Schizophrenia is one of the most serious disorders affecting human health today, with complex and diverse signs and symptoms, usually divided into positive, negative, cognitive, affective, and motor symptoms. Currently, schizophrenia is not a preventable disorder; however, implementing effective prevention measures for people in the ultra-high risk (UHR) stage in an effort to reduce risk factors may help reduce its incidence. Early assessment and intervention are difficult but important. This article reviews the research advances in early prevention and intervention for schizophrenia. Early prevention Primary prevention targets all healthy individuals and aims to reduce the number of new cases; secondary prevention and early intervention should be used to identify and treat patients at the early signs of the disease, i.e., the pre-onset and prodromal stages, with the aim of impeding disease progression; tertiary prevention refers to measures to prevent incapacitation of individuals affected by the disease and to reduce relapse, disease-induced social and legal problems, and associated suicide rates. Early prevention and intervention in schizophrenia has positive implications. Universal prevention Although it is not clear which risk factors should be included in the universal prevention of schizophrenia, reports suggest that certain risk factors can increase the likelihood of developing schizophrenia and are generally recognized. These risk factors include: biological indicators, susceptibility genes, or neuropsychological abnormalities. A study conducted in Norway and Denmark confirmed that educating the general public about recognizing signs and symptoms of psychosis through schools, general practitioners, and mass media can reduce the duration of untreated psychosis (DUP) (i.e., the time it takes from onset to treatment). Other examples of universal prevention include instructing women of childbearing age on prenatal care and reducing prenatal and postnatal risk factors; and improving public health measures to reduce the use of prohibited drugs. More recently, the role of diet has received increasing attention, for example, the role of polyunsaturated fatty acids and vitamin D in preventing the progression of schizophrenia. Selective prevention, also known as targeted prevention, addresses risk factors for the development of schizophrenia. These risk factors (environmental and genetic) are obtained on a case-by-case screening basis. Several environmental factors have been reported to be associated with an increased risk of developing schizophrenia, including prenatal infection or malnutrition, perinatal complications, winter birth, lack of effective protection in the home environment, experience of physical and sexual abuse during childhood, urbanization of the living environment, marijuana use, unemployment, marital status, and migration. The correlation between genetic factors and gene-environment interactions and the onset of schizophrenia may be 80%. Studies have shown that having a family member with schizophrenia leads to a significant increase in the prevalence of the disorder in the family, as Keshavan et al. reported an increased incidence of psychotic behavior abnormalities in late childhood and adolescence in the offspring of parents with schizophrenia compared to children of normal parents. However, there is insufficient evidence to support a definitive association between genetic variants and the onset of schizophrenia, so its diagnostic significance is unclear. The key issue in directional prevention is the early recognition of the characteristic signs and symptoms of mental illness. Early symptoms of schizophrenia include mild positive symptoms, negative symptoms, cognitive impairment, and motor impairment, which some scholars refer to as the “ultra-high risk stage (UHR). Because many high-risk individuals do not ultimately develop schizophrenia, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced the concept of “mild psychotic syndrome (APS)” to describe it. However, the DMS-5 concluded that the available data were insufficient to establish sufficiently reliable criteria for the assessment of APS to be clinically applicable. Therefore, further research is needed to clarify the concept of APS. As mentioned above, UHR has no specific symptoms and is therefore difficult to identify a priori, and knowledge of this stage has been gained mainly through retrospective studies of patients with schizophrenia. Studies have shown that the use of UHR can identify populations vulnerable to schizophrenia. More than one-third of the population of UHR subjects not receiving antipsychotic medication develop a critical state of schizophrenia within 1 year; at 10 years of follow-up, the proportion developing schizophrenia approaches 70%. It has also been shown that individuals with predominantly negative symptoms and cognitive impairment in the UHR population have a higher probability of developing schizophrenia, characteristics that are beneficial for early identification of UHR. Retrospective studies have found that of the three prevention interventions, the most cost-effective is directed prevention. This approach is more effective and more ethical, with fewer overall adverse effects. Therefore, the majority of clinical prevention interventions are focused on individuals with prodromal symptoms. For individuals with schizophrenia and related prodromal symptoms, interventions may be attenuated and delayed as appropriate. Early intervention has been applied in three areas: targeted prevention for individuals with precursors or prodromal symptoms of psychosis, treatment measures to improve prognosis for individuals with confirmed psychosis, and identification of individuals with untreated illness. Research Advances in Early Intervention Early intervention can help reduce the morbidity and disability associated with schizophrenia. However, due