Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide1, poses a major challenge to genetic analysis. To date no robustly replicated genetic loci have been identified 2, despite analysis of more than 9,000 cases3. Using low coverage genome sequence of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P-value = 2.53×10−10) the other in an intron of the LHPP gene (P = 6.45×10−12). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

SummaryAdversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14, odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease.

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The 915-MHz cooled-shaft microwave antenna can lead to deeper penetration of liver tissue and can yield a significantly larger ablation zone than the 2,450-MHz cooled-shaft antenna in in vivo porcine livers. In light of the result, 915-MHz cooled-shaft microwaves may be more effective for tumor ablation, especially for large tumors.

Schizophrenia (SCZ) is a complex and heterogeneous mental disorder that affects about 1% of global population. In recent years, considerable progress has been made in genetic studies of SCZ. A number of common variants with small effects and rare variants with relatively larger effects have been identifi ed. These variants include risk loci identifi ed by genome-wide association studies, rare copy-number variants identifi ed by comparative genomic analyses, and de novo mutations identified by high-throughput DNA sequencing. Collectively, they contribute to the heterogeneity of the disease. In this review, we update recent discoveries in the fi eld of SCZ genetics, and outline the perspectives of future directions.