A survey of schizophrenia related studies

September 19, 2019 / BIOON / -- this issue brings you the latest research progress on schizophrenia I hope readers will like it 1 Cell: targeted activation of PV neurons in a critical time window is expected to treat schizophrenia doi: 10.1016/j.cell.2019.07.023 Although the induction process occurs earlier, schizophrenia occurs in early adulthood, which suggests that it may involve pathological changes in susceptible individuals during late brain development In a new study, using a genetic mouse model of schizophrenia, pico Caroni and his team from the Swiss Institute of Friedrich Mitchell (FMI) found that, like human patients, characteristic network and cognitive deficits only occur in adult mice They then confirmed that during the sensitive time window of late adolescence, these defects could be permanently prevented by specific treatment The relevant research results were recently published in the journal Cell, and the title of the paper is "long lasting rescue of network and coherent dysfunction in a genetic schizophrenia model" Schizophrenia affects about 1% of the world's population It is a mental disease characterized by confusion, false belief, difficulties in social relations, cognitive defects, abnormal movement, and dullness of emotion and motivation A prominent feature of this serious chronic disease is that its symptoms first appear in the transitional period between late adolescence and early adulthood Schizophrenia treatment focuses on symptoms, usually composed of antipsychotics The causes of schizophrenia are complex They include environmental factors - such as problems during birth, psychosocial factors, stress and marijuana consumption during adolescence - and similar contributions from genetic factors In most cases, genetic factors involve a large number of gene mutations, each of which makes a small contribution to the disease In order to study the underlying causes of a complex genetic disease, people need to focus on the simpler genetic model as much as possible, that is, carrying a clearly defined mutation of human or animal, and / or they show a higher incidence rate In schizophrenia, such genetic models include people with 22q11DS syndrome, which is caused by partial deletion of chromosome 22 The risk of schizophrenia in these people increases 20-30 times This led the researchers to develop mice that carried the corresponding deletions in order to use them as models of schizophrenia for laboratory research (these mice are called "lgdel mice," but for simplicity, they are called "schizophrenic mice" here.) Using a schizophrenic mouse model, the Caroni team set out to study the defects that schizophrenic mice showed and how to treat and prevent them They found that what is known to exist in human patients also exists in schizophrenic mice: network and cognitive dysfunction in late adolescence Like human patients, adult mice show severe dysfunction in specific types of neurons called PV neurons, in which PV neurons are important mediators of neural networks This dysfunction leads to network synchronization defects, which is a sign of schizophrenia It is worth noting that the antipsychotics Department temporarily suppresses the Internet and cognitive deficits in adult schizophrenic mice Although PV neuronal dysfunction only spreads in the brain in adulthood, they are already present in the hippocampus of adolescent schizophrenic mice Since late adolescence represents a time window, and it is important for late brain maturity to rely on the coordination of hippocampal and cortical PV neurons, the Caroni team hypothesized that hippocampal dysfunction during adolescence may interfere with normal brain maturity in schizophrenic mice The researchers looked at whether they could prevent the onset of schizophrenia by suppressing network dysfunction in the most critical time window, which, despite the strong genetic background, was long enough to allow adult brain function to transition to normal These researchers have succeeded in this They found that during the transition period between late adolescence and adulthood, repeated treatment of hippocampal PV neural network with common antipsychotics or specific PV neuron genetic activators within 6-10 days could completely and permanently save the network dysfunction and cognitive impairment of adult schizophrenic mice "Our results in a genetic mouse model support the assumption that a critical developmental time window affects the transition between late adolescence and adulthood - and that schizophrenia can be prevented from progressing by being treated in that time window," Caroni said It is possible to develop treatment strategies based on this study to prevent schizophrenia in high-risk groups " 2 NAT commun: key genetic locus promotes the occurrence of schizophrenia and bipolar disorder doi: 10.1038/s41467-019-09786-7 a newly discovered epigenetic hot spot of schizophrenia and bipolar disorder may provide a new way for scientists to design more effective treatment methods and biomarker based screening strategies More than 100 million people around the world suffer from schizophrenia or bipolar disorder, which is characterized by hallucinations, delusions and irregular thinking processes They are all related to the excessive production of neurotransmitter dopamine Although effective drugs do exist, they usually have some side effects, such as emotional retardation, weight gain and motor disorders, which are usually related to Parkinson's disease At present, there are no effective biomarkers for