to the lack of effective early identification methods, the diagnosis of schizophrenia is usually established only after the patient presents with specific psychotic symptoms. This invariably prolongs the DUP, and a longer DUP represents a relatively poorer treatment outcome. On the other hand depression and suicide risk are increased, which may increase substance abuse and delinquency and raise the cost of treatment. Several early intervention studies for UHR have been reported successively. The Personal Assessment and Crisis Evaluation Service (PACE), conducted by the Early Psychosis Prevention Intervention Centre (EPPIC) established at the University of Melbourne, Australia, is the world’s first study based on early assessment, treatment intervention for schizophrenia. The study conducted PACE assessments for UHR populations, i.e., assessment and intervention for people at high risk for psychosis. The first tool for assessing UHR, the Comprehensive Assessment of At-Risk Mental Status (CAARMS), was developed. The study included 59 patients who met the criteria for UHR from 1996 to 2000 and divided them into two groups: one group received low-dose risperidone combined with cognitive-behavioral therapy (special intervention group) and the other group served as a control group with only some basic interventions necessary. Both interventions were observed for 6 months, and follow-up was continued for 6 months after discontinuation of the intervention. It was found that the special intervention group developed psychosis at a smaller rate than the control group (5.7% and 9.7%, respectively; P<0.05). However, the differences between the groups at the later stages of observation (after 12 months of treatment and during the follow-up period of 3 to 4 years after treatment) were statistically evaluated as non-significant. However, prospective analysis of these data revealed that a lower percentage of subjects who completed treatment in the special intervention group progressed to psychosis compared to the control group. The significance of this intervention effect, and whether it was caused by risperidone, or was a result of cognitive behavioral treatment, or an interaction of the two, is unclear. Although the study lacks a blinded scientific basis, it at least suggests the possibility that pharmacotherapy may delay or even avoid progression to schizophrenia. Based on PACE, the North American Multicenter Collaboration for Early Intervention in Schizophrenia through Identification, Management, and Education of Risk Factors (PRIME) , this is the first randomized, double-blind, placebo-controlled clinical study to examine early interventions. The study randomized 60 outpatients with prodromal symptoms and seeking treatment in the United States and Canada to either the treatment group (olanzapine, n=31) or the placebo group (n=29) for 1 year of treatment followed by 1 year of follow-up. 16.1% of those found to have converted to psychosis during treatment at 1 year were in the olanzapine group and 37.9% in the placebo group. Although this difference between groups was not statistically significant (perhaps related to the small sample size of the study), it does at least suggest that olanzapine may reduce or delay the likelihood of conversion to psychiatric disorders. Cross-sectional data from this trial found an improvement in psychiatric symptoms in the olanzapine group compared with the placebo group, with a significant effect after 8 weeks of treatment (p<0.05). However, at this time, weight gain was significant in the olanzapine group, with mean weight gains of 4.0 and 0.3 kg in both groups (P < 0.05). Similar studies have developed a variety of early identification and assessment tools, including the Bonn Basic Symptom Assessment Scale (BSABS), the Schizophrenia Prediction Tool for Adults (SP-A), the Early Identification Questionnaire (ERIraos), and the Basel Early Detection Checklist (BED), each of which has its own characteristics for identifying symptoms and assessing disease transformation, and are not described here. In a randomized, double-blind study conducted between 2004 and 2007, patients with UHR were divided into a treatment group (n=41, long-chain omega-3 polyunsaturated fatty acids) and a placebo group (n=40). analysis at 1 year showed that fewer patients in the treatment group progressed to psychosis (4.9%), compared with the placebo group (27.5%). The difference was significant. Also, long-chain omega-3 polyunsaturated fatty acids significantly reduced positive and negative symptoms and general symptoms in patients. Studies of early psychosocial interventions in schizophrenia have focused on cognitive behavioral therapy (CBT). morrison et al. divided 74 patients with UHR into CBT and control groups for a 3-year intervention and showed significant improvement in psychotic symptoms in the CBT group. Several similar studies have also shown that cognitive therapy or CBT as an early intervention can significantly reduce the transition to psychosis in the UHR population. In conclusion, schizophrenia is still not a preventable disorder. However, efforts to reduce preventable risk factors by achieving preventive interventions for the UHR population may reduce its incidence. Unfortunately, current research data are not sufficient to provide information on how to reliably identify risk. Current recommendations favor the use of individualized interventions while considering the risk-benefit ratio. Specific problems are analyzed on a case-by-case basis. Only a minority of patients with UHR eventually convert to schizophrenia. Although a range of interventions have been effective in reducing the incidence of transition to schizophrenia, large studies and long-term follow-up are lacking. Fortunately, the APS proposed by the DSM-5 may provide researchers with the opportunity to conduct more research and identify more reliable prevention interventions.