At the time of discharge from their first stay in psychiatric hospital, 78 male schizophrenic patients were randomly assigned to a family intervention (experimental) group or a ‘standard care’ control group and were followed for the next 18 months. The family intervention consisted of both group and individual counselling sessions every 1–3 months that focused on education about the illness and on methods of dealing with the patient. There was a significantly lower rate of hospital readmission in the family intervention group than in the control group (15.4% versus 53.8%, χ2= 12.75, P<0.01), and the mean hospital-free period for those who were readmitted was significantly longer in the experimental group than in the control group (245 days versus 130 days, t =2.91, P<0.01). Moreover, the clinical status and overall level of functioning in patients who were not readmitted were significantly better in experimental subjects than in control subjects. Stratified analysis showed that family intervention and regular use of medication had independent and additive effects on the outcome. During the 18 months after the index discharge patients who did not take medication regularly and who did not receive family intervention were 7.9 times as likely to be readmitted to hospital as patients who took medication regularly and received family intervention.

Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c.572G>T, p.191Gly>Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m.11778G>A mutation to cause visual failure. We performed functional assays by using lymphoblastoid cell lines derived from members of Chinese families (asymptomatic individuals carrying m.11778G>A mutation, or both m.11778G>A and heterozygous p.191Gly>Val mutations and symptomatic subjects harboring m.11778G>A and homozygous p.191Gly>Val mutations) and controls lacking these mutations. The 191Gly>Val mutation reduced the YARS2 protein level in the mutant cells. The aminoacylated efficiency and steady-state level of tRNA(Tyr) were markedly decreased in the cell lines derived from patients both carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The failure in tRNA(Tyr) metabolism impaired mitochondrial translation, especially for polypeptides with high content of tyrosine codon such as ND4, ND5, ND6 and COX2 in cells lines carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The YARS2 p.191Gly>Val mutation worsened the respiratory phenotypes associated with m.11778G>A mutation, especially reducing activities of complexes I and IV. The respiratory deficiency altered the efficiency of mitochondrial ATP synthesis and increased the production of reactive oxygen species. Thus, mutated YARS2 aggravates mitochondrial dysfunctions associated with the m.11778G>A mutation, exceeding the threshold for the expression of blindness phenotype. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutation and mutated nuclear-modifier YARS2.

To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, P(combined) = 3.42 × 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, P(combined) = 2.97 × 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, P(combined) = 1.26 × 10(-118), OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.

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