Schizophrenia is a very complicated disease in biology and methodology. The etiology, pathogenesis, treatment and prevention of schizophrenia have always been the central topic of psychiatric research. The traditional medical model emphasizes biological etiology. According to this view, schizophrenia is a disease with unknown causes. Because, since the discovery of pathogenic microorganisms, people are used to treating the causes of various diseases as a single factor. If no single reason can be found, it is considered as "unknown reason". Many common diseases can be considered as unexplained, such as hypertension and gastric ulcer. Schizophrenia certainly falls into this category. However, this traditional concept has changed, which is reflected in the transformation of disease model since 1970s, that is, from the original biomedical model to the bio-psychological-social medical model. This means that for most diseases, the onset is not absolutely determined by a single factor. For example, if you are infected with mycobacterium tuberculosis, you may not get tuberculosis (in fact, most people will not get tuberculosis). Whether you get sick or not depends on your mental and physical condition at that time, which is closely related to your environmental conditions. As far as schizophrenia is concerned, some people think that it is also the result of a combination of many factors. Some people even think that even in the future, it is impossible to find a single pathogenic factor that can explain all schizophrenia. Therefore, the etiological research introduced in this paper will involve clinical genetics, molecular genetics, brain imaging, neural development and psychosocial factors.
As a complex organ with a tightly protected structure, the human brain has very complex functions. In research, it is generally difficult to obtain a large number of living brain specimens; Moreover, patients with schizophrenia are either impaired in cognitive ability or unable to cooperate with researchers as required; In addition, long-term use of antipsychotic drugs changes the biochemical state of the brain, which in turn affects the structure, function or other aspects of the brain; Drug withdrawal will lead to recurrent mental symptoms; The diversity of symptoms is also the difficulty of research. Just like a patient, symptoms fluctuate at different times. In addition, the diversity and fluctuation of symptoms will be difficult to identify because of the use of antipsychotics, and so on, which constitute the complexity of schizophrenia research. It is because of the complexity of these studies that it is difficult to study the etiology of schizophrenia. So far, the cause of this disease has not been fully understood.
1. The results of population genetics research on genetic factors prove that schizophrenia is a complex disease with polygenic inheritance, and its heritability is 60% ~ 80%. So genetic factors are the most likely quality factors of schizophrenia. The earliest family study found that the probability of relatives of schizophrenia patients suffering from the disease was several times higher than that of ordinary residents, and the prevalence rate increased with the close blood relationship; The more serious the proband's illness is, the higher the probability of relatives getting sick. Kallmann( 1938) counted the incidence of schizophrenia proband 1 087 relatives. The incidence among relatives at all levels was 4.3% ~ 16.4%, among which children, siblings and parents were the highest. Shanghai (1958) investigated 54576 family members of 165438 schizophrenic patients. Among close relatives, parents and siblings have the highest prevalence of schizophrenia. The study of schizophrenic twins shows that the comorbidity rate of identical twins is 4 ~ 6 times that of fraternal twins (Kallmann,1946; Kringlen, 1967). In order to exclude the environmental factors of the disease, the study on twins and foster children found that the comorbidity rate of identical twins (MZ) was three times that of identical twins (DZ). Parents are schizophrenics, and the prevalence rate of their children after foster care is the same as that of those without foster care, which is significantly higher than that of foster children with normal parents. Heston (1966) separated 47 children of mothers with this disease from foster families and raised them by healthy parents, and compared them with 50 children of healthy parents. By adulthood, five people in the experimental group suffered from schizophrenia and 22 people had pathological personality. There were no schizophrenics in the control group, but 9 people had morbid personality, and the difference was significant. It suggests that genetic factors play an important role in schizophrenia.
In 1980s, after linkage analysis of the corresponding chromosome region (SherringtonR, 1988), Sherrington proposed that there was a dominant gene leading to schizophrenia in the long arm of chromosome 5. 1 year later, after a large-scale sample study, Sherrington's research team canceled this hypothesis. At present, most authors believe that it is almost impossible to find a specific gene that controls the onset of schizophrenia. A large number of experimental research results suggest that schizophrenia may be polygenic inheritance, which is caused by the superposition of several genes.
