Linkage analysis of a completely ascertained sample of familial schizophrenics and bipolars from Palau, Micronesia

We report on linkage analysis of a completely ascertained population of familial psychosis derived from the oceanic nation of Palau. Palau, an archipelago of islands in the Southern Pacific, currently has a population of approximately 23,000 individuals. The peoples of Palau populated these islands recently in human history, approximately 2,000 years ago. As both historical and genetic evidence suggest, the population is far more homogeneous than most other populations undergoing genetic studies, and should therefore prove quite useful for mapping genetic variants having a meaningful impact on susceptibility to psychotic disorders. Moreover, for our study, essentially all on-island schizophrenics (150) and individuals with other psychotic disorders (25) participated. By analysis of narrow (only schizophrenia) and broad (all psychosis) diagnostic schemes, two-point linkage analyses suggest that two regions of the genome harbor genetic variants affecting liability in most families, 3q28 (LOD=3.03) and 17q32.2 (LOD=2.80). Results from individual pedigrees also support 2q37.2, 2p14, and 17p13 as potentially harboring important genetic variants. Most of these regions have been implicated in other genetic studies of psychosis in populations physically quite distant from this Oceanic population, although some (e.g., 3q28) appear to be novel results for schizophrenia linkage analyses.     

Cortisol and prolactin concentrations during three different seasons in relocated Brahman and Hereford bulls

The objective of this study was to evaluate seasonal changes of cortisol and prolactin (PRL) concentrations in Brahman and Hereford bulls moved to locations that differ in geographical and environmental conditions. Postpubertal Hereford bulls from Montana (n = 15) and Nebraska (n = 15) and Brahman bulls from Texas (n = 18) were located in or relocated to Montana, Nebraska or Texas so that each location had 5 Montana Herefords, 5 Nebraska Herefords and 6 Texas Brahman bulls. Blood samples were collected at 20-minute intervals for 8 hours in November (Fall 1), April (Spring) and November (Fall 2) of the next year. These dates corresponded to 6, 12 and 18 months, respectively, after relocation in May of the first year. Cortisol concentrations were higher (P<0.05) in Fall 1 than in Fall 2 and were higher (P<0.05) for bulls in Montana than for bulls in Texas. The decrease in cortisol concentrations from Fall 1 to Fall 2 was negatively related (P<0.05) to age and weight. There was a three-way interaction (P<0.05) of breed-type origin, location and season for PRL concentrations. Seasonal patterns of PRL concentrations differed between relocated Texas Brahman and Hereford bulls, and patterns for relocated bulls differed from those of the nonrelocated bulls. Seasonal patterns of PRL were influenced to a greater extent by relocation in Texas Brahman bulls than in Hereford bulls.     

Linkage analysis of schizophrenia with five dopamine receptor genes in nine pedigrees

Alterations in dopamine neurotransmission have been strongly implicated in the pathogenesis of schizophrenia for nearly 2 decades. Recently, the genes for five dopamine receptors have been cloned and characterized, and genetic and physical map information has become available. Using these five loci as candidate genes, we have tested for genetic linkage to schizophrenia in nine multigenerational families which include multiple affected individuals. In addition to testing conservative disease models, we have used a neurophysiological indicator variable, the P50 auditory evoked response. Deficits in gating of the P50 response have been shown to segregate with schizophrenia in this sample and may identify carriers of gene(s) predisposing for schizophrenia. Linkage results were consistently negative, indicating that a defect at any of the actual receptor sites is unlikely to be a major contributor to schizophrenia in the nine families studied.     

Smoking and pulmonary function in five Solomon Island populations.

The relationship between smoking and lung function was examined in a large sample of healthy Solomon Island Melanesians and Polynesians as part of a multidisciplinary study carried out in 1985 and 1986. Comparisons are made between samples of smokers and non-smokers to determine if smoking is associated with a reduction in pulmonary function among males and females between 25 and 75 years of age. The results of this study indicate that cigarette smoking causes significant reductions in the pulmonary function of these populations. In addition, a clear difference in pulmonary function between males and females, as well as a general reduction in female FEV1 values, suggests that cooking smoke inhalation may be operating as a possible risk factor to the pulmonary health of women. Further research is needed to quantify exposure to smoke of both males and females and relate this measure to declines in pulmonary function.     

Insulin sensitivity and glucose effectiveness from three minimal models: effects of energy restriction and body fat in adult male rhesus monkeys

The minimal model of glucose disappearance (MINMOD version 3; MM3) and both the one-compartment (1CMM) and the two-compartment (2CMM) minimal models were used to analyze stable isotope-labeled intravenous glucose tolerance test (IVGTT) data from year 10 of a study of the effect of dietary restriction (DR) in male rhesus monkeys. Adult monkeys were energy restricted (R; n = 12) on a semipurified diet to approximately 70% of control (C) intake (ad libitum-fed monkeys; n = 12). Under ketamine anesthesia, fasting insulin levels were greater among C monkeys. Insulin sensitivity estimates from all models were greater in R than C monkeys, whereas glucose effectiveness estimates were not consistently greater in R monkeys. Fasting plasma glucose as well as hepatic glucose production and clearance rates did not differ between groups. Body fat, in part, statistically mediated the effect of DR to enhance insulin sensitivity indexes. Precision of estimation and intermodel relationships among insulin sensitivity and glucose effectiveness estimates were in the ranges of those reported previously for humans and dogs, suggesting that the models may provide valid estimates for rhesus monkeys as well. The observed insulin sensitivity indexes from all models, elevated among R vs. C monkeys, may be explained, at least in part, by the difference in body fat content between these groups after chronic DR.     

Failure of naloxone to stimulate luteinizing hormone secretion during pregnancy and steroid treatment of ovariectomized beef cows

The response of serum luteinizing hormone (LH) to naloxone, an opiate antagonist, and gonadotropin-releasing hormone (GnRH) was measured in cows in late pregnancy to assess opioid inhibition of LH. Blood samples were collected at 15-min intervals for 7 h. In a Latin Square arrangement, each cow (n = 6) received naloxone (0, 0.5, and 1.0 mg/kg BW, i.v.; 2 cows each) at Hour 2 on 3 consecutive days (9 +/- 2 days prepartum). GnRH (7 ng/kg body weight, i.v.) was administered at Hour 5 to all cows on each day. Mean serum LH concentrations (x +/- SE) before naloxone injection were similar (0.4 +/- 0.1 ng/ml), with no serum LH pulses observed during the experiment. Mean serum LH concentrations post-naloxone were similar (0.4 +/- 0.1 ng/ml) to concentrations pre-naloxone. Mean serum LH concentrations increased (p less than 0.05) following GnRH administration (7 ng/kg) and did not differ among cows receiving different dosages of naloxone (0 mg/kg, 1.44 +/- 0.20; 0.5 mg/kg, 1.0 +/- 0.1; 1.0 mg/kg, 0.9 +/- 0.1 ng/ml). In Experiment 2, LH response to naloxone and GnRH was measured in 12 ovariectomized cows on Day 19 of estrogen and progesterone treatment (5 micrograms/kg BW estrogen: 0.2 mg/kg BW progesterone) and on Days 7 and 14 after steroid treatment. On Day 19, naloxone failed to increase serum LH concentrations (Pre: 0.4 +/- 0.1; Post: 0.4 +/- 0.1 ng/ml) after 0, 0.5, or 1.0 mg/kg BW.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative

We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P<.05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P<.10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder.