Most genes² associated with psychiatric illnesses are expressed before birth in the developing human brain, a massive study headed by Yale University researchers discovered. In addition, hundreds of genetic³ differences were found between males and females as their brains take shape in the womb, the study in the Oct. 27 issue of the journal Nature shows. The creation of a hundred billion brain cells and the incalculable number of connections between them is such a complex task that 86 percent of 17,000 human genes studied are recruited in the effort. The study tracked not only what genes are involved in development, but where and when they are expressed, or activated⁴.

"We knew many of the genes involved in the development of the brain, but now we know where and when they are functioning in the human brain," said Nenad Sestan, associate professor of neurobiology, researcher for the Kavli Institute for Neuroscience and senior author of the study. "The complexity⁵ of the system shows why the human brain may be so susceptible⁶ to psychiatric disorders⁷."

The study identified genes expressed in the human brain, and when and where in the brain they were expressed in 1340 tissue samples taken from 57 subjects aged⁸ from 40 days after conception to 82 years. The analysis of 1.9 billion data points gives an unprecedented⁹（空前的） map of genetic activity in the brain at different stages of development. In dramatic fashion, the findings show just how much of the human brain is shaped prior to birth.

For instance, the team analyzed¹⁰ genes and variants¹¹ previously¹² linked with autism and schizophrenia（精神分裂症） , the symptoms of which are evident in the first few years of life or during early adulthood¹³, respectively. The new analysis shows molecular¹⁴ evidence of expression of these suspect genes prior to birth.

"We found a distinct pattern of gene¹ expression and variations prenatally in areas of the brain involving higher cognitive¹⁵ function," Sestan said. "It is clear that these disease-associated genes are developmentally regulated."

The team also looked for differences in brains of males and females. They expected to find clear differences in Y chromosome¹⁶ genes that are possessed¹⁷ only by males. However, they also demonstrated that men and women showed distinct differences in many genes that are shared by both sexes -- both in whether the gene was expressed and the level of the gene's activity. Most of the differences were noted¹⁸ prenatally.

Researchers from the Lieber Institute for Brain Development, National Institute of Mental Health, Virginia Commonwealth¹⁹ University, and Newcastle University contributed to the study.

Co-lead authors from Yale are Hyo Jung Kang, Yuka Imamura Kawasawa, Feng Cheng, Ying Zhu, Xuming Xu and Mingfeng, Other authors affiliated²⁰ with Yale are André M. M. Sousa, Mihovil Pletikos, Kyle A. Meyer, Goran Sedmak, Yurae Shin, Matthew B. Johnson, Zeljka Krsnik, Simone Mayer, Sofia Fertuzinhos, Sheila Alexander Vortmeyer, Shrikant Mane and Anita Huttner.