Gottesman et al. (1982) consulted the genetic literature about schizophrenia, and summarized 18 according to their own research, as a summary of the clinical genetics research of schizophrenia in the 20th century.
(1) The lifetime risk of schizophrenia is 1% (until the age of 55).
(2) The closer the blood relationship with the schizophrenic (proband), the higher the risk.
(3) The severity of the proband's illness and the number of patients in his relatives are directly proportional to his risk.
(4) There is no obvious gender difference in risk (that is, sex-linked inheritance can be excluded).
(5) The comorbidity rate of identical twins (MZ) suffering from schizophrenia is three times that of identical twins (DZ) and 35 ~ 60 times that of the general population.
(6) Half of MZ patients are not sick.
(7) The prevalence rate of children of this semi-disease-free MZ is the same as that of children of this disease patient, indicating that their genotypes are not completely clear.
(8) If MZ is raised alone and together, the comorbidity rate is the same (indicating that the comorbidity rate of MZ is not caused by close emotional contact).
(9) The prevalence rate of children of schizophrenics raised by others at birth is the same as that of their own caregivers (indicating that the main reason for their illness is not the acquired parenting style or other diseases).
(10) The prevalence rate of adopters (adoptive parents) of schizophrenia patients is not high (indicating that schizophrenia is not "infected" by infectious diseases caused by some physical or psychological factors).
(1 1) Children of normal people are adopted by others, and one of their adoptive parents suffers from schizophrenia, which does not increase the prevalence of adopted children, thus denying that schizophrenia is caused by parents' pathological upbringing.
(12) The prevalence of schizophrenia in the families of patients with schizophrenia-like psychosis after brain injury or epilepsy did not increase.
(13) For those who have no family history of schizophrenia, there is no specific environmental factor that can lead to schizophrenia without exception.
(14) The prevalence of schizophrenia is related to social class. It is more common in the poor class, but it is mostly caused by illness.
(15) The prevalence rate of twins is not higher than that of ordinary people, thus denying the view that when twins themselves become mental stimulation, twins are prone to perinatal trauma, so they are prone to schizophrenia.
(16) The main mental illness in childhood (such as childhood autism) has nothing to do with schizophrenia.
(17) Multi-factor and multi-gene genetic model can best illustrate the above facts.
(18) With current methods, it is impossible to identify schizophrenia before its onset.
However, some scholars have questioned the above research. If at least half of MZ people are not sick, does this mean that the environment also plays a role? MZ of different diseases can inherit diseases at the same high frequency, which not only shows that there is incomplete externalization, but also is related to the difference of "microenvironment" between them. Whether the inconsistency of some research results is affected by the inconsistency of diagnostic criteria; Wait a minute. Murray( 1985) and other scholars therefore believe that the etiology of schizophrenia has two independent mechanisms, one is mainly genetic factors and the other is mainly environmental factors. This view is in line with the current research trend, but needs to be confirmed by research.
2. Neurobiochemical Pathology The rapid development of neuroscience such as neurobiochemistry, physiology and psychopharmacology and the application of brain imaging technology in clinical research have promoted the research on the neurobiochemical basis of this disease, mainly in the following aspects:
(1) Dopamine Hyperfunction Hypothesis: Dopamine Hyperfunction Hypothesis mainly comes from the research of psychopharmacology. Psychotropic drug amphetamine can cause paranoid symptoms of acute schizophrenia in normal people. The pharmacological action of amphetamine is to inhibit the reuptake of DA by central synapse and increase the dopamine content in the receptor site. In addition, the pharmacological action of antipsychotics is to play a therapeutic role by blocking the function of DA receptor, an Ada receptor blocker. Later, it was further confirmed that the efficacy of antipsychotics was related to the affinity of D2 receptor. However, clozapine is an exception. At the general clinical therapeutic dose, the affinity with D2 receptor is weak, and the affinity with D4 receptor is high. In addition, the efficacy of antipsychotic drugs is not specifically aimed at schizophrenia, but also effective for mania.
