Van Gogh, who was treated in a psychiatric hospital, and John Nash, an economist who has suffered from schizophrenia all his life, likened depression to Churchill, the "black dog" of his heart......

These celebrities who have achieved great things in the fields of art and science always seem to confirm the famous saying that "there is a fine line between a genius and a madman".

The summary of famous people's deeds may not be of universal significance, but recently, this sentence has been scientifically proven at the cellular level.

3月20日，國際頂尖學術期刊Nature發表了一篇論文，由西湖大學、西湖實驗室、未來產業研究中心楊劍課題組開發的新技術方法定位了精神分裂症、抑鬱症相關細胞在大腦內的分佈。

The results show that a class of neurons associated with schizophrenia is mainly distributed in the dorsal hippocampus of the brain, and this position is very close to the location of the cells related to IQ, and even some overlap.

How is Cell Navigation composed?

When we stare at the CT images of the brain, those seemingly uniform gray matter areas actually hide the fateful code.

The technical method developed by Yang Jian's team is named "gsMap", and from the name, we can understand that they seem to provide the world with a navigation map of the cells from the disease, which can essentially find which cells are most related to the disease, and where these cells are distributed in our body.

Our brain has the setting of "the most mysterious organ in the human body", and until now, human cognition of the brain has always been shrouded in fog, and even the most advanced 7T magnetic resonance imaging is difficult to capture the subtle molecular storm in the brain of schizophrenic patients. It's like an economist who has satellite images of the world but can't discern an impending financial crisis from aerial footage.

Distribution of nerve cells associated with schizophrenia along the ventral-dorsal axis in the hippocampal CA1 region of adult mice

In the era of data floods, Yang Jian's lab cleverly combined the world's largest genetic database, the genome-wide association study (GWAS), with another spatial transcriptome (ST).

"It can be said that we have combined a 'genetic notebook' that records the genetic variation of millions of people and the association of diseases with the world's most advanced 'map' of brain cells into a 'navigation map'." Yang Jian introduced.

Things that are "engraved in the DNA".

People's behavioral traits such as drinking coffee, physical characteristics such as being tall, short, fat and thin, and more susceptible to diseases are mostly influenced by genes.

This time, when the team "navigated" depression and schizophrenia, a type of neuronal called glutamatergic, it revealed a striking duality.

The neuronal population on the dorsal side of the hippocampus is associated with both high IQ and schizophrenia risk; Another group of neurons curled up deep in the prefrontal lobe, whose synaptic plasticity is abnormal, corresponds to the emotional swamp of depressed patients.

The use of clinical depression medication disproves the team's research.

Combined with the existing drug database, the team found that the deep part of the medial prefrontal cortex, which is closely related to depression, has a large number of psychotropic drug targets, which are 16 times higher than those in other cerebral cortex regions.

"Open source technology": I hope to benefit mankind as soon as possible

"At present, mental diseases such as schizophrenia, depression, and autism, even with the most advanced medical imaging technology in the world, there is no way to know the cause," Yang Jian said, "Not only mental diseases, but many complex lesions often do not manifest as plaques, nodules, and cysts, but quietly occur in more hidden cell corners." ”

This new technology and approach will have the ability to provide higher efficiency and new perspectives for mechanistic research and precise intervention of these complex diseases.

The publication of this paper will be just the beginning of the story. At present, the research team has open-sourced the gsMap algorithm, which is like putting the fire into the campfire of science, hoping to become a tool for many research groups.

"Since gsMap has no species limitations, we were pleasantly surprised to see that scientists in the field of plant research had already applied our method before the publication of the paper." Yang Jian said.

Precision drug development, exploration of the principles of cancer, Alzheimer's disease and other diseases...... At present, the team has also established cooperation with Westlake University or many international laboratory research groups, hoping that those once vague pathogenic mechanisms can be revealed in the coordinate system of gsMap "navigation", illuminating the long road of human self-understanding.