screening and tracking the progress of any disease "Since the 1970s, we have known that the effectiveness of antipsychotics is directly related to the ability to block dopamine signaling However, the exact mechanism that leads to mental symptoms leading to excessive dopamine in the brain is not clear, "said Viviane, author of the article." we now have a biological explanation that can help people with these diseases really play a role " In this study, the authors and others found a series of epigenetic markers, which can accelerate the production of dopamine and disturb the synapses of the brain These information centers transmit fast neural information responsible for health functions As a result, the malignant changes of brain tissue and chemical balance aggravate the symptoms of psychosis "Like many other neurological diseases, schizophrenia and bipolar disorder usually occur in the years before symptoms become apparent We hope that our findings may lead to new biomarker screening risks, so that early intervention can be carried out " 3 NAT Genet: more than 400 risk genes related to schizophrenia have been identified Doi: 10.1038/s41588-019-0364-4 recently, an international journal Nature In a research report on genetics, researchers from Sinai Mountain hospital used a new machine learning method to study more than 100000 people 413 genes related to schizophrenia were identified in 13 regions of the brain Detection and analysis of gene expression in tissues can not only help researchers identify genes related to schizophrenia The brain regions with abnormal expression can also be found Although it affects less than 2% of the world's population, schizophrenia is still one of the main causes of people's physical disability Although the prevalence of the disease is relatively low, it will have a significant impact on public health and social economy, mainly the re-entry of patients and treatment costs What's more, although it is generally believed that multiple genes increase the risk of schizophrenia, researchers are not clear about the specific molecular mechanism behind this In this study, researchers used genome-wide association to study joint transcriptome accountability In the study of impact, schizophrenia related diseases are identified at the tissue level; researchers observe the differences of multiple loci of genetic code to see whether mutations are more easily found in individuals with specific characteristics, such as schizophrenia Transcriptome attribution is a new machine learning technology, which can help researchers in the inaccessible The association between disease and gene expression is detected in tissues such as the brain The researchers studied 40299 schizophrenics and 62264 controls, and found that genes related to schizophrenia may be expressed throughout the development process, including the special stage of pregnancy, individual adolescence and adulthood In addition, the researchers also analyzed the characteristics of different regions of the brain that mediate different risks of schizophrenia, and found that most of the connections came from the dorsolateral prefrontal cortex Professor Laura huckins, the researcher, said that the prediction model we have developed may help us to study the expression of prediction genes in schizophrenia and identify new risk genes related to schizophrenia In particular, we found that the risk genes of schizophrenia have been expressed during the development of the body, including the early pregnancy and so on At last, the researchers said that by using transcriptome accountability technology and genome-wide association research, we hope that in the later stage, we can not only clarify the new risk genes related to schizophrenia, but also provide targets and ideas for the development of new treatments for schizophrenia 4 JAMA psychiatry: real hammer! The effect of multi drug combination is better than that of single drug! Doi: 10.1001/jamapsychiatry.2018.4320 a new study found that in the maintenance treatment of schizophrenia, compared with the treatment with a single drug, the combination of two specific drugs is related to the reduction of the risk of recurrence The study was recently published in JAMA In psychiatry, completed by researchers at the Karolinska Institute, the researchers said the current guidelines should be revised to oppose the classification of all antipsychotic drugs The efficacy of antipsychotics in the prevention of relapse has been controversial, and it is generally believed that the use of a variety of drugs will damage the health of the body, but there is little evidence for this view, and the combination of antipsychotics is also common Researchers from the Karolinska Institute conducted a large study to determine whether there was a difference in the risk of psychiatric relapse after patients were treated with a single drug versus multiple drugs The study involved 62000 patients, all treated in Finland between 1972 and 2014 The researchers then tracked the patients to see if they were readmitted for psychiatric care, an indicator of disease recurrence The average follow-up time was 14.1 years, and to avoid differences between patients, the researchers conducted an individual analysis of them The results showed that compared with single drug, multi drug combination would reduce the risk of disease recurrence, but not all drug combinations had this effect Aripiprazole combined with clozapine had the best effect Compared with clozapine alone, the risk was reduced by 14% - 23%, while clozapine alone had the best effect