ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia and healthy subjects.

BACKGROUND: Genetic variation in the gene encoding ZNF804A, a risk gene for schizophrenia, has been shown to affect brain functional endophenotypes of the disorder, while studies of white matter structure have been inconclusive. METHOD: We analysed effects of ZNF804A single nucleotide polymorphism rs1344706 on grey and white matter using voxel-based morphometry (VBM) in high-resolution T1-weighted magnetic resonance imaging scans of 62 schizophrenia patients and 54 matched healthy controls. RESULTS: We found a significant (p < 0.05, family-wise error corrected for multiple comparisons) interaction effect of diagnostic group x genotype for local grey matter in the left orbitofrontal and right and left lateral temporal cortices, where patients and controls showed diverging effects of genotype. Analysing the groups separately (at p < 0.001, uncorrected), variation in rs1344706 showed effects on brain structure within the schizophrenia patients in several areas including the left and right inferior temporal, right supramarginal/superior temporal, right and left inferior frontal, left frontopolar, right and left dorsolateral/ventrolateral prefrontal cortices, and the right thalamus, as well as effects within the healthy controls in left lateral temporal, right anterior insula and left orbitofrontal cortical areas. We did not find effects of genotype of regional white matter in either of the two cohorts. CONCLUSIONS: Our findings demonstrate effects of ZNF804A genetic variation on brain structure, with diverging regional effects in schizophrenia patients and healthy controls in frontal and temporal brain areas. These effects, however, might be dependent on the impact of other (genetic or non-genetic) disease factors.

Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia.

BACKGROUND: Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls. METHOD: Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer). RESULTS: In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls. CONCLUSIONS: This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.

Choledochotomy for calculous disease in the elderly.

To determine the risk of operations on the biliary tract in the elderly, we retrospectively examined 56 patients 80 years of age or older undergoing choledochotomy for calculous disease and compared their outcomes with those of a contemporary group of 257 patients undergoing similar surgery. Thirty of 56 elderly patients (54%) required urgent surgery for acute cholangitis, acute cholecystitis, or obstructive jaundice (serum bilirubin greater than 5 mg/dL), compared with 97 of 257 younger patients (38%) (p = 0.029). Mortality in elderly patients was significantly higher (5 of 56) than in younger (6 of 257) patients (p = 0.015). In three of the five patients who died, urgent surgery was performed for obstructive jaundice, reflecting the higher mortality experienced by jaundiced patients in the entire series (9.4%). Biliary cultures grew organisms in 25 of 27 elderly patients (93%). This is in contrast to findings of bactibilia in 62 of 118 patients (53%) under the age of 80 (p = 0.001). Similarly, preoperative blood cultures were positive more often in elderly (63%) than in younger patients (26%) (p = 0.007). Mean postoperative hospital recovery was longer in the elderly group (16.2 +/- 8.5 days) than in the younger group (12.2 +/- 9.3 days) (p = 0.002). In conclusion, elderly patients, particularly those with obstructive jaundice, are at higher risk for complicated biliary tract disease necessitating choledochotomy. They appear to be more susceptible to bactibilia and bacteremia, and require longer hospital recovery than younger patients.

The role of early surgical intervention in civilian gunshot wounds to the head.

Surgical management of gunshot wounds of the head has remained a controversial issue in the care of civilian patients. In an attempt to determine who might benefit from aggressive surgical intervention, we examined 89 patients over a 3-year period who had suffered cranial gunshot wounds and had at least one computed tomographic scan of the head after admission. Patients were divided into those receiving early (less than 24 hours) surgical intervention (ES, n = 27), late (greater than 24 hours) surgical intervention (LS, n = 6) or no surgical intervention (NS, n = 56). Overall mortality was 63%. Ten of 27 patients (37%) in the ES group died compared with 46 of 56 patients (82%) in the NS group (p less than 0.0001). Glasgow Coma Scale (GCS) scores in the ES group averaged 7.86 +/- 4.72 and in the NS group 5.59 +/- 4.42 (p less than 0.05). The GCS scores in the LS group (all of whom survived) were significantly higher than those of the other two groups, 12.17 +/- 4.10. The number of patients with GCS scores of 3 or 4 on admission was significantly less in the ES (41%) than in the NS group (66%, p = 0.035) and survival was better with surgery (36%) than without (3%, p = 0.007). Patients with mass lesions (clot, ventricular blood) were more often found in the ES group (17/27) than in the NS group (18/56) (p = 0.008). Patients with bihemispheric injuries fared better with surgery (7 of 14 survivors) than without (2 of 33 survivors, p = 0.0003). Only one infectious complication (brain abscess) was encountered in the LS group. No delayed intracranial complications in survivors in the NS group were seen.(ABSTRACT TRUNCATED AT 250 WORDS)