Description Schizophrenia is a severe psychiatric disorder that affects approximately 1% of the general population. It affects people differently as the symptoms can vary from person to person and some people have many symptoms while others may have only a few. Symptoms are generally characterized as positive or negative, though there is overlap. More specifically, positive symptoms refer to exaggerated behavior such as delusions or hallucinations. Delusions are defined as beliefs that are contrary to fact such as believing that others can read one’s mind. Hallucinations are defined as alterations in hearing, seeing, tasting, or smelling things where the person experiences sensations which others do not experience, such as hearing voices or seeing things that others do not hear or see. Other positive symptoms include disorganized speech or behavior where the person’s behavior appears disorganized and even their speech is difficult to understand. In contrast, negative symptoms involve the absence of behavior and include lose of interest in everyday life activities, lack of feeling or emotion (apathy) or inappropriate feelings, lack of motivation, and lack of pleasure (anhedonia). Heterogeneous Disorder Schizophrenia is also often described as a heterogeneous disorder because there are many different symptoms observed, as alluded to previously, and also because there are likely many different underlying causes that are as yet unknown. It is among the most severe of psychiatric disorders because it affects all aspects of motivation, thinking, memory, decision-making, affect, emotional expression, and social communication. All of these functions are altered in schizophrenia. Schizophrenia is also generally diagnosed at a time when young people are beginning to become young adults, i.e., at the prime of their lives. There is also a difference in the diagnosis between men and women where men diagnosed with schizophrenia usually start to show symptoms between their late teens and early 20s, while women usually develop symptoms during their mid-20s to early 30s. Additionally, in terms of past history, sometimes people diagnosed with schizophrenia showed more attenuated symptoms that dated back to childhood, while others who were later diagnosed with schizophrenia showed no early symptoms and showed normal development through their childhood. Historically Schizophrenia was described more than 100 years ago, and yet the cause is still unknown. Early in the 20th century, schizophrenia was described as “dementia praecox”, or early dementia, but it was also described as “the schizophrenias” to emphasize the separation between thinking and emotions that is observed in these individuals. The word “schizophrenia” itself is derived from the Greek word skhizein, meaning “to split”, and the Greek word Phrenos (phren) meaning “diaphragm, heart, mind”. During this time period it was believed that ultimately the symptoms of schizophrenia would be linked to an underlying brain disorder, but the technology was such that discerning brain alterations was not promising and this area of investigation was not followed again in any meaningful way until the mid 1970’s (see below). The name schizophrenia has, nevertheless, been retained, to this day, and there was an effort to describe five different subtypes including paranoid schizophrenia, to describe people who appear to be more afflicted by paranoid thoughts including the belief that others are plotting against them. Catatonic schizophrenia is a term that is used less frequently. It is a term used to describe the unusual lack of motor behavior where people appeared to be frozen in their movements and where an arm could be moved above the head and the person would leave it there. Disorganized, formerly hebephrenic, was used to describe the disorganization and silliness that was observed in some diagnosed with schizophrenia, though this term is also not often used today. Undifferentiated schizophrenia describes those individuals who show symptoms that fit more than one type. Finally, Residual schizophrenia is a term used to describe a subtype where most symptoms have disappeared though some, such as hallucinations remain. Of note, however, these five descriptions of subtypes of schizophrenia are not generally in use today as it is believed that the symptoms observed are more useful for diagnosing and treating schizophrenia. Other terms that have also been used more recently include descriptions of the different stages of the illness. For example, acute schizophrenia or first episode schizophrenia are terms used to describe the early stages of schizophrenia, and prodrome or clinical high risk, are used to describe those who are most at risk for developing schizophrenia, either because they have more than one first degree relative with schizophrenia, or because they show symptoms that suggest schizophrenia though they do not meet all of the criteria that one expects to see. Advanced Imaging Tools Needed One of the problems with investigating disorders such as schizophrenia is that the tools available in the past to evaluate subtle, small changes in the brain were rather crude. Thus most of the work done in the past century to investigate brain structural abnormalities in schizophrenia was based on methods that were crude, prone to error, and it therefore did not further our knowledge and understanding of brain abnormalities in schizophrenia. This is not to say, however, that structural brain abnormalities were not thought to underlie the symptoms observed in schizophrenia. In fact, early documentation of abnormal brain structures from post-mortem studies of schizophrenia led to the formulation of quite specific hypotheses concerning the relations between brain and behavior. These early studies, however, were hampered by inconsistent findings, crude measurement techniques, and carefully methodologically controlled studies often led to negative findings. This turn of events led many investigators to conclude that there were no structural brain abnormalities observed in schizophrenia that could not also be seen in normal controls. Progress in this area of research thus came to a near standstill and it was not until 1976, with the advent of computed tomography (CT), that the first CT study of schizophrenia reported abnormally large lateral ventricles in schizophrenic patients. This one study led to numerous CT studies, which confirmed abnormalities in the brains of schizophrenic patients, and this one study led to a renewed interest in investigating such abnormalities in schizophrenia. The early CT studies evaluated only ventricular size and did not evaluate local regions of interest nor could gray and white matter be differentiated. With the advent of MR imaging, gray and white matter could be evaluated and thus a new tool was added. In 1984, the first MR study of schizophrenia was reported in the literature. Many studies followed, but most were based on magnets with a field strength less than 1.0, and the slice thickness was often 1 cm or more. Moreover, there were no methods for evaluating gray and white matter throughout the brain. The first study to use contiguous slices of the entire brain (1.5 mm coronal and 3 mm axial) was done by our group and the findings were reported in The New England Journal of Medicine (1992). Here, we reported small but important gray matter volume reduction in schizophrenic patients, compared to controls, in the amygdala-hippocampal complex, in parahippocampal gyrus, and in superior temporal gyrus, on the left. The latter changes were also correlated with disordered thinking and were thus suggestive of a disturbance in an important neural circuit involved in verbal processing and consolidation of information that involve both the amygdala-hippocampal complex and the superior temporal gyrus. These findings in schizophrenia would not have been possible without the advances in imaging technology that have continued to this day and include also functional imaging where alterations in different brain circuits involving attention, memory, etc. can be probed as well as diffusion imaging where white matter connections in the brain can be studied in order to understand better the neuropathology of schizophrenia so that targeted interventions can begin to be translated from the research domain to the clinical domain. Genetics One of the greatest risks for schizophrenia is to have a first degree relative with schizophrenia, which increases the risk by 10% as compared to 1% in the general population. Additionally, if both parents are diagnosed with schizophrenia then the risk is about 50%. The risk is also increased if one has a monozygotic twin (one egg that splits/identical twin) with schizophrenia, where the risk is increased to 40% to 65%. Note, however, that this percent is not 100% for an identical twin, suggesting that genes are likely contributory rather than causal. Other factors influencing increased risk include velocardiofacial syndrome, a chromosomal deletion disorder (chromosome 22q11), where the risk is approximately 30%, although other psychiatric disorders such as bipolar disorder are also increased. The conclusion to be drawn here is that it is likely that many genes are involved in a contributory role in the development of schizophrenia. There is thus no single gene that causes schizophrenia. Evidence suggests that the role of genes is more complicated and it is more likely that there are a number of genes, all with small effects, although transmission and expression is still not known. There is also clearly some genetic overlap between schizophrenia and bipolar disorder as well as likely autism spectrum disorders. Finally, there are higher rates of what are called “rare genetic mutations” that involve many different genes that likely impact brain development. These changes, along with environmental events such as exposure to viruses, birth complications, and other factors all likely contribute to this complex disorder that is only observed among humans. Today and the Future Today, there is an appreciation that schizophrenia is a very complex brain disorder that we are just beginning to understand in terms of the neural circuits that are affected in the brain. The changes observed in the brain are subtle and we are still trying to understand their implications. There is also an appreciation that the brain is far more plastic than has previously been thought, and thus alterations in the brain may not be associated with a poor prognosis. In fact discovering changes early in the course of the illness may lead to early interventions that may lead to halting progressive changes that characterize chronic states of schizophrenia that can be debilitating both to the person, the person’s family, and the larger community. There is also a focus today on looking more closely at those who are at the prodrome stage or who are at higher risk for developing schizophrenia so that intervention can be implemented early and perhaps prevent a future diagnosis of schizophrenia. Today there is also an appreciation of the role that genes play in schizophrenia. While there is no one gene that causes schizophrenia, today there is a better understanding of the effect of a small number of genes that are associated with a diagnosis of schizophrenia. Better treatments are also available today and many of those diagnosed with schizophrenia are able to live independent lives. There is no cure for schizophrenia today. Continued research is thus absolutely critical to advance our understanding of schizophrenia and to learn how to treat it and ultimately to prevent and to cure schizophrenia. We need to understand more about brain alterations, the role of genes, and associations with behavior in order to develop better treatments and ultimately to prevent or even cure this severe mental disorder. For more information about schizophrenia, the reader is referred to the links in Helpful Resources. Helpful Resources. Below are several links that may be helpful in understanding what is schizophrenia. We encourage you to follow up on the knowledge provided in these links. Schizophrenia is a severe psychiatric disorder that affects approximately 1% of the general population. It affects people differently as the symptoms can vary from person to person and some people have many symptoms while others may have only a few. Symptoms are generally characterized as positive or negative, though there is overlap. More specifically, positive symptoms refer to exaggerated behavior such as delusions or hallucinations. Delusions are defined as beliefs that are contrary to fact such as believing that others can read one’s mind. Hallucinations are defined as alterations in hearing, seeing, tasting, or smelling things where the person experiences sensations which others do not experience, such as hearing voices or seeing things that others do not hear or see. Other positive symptoms include disorganized speech or behavior where the person’s behavior appears disorganized and even their speech is difficult to understand. In contrast, negative symptoms involve the absence of behavior and include lose of interest in everyday life activities, lack of feeling or emotion (apathy) or inappropriate feelings, lack of motivation, and lack of pleasure (anhedonia). Schizophrenia is also often described as a heterogeneous disorder because there are many different symptoms observed, as alluded to previously, and also because there are likely many different underlying causes that are as yet unknown. It is among the most severe of psychiatric disorders because it affects all aspects of motivation, thinking, memory, decision-making, affect, emotional expression, and social communication. All of these functions are altered in schizophrenia. Schizophrenia is also generally diagnosed at a time when young people are beginning to become young adults, i.e., at the prime of their lives. There is also a difference in the diagnosis between men and women where men diagnosed with schizophrenia usually start to show symptoms between their late teens and early 20s, while women usually develop symptoms during their mid-20s to early 30s. Additionally, in terms of past history, sometimes people diagnosed with schizophrenia showed more attenuated symptoms that dated back to childhood, while others who were later diagnosed with schizophrenia showed no early symptoms and showed normal development through their childhood. Schizophrenia was described more than 100 years ago, and yet the cause is still unknown. Early in the 20th century, schizophrenia was described as “dementia praecox”, or early dementia, but it was also described as “the schizophrenias” to emphasize the separation between thinking and emotions that is observed in these individuals. The word “schizophrenia” itself is derived from the Greek word skhizein, meaning “to split”, and the Greek word Phrenos (phren) meaning “diaphragm, heart, mind”. During this time period it was believed that ultimately the symptoms of schizophrenia would be linked to an underlying brain disorder, but the technology was such that discerning brain alterations was not promising and this area of investigation was not followed again in any meaningful way until the mid 1970’s (see below). The name schizophrenia has, nevertheless, been retained, to this day, and there was an effort to describe five different subtypes including paranoid schizophrenia, to describe people who appear to be more afflicted by paranoid thoughts including the belief that others are plotting against them. Catatonic schizophrenia is a term that is used less frequently. It is a term used to describe the unusual lack of motor behavior where people appeared to be frozen in their movements and where an arm could be moved above the head and the person would leave it there. Disorganized, formerly hebephrenic, was used to describe the disorganization and silliness that was observed in some diagnosed with schizophrenia, though this term is also not often used today. Undifferentiated schizophrenia describes those individuals who show symptoms that fit more than one type. Finally, Residual schizophrenia is a term used to describe a subtype where most symptoms have disappeared though some, such as hallucinations remain. Of note, however, these five descriptions of subtypes of schizophrenia are not generally in use today as it is believed that the symptoms observed are more useful for diagnosing and treating schizophrenia. Other terms that have also been used more recently include descriptions of the different stages of the illness. For example, acute schizophrenia or first episode schizophrenia are terms used to describe the early stages of schizophrenia, and prodrome or clinical high risk, are used to describe those who are most at risk for developing schizophrenia, either because they have more than one first degree relative with schizophrenia, or because they show symptoms that suggest schizophrenia though they do not meet all of the criteria that one expects to see. One of the problems with investigating disorders such as schizophrenia is that the tools available in the past to evaluate subtle, small changes in the brain were rather crude. Thus most of the work done in the past century to investigate brain structural abnormalities in schizophrenia was based on methods that were crude, prone to error, and it therefore did not further our knowledge and understanding of brain abnormalities in schizophrenia. This is not to say, however, that structural brain abnormalities were not thought to underlie the symptoms observed in schizophrenia. In fact, early documentation of abnormal brain structures from post-mortem studies of schizophrenia led to the formulation of quite specific hypotheses concerning the relations between brain and behavior. These early studies, however, were hampered by inconsistent findings, crude measurement techniques, and carefully methodologically controlled studies often led to negative findings. This turn of events led many investigators to conclude that there were no structural brain abnormalities observed in schizophrenia that could not also be seen in normal controls. Progress in this area of research thus came to a near standstill and it was not until 1976, with the advent of computed tomography (CT), that the first CT study of schizophrenia reported abnormally large lateral ventricles in schizophrenic patients. This one study led to numerous CT studies, which confirmed abnormalities in the brains of schizophrenic patients, and this one study led to a renewed interest in investigating such abnormalities in schizophrenia. The early CT studies evaluated only ventricular size and did not evaluate local regions of interest nor could gray and white matter be differentiated. With the advent of MR imaging, gray and white matter could be evaluated and thus a new tool was added. In 1984, the first MR study of schizophrenia was reported in the literature. Many studies followed, but most were based on magnets with a field strength less than 1.0, and the slice thickness was often 1 cm or more. Moreover, there were no methods for evaluating gray and white matter throughout the brain.The first study to use contiguous slices of the entire brain (1.5 mm coronal and 3 mm axial) was done by our group and the findings were reported in The New England Journal of Medicine (1992). Here, we reported small but important gray matter volume reduction in schizophrenic patients, compared to controls, in the amygdala-hippocampal complex, in parahippocampal gyrus, and in superior temporal gyrus, on the left. The latter changes were also correlated with disordered thinking and were thus suggestive of a disturbance in an important neural circuit involved in verbal processing and consolidation of information that involve both the amygdala-hippocampal complex and the superior temporal gyrus. These findings in schizophrenia would not have been possible without the advances in imaging technology that have continued to this day and include also functional imaging where alterations in different brain circuits involving attention, memory, etc. can be probed as well as diffusion imaging where white matter connections in the brain can be studied in order to understand better the neuropathology of schizophrenia so that targeted interventions can begin to be translated from the research domain to the clinical domain. One of the greatest risks for schizophrenia is to have a first degree relative with schizophrenia, which increases the risk by 10% as compared to 1% in the general population. Additionally, if both parents are diagnosed with schizophrenia then the risk is about 50%. The risk is also increased if one has a monozygotic twin (one egg that splits/identical twin) with schizophrenia, where the risk is increased to 40% to 65%. Note, however, that this percent is not 100% for an identical twin, suggesting that genes are likely contributory rather than causal. Other factors influencing increased risk include velocardiofacial syndrome, a chromosomal deletion disorder (chromosome 22q11), where the risk is approximately 30%, although other psychiatric disorders such as bipolar disorder are also increased. The conclusion to be drawn here is that it is likely that many genes are involved in a contributory role in the development of schizophrenia. There is thus no single genethat causes schizophrenia. Evidence suggests that the role of genes is more complicated and it is more likely that there are a number of genes, all with small effects, although transmission and expression is still not known. There is also clearly some genetic overlap between schizophrenia and bipolar disorder as well as likely autism spectrum disorders. Finally, there are higher rates of what are called “rare genetic mutations” that involve many different genes that likely impact brain development. These changes, along with environmental events such as exposure to viruses, birth complications, and other factors all likely contribute to this complex disorder that is only observed among humans. Today, there is an appreciation that schizophrenia is a very complex brain disorder that we are just beginning to understand in terms of the neural circuits that are affected in the brain. The changes observed in the brain are subtle and we are still trying to understand their implications. There is also an appreciation that the brain is far more plastic than has previously been thought, and thus alterations in the brain may not be associated with a poor prognosis. In fact discovering changes early in the course of the illness may lead to early interventions that may lead to halting progressive changes that characterize chronic states of schizophrenia that can be debilitating both to the person, the person’s family, and the larger community. There is also a focus today on looking more closely at those who are at the prodrome stage or who are at higher risk for developing schizophrenia so that intervention can be implemented early and perhaps prevent a future diagnosis of schizophrenia. Today there is also an appreciation of the role that genes play in schizophrenia. While there is no one gene that causes schizophrenia, today there is a better understanding of the effect of a small number of genes that are associated with a diagnosis of schizophrenia. Better treatments are also available today and many of those diagnosed with schizophrenia are able to live independent lives.
There is no cure for schizophrenia today. Continued research is thus absolutely critical to advance our understanding of schizophrenia and to learn how to treat it and ultimately to prevent and to cure schizophrenia. We need to understand more about brain alterations, the role of genes, and associations with behavior in order to develop better treatments and ultimately to prevent or even cure this severe mental disorder. For more information about schizophrenia, the reader is referred to the links in Helpful Resources.
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