The direct evidence supporting the hypothesis of DA hyperfunction comes from the study of DA receptor in patients. Crow( 1984) and others found that the number of D2 receptors in basal ganglia and nucleus accumbens increased due to the binding of 3H- pirenone with the receptors in patients' brain samples. Later studies found that it was positively correlated with the positive symptoms evaluated by patients before they died (r=0.70), while the negative symptoms were not. Homovanillic acid (HVA) is a metabolite of dopamine. Many studies have found that plasma HVA is positively correlated with patients' mental symptoms, and the plasma HVA level is higher in patients with severe mental symptoms (Picker, 1986). However, some data also show that the plasma HVA of patients with chronic schizophrenia is lower than that of normal people.
PET study: The binding capacity of DA receptor in patients' brain can be quantitatively studied by labeling DA ligand with appropriate nuclides. A study with 1 1C- methylpiperidone as ligand reported that there was no difference in D2 receptor density in the striatum of schizophrenic patients (Tune, 1985). In another study, D2 receptors were determined with 1 1C- raclopramide as ligand, and it was found that the number of D2 receptors in the globus pallidus of schizophrenia was higher than that of normal people (Crawley, 1986).
However, the final conclusion of the function of DA receptor in this disease needs more research work.
(2) Glutamate biochemical hypothesis: Glutamate is the main excitatory transmitter of cortical neurons, and it is the amino acid neurotransmitter of extracortical projection neurons and internal projection neurons. Glutamate receptors, including kainic acid receptors, in the brain tissue of schizophrenic patients at autopsy were studied by radioligand binding method. Acid (KA), α-amino -3- hydroxy -5- methyl -4 isoxazole (AMPA) and N- methyl -D- aspartic acid (NMDA). It was found that the binding force of KA receptor was enhanced in the limbic cortex, especially in the frontal lobe of AMPA and NMDA receptor.
Some studies have found that the level of NAAG in hippocampus and prefrontal cortex of schizophrenic patients is increased, and the content of related enzyme NAALADase is decreased. NAALADase exists in glutamate neurons, and it decomposes glutamate compound NAAG(N- acetylglutamic acid) in neurons into NAA and glutamic acid. Using 1H-MRS imaging technology, the contents of glutamate compounds and their metabolic enzymes in many parts of living brain can be measured simultaneously. It was found that the NAA of schizophrenic patients was significantly lower than that of the control group. This result is consistent with the result of NAALADase activity in autopsy of schizophrenic patients. Neurobiochemical pathology supporting glutamate and its metabolic enzyme pathway in some parts of schizophrenic patients (WeinbergerDR, 1997).
Clinically, glutamate receptor antagonists, such as PCP, ketamine and other NMDA receptor antagonists, can cause transient mental symptoms, hallucinations and delusions, increase the BPRS score, and also cause negative symptoms. It is speculated that NMDA receptor dysfunction plays an important role in the pathophysiology of schizophrenia.
NMDA receptor can be activated not only by glutamate, but also by glycine, which can bind to the agonist site of NMDA complex. In animal experiments, the administration of large amounts of glycine through the blood-brain barrier can increase the central glycine content and reverse the behavioral effects of NMDA antagonists. In clinical research, high-dose glycine (>; 30g/d) can obviously improve the negative symptoms of schizophrenia. It is suggested that the treatment of glycine may become a new way to deal with negative symptoms of schizophrenia (JavittDC, BallA, 1999), which increases the interest of researchers in this field.
(3) Hypothesis of functional imbalance between dopamine system and glutamate system: Understanding the importance of glutamate neurotransmitters does not exclude the functions of DA and other systems. M Carlsson (1990+0990) pointed out that the function of the cerebral cortex to control sensory input and alert level is accomplished through a feedback system including striatum, thalamus and midbrain reticular structure. Stimulating DA mechanism can increase sensory input and alert level; However, the cortical striatum glutamate system plays an inhibitory role. Therefore, the author thinks that schizophrenia is caused by the imbalance between subcortical DA function system and glutamate function system.
3. In addition to genetic factors, the biological and social psychological factors in the environment, psychological stress in the environment and the influence of physical diseases have always been an important aspect of the etiological study of schizophrenia. Many data show that schizophrenia is related to psychosocial factors, but so far no psychological factors have been found that can determine the occurrence of schizophrenia. Some very serious stimuli did cause mental illness in some healthy people in the past, but did they cause schizophrenia or reactive psychosis? This diagnosis is controversial. Psychosocial factors used to be called psychogenic factors, which were put forward by Sommer in 1894. At that time, it meant "morbid state caused by ideas". Later, the scope was expanded to include not only concepts, but also experience, emotion and environmental conditions. So in the past 20 years, it has gradually turned into psychological and social factors. Bolton (1984) proposed that all psychological and social factors related to diseases should meet the following conditions: they must be reasonable; There must be blows and setbacks in the process of achieving life goals; We must be able to clearly explain the relationship between these factors and the disease according to the situation before and after the illness (Bolton thinks that some of Freud's explanations are ambiguous and unverifiable). The research on psychosocial factors of schizophrenia can be summarized as the following aspects.
(1) Socio-psychological factors: American psychiatrists and sociologists cooperated in research and investigation, and found that among the poor living in Chicago, the first hospitalization rate of schizophrenia was the highest, especially schizophrenia (Faris, Dunham, 1930 ~ 1933). Based on the data of community survey near new york, it is found that the prevalence rate is negatively correlated with social class. The ratio of the prevalence rate of low economic and social strata to high economic and social strata is 9∶ 1, and the prevalence rate of low economic strata is the highest (HollingheadRedlish, 1958). According to the epidemiological survey data of mental disorders in communities of Taiwan Province Province, the prevalence rate of mental disorders is inversely proportional to the socio-economic and educational level, with the highest prevalence rate among people without occupation or low skills (Lin, 1953). From 65438 to 0982, the data of collaborative epidemiological survey of mental illness in the whole country 12 region found a similar relationship with the above: the prevalence rate of schizophrenia in people with low economic level was 10. 16‰, and the unemployment rate was 7.50 ‰ ~ 25.4 ‰, which was significantly higher than that in people with high economic level. , 1986)。
(2) Family upbringing environment: Some people think that schizophrenics live in broken families (parents divorced, died or left) in their childhood, but later studies failed to confirm this view. It is also found that there are more patients with eccentric or neurotic parents, which is more than 1 times that of normal people. It is also found that the relationship between the parents of patients is abnormal (either they are bent on their own way or one party is too obedient to the other), but some reports do not support it. The abnormal relationship between parents and children has been highly valued in Britain and America. This abnormal relationship can be divided into two types, namely, excessive participation and insufficient participation. The former includes overprotection and dependence. And the latter includes the idea of rejection and disrespect. Later research found that more parents care too much and care too little. Whether this excessive worry is the cause or result of schizophrenia is still controversial. Some people think it is the reason, so this kind of mother is called "schizophrenic mother"; Some people think it is the result, because the mother thinks the child is "fragile", so she is particularly concerned about protection. In addition, some people have studied the communication between schizophrenic patients and their parents, and think that many of these parents are unharmonious in marriage, and communication between them and their children often has problems and cannot be well coordinated, that is, "abnormal family communication". Such children are prone to schizophrenia in the future. Although the research on this relationship acknowledges this phenomenon, it does not think that this is the cause, but may be the result of children's own problems.
(3) Personality problem: At the beginning of the 20th century, it was thought that many schizophrenics developed from bad personality before illness, and most of them were so-called split-like personalities. Personality disorders before illness are often fully manifested in adolescence, before which they can be similar to ordinary children. Whether the personality problem is the cause is still controversial, and it is generally considered that it is not the direct cause. Bleuler once thought that patients with schizophrenia were easily incompatible with others (including family members) because of their strange personality since childhood, which caused interpersonal tension and further developed conflicts, and became a pathogenic psychosocial factor. But there are also views that the isolation of schizophrenia from society and people is not the cause, but the result of illness. Due to the disease, the patient's will is reduced, cognitive function is impaired, and health habits are bad. In addition to the symptoms of the disease itself, the patient's employment opportunities are almost lost, and it is difficult to maintain a social status above the middle level. With the development of the disease, its social status will further decline. This view is supported by some research results.
(4) Life events: Whether life events (generally unpleasant events) can cause schizophrenia, the following points must be made clear when analyzing this problem: ① Some life events can really affect the specific manifestations of symptoms, but it is not certain that it is the cause. ② It is necessary to distinguish whether a life event is the cause or the consequence of a disease. The causal relationship of such a large number of life events is very complicated, and only a few life events (such as earthquakes and wars) can be said not to be the result of personal activities. (3) Life events have pathogenic effects on this person, but not necessarily on another person; At this time, it has pathogenic effect, and at other times it may not have pathogenic effect, so it cannot be generalized. Therefore, when analyzing the significance of life events, we must take into account personal past experience, personality characteristics, current situation, physical condition and social and cultural background. Generally speaking, there is a tendency to think that life events as a single factor are not the cause of schizophrenia.
The recent comparative study of early stress and adult psychopathology shows that (AgidO, ShapivaB, 1999): the loss of parents in childhood (referring to the death or permanent separation of parents before 17 years old) is significantly higher than that of 76 age-matched, gender-matched, race-matched and age-matched control groups (OR=3.8, p = 0).
Long-term neurobiological research on animals with separated parents shows that early life experiences will affect the stress response of adult animals. During the life of animals, the response of hypothalamus-pituitary-adrenal (HPA) axis to stress is strengthened, the hypothalamic corticotropin releasing factor (CRF) in cerebrospinal fluid is continuously increased, the CRF receptor density in pituitary is decreased, and the CRF mRNA level is increased. The author thinks that this can also be applied to human beings, and bereavement in early years can affect the vulnerability of human psychopathology through the change of stress response (1999).
4. Neurodevelopmental research For many years, it has been believed that schizophrenia is caused by pathological changes in the brain in early adulthood. This hypothesis is supported by Kraepelin's concept of Alzheimer's disease and the clinical decline process of the disease. From this concept, most patients' brains are relatively normal before the onset of early adulthood, and any pathological changes in the brain caused by the disease will become more obvious because of the progress of the disease. This conceptual model is consistent with most known adult brain dysfunction, including metabolic or infectious encephalopathy (hereditary or sporadic) and degenerative diseases.
From the above hypothesis to the study of pathological nerve development, the concept of schizophrenia has undergone major historical changes. The reason is that there is repeatable evidence of cortical dysplasia, and a neurobiological model is established to explain the relationship between the above dysplasia and the clinical characteristics of the disease.
According to the theory of neural development, nerve cells migrate in the second trimester of pregnancy, which determines the hierarchical arrangement and location of cortical neurons and their internal relations. The above structure will last a lifetime. Even if cell loss or secondary lesions occur, it will not change. If the migration of nerve cells fails at this stage, it will lead to cortical development disorder. The research data of brain abnormalities in schizophrenia show that. Schizophrenia patients have slight multifocal or diffuse anatomical variation, which occurs before the onset and is relatively constant. In addition, the study of cortical cell structure shows that there are genetic defects in the prefrontal cortex, marginal cortex and the communication structure between them in schizophrenia patients, which can not regulate the activity of dopamine under environmental stress in early adulthood. All the above studies suggest that schizophrenia patients have neurodevelopmental defects, and there are the following etiological explanations for this developmental defect in the second trimester of pregnancy.
(1) Obstetric abnormality: Obstetric complication (OC) as the cause of schizophrenia. This is the focus of many studies in the past 30 years. At present, most studies show that mothers of schizophrenics are more prone to OC during pregnancy and childbirth. Goodman (1988) thinks that oc increases the risk of schizophrenia by at least 1%. In addition, although OC is common in some environments, the incidence of schizophrenia in these environments has not increased, so OC's prediction of schizophrenia is poor. He believes that schizophrenia leads to OC, that is, the existing embryo abnormality increases the susceptibility of OC. This view is more and more certain, and it is more and more consistent with the research data of neuropathology.
(2) Prenatal viral infection: The viewpoint of perinatal viral infection is very challenging. Viral infection during pregnancy in Helsinki, a survey of environmental risk factors during pregnancy found that schizophrenic mothers had more physical diseases in the second half of pregnancy, and their symptoms were equivalent to viral infection. 1957 There was an outbreak of influenza A2 in Helsinki, Finland. Mednick diagnosed young people (26. 16 years old) born in this area from 0958 10/5 to August 2009 14 as schizophrenia. The authors speculate that viral infection affects fetal nerve development, which is related to the structural disorder of cortical nerve cells in schizophrenic patients. But this view is not perfect enough. There are still many contradictions in the survey data of influenza virus in Europe from 65438 to 0957, which can not be solved so far. Even if these contradictions are solved and positive results are achieved, influenza virus infection is at most the cause of a few cases. In addition, even the positive results emphasize the developmental disorder in the second trimester from one side. It increases the risk of schizophrenia, and its mechanism is difficult to explain from the perspective of viral epidemiology.
(3) Complications during pregnancy and perinatal period: The Danish scholar Schulsinger conducted a prospective survey on children whose mothers suffered from severe schizophrenia in 65438-0962. The author collected the original data of 166 high-risk baby midwives. Obstetric complications were scored on a scale of 0-4. Follow-up from 65438 to 0972 showed that there were three clinical conditions: schizophrenia, borderline schizophrenia and no psychosis. The author found that the score of complications in schizophrenia group was significantly higher than that in borderline schizophrenia group. It is considered that the genetic load of the two groups is similar, and whether they are sick or not depends on the influence of environmental factors.
(4) Other causes: For example, alcohol will have a negative impact on embryonic development, leading to some visible changes in schizophrenia, such as migration defects and cortical volume reduction. However, epidemiological data do not support the statement that maternal alcoholism is an important risk factor for schizophrenia. Studies have found that mothers' hunger in the first 1 week of pregnancy is related to the increase of children suffering from schizophrenia. Because the relationship between this neuropathological change and schizophrenia is uncertain, it is difficult to integrate it with other neurodevelopmental data.
If schizophrenia is indeed related to abnormal neurodevelopment, how to explain that the onset of schizophrenia is often 20 years after abnormal neurodevelopment? There are two hypotheses to explain this problem: ① Another pathological process that occurs during clinical onset. For example, feinberg thinks that the disorder of synaptic reorganization in adolescence is the cause of schizophrenia. It has also been suggested that synaptic reorganization disorder is the secondary reaction of abnormal development in uterus, which shows obvious neurobiological and clinical significance in adolescence. ② There is no other pathological process in adolescence, but the abnormal development in the past interacts with the normal development of adolescence, which eventually leads to schizophrenia. For the above hypothesis, some scholars have proposed a further neurobiological model. They believe that mental illness is the product of the loss of frontal lobe communication function and brain development problems in late adolescence. That is to say, in a mature brain, other nervous systems or neurons have been unable or unable to perform this function. At this time, the early cortical developmental defects associated with schizophrenia show clinical significance and may have a delayed effect on the regulation of dopamine system in the brain.
5. Hypothesis of brain pathology, brain structure changes and abnormal nerve development caused by the application of new technologies, new technologies in CT, MRI and histopathology research emphasize diagnostic criteria and control group in the selection of clinical cases, and it is not uncommon to find abnormal brain structure in schizophrenia.
CT and MRI showed that some schizophrenic patients had more obvious changes in brain structure than normal people of the same age, and the patients had enlarged lateral ventricle (Johnstone, 1976). These changes were found in schizophreniform patients 1 (Weinberger, 1982). The study of magnetic resonance imaging confirmed that the ventricles of schizophrenic patients were enlarged, the structures of cerebral cortex, forehead and cerebellum became smaller, and the area, length and thickness of corpus callosum were different from those of the control group (Andreasen, 1986). At the same time, repeated examination in the course of the disease did not find that the ventricle continued to expand, suggesting that this abnormality was not caused by the progressive development of the disease. Recently, 16 patients with schizophrenia, 17 patients with affective psychosis and 18 age-matched normal people were studied by MRI. The results of quantitative analysis show that the volume of the left posterior superior temporal gyrus in the first-episode schizophrenic patients is obviously smaller than that in the first-episode affective psychosis patients, with obvious asymmetry: the left side is smaller than the right side, indicating that the temporal lobe of the first-episode schizophrenic patients is abnormal and the gray matter of the left posterior superior temporal gyrus is smaller, which is unique to schizophrenia (Hirayasu, Shenton, 1998). The left temporal gyrus is of special significance to schizophrenia, because the function of this cortex is related to auditory and speech processes. The latter is often destroyed by schizophrenia. This study ruled out that these structural abnormalities were caused by chronic or nerve blockers (HirayasuY, 1998).
Whether ventricular enlargement is related to environmental factors or genetic factors. 15 pairs of schizophrenic twins (Suddath, 1990) with different zygotic diseases were studied by MRI. It is found that a considerable proportion of sick and non-sick compatriots have abnormal brain structure, which shows that the changes of brain structure in schizophrenia patients are at least partly related to genetic factors. A prospective survey of high-risk children by Danish authors found that the ventricular enlargement of schizophrenic patients was obvious when they grew up, and there were obvious perinatal complications during pregnancy. It is speculated that the changes of brain structure partly reflect the damage of central nervous system in early years.
Crow et al. (1990) studied the pathomorphology of 22 autopsy brain samples of schizophrenia and 26 age-matched control brain samples. It was found that the ventricles of the patients were expanding backwards and left and right asymmetrically, mainly located in the left temporal angle. This abnormality is not accompanied by an increase in the number of glial cells. The author thinks that the increase of left temporal angle may be caused by brain retardation. In the normal brain development process, the structure of temporal lobe and occipital lobe develops relatively late, and the left side is later than the right side. Therefore, it is speculated that the abnormal brain structure of patients with this disease comes from the genetic control of brain development asymmetry.
Detailed histopathological study showed that the cell structure of hippocampus, frontal cortex, cingulate gyrus and olfactory cortex was disordered. These changes are not accompanied by the proliferation of glial cells. It is speculated that the abnormal migration or differentiation of neurons in the brain development stage destroys the normal cortical communication mode, and the hypothesis of abnormal neural development is put forward (StefanMD, MurrayRM, 1997). Study on adaptive function of schizophrenic patients before onset: It was found that quite a few patients had obvious adaptive dysfunction before onset. 168 schizophrenic patients diagnosed by DSM-ⅲ-Rⅲ-R were assessed with the Pre-illness Adaptation Scale (PAS). Two family members acted as insiders, and it was found that 35% of schizophrenics had obvious pre-illness dysfunction (Claire, 1999). From childhood, early adolescence to late adolescence, PAS scores gradually increased. The earlier the onset age, the more serious the dysfunction. The author thinks that the pre-illness dysfunction in different age stages represents the continuity of the same course of disease, which supports the hypothesis of neural development of this disease. The cause of neuronal migration disorder is not clear. Some authors speculate that genetic factors or viral infection may play a role.
Existing data show that genetic factors are very important for the occurrence of schizophrenia, although the genetic model is unknown. Recently, some data show that schizophrenia has abnormal neurological development, but it is not clear whether it is caused by this disease to some extent. Most scholars believe that schizophrenia is the result of the interaction between genetic factors and environmental factors. Environmental factors include fetal infection, perinatal and delivery injuries and social psychological stress. The research data suggest that schizophrenia can be accompanied by changes in brain structure: lateral ventricle enlargement, especially temporal lobe and frontal lobe, can be seen in the early stage of the disease and has nothing to do with the development of the disease. It is not clear whether these changes are due to the genetic control of asymmetric brain development or related to complications such as maternal pregnancy and perinatal infection. Antipsychotic drugs that can block DA receptor can control the symptoms of schizophrenia, but whether there is DA system hyperfunction in schizophrenic patients needs further confirmation.
(2) Pathogenesis
More than half a century's family investigation and investigation data of twins and foster children prove that genetic factors play a certain role in the occurrence of this disease. Domestic family survey data show that the prevalence rate of relatives of schizophrenia patients is 6.2 times that of ordinary residents. Twin research shows that the comorbidity rate of identical twins with almost the same genetic information is much higher than that of identical twins with incomplete genetic information. Based on the research data of 1 1 in recent years, the comorbidity rate of monozygotic twins (56.7%) is 4.5 times that of monozygotic twins (12.7%) and 35-60 times that of the general population. It shows that genetic factors play an important role in the occurrence of this disease. Research on foster children also proves that genetic factors are diseases.