characterisation of human genome function.

Open angle glaucoma (OAG) is a complex disorder with varying etiologies due to multiple genes and environmental effects. This genetic heterogeneity can confound efforts to map loci. Increased homogeneity in a sample can be achieved using either ordered subset analysis (OSA) which groups families, or individual OSA (IOSA), which groups individuals based on disease related covariates. Recently, GLC1I was mapped to 15q11-13 in families with early adult onset of OAG. We tested for linkage to GLC1I in an independent sample of 167 individuals in 25 multiplex OAG families of European descent. We carried out nonparametric linkage analysis on the complete set of 25 families and obtained a maximum LOD score of 1.00 at 9.0 cM. Using mean age at diagnosis (AAD) across the affected individuals within each family to order the families as a proxy for age at onset, we found a maximum OSA LOD score of 2.09 (p=0.021) at 26.1 cM. The mean (+/-s.d.) AAD across the 14 earlier AAD families that contributed to the OSA LOD score was 50.6 years (+/-5.38); the mean AAD for the other 1210 later AAD families that did not contribute to the OSA LOD score (the high-AAD) was 61.7 years (+/-3.50). We also ran IOSA on our families using AAD as our covariate on which to subset affected individuals. The maximum LOD score was 1.01 at 14.3 cM when ordering subjects from early to late AAD. Ordered subset analysis of this sample has provided evidence of linkage close to the previously identified GLC1I glaucoma locus on 15q11-13 in families with middle-aged mean age at diagnosis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is believed to have a genetic basis. However, no specific susceptibility gene or region has been conclusively identified.The objective of this study was to duplicate a previous study that localized a PCOS susceptibility region to chromosome 19p13.2 and to narrow the susceptibility region.This study was designed to test for genetic linkage and association between PCOS and short tandem repeat polymorphisms in 367 families, by analysis of linkage and family-based association.The study was conducted at academic medical centers.We studied 367 families of predominantly European origin with at least one PCOS patient. Families included 107 affected sibling (sister) pairs (ASPs) in 83 families, and 390 trios with both parents and an affected daughter. The data set comprises two independent groups. Set 1 consists of 44 ASPs and 163 trios. Set 2 consists of 63 ASPs and 227 trios.The intervention was the drawing of blood for DNA extraction.We employed measures of evidence for linkage and association between PCOS and 19 STRs.Linkage with PCOS was observed over a broad region of chromosome 19p13.2. The strongest evidence for association was observed with D19S884 (chi2 = 11.85; nominal P0.0006; permutation P = 0.034) and duplicated our earlier findings.The present analysis suggests that a PCOS susceptibility locus maps very close to D19S884. Additional studies that systematically characterize DNA sequence variation in the immediate area of D19S884 are required to identify the PCOS susceptibility variant.

With the advent of high-density DNA marker data sets for the mouse and other model systems, 100 or more genotype are routinely generated from large groups of mice. Issues of the accuracy and reliability of the genotyping are extremely important but often not addressed until genetic analysis is conducted. Simple tests that rely on the robust predictions arising from Mendelian genetics can be made quickly in the molecular laboratory as the data are generated, and require only a spreadsheet program. In this report, genotype data from 392 mice tested at 96 marker sites were analyzed for errors that are typical when handling large volumes of data generated in a repetitive process. The testing consisted of: (1) repeating the genotyping of approximately 1% of the samples; (2) examining the deviation from the expected segregation ratio ( 1:2:1 ) on a marker-by-marker basis; and (3) testing the correlation of the genotype at one marker with that at neighboring genetic markers on a chromosome. These three steps allowed analysis at the level of the microtiter plate, where errors are most likely to occur. A set of 96 dinucleotide repeat markers that are polymorphic between the C57BL/6J and DBA/2J mouse strains and can be multiplexed is reported for use in other genotyping projects.

In a sporadic case of autism and language deficit due to auditory processing defects, molecular genetic studies revealed that a chromosomal deletion occurred in the 13q12→q13 region. No chromosome abnormalities were detected in the parents. We determined that the deletion occurred on the paternally derived chromosome 13. There are two previous reports of chromosome 13 abnormalities in patients with autism. The deletion in the subject described in this paper maps between the two chromosome 13 linkage peaks described by Bradford et al. (2001) in studies of subjects with autism and language deficits. The 9-Mb region deleted in the patient described here contains at least four genes that are expressed in brain and that play a role in brain development. They are NBEA, MAB21L1, DCAMKL1 and MADH9. These genes therefore represent candidate genes for autism and specific language deficits. Copyright © 2002 S. Karger AG, Basel.

Background: Autism is a pervasive developmental disorder characterized by a triad of deficits: qualitative impairments in social interactions, communication deficits, and repetitive and stereotyped patterns of behavior. Although autism is etiologically heterogeneous, family and twin studies have established a definite genetic basis. The inheritance of idiopathic autism is presumed to be complex, with many genes involved; environmental factors are also possibly contributory. The analysis of chromosome abnormalities associated with autism contributes greatly to the identification of autism candidate genes. Case presentation: We describe a child with autistic disorder and an interstitial deletion on chromosome 4q. This child first presented at 12 months of age with developmental delay and minor dysmorphic features. At 4 years of age a diagnosis of Pervasive Developmental Disorder was made. At 11 years of age he met diagnostic criteria for autism. Cytogenetic studies revealed a chromosome 4q deletion. The karyotype was 46, XY del 4 (q31.3-q33). Here we report the clinical phenotype of the child and the molecular characterization of the deletion using molecular cytogenetic techniques and analysis of polymorphic markers. These studies revealed a 19 megabase deletion spanning 4q32 to 4q34. Analysis of existing polymorphic markers and new markers developed in this study revealed that the deletion arose on a paternally derived chromosome. To date 33 genes of known or inferred function are deleted as a consequence of the deletion. Among these are the AMPA 2 gene that encodes the glutamate receptor GluR2 sub-unit, GLRA3 and GLRB genes that encode glycine receptor subunits and neuropeptide Y receptor genes NPY1R and NPY5R. Conclusions: The deletion in this autistic subject serves to highlight specific autism candidate genes. He is hemizygous for AMPA 2, GLRA3, GLRB, NPY1R and NPY5R. GluR2 is the major determinant of AMPA receptor structure. Glutamate receptors maintain structural and functional plasticity of synapses. Neuropeptide Y and its receptors NPY1R and NPY5R play a role in hippocampal learning and memory. Glycine receptors are expressed in very early cortical development. Molecular cytogenetic studies and DNA sequence analysis in other patients with autism will be necessary to confirm that these genes are involved in autism. © 2004 Ramanathan et al; licensee BioMed Central Ltd.