Chapter 14 Flashcards

Question

statistics

Answer 1

Schizophrenia defies our desire for simplicity. We have seen how very different symptoms can be displayed by individuals who would all be considered to have the disorder; in some people the symptoms develop slowly, and in others they occur suddenly. Schizophrenia is generally chronic, and most people with the disorder have a very difficult time functioning in society. This is especially true of their ability to relate to others; they tend not to establish or maintain significant relationships, and therefore many people with schizophrenia never marry or have children. Unlike the delusions of people with other psychotic disorders, the delu- sions of people with schizophrenia are likely to be outside the realm of possibility. Finally, even when individuals with schizo- phrenia improve with treatment, they are likely to experience difficulties throughout their lives. Worldwide, the lifetime prevalence rate of schizophrenia is roughly equivalent for men and women, and it is estimated from 0.2 to 1.5 percent in the general population (Ho et al., 2003), which means the disorder will affect about 1 percent of the popu- lation at some point (Erlich et al., 2014). Simon Fraser University researcher Elliot Goldner and his colleagues suggested that the one-year prevalence of schizophrenic disorders in the British Columbia population was 0.4 percent (Goldner et al., 2003). The 2012 Canadian Community Health Survey—Mental Health (CCHS) estimated that 1.3 percent of Canadians 15 years of age and older had received a diagnosis of schizophrenia or psychosis in their lifetime, with similar rates for men and women (Statistics Canada, 2012). The CCHS does not cover First Nations people living on reserve. However, using Census and hospital discharge data, Statistics Canada estimates that First Nations people living both on and off reserve have almost double the acute care hospi- talization rates for schizophrenic/psychotic disorders that Canadi- ans of non-Aboriginal identity have (Carrière et al., 2018). Life expectancy is slightly less than average, partly because of the higher rate of suicide and accidents among people with schizophrenia (Ho et al., 2003), but also because of higher rates of obesity, smoking, angina, and respiratory problems, as well as health problems associated with medication to treat schizophrenia (Seeman, 2007). One recent study out of the province of Ontario estimated that 11.7 percent of all suicide victims, more than 1 in 10, were individuals with schizophrenia spectrum disorder (Zaheer et al., 2018). Although some disagreement exists about the distribution of schizophrenia between men and women, the difference between the sexes in age of onset is clear. For men, the likelihood of onset diminishes with age. The onset for women is lower than for men until age 36, when the relative risk for onset switches, with more women than men being affected later in life (Howard et al., 1993). Women appear to have more favourable outcomes than men (Ho et al., 2003).

Answer 2

The more severe symptoms of schizophrenia first occur in late adolescence or early adulthood, although we saw that there may be signs of the development of the disorder in early childhood (Murray & Castle, 2012). Children who go on to develop schizo- phrenia show early clinical features, such as mild physical abnor- malities, poor motor coordination, and mild cognitive and social problems (Golembo-Smith et al., 2012; Matheson et al., 2013; Welham et al., 2008). Unfortunately, these types of early prob- lems are not specific enough to schizophrenia—meaning they could also be signs of other problems, such as the neurodevelop- mental disorders we review in Chapter 15—to be able to say for sure that a particular child will later develop schizophrenia. Up to 85 percent of people who later develop schizophrenia go through a prodromal stage—a one- to two-year period when less severe yet unusual behaviours start to show themselves but before serious symptoms occur (Jablensky, 2012). These behaviours (which you should recognize from Chapter 13 as symptoms seen in schizotypal personality disorders) include ideas of reference (thinking insignificant events relate directly to them), magical thinking (believing they have special abilities, such as being clair- voyant or telepathic), and illusions (such as feeling the presence of another person when they are alone). In addition, other symp- toms are common, such as isolation, marked impairment in func- tioning, and a lack of initiative, interests, or energy (Addington et al., 2015). Once symptoms begin to appear, it can take anywhere from 2 years to around 10 years before a person at high risk (e.g., mild positive symptoms, decline in functioning) meets the full criteria for a psychotic disorder (Nelson et al., 2013). The highest period of risk can be in the first two years for patients to develop a full- fledged psychotic disorder. Risk factors for going from high risk to developing the disorder include the length of duration of symp- toms before seeking help, baseline functioning, as well as the presence of negative symptoms and disorganized symptoms (Addington et al., 2015, Nelson et al., 2013). Part of the delay in seeking help may be the result of hiding symptoms from others (sometimes because of increasing paranoia). Personality factors and the amount and quality of social support may also play a role in the amount of time it takes a person to first seek treatment for psychotic symptoms (Ruiz-Veguilla et al., 2012). Once treated, patients will often improve. Unfortunately, most will also go through a pattern of relapse and recovery (Emsley et al., 2013). This relapse rate is important when discussing the course of schizophrenia. People with schizophrenia have a poorer progno- sis than those with most of the other disorders we describe in this book—including a high risk of suicide—although a significant number of individuals can experience long periods of recovery (Jablensky, 2012). ■ Figure 14.1 illustrates the data from one study that show the course of schizophrenia among four proto- typical groups (Shepherd et al., 1989). As you can see, about 22 percent of the group had one episode of schizophrenia and improved without lasting impairment. The remaining 78 percent experienced several episodes with differing degrees of impair- ment between them.

Answer 3

Because schizophrenia is so complex, the diagnosis itself can be controversial. Some have argued that “schizophrenia” does not really exist but is a pejorative label for people who behave in ways outside the cultural norm (e.g., Laing, 1967; Szasz, 1961). Although the idea that schizophrenia exists only in the minds of mental health professionals is certainly provocative, this extreme view is contradicted by experience. As clinicians, we have had a great deal of contact with people who have this disorder and with their families and friends, and the tremendous amount of emotional pain resulting from schizophrenia gives definite credence to its existence. In addition, many people in extremely diverse cultures have the symptoms of schizophrenia, which supports the notion that it is a reality for many people worldwide (Ihara et al., 2003; Patel & Andrade, 2003). Schizophrenia is thus universal, affecting all racial and cultural groups studied so far. The course and outcome of schizophrenia vary from culture to culture. For example, in Colombia, India, and Nigeria, more people improve significantly or recover than in other countries (Leff et al., 1992). These differences may be due to cultural varia- tions or biological influences, such as immunization, but we cannot yet explain these differences in outcomes. Surprisingly, outcomes are better in poor countries, and some have suggested the controversial idea that lack of access to pharmacological treat- ments may be the reason (Whitaker, 2011). Research from England suggests that proportionately more blacks receive the diagnosis of schizophrenia than do whites. One possibility is that people from ethnic minority groups may be victims of bias and stereotyping (Lewis et al., 1990); in other words, they may be more likely to receive a diagnosis of schizo- phrenia than members of a dominant group. One prospective study of schizophrenia among different ethnic groups in London found that although the outcomes of schizophrenia appear similar across various ethnic groups, blacks were more likely to be detained against their will, brought to the hospital by police, and given emergency injections (Goater et al., 1999). A study by Eric Jarvis at McGill University similarly found that black immigrants with schizophrenia were more likely to have police contact and be subject to compulsory hospital admissions, and that Afro-Carib- bean immigrants had the highest rates of schizophrenia of all immigrant groups (Jarvis, 1998). Anthony Feinstein of the University of Toronto disagrees with this conclusion. He and his colleague conducted another study in England and again found minority ethnicity to be associated with an increased risk for psychiatric hospitalization (Feinstein & Holloway, 2002). However, they found no evidence that ethnic minority patients were being inappropriately admitted. They suggest instead that other factors (e.g., more frequent cannabis abuse) may contribute to the higher rates of psychiatric admissions among ethnic minor- ities. Later in this chapter, we discuss the possible role of canna- bis use in the onset of schizophrenia.

Answer 4

We could argue that few areas of psychopathology so clearly illustrate the enormous complexity and intriguing mystery of genetic influences on behaviour than does the phenomenon of schizophrenia (Murray & Castle, 2012). Despite the possibility that schizophrenia may be several different disorders, we can safely make one generalization: genes are responsible for making some individuals vulnerable to schizophrenia. We will look at a range of research findings from family, twin, adoption, offspring of twins, and linkage and association studies (Faraone et al., 1999). We conclude by discussing the compelling reasons that no single gene is responsible for schizophrenia; rather, multiple gene variances combine to produce vulnerability (Murray & Castle, 2012).

Answer 5

In 1938, German researcher Franz Kallmann published a major study on the families of people with schizophrenia. Kallmann (1938) examined family members of more than 1000 persons diagnosed with schizophrenia in a Berlin psychiatric hospital. Several of his observations continue to guide research today. Kallmann showed that the severity of the parent’s disorder influ- enced the likelihood of the children having schizophrenia: the more severe the parent’s schizophrenia, the more likely the chil- dren were to develop it also. Another observation was important: all forms of schizophrenia (e.g., the historic categories such as catatonic and paranoid) were seen within the families. In other words, it does not appear that you inherit a predisposition for what was previously diagnosed as paranoid schizophrenia. Instead, you may inherit a general predisposition for schizophre- nia that manifests in the same form or a different one from that of your parent. More recent research from Ireland confirms this observation and suggests that families that have a member with schizophrenia are at risk not just for schizophrenia alone or for all psychological disorders; instead, there appears to be some famil- ial risk for a spectrum of psychotic disorders related to schizo- phrenia (Kendler et al., 1993). Gottesman (1991) famously summarized the data from about 40 studies of schizophrenia, as shown in ■ Figure 14.2. The most striking feature of this graph is its orderly demonstration that the risk of having schizophrenia varies according to how many genes an individual shares with someone who has the disorder. Dr. Allan F. Mirsky/National Institute of Mental Health For example, you have the greatest chance (approximately 48 percent) of having schizophrenia if it has affected your identi- cal (monozygotic) twin, a person who shares 100 percent of your genetic information. Your risk drops to about 17 percent with a fraternal (dizygotic) twin, who shares about 50 percent of your genetic information. And having any relative with schizophrenia makes you more likely to have the disorder than someone in the general population without such a relative (about 1 percent).

Answer 6

If they are raised together, identical twins share 100 percent of their genes and 100 percent of their environment, whereas frater- nal twins share only about 50 percent of their genes and 100 percent of their environment. If the environment is solely responsible for schizophrenia, we would expect little difference between identical and fraternal twins with regard to this disorder. If only genetic factors are relevant, both identical twins would always have schizophrenia (be concordant) and the fraternal twins would both have it about 50 percent of the time. Research from twin studies indicates that the truth is somewhere in the middle (Braff et al., 2007; van Os et al., 2010). In one of the most fascinating of nature’s experiments, identi- cal quadruplets, all of whom have schizophrenia, have been stud- ied extensively. Nicknamed the “Genain” quadruplets (from the Greek, meaning “dreadful gene”), these women have been followed by researchers for years (e.g., Mirsky et al., 2000, 2013; Rosenthal, 1963). In a sense, the women embody the complex interaction between genetics and the environment. All four shared the same genetic predisposition, and all were brought up in the same particularly dysfunctional household; yet the time of onset for schizophrenia, the symptoms and diagnoses, the course of the disorder, and, ultimately, their outcomes differed significantly from sister to sister. For example, Hester was the first to experi- ence severe symptoms of schizophrenia, at age 18; her sister Myra was not hospitalized until six years later. Hester never finished high school or lived independently. Myra was deemed to have a milder form of schizophrenia and had the most successful life course of the four sisters; she had the most education, was able to work, and was the only sister to marry and have children In 2011, Hester was deceased, and Myra, at the age of 81, was still able to live independently with some assistance from commu- nity supports (Mirsky et al., 2013). One genetic explanation for these differences may be the pres- ence of de novo mutations in the sisters. These are genetic muta- tions that can occur as a result of a mutation in a germ cell (egg or sperm) of one of the parents or, perhaps in the case of these sisters, in the fertilized egg after conception. The case of the Genain quadruplets also reveals an important consideration in studying genetic influences on behaviour—unshared environ- ments (Plomin, 1990). We tend to think that siblings, and espe- cially identical multiples, are brought up the same way. The impression is that “good” parents expose their children to favour- able environments, and “bad” parents give them unsound experi- ences. But even identical siblings can have very different prenatal and family experiences and can therefore be exposed to varying degrees of stress. For example, Hester, the last-born sister, was the smallest and was believed to have suffered more brain injury at birth than her sisters. Myra received preferential treatment from her parents, while Hester received harsh treatment. She was described by her parents as a habitual masturbator and was circumcised at the advice of a physician. This unusual case demonstrates that even siblings who are very close in every aspect of their lives can still have considerably different experiences physically and socially as they grow up, which may result in vastly different outcomes. The sisters also provide evidence that cognitive abilities may be maintained. A follow-up neuropsycho- logical study showed the progression of their disorder stabilized, in fact may have improved, when they were assessed at age 66 (Mirsky et al., 2000). In 2011, a follow-up study of the two surviving sisters (Nora and Myra were 81 then) also showed maintenance of cognitive abilities (Mirskey et al., 2013).

Answer 7

Several adoption studies have distinguished the roles of the envi- ronment and genetics as they affect schizophrenia. These studies often span many years; because people often do not show the first signs of schizophrenia until early adulthood, researchers need to be sure all the offspring reach that point before drawing conclu- sions. Many schizophrenia studies are conducted in Europe, primarily because of the extensive and comprehensive records kept in many of these countries. The largest adoption study was conducted in Finland (Tienari, 1991). From a sample of almost 20 000 women with schizophre- nia, the researchers found 190 children who had been given up for adoption. The data from this study support the idea that schizo- phrenia represents a spectrum of related disorders, all of which overlap genetically. If an adopted child had a biological mother with schizophrenia, he or she had about a 5 percent chance of having the disorder (compared with about only 1 percent in the general population). However, if the biological mother had schizophrenia or one of the related psychotic disorders (e.g., delu- sional disorder, schizophreniform disorder), the risk that the adopted child would have one of these disorders rose to about 22 percent (Tienari et al., 2003, 2006). Even when raised away from their biological parents, children of parents with schizophre- nia have a much higher chance of having the disorder themselves. At the same time, there appears to be a protective factor if these children are brought up in healthy, supportive homes. In other words, a gene–environment interaction was observed in this study, with a good home environment reducing the risk of schizo- phrenia (Gilmore, 2010; Wynne et al., 2006).

Answer 8

Twin and adoption studies strongly suggest a genetic component for schizophrenia, but what about children who develop schizophrenia even though their parents do not? For example, the study by Tienari and colleagues (2003, 2006) we just discussed found that 1.7 percent of the children with parents without schizophrenia developed schizophrenia. Does this mean you can develop schizo- phrenia without “schizophrenic genes”? Or are some people carri- ers, having the genes for schizophrenia but for some reason not showing the disorder themselves? An important clue to this question comes from research on the children of twins with schizophrenia. In a study begun in 1971, 21 identical twin pairs and 41 frater- nal twin pairs with a history of schizophrenia were identified along with their children (Fischer, 1971; Gottesman & Bertelsen, 1989). The researchers wanted to determine the relative likeli- hood that a child would have schizophrenia if his or her parent did, and if the parent’s twin had schizophrenia but the parent did not. ■ Figure 14.3 illustrates the findings from this study. For example, if your parent is an identical (monozygotic) twin with schizophrenia, you have about a 17 percent chance of having the disorder yourself, a figure that holds if you are the child of an unaffected identical twin whose co-twin has the disorder. Conversely, look at the risks for the child of a fraternal (dizy- gotic) twin. If your parent is the twin with schizophrenia, you have about a 17 percent chance of having schizophrenia yourself. If your parent does not have schizophrenia but your parent’s fraternal twin does, your risk is only about 2 percent. The only way to explain this finding is through genetics. The data clearly indicate that you can have genes that predispose you to schizo- phrenia, not show the disorder yourself, but still pass on the genes to your children. In other words, you can be a carrier for schizo- phrenia. This is some of the strongest evidence yet that people are genetically vulnerable to schizophrenia. Remember, however, the chance of inheritance is only 17 percent, meaning that other factors help determine who will have this disorder.

Answer 9

An interesting study by Caspi and colleagues (2005), conducted with the large New Zealand sample described in Chapter 2, extended the study of genetic factors to examine the possibility of a gene by environment interaction in the development of schizo- phrenia. Cannabis use in youth is an established but modest risk factor for psychosis in adulthood. Yet, clearly, most people who use marijuana do not develop psychosis! Caspi and colleagues tested whether there might be certain genetically vulnerable indi- viduals who are particularly susceptible to the effects of cannabis initiating psychosis. Indeed, they found that the combination of a particular genetic profile (i.e., carriers of the catechol-O- methyltransferase [COMT] valine [VAL] 158 allele as compared with those with two copies of the methionine [MET] allele) was particularly likely to develop schizophrenia in adulthood. But this was only true if these individuals had used cannabis as teenagers. This study suggests the interesting possibility that certain genes may act as vulnerability factors that interact with specific envi- ronmental pathogens at crucial developmental stages, leading to the development of schizophrenia (Caspi et al., 2005).

Answer 10

Genetic linkage and association studies rely on traits, such as blood types (whose exact location on the chromosome is already known), that are inherited in families along with the disorder we are looking for—in this case, schizophrenia. Because we know the location of the genes for these traits (called marker genes), we can make a rough guess about the location of the disorder genes that are inherited along with them. To date, researchers have looked at several sites for genes that may be responsible for schizophrenia. For example, regions of chromosomes 1, 2, 3, 5, 6, 8, 10, 11, 13, 20, and 22 are implicated in this disorder (Kirov & Owen, 2009). Three of the most reliable genetic influences that make one susceptible to schizophrenia include sections on chromosome 8 called Neuregulin 1 (or NRG1), chromosome 6 (called dystrobrevin-binding protein 1 or DTNBP1), and chro- mosome 22 (called catecholamine O-methyl transferase or COMT) (Murray & Castle, 2012). The COMT gene is of particu- lar interest to scientists, because it plays a role in dopamine metabolism, which we will see has been implicated in the etiol- ogy of schizophrenia. A recent study that combined one of the largest samples (i.e., 36 989 cases of individuals with schizo- phrenia and 113 075 controls) identified 128 independent asso- ciations and 108 loci that meet genome-wide significance, 83 of which were new. This further strengthens the theory that genetic risk arises from a large number of common genes each with a small effect that might be detected by genome-wide association studies (Ripke et al., 2014).

Answer 11

In the search for markers, researchers look for common traits other than the symptoms of the disorder itself. If some people have the positive symptoms of schizophrenia, others have the negative symptoms, and still others have a mixture of these symp- toms, yet they all have a particular problem completing a certain task, the skill deficit would be very useful for identifying what else these people may have in common. Several potential markers for schizophrenia have been studied over the years. As noted by McGill University psychologist Gillian O’Driscoll and her colleagues, one of the more highly researched markers is called smooth-pursuit eye movement or eye-tracking (O’Driscoll et al., 1998). While keeping your head still, you must be able to track a moving pendulum, back and forth, with your eyes. The ability to track objects smoothly across the visual field is deficient in many people who also have schizo- phrenia (e.g., Clementz & Sweeney, 1990); it does not appear to be the result of drug treatment or institutionalization (Lieberman et al., 1993). It also seems to be a problem for relatives of these people (Thaker & Avila, 2003). Although these eye-tracking defi- cits appear to be associated with both negative and positive symp- toms, they are most strongly associated with positive symptoms (Holahan & O’Driscoll, 2005). When all these observations are combined, they suggest an eye-tracking deficit may be a marker for schizophrenia that could be used in further study (O’Driscoll et al., 1998).

Answer 12

As we have seen, schizophrenia involves more than one gene, a phenomenon referred to as quantitative trait loci (Levinson et al., 1998; Plomin et al., 1994). The schizophrenia we see most often is probably caused by several genes located at different sites throughout the chromosomes. This model would also clarify why there can be gradations of severity in people with the disorder (from mild to severe), and why the risk of having schizophrenia increases with the number of affected relatives in the family.

Answer 13

The belief that schizophrenia involves a malfunctioning brain goes back as far as the writings of Emil Kraepelin (1856–1926). It is therefore not surprising that a great deal of research has focused on the brain. Before we discuss some of this work, however, be forewarned: to study abnormalities in the brain for clues to the cause of schizophrenia is to face all the classic prob- lems of doing correlational research, which we discussed in Chapter 4. For example, if a person has schizophrenia and too much of a neurotransmitter, (1) does too much neurotransmitter cause schizophrenia, (2) does schizophrenia create too much of the neurotransmitter, or (3) does something else cause both the schizophrenia and the chemical imbalance? Keep this caveat in mind as you review the following research.

Answer 14

One of the most enduring yet still controversial theories of the cause of schizophrenia involves the neurotransmitter dopamine (Harrison, 2012). Before we consider the research, however, let’s review briefly how neurotransmitters operate in the brain and how they are affected by neuroleptic medications, which reduce hallu- cinations and delusions. In Chapter 2, we discussed the sensitivity of specific neurons to specific neurotransmitters and described how they cluster throughout the brain. The top of ■ Figure 14.4 shows two neurons and the important synaptic gap that separates them. Neurotransmitters are released from the storage vessels (synaptic vesicles) at the end of the axon, cross the gap, and are taken up by receptors in the dendrite of the next axon. Chemical messages are transported in this way from neuron to neuron throughout the brain. This process can be influenced in a number of ways, and the rest of Figure 14.4 illustrates some of them. The chemical messages can be increased by agonistic agents or decreased by antagonistic agents. Antagonistic effects slow down or stop messages from being transmitted by preventing the release of the neurotransmitter, blocking uptake at the level of the dendrite, or causing leaks that reduce the amount of neurotransmitter ulti- mately released. Conversely, agonistic effects assist with the transference of chemical messages and, if extreme, can produce too much neurotransmitter activity by increasing production or release of the neurotransmitter, and by affecting more receptors at the dendrites. What we’ve learned about antipsychotic medications points to the possibility that the dopamine system is too active in persons with schizophrenia. The simplified picture in Figure 14.4 does not show that there are actually different receptor sites and that a chemical, such as dopamine, produces different results depending on which of those sites it affects. In schizophrenia, attention has focused on two dopamine sites, referred to simply as D1 and D2. As we will see, D2 is of particular interest to researchers in this field. In a story that resembles a mystery plot, several pieces of circumstantial evidence are clues to the role of dopamine in schizophrenia: 1. Antipsychotic drugs (neuroleptics) that are often effective in treating people with schizophrenia are dopamine antagonists, partially blocking the brain’s use of dopamine (Creese et al., 1976; Seeman et al., 1976). 2. These drugs can produce negative side effects similar to those in Parkinson’s disease, a disorder known to be due to insuf- ficient dopamine. 3. The drug L-dopa, a dopamine agonist used to treat people with Parkinson’s disease, produces schizophrenia-like symp- toms in some people (Davidson et al., 1987). Amphetamines, which also activate dopamine, can make psychotic symptoms worse in some people with schizo- phrenia (van Kammen et al., 1982). In other words, when drugs are administered that are known to increase dopamine (agonists), schizophrenic behaviour increases; when drugs that are known to decrease dopamine activity (antag- onists) are used, schizophrenic symptoms tend to diminish. Taking these observations together, researchers theorized that schizophrenia in some people was attributable to excessive dopa- mine activity. Despite these observations, some evidence is inconsistent with the dopamine theory (Javitt & Laruelle, 2006): 1. A significant number of people with schizophrenia are not helped by the use of dopamine antagonists. 2. Although the neuroleptics block the reception of dopamine quite quickly, the relevant symptoms subside only after several days or weeks, much more slowly than researchers would expect. 3. These drugs are only partly helpful in reducing the negative symptoms (e.g., flat affect, anhedonia) of schizophrenia. In addition to these concerns, there is evidence of a double- edged sword with respect to schizophrenia. A medication called clozapine is effective with many people who were not helped with traditional neuroleptic medications (Agid et al., 2007; Tauscher et al., 2004; Wahlbeck et al., 1999). That’s the good news. But as pointed out by Shitij Kapur and his colleagues in Toronto, the bad news for the dopamine theory is that clozapine is one of the weak- est dopamine antagonists by far, much less able to block the dopamine sites than other drugs (Kapur et al., 1999). Why would a medication inefficient at blocking dopamine be effective as a treatment for schizophrenia if schizophrenia is caused by exces- sive dopamine activity? The answer may be that although dopamine is involved in the symptoms of schizophrenia, its role is more complicated than we once thought (Potter & Manji, 1993). Current thinking points to at least three specific neurochemical abnormalities simultane- ously at play in the brains of people with schizophrenia. Strong evidence now leads us to believe that schizophrenia is partially the result of excessive stimulation of striatal dopamine D2 receptors (Laruelle et al., 2003). Recall that the striatum is part of the basal ganglia found deep within the brain. These cells control movement, balance, and walking, and they rely on dopamine to function. Huntington’s disease (which involves problems in motor function) involves deterioration in this brain area. How do we know that excessive stimulation of D2 receptors is involved in schizophrenia? One clue is that most effective antipsychotic drugs all share dopamine D2 receptor antagonism (Ho et al., 2003), meaning they help block the simulation of the D2 receptors. A second area of interest to scientists investigating the cause of schizophrenia is the observation of a deficiency in the stimula- tion of prefrontal D1 receptors (Koh et al., 2003). Therefore, although some dopamine sites may be overactive (e.g., striatal D2), a second type of dopamine site in the part of the brain that we use for planning and organizing (prefrontal D1 receptors) appears to be less active and may account for negative symptoms of schizophrenia, such as avolition. As we discuss later in this chapter, lower prefrontal activity in people with schizophrenia is referred to as hypofrontality. Finally, a third and more recent area of neurochemical interest involves research on alterations in prefrontal activity involving glutamate transmission (Goff & Coyle, 2001). Glutamate is an excitatory neurotransmitter that is found in all areas of the brain and is only now being studied in earnest. Like dopamine, gluta- mate has different types of receptors. The ones being studied for their role in schizophrenia are the N-methyl-D-aspartate (NMDA) receptors. The effects of certain drugs that affect NMDA recep- tors point to clues to schizophrenia. Two recreational drugs described in Chapter 12—phencyclidine (PCP) and ketamine— can result in psychotic-like behaviour in people without schizo- phrenia and can exacerbate psychotic symptoms in those with schizophrenia. Both PCP and ketamine are NMDA antagonists, suggesting that a deficit in glutamate or blocking of NMDA sites may be involved in some of the symptoms of schizophrenia (Goff & Coyle, 2001). You can see that research on these two neurotransmitters is complex and awaits clarification. However, advances in technology are leading us closer to the clues behind this enigmatic disorder and closer still to better treatments.

Answer 15

vidence for neurological damage in people with schizophrenia comes from a number of observations. Many children with a parent who has the disorder, and who are therefore at risk, tend to show subtle but observable neurological problems, such as abnormal reflexes and inattentiveness (Buka et al., 2013). These difficulties are persistent: adults who have schizophrenia show deficits in their ability to perform certain tasks and to attend during reaction time exer- cises (Cleghorn & Albert, 1990). Such findings suggest that brain damage or dysfunction may cause or accompany schizophrenia, although no single site is probably responsible for the whole range of symp- toms (Harrison, 2012). One of the most reliable observations about the brain in people with schizophrenia involves the size of the ventricles (see ■ Figure 14.5). As early as 1927, researchers noted that these liquid-filled cavi- ties showed enlargement in some but not all of the brains examined in people with schizophrenia (Jacobi & Winkler, 1927). Since then, more sophisticated techniques have been developed for observing the brain, and in the dozens of studies conducted on ventricle size, the great majority show abnormally large lateral and third ventricles in people with schizophrenia (Harrison, 2012). Ventricle size in itself may not be a problem, but the dilation (enlargement) of the ventricles indicates that either adjacent parts of the brain have not developed fully or have atro- phied, thus allowing the ventricles to become larger. Ventricle enlargement is not seen in everyone who has schizo- phrenia. Several factors seem to be associated with this finding. For example, enlarged ventricles are observed more often in men than in women (Abel et al., 2010). Ventricles seem to enlarge in proportion to age and to the duration of the schizophrenia. One study found that individuals with schizophrenia who were exposed to influenza prenatally may be more likely to have enlarged ventricles (Takei et al., 1996). We touched on the concept of unshared environments in the section on genetics (Jang, 2005; Plomin, 1990). Although mono- zygotic twins are identical genetically, they can experience a number of environmental differences, even before they are born. For instance, in the intrauterine environment twins must compete for nutrients, and they may not be equally successful. In addition, birth complications, such as the loss of oxygen (anoxia), could affect only one of the twins (Murray & Castle, 2012). Obstetrical complications appear often among twins with schizophrenia in discordant identical pairs and among the more severely affected if both twins have schizophrenia (McNeil, 1987). Different expe- riences among twins who are already predisposed to the disorder could damage the brain and cause the types of symptoms we associate with schizophrenia (Williams et al., 2013). The frontal lobes of the brain have also interested people look- ing for structural problems associated with schizophrenia. This area may be less active in people with schizophrenia than in people without the disorder, a phenomenon known as hypofrontality (hypo means “less active” or “deficient”). Neuropsychological research by several Canadian teams has shown that patients with schizophrenia perform poorly relative to comparison groups on cognitive tasks known to be related to functioning of the frontal lobes (e.g., Zakzanis et al., 2000). For example, James Everett and his colleagues at Laval University showed that patients with schizophrenia performed more poorly than healthy controls on a task called the Wisconsin Card Sorting Task—a test requiring planning and organization abilities subserved by the frontal lobes (Everett et al., 2001). Further research suggests that deficient activity in a particular area of the frontal lobes, the dorsolateral prefrontal cortex (DLPFC), may be implicated in schizophrenia (e.g., Berman & Weinberger, 1990). When people with and with- out schizophrenia are given tasks that involve the DLPFC, less activity (measured by cerebral blood flow) is recorded in the brains of those with schizophrenia. A meta-analytic study showed that hypofrontality distinguishes about half of schizophrenia patients from people without schizophrenia (Davidson & Heinrichs, 2003). Hypofrontality also seems to be associated with the negative symptoms of schizophrenia (Andreasen et al., 1992) and with the eye-tracking deficits mentioned earlier (O’Driscoll et al., 1999). It appears that several brain sites are implicated in the cogni- tive dysfunction observed among people with schizophrenia, especially the prefrontal cortex, various other related cortical regions, and subcortical circuits including the thalamus and the stratum (Shenton & Kubicki, 2009). Remember that this dysfunc- tion seems to occur before the onset of schizophrenia. In other words, brain damage may develop progressively, beginning before the symptoms of the disorder are apparent, perhaps prena- tally (Weinberger, 1995).

Answer 16

A curious fact about schizophrenia is that, according to some authors, no adequate descriptions of people having this disorder appear earlier than about 1800 (e.g., Gottesman, 1991). If you look at historic records or read ancient literature, you can find people with such disorders as intellectual disability, mania, depression, and dementia. Even William Shakespeare, who describes most human conditions, mentions nothing that resembles our current image of schizophrenia. Historically, such an obvious aberration of behaviour is puzzlingly absent. (However, there is now some evidence that at least a few cases of schizophrenia-like disorder may have existed as early as the 14th century; Heinrichs, 2003.) One intriguing hypothesis is that schizophrenia is a recent phenomenon, appearing only during the past 200 years and that, like AIDS, it may involve some newly introduced virus (Gottes- man, 1991). In other words, a “schizo-virus” could have caused some cases of this debilitating disorder (Torrey, 1988b). In fact, evidence suggests that a virus-like disease may account for some cases (Kirch, 1993). The higher prevalence of schizophrenia among men living in urban areas (Lewis et al., 1992) implies that they are more likely to have been exposed to infectious agents than are their peers in less populated areas. Several studies have shown that schizophrenia may be associ- ated with prenatal exposure to influenza. For example, Mednick and colleagues followed a large number of people after a severe Type A2 influenza epidemic in Helsinki, Finland, and found that those whose mothers were exposed to influenza during the second trimester of pregnancy were much more likely to have schizo- phrenia than others (Cannon et al., 1991). This observation has been confirmed by some researchers (e.g., O’Callaghan et al., 1991; Venables, 1996) but not by others (e.g., Buchanan & Carpenter, 2005; Selten et al., 2009). A parasite has also been implicated in the etiology of schizo- phrenia. Toxoplasma gondii is most often found in cats and particularly in the feces of cats. Transmission to humans is done by ingestion of oocysts from litter boxes. In a recent meta- analysis of 23 studies, people diagnosed with schizophrenia were two to three times more likely to have antibodies in their blood, compared with people without schizophrenia (Torrey et al., 2007). The parasite is able to affect brain function in utero, so pregnant women are now asked in many places to remove litter boxes from their homes as a precaution. Evidence that in utero events may be associated with schizo- phrenia has led researchers to look further into this area. Among the types of cells that normally migrate to the cortex during this period are the fingertip dermal cells, which are responsible for the number of fingerprint ridges. Although there is no such thing as an abnormal number of ridges, identical twins generally have the same number. However, if some interruption in second-trimester fetal development resulted in schizophrenia (when, according to the viral theory, a virus may have its effect), it would also affect the fingertip dermal cells. Researchers compared the fingerprint ridges of identical twins who were discordant for schizophrenia with those of identical twins without schizophrenia (Bracha et al., 1992). They found that the number of ridges on the fingertips of the twins without schizophrenia differed very little from each other; however, they differed a great deal among about one-third of the twin pairs who were discordant for schizophrenia. This study suggests that ridge count may be a marker of prenatal brain damage. Although there is no characteristic fingerprint for schizo- phrenia, this physical sign may add to our understanding of the second-trimester conditions that can trigger the genetic predispo- sition for schizophrenia (Weinberger, 1995).

Answer 17

That one identical twin may develop schizophrenia and the other may not suggests that schizophrenia involves something in addi- tion to genes. We know that early brain trauma, perhaps resulting from a second-trimester virus-like attack or obstetrical complica- tions, may generate physical stress that contributes to schizophre- nia. All these observations show clearly that schizophrenia does not fall neatly into a few simple causal packages. For instance, not all people with schizophrenia have enlarged ventricles, nor do they all have hypofrontality or excessive activity in their dopamine systems. The causal picture may be further complicated by psycho- logical and social factors. We next look at research into psychoso- cial factors. Do emotional stressors or family interaction patterns initiate the symptoms of schizophrenia? If so, how might those factors cause people to relapse after a period of improvement?

Answer 18

It is important to learn how much and what kind of stress makes a person with a predisposition for schizophrenia develop the disorder itself. Think back to the two cases we presented near the beginning of this chapter. Did you notice any precipitating events? Arthur’s father had died several years earlier, and he was laid off from his job right around the time his symptoms first appeared. David’s uncle had died the same year he began acting strangely. Were these stressful events just coincidences, or did they contribute to the men’s later problems? Researchers have studied the effects of a variety of stressors on schizophrenia. Living in a large city, for example, is associated with an increased risk of developing schizophrenia, suggesting that the stress of urban living may precipitate its onset (Boydell & Allardyce, 2011). Dohrenwend and Egri (1981) observed that otherwise healthy people who engage in combat during a war often display temporary symptoms that resemble those of schizo- phrenia. In an early study, Brown and Birley (1968; Birley & Brown, 1970) examined people whose onset of schizophrenia could be dated within a week. These individuals had experienced a high number of stressful life events in the three weeks just before they started showing signs of the disorder. In a large-scale study sponsored by the World Health Organization, researchers also looked at the role of life events in the onset of schizophrenia (Day et al., 1987). This cross-national study confirmed the find- ings of Brown and Birley across eight different research centres. The retrospective nature of such research creates problems, however. Each study relies on after-the-fact reports, collected after the person showed signs of schizophrenia. We always wonder whether such reports are biased in some way and there- fore misleading (Hirsch et al., 1992). One study used a prospec- tive approach to examine the impact of stress on relapse. Ventura et al. (1989) identified 30 people with recent-onset schizophrenia and followed them for a year. The researchers interviewed the subjects every two weeks to learn whether they had experienced any stressful life events and whether their symptoms had changed. Notice that, unlike the previous studies, this research examines the factors that predict the recurrence of schizophrenic symptoms after a period of improvement. During the one-year assessment period, 11 of the 30 people had a significant relapse—that is, their symptoms returned or worsened. Like Brown and Birley, Ventura et al. found that relapses occurred when stressful life events increased during the previous month. Other research demonstrates that stressful life events can increase depression among people with schizophrenia, which in turn may contribute to relapse (Ventura et al., 2000). An important finding from the first study is that, although the people experienced more stressful events as a group just before their relapse, 55 percent did not have a major life event during the previous month. Other factors must account for the return of symptoms among these people (Bebbing- ton et al., 1993; Ventura et al., 1992). Another important area in the study of the impact of stress on schizophrenia is research showing a significant negative correla- tion between social class and schizophrenia. In other words, there is a significant tendency for individuals with schizophrenia to be found in the lowest social classes. This finding has been repli- cated in a variety of cultures (e.g., Hollingshead & Redlich, 1958; Kohn, 1968). There are at least two possible explanations for this finding. The first explanation pertains to stress affecting schizo- phrenia rates: It could be that life in the lower social classes is stressful, predisposing those from the lower social classes to an increased likelihood of schizophrenia. This explanation is known as the sociogenic hypothesis. The second explanation pertains to the adverse effects of schizophrenia on a person’s ability to hold a job. If the illness makes them less able to hold a job, individuals with schizophrenia may experience a downward social drift into the lower social classes. This second explanation is known as the social selection hypothesis. Although results have certainly been mixed, findings generally favour the social selection over the sociogenic hypothesis in terms of explaining the relation of social class and schizophrenia (see Dohrenwend et al., 1992). This should not be taken to mean that social environment does not play a role in schizophrenia, however. Take for example, the research on the role of social support, which we will examine next. Elsewhere in this book, we examined how social support can exert a moderating influence in reducing the negative impact of stress in both physical and mental health disorders. Although investigations of social support in schizophrenia have been rela- tively sparse, some Canadian research supports its importance in this disorder as well. A longitudinal study by David Erickson and Morton Beiser at the University of Ottawa and the Centre for Addiction and Mental Health showed that higher levels of social support from non-family members in the social network predicted better outcomes five years later among patients experiencing their first episode of schizophrenia (Erickson et al., 1998). But what of the role of family members? We look at this important influence next.

Answer 19

A great deal of research has studied how interactions within the family affect people who have schizophrenia. For example, at one time the term schizophrenogenic was used to describe a mother whose cold, dominant, and rejecting nature was thought to cause schizophrenia in her children (Fromm-Reichmann, 1948). In addition, the term double bind was used to portray a type of communication style that produced conflicting messages, which, in turn, caused schizophrenia to develop (Bateson, 1959). Here, the parent presumably communicates messages that have two conflicting meanings; for example, a mother responds coolly to her child’s embrace but says, “Don’t you love me anymore?” when the child withdraws. Although these theories are no longer supported, they have been—and in some cases continue to be— destructive, producing guilt in parents who are persuaded that their early mistakes caused devastating consequences. Recent work has focused more on how family interactions contribute not to the onset of schizophrenia itself, but to relapse after initial symptoms are observed. Research has focused on a particular emotional communication style known as expressed emotion (EE). This concept was formulated by Brown and colleagues in London, England. Following a sample of people who had been discharged from the hospital after an episode of schizophrenic symptoms, the researchers found that former patients who had limited contact with their relatives did better than patients who spent longer periods with their families (Brown, 1959). Additional research results indicated that if the level of criticism (disapproval), hostility (animosity), and emotional over- involvement (intrusiveness) expressed by the families was high, patients tended to relapse (Brown et al., 1962). Other researchers, including John Cole of the London Psychi- atric Hospital and Shahe Kazarian of the University of Western Ontario, have since found that ratings of high EE in a family are a good predictor of relapse among people with chronic schizo- phrenia (Bebbington et al., 1995; Kazarian et al., 1990). In fact, if you have schizophrenia and live in a family with high EE, you are 3.7 times as likely to relapse as if you lived in a family with low EE (Kavanagh, 1992; Parker & Hadzi-Pavlovic, 1990). Family communications involving high levels of EE are char- acterized by intrusiveness, high levels of emotional response, a negative attitude toward the illness on the part of family members, and low tolerance and unrealistic expectations of the patient (Cole & Kazarian, 1988). Research from Laval University researchers Helene Provencher and Frank Fincham (2000) demonstrates that, unfortunately, it is common for family members to see a patient’s schizophrenia symptoms as being intentional. The literature on EE is valuable to our understanding of why symptoms of schizophrenia recur. It may also help people with this disorder to reduce the chance of further psychotic episodes (Cechnicki et al., 2013; Mueser et al., 1993). An interesting issue that arises when studying family influ- ences is whether what we see is unique to our culture or is univer- sal. Looking at EE across different cultures may help us learn whether it is a cause of schizophrenia (Breitborde et al., 2010). Remember that schizophrenia is observed at about the same rate worldwide, with a prevalence of about 1 percent in the global population. If a factor like high EE in families is a causal agent, we should see the same rates in families across cultures; in fact, however, they differ, as you can see in ■ Figure 14.6. These data come from an analysis of the concept of EE in several studies, from India, Mexico, Great Britain, and North America (Jenkins & Karno, 1992). The differences suggest there are cultural variations in how families react to someone with schizo- phrenia, and their reactions may not cause the disorder (Singh et al., 2013). And, what may appear to be overinvolvement in one culture may be viewed as supportive in other cultures. As pointed out by the research of Suzanne King at the Douglas Hospital in Montréal, however, it is also very important to consider the possi- bility that critical comments and emotional overinvolvement may be family responses to a patient’s unusual and disturbing behav- iour rather than a cause (King, 2000). In fact, research does show that certain kinds of patient behaviours do evoke hostility in family members, supporting the position that the relation between the behaviour of patients with schizophrenia and EE in family members is indeed a reciprocal process (e.g., Cook et al., 1989; Miklowitz et al., 1989).

Answer 20

If you remember our descriptions of Arthur and David, you will recall their families’ concern for them. Arthur’s mother spoke of the “living nightmare” and David’s aunt expressed concern for both her safety and David’s. In each case, the family was desper- ate to help, but what do you do for someone who has delusions, hears his dead uncle’s voice, or can’t communicate complete thoughts? The search for help has taken many paths, sometimes down some very disturbing roads; for example, in the 16th century, primitive surgery was conducted to remove the “stone of madness,” which was thought to cause disturbed behav- iour. As barbaric as this practice may seem today, it is not very different from the prefrontal lobotomies performed on people with schizophrenia as late as the 1950s. This procedure severed the frontal lobes from the lower portion of the brain, which some- times calmed the patient but also caused cognitive and emotional deficits. Even today, some societies use crude surgical procedures to eliminate the symptoms of schizophrenia. In Kenya, for instance, Kisii tribal doctors listen to their patients to find the location of the noises in the patients’ heads (hallucinations), then get them drunk, cut out a piece of scalp, and scrape the skull in the area of the voices (Mustafa, 1990). In the Western world today, treatment usually begins with one of the neuroleptic drugs that help reduce the symptoms of schizo- phrenia for many people. They are typically used in combination with a variety of psychosocial treatments to reduce relapse, compensate for skills deficits, and improve cooperation for taking the medications (Cunningham Owens & Johnstone, 2012). - biological intErvEntions - psychosocial intErvEntions - trEatmEnt across culturEs - prEvEntion

Answer 21

Researchers have assumed for more than a century that schizo- phrenia requires some form of biological intervention. Emil Krae- pelin, who so eloquently described dementia praecox in the late 19th century, saw the disorder as a brain disease. Lacking a biological treatment, he routinely recommended that the physi- cian use “good patience, kindly disposition, and self-control” to calm excited patients (Nagel, 1991). This approach was seen as only a temporary way of helping the person through disturbing times and was not thought to be an actual treatment. During the 1930s, several novel biological treatments were tried. One approach was to inject massive doses of insulin—the drug that given in smaller doses is used to treat diabetes—to induce comas in people who have schizophrenia. Insulin coma therapy was thought for a time to be helpful, but closer examina- tion showed it carried great risk of serious illness and death. During this time psychosurgery, including prefrontal lobotomies, was introduced; and in the late 1930s, electroconvulsive therapy (ECT) was advanced as a treatment for schizophrenia. As with earlier drastic treatments, initial enthusiasm for ECT faded because it was found not to be beneficial for most people with schizophrenia—although it is still used with a limited number of people today (Fink & Sackeim, 1996; Zervas et al., 2012). As we explained in Chapter 8, ECT is sometimes recommended for people who experience very severe episodes of depression. A breakthrough in the treatment of schizophrenia came during the 1950s with the introduction of several drugs that relieved symptoms in many people (Cunningham Owens & Johnstone, 2012; Lehmann & Ban, 1997; Potkin et al., 1993). Called neuro- leptics (meaning “taking hold of the nerves”), these medications provided the first real hope that help was available for people with schizophrenia. The psychiatrist Heinz Lehmann is credited by many (e.g., Dongier, 1999) with introducing neuroleptic medications for the treatment of schizophrenia to North America. Lehmann conducted a study demonstrating the effectiveness of chlorpromazine with about 200 patients who had schizophrenia at the Douglas Hospital in Montréal (Lehmann & Hanrahan, 1954). When they are effective, neuroleptics help people think more clearly and reduce or eliminate hallucinations and delusions. They work by affecting the positive symptoms (delusions, hallu- cinations, agitation) and to a lesser extent the negative and disor- ganized ones, such as social deficits. Recall from our discussion of the dopamine theory of schizo- phrenia that the neuroleptics are dopamine antagonists. One of their major actions in the brain is to interfere with the dopamine neurotransmitter system. They can also affect other systems, however, such as the serotonergic system. We are just beginning to understand the mechanisms by which these drugs work. In general, each drug is effective with some people and not with others. Clinicians and patients often must go through a trial- and-error process to find the medication that works best, and some individuals do not benefit significantly from any of them. The earliest neuroleptic drugs, called conventional antipsychot- ics, are effective for approximately 60 to 70 percent of persons who try them (American Psychiatric Association, 2000b; Cunningham Owens & Johnstone, 2012). Many people are not helped by antipsychotics