| 1 | Schizophr. Res. 2005 Dec 80: 331-42 |
|---|---|
| PMID | 16006103 |
| Title | Maternal-fetal blood incompatibility and the risk of schizophrenia in offspring. |
| Abstract | Predicated on a maternal immune response to paternally inherited foreign fetal blood antigens, we hypothesized that maternal-fetal blood incompatibility increases susceptibility to schizophrenia in the offspring. The relation between schizophrenia and maternal-fetal blood incompatibility, arising from the D antigen of the Rhesus (Rh) and the ABO blood group antigens, was examined in a cohort of live-births. The data were drawn from the Prenatal Determinants of schizophrenia Study, a cohort of births occurring between 1959 and 1967 to women enrolled in a Kaiser Permanente Plan-Northern California Region (KP). Adult offspring belonging to the KP from 1981 to 1997 were followed for the incidence of schizophrenia spectrum disorder (SSD). Cox proportional hazards regression was the primary analytic technique. Among second and later born offspring, the adjusted incidence rate ratio (RR(adj)) of SSD was 1.80 (95% CI=0.71-4.58) for the Rh incompatible offspring compared with the Rh compatible offspring; with the males exhibiting higher rate ratio (RR(adj)=2.37; 95% CI=0.82-6.86) than the females (RR(adj)=0.93 95% CI=0.12-7.01). Among all offspring, the RR(adj) for ABO incompatibility was lower and the elevated rate ratio was similarly limited to the males (RR(adj)=1.68; 95% CI=0.76-3.70). For Rh and/or ABO incompatibility, the RR(adj) was 1.57 (95% CI=0.87-2.82). A statistically significant result was detected only for the male offspring (RR(adj)=2.22; 95% CI=1.10-4.47). Although the results should be interpreted with caution given the few events of SSD, the findings extend the line of evidence that maternal-fetal blood incompatibility is a risk factor for schizophrenia spectrum disorder; with the strongest evidence to date implicating that the susceptibility pertains only to male offspring. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2011 Aug 35: 1525-9 |
| PMID | 21570439 |
| Title | Maternal-fetal blood incompatibility and neuromorphologic anomalies in schizophrenia: Preliminary findings. |
| Abstract | Prior research has shown that maternal-fetal Rhesus (Rh) and ABO blood incompatibility increase the risk for schizophrenia. In the present study, the relationship between blood incompatibility and volumes of brain structures previously implicated in schizophrenia was assessed in schizophrenia cases and controls from a large birth cohort. Rh/ABO incompatible cases had significantly reduced cortical gray matter volume compared to compatible cases, a finding which appears to be driven by significant volume reductions in the dorsolateral prefrontal cortex and inferior frontal cortex. Larger hippocampal and putamen volumes were also observed in exposed controls compared to unexposed controls. Although the sample size is small and replications are required, these data suggest that maternal-fetal blood incompatibility may increase the risk for altered brain morphology in both schizophrenia and in controls. The findings also suggest that the larger hippocampal volume in exposed controls may indicate a mechanism of adaptive resilience which diminishes the risk that controls will develop schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | Hum. Genet. 2011 Nov 130: 635-43 |
| PMID | 21509519 |
| Title | Linkage analysis of plasma dopamine ?-hydroxylase activity in families of patients with schizophrenia. |
| Abstract | Dopamine ?-hydroxylase (D?H) catalyzes the conversion of dopamine to norepinephrine. D?H enters the plasma after vesicular release from sympathetic neurons and the adrenal medulla. Plasma D?H activity (pD?H) varies widely among individuals, and genetic inheritance regulates that variation. Linkage studies suggested strong linkage of pD?H to ABO on 9q34, and positive evidence for linkage to the complement fixation locus on 19p13.2-13.3. Subsequent association studies strongly supported DBH, which maps adjacent to ABO, as the locus regulating a large proportion of the heritable variation in pD?H. Prior studies have suggested that variation in pD?H, or genetic variants at D?H, associate with differences in expression of psychotic symptoms in patients with schizophrenia and other idiopathic or drug-induced brain disorders, suggesting that DBH might be a genetic modifier of psychotic symptoms. As a first step toward investigating that hypothesis, we performed linkage analysis on pD?H in patients with schizophrenia and their relatives. The results strongly confirm linkage of markers at DBH to pD?H under several models (maximum multipoint LOD score, 6.33), but find no evidence to support linkage anywhere on chromosome 19. Accounting for the contributions to the linkage signal of three SNPs at DBH, rs1611115, rs1611122, and rs6271 reduced but did not eliminate the linkage peak, whereas accounting for all SNPs near DBH eliminated the signal entirely. Analysis of markers genome-wide uncovered positive evidence for linkage between markers at chromosome 20p12 (multi-point LOD = 3.1 at 27.2 cM). The present results provide the first direct evidence for linkage between DBH and pD?H, suggest that rs1611115, rs1611122, rs6271 and additional unidentified variants at or near DBH contribute to the genetic regulation of pD?H, and suggest that a locus near 20p12 also influences pD?H. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |