How is Schizophrenia Diagnosed?

The diagnosis of schizophrenia cannot be made based on the results of an ob­jective diagnostic test or laboratory measure, though we and others are working towards this. Instead, clinicians diagnose schizophrenia based on behaviour and psychopathology (including the symptoms described in the previous chapter). These require the subjective interpretation of clinicians, but they can be as­sessed reliably. The definitions of major mental illnesses used by clinicians are presented in the Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association (in the United States) and the World Health Organization’s International Classification of Diseases (ICD) in other countries. These def­initions are updated from time to time to reflect gains in knowledge, or to reflect modern thinking on the similarities and differences between certain disorders. From one edition to the next, some diagnoses are revised, some are added, and some vanish altogether, only to be replaced or absorbed under other diagnoses. The diagnostic criteria for schizophrenia as defined by the most recent version of the DSM (DSM- 5) include the presence of two or more of the following symptoms: delusions, hallucinations, disorganized speech, disorganized or cata­tonic behaviour, and negative symptoms. At least one of the two must be delu­sions, hallucinations, or disorganized speech, while the second symptom type required for diagnosis could be any of the remaining four criteria. The require­ment of delusions, hallucinations, or disorganized speech maintains the resem­blance of the modern- day diagnosis to that first described by the clinician Emil Kraepelin over a century ago. Kraepelin’s discovery that schizophrenia is marked by a chronic and gradually worsening course is seen in modern- day criteria as well. A DSM-5 diagnosis of schizophrenia requires continuous signs of illness for at least 6 months, during which the individual must show at least 1 month of active symptoms (less if well treated). The diagnosis also requires social or work deterioration over a signifi­cant amount of time. Lastly, the diagnosis requires that the observed symptoms are not due to some other medical condition, including other psychiatric disorders such as bipolar disorder or major depressive disorder.

What Courses and Outcomes are Possible in Schizophrenia?

Kraepelin described one of the core features of schizophrenia to be its progres­sively worsening course with little chance of recovery. In contrast, mood dis­orders were thought to have an episodic course with good functioning between bouts of mania and depression, and a relatively good outcome. The ensuing dec­ades of research have painted a more complex picture of the course and outcome of schizophrenia. Most notably, in contrast to Kraepelin’s bleak outlook, a fair number of individuals can more or less successfully recover from schizophrenia. Dr Manfred Bleuler, son of Dr Eugen Bleuler, reported a 20- year follow-up of over 200 individuals with schizophrenia excluding those who had either died or shown little psychiatric stability over the previous 5 years. Bleuler noted that one in five patients had recovered to normal levels of social functioning and were free of psychotic symptoms. Furthermore, one in three patients had a relatively good outcome. Thus, while patients still experienced hallucinations and delu­sions, they showed only mild problems in social functioning and very few visible behavioural problems. These results are quite remarkable given that the study was completed prior to the discovery of antipsychotic medications.Dr Luc Ciompi was able to follow nearly 300 patients for as long as 50 years after hospitalization. Using Bleuler’s categories of outcome, Ciompi found 27% of the patients to be fully recovered, 22% to have mild symptoms, 24% to have moderately severe symptoms, and 18% to have severe symptoms. Nine per cent of the sample had an uncertain outcome. A progressively worsening, gradual, and serious onset was seen in about half of the affected individuals, while a sudden or acute onset of illness with little or no problems in premorbid func­tioning was found for the rest of the sample. About half of the individuals with schizophrenia had a continuous course of illness, and the remainder had an episodic course. In addition, an episodic course was more likely among patients with acute onset. Acute onset and episodic course were both associated with better long- term outcome.A study performed by Dr Ming Tsuang and team, known as the Iowa 500 study, followed 186 individuals with schizophrenia, 86 with bipolar disorder, and 212 with major depressive disorder for 35– 40 years.

Is Schizophrenia A Neurodevelopmental Disorder?

The research we have discussed suggests that schizophrenia occurs when ab­normal genes and environmental risk factors combine to cause brain dys­function. In the past two decades, several researchers— notably Drs Daniel Weinberger, Larry Seidman, and Patricia Goldman- Rakic— have concluded that schizophrenia is a neurodevelopmental brain disorder. This suggests that schizophrenia emerges because of the way the brain is built early in life. To understand this concept, consider brain disorders that do not have a neurodevelopmental origin but instead, come about because of the way the brain breaks down after it is developed. We call these disorders neurodegenerative be­cause the causes of the disease attack and degrade a normal brain. The senility of old age, which doctors call dementia, is a common example. When some people age, their brain is degraded by events such as many strokes or the rav­ages of Alzheimer’s disease. After a few years, a person who once functioned normally can no longer do simple tasks. Other examples are acquired brain syndromes, which occur after an injury to the head, and disorders due to the in­gestion of toxic substances (e.g., drugs, lead paint). In each of these cases, some external agent has acted on a normal brain to make it abnormal. In neurodevelopmental disorders, the brain does not develop (i.e., grow) prop­erly. In other words, it was never really normal to begin with. We know that genes contain the ‘blueprint’ for building the brain. For schizophrenia, this blueprint contains errors so that the brain is not ‘built’ correctly. Dr Patricia Goldman- Rakic suggested that certain brain cells in individuals with schizophrenia do not ‘migrate’ correctly during development. That is, normal brain development re­quires that cells locate themselves in the right spot and connect to one another in specific patterns. In schizophrenia, it may be that some cells are in the wrong place, some do not make necessary connections, and others make connections that should not be made. It is as if the blueprint for a home told the electrician to put the light switch for the kitchen in the living room.

Is Schizophrenia Inherited?

We have known for some time, from family studies done in Europe in the first half of the 1900s, that schizophrenia runs in families. These studies found the risks for the parents, brothers, and sisters of people with schizophrenia to be be­tween 4% and 14%— on average about ten times as high as that for the general population. For children of those with schizophrenia, the risk was 12%, nearly 15 times the general population risk. When both parents had schizophrenia, the risk increased to about 40%. The risk to uncles and aunts, nephews and nieces, grandchildren, and half- brothers or -sisters was roughly three times the risk in the general population. This risk was much lower than the risk to the relatives in the immediate family circle. On the whole, these pioneering studies showed thatthe closer the blood relationship of a person to an individual with schizophrenia, the higher the risk for the disorder.Modern studies using morestrict research methods and reliable definitions of schizophrenia also found the disorder to run in families. However, they find risk estimates that are a bit lower than those found in earlier studies. For ex­ample, in a large family study from Iowa, Tsuang and his team reported the risk of schizophrenia to brothers and sisters of individuals with schizophreniato be about 3%. This level of risk was five times greater than the risk to relatives of persons without schizophrenia. Other modern studies found similar results. Diagnostic practises seem to play a strong role in these different estimates. The early European studies usually used a fairly broad definition of the illness while the modern studies used a strict criterion- based diagnosis developed for use in research. Indeed, modern researchers have noted that their family risk figures for schizophrenia are similar to the figures obtained by the earlier European studies when atypical cases are included in the definition of schizophrenia. In other words, the level of risk that we can pin on a family history of schizophrenia depends on how broadly we define the disorder and whether or not we include atypical cases and spectrum disorders.

How Common is Schizophrenia?

To this point, we have been providing consensus descriptions of schizophrenia, what it is and what it is not, and describing the means by which it is detected and diagnosed. In this and later chapters, we present the evidence about the causal factors, treatments, and outcomes of schizophrenia from scientific studies. Such studies sometimes find results that differ from each other due to differences in the methods used or the types of patients that are studied. Random differences in measurement between studies also leads to discrepancies, which is perfectly normal.How, then, can we come to firm conclusions in the presence of variable results from different studies? Our approach as scientists, and as authors trying to distil the facts, is to always rely on the preponderance of evidence, or the best estimate that can be made when putting all the evidence together. Thus, as we present the facts moving forward, we will base our claims on the largest studies avail­able, since these usually give more reliable results than small studies. Whenever possible, we will present the results of analyses that put the results of otherstudies together using a formal statistical method called ‘meta- analysis’. Thus, instead of comparing and contrasting the results from two or more studies, we will let the reader know the overall result found when all studies were pooled together. In some instances, however, it is instructive to compare and contrast studies because each study tells us something different and uniquely important, and we will point this out when doing so.In this chapter, we describe the epidemiology of schizophrenia. Epidemiology is a branch of science concerned with the distribution and determinants of illness in the population, and the transmission of illness within families. Two important epidemiologic measures of disease burden in society are prevalence and incidence. The prevalence of schizophrenia (i.e., the number of affected individuals in the population) has been estimated at least 60 times in 30 dif­ferent countries. The prevalence estimates seen in these studies are very consistent, despite cultural differences between samples and the dif­ferent methods used and timeframes sampled in the studies.

What is Not Schizophrenia?

The words ‘schizophrenia’ and ‘schizophrenic’ are often misused in daily con­versation, in literature and film, and even in the popular news media. They mean different things to different people: an attitude of mind, a type of personality, or a psychiatric illness. For example, someone who can’t make up his mind, or who has feelings of both love and hate for something, may be falsely called schizo­phrenic (‘ambivalent’ is the more proper term). In some cultures, especially in the past, schizophrenia was seen as a sign of possession by an evil spirit or even as a sign of religious superiority. Individuals with schizophrenia were either pun­ished or praised in accord with the beliefs of their culture.Today, the most common misconception is that a person with schizophrenia has a ‘split’ personality or multiple personalities. Examples of this in film include Me, Myself, and Irene, in which the main character is diagnosed with ‘advanced delusionary schizophrenia with involuntary narcissistic rage’ instead of what appears to be dissociative identity (formerly known as multiple personality) dis­order. Even films that do a decent job depicting schizophrenia can get some aspects wrong; for example, A Beautiful Mind, which we earlier cited as a rela­tively well-done depiction of the disorder, also misses the mark by exaggerating the role of visual hallucinations of full- figure humans in guiding the main char­acter through various and extensive ‘missions’.The correct use of the word ‘schizophrenia’ is as a diagnostic term used to define a specific mental condition based on clear criteria. As described in our chapters on symptoms and on how schizophrenia is diagnosed, differential diagnosis is essential; that is, determining if the symptoms are really indica­tive of schizophrenia or of other conditions. Recognizing if mood disturbances (including depression and/ or mania), delusions (particularly grandiosity and delusions of sin or guilt), hallucinations, and disorganization are not actually reflective of a mood disorder, substance use disorder, or developmental or neuro­logical disorder is essential, since each type of disorder has a different treatment. Furthermore, it is vital to consider cultural context when determining if behav­iour is truly bizarre and qualifies for a diagnosis or is simply normal within the individual’s social setting.

What are the Symptoms of Schizophrenia?

Schizophrenia symptoms fall into two categories: positive and negative symp­toms. Positive symptoms are behaviours or experiences outside the normal range of human activities. Hearing voices is a good example. Negative symp­toms are behaviours that are removed from the normal range. A reduced ex­perience of pleasure is a good example. Positive symptoms are prominent during the ‘active’ phase of the illness, when an affected individual is most disturbed and disruptive. The active phase is the phase that will more often lead to the individual’s referral for care. This is often because the affected individual will be doing or saying things that upset or disturb people around them, or at least get their attention and draw concern. For example, an individual with delusions might complain to her spouse that she is being followed by aliens and demandthat he help her find a way to stop them. Negative symptoms are most visible during the ‘prodromal’ and ‘residual’ phases of the illness. The prodromal phase comes before the first active phase (so actually occurs before a diagnosis of schizophrenia is ever made), and a residual phase follows each active phase.This class of symptoms most often includes delusions and auditory, visual, or other sensory hallucinations. Positive symptoms can be divided into percep­tual (i.e., affecting perception, or the ability to become aware of some stimulus through the senses), cognitive (i.e., impacting ways of thinking), emotional, or motor (physical) signs. Because these symptoms are so easy to recognize, even to the untrained eye, they make up a large part of the layperson’s general view of schizophrenia.Auditory hallucinations are the most common perceptual problems seen in schizophrenia. Many times, these hallucinations take the form of a voice, some­times making a running commentary on the individual’s thoughts or behaviours. Sometimes they take the form of several voices, each talking with the other. Some individuals with schizophrenia have visual, olfactory (i.e., affecting the sense of smell), or gustatory (i.e., affecting taste) hallucinations, but these are rare. Somatic hallucinations may also occur, in which the altered perception centres at or on the body’s organs.

How Can Affected Individuals and Their Families Cope with Schizophrenia?

It can be overwhelming to deal with the schizophrenia, either personally or as someone who cares for or about an affected individual. One may also be over­whelmed by trying to digest all the facts that we have shared here about this highly complex disorder. As scientists, we too find it overwhelming to lament how much we still don’t know, and how to use what we do know to make real change for affected individuals. But having the facts at hand gives some sense of control. It is important, then, to clarify at this stage what affected individuals and their families can do to cope with the disorder, both day to day and in an emergency. Affected individuals learn to cope with schizophrenia symptoms by trial and error. When they have a worsening of symptoms, they may learn to seek hospital admission rather than resist it. Over time they learn that stopping or changing medication leads to a relapse of positive symptoms. They may be able to adjust the dose of drugs to avoid severe side effects, yet maintain a level that prevents symptom flare- ups. Clearly, not all individuals with schizophrenia can do this. Nearly half of indi­viduals with schizophrenia who are treated on an outpatient basis fail to take their medication; the relapse rate is high among such patients. Patients should be under continuous supervision by their psychiatrist during drug therapy. Even if they discover how to adjust the drug dose, they should share and discuss these experiences with their psychiatrist and not attempt to make changes on their own. If the patient finds it difficult to remember to take tablets, long- acting injections of medication are available; one injection works for an average of 2– 4 weeks. Patients should faithfully follow their doctor’s prescription and receive the in­jection regularly; with time this can be adjusted as needed. The family has an important role to play in reminding patients to take medicine regularly or to visit the doctor for injections. This is particularly true if the indi­vidual becomes reluctant to follow doctor’s orders and relapse seems imminent.

How Does the Environment Influence Schizophrenia?

Although there is very strong evidence for a genetic piece to schizophrenia, the lack of full concordance between identical twins shows that the environment also plays a role. We define an ‘environmental risk factor’ as any event that is not due to genes, specifically the individual differences in the DNA sequence.These events may be biological (e.g., head injuries, viral infections), psycho­logical (e.g., disrupted family relationships), or social (e.g., poverty).Over the past few decades, scientists have found evidence for environmental risk factors in at least some cases of schizophrenia. Before reviewing this research, we must make an important distinction: some environmental factors may cause or contribute to schizophrenia while others modify or change the illness in someone who is already sick. In this book we use the term ‘cause’ to refer to any factor that can produce the illness or increase the chance of illness in someone who has not yet been affected by schizophrenia. This cause does not have to be either necessary or sufficient. This means that other causes may exist that also produce the illness, and that any given cause may need to interact with other causes for the disorder to occur. We use the term ‘modifier’ to refer to anything that changes the symptoms of the illness in someone who is already affected. As we discuss in a later chapter, knowing modifiers can help with the treatment of the disorder. However, they should not be confused with causes.Scientists who study schizophrenia and other psychiatric disorders have long ago abandoned the ‘nature–nurture’ controversy. In the past, many philo­sophers and scientists had taken one of two extreme positions. Some believed that psychiatric illness was only caused by innate or genetic factors; others felt that mental illness was the sole product of adverse environmental events. Today, we know that the question ‘genes or environment?’ is too simplistic. As Dr Paul Meehl realized several decades ago, the better question is much more com­plex: ‘What group of environmental risk factors work together with which genes to produce schizophrenia?’Before discussing specific environmental risk factors that may cause schizo­phrenia we should clarify why we believe that the study of such factors is es­sential.

How is Schizophrenia Treated?

In earlier chapters, we described the many advances in our understanding of schizophrenia. Unfortunately, we still do not have a detailed blueprint of what exactly goes wrong in the brain in schizophrenia, or a means for ‘fixing’ the brain. But even without a clear grasp of all the underlying, hidden facts, we have still made many gains. While we search for more clues, we need to use the facts on hand to help individuals with schizophrenia and their families to relieve their suffering. As the saying goes, ‘The perfect is the enemy of the good’, and some good treatment options exist. So while we work toward a perfect under­standing of schizophrenia and develop treatments that are targeted toward each individual’s personal form of the disorder, we must rely on the evidence for existing treatments to separate the ‘good’ from the ‘bad’. Bad treatments are those that are ineffective, counterproductive, or have a high risk of very serious side effects. Good treatments are those that have good evidence of helping a fair number of patients to reduce at least the positive symptoms of the disorder while having a relatively low risk of serious side effects. No current treatment for the disorder will work for all affected individuals, and we do not yet have a way of being able to tell before treatment what chance the affected individual has of improving with a given treatment. These are all goals for future research, including the discovery of brand new medicines. For now, we review the cur­rently available treatments with the best evidence of being able to help a good number of patients. The onset of schizophrenia can be frightening, for both affected individuals and their families. Affected individuals begin to express many odd beliefs: that people are trying to harm them— friends, relatives, strangers, or celebrities; that others can hear their thoughts as if spoken aloud; that voices talk to them, even when they are alone. In addition, they cannot express feelings and thoughts clearly and are frustrated by the doubts expressed by relatives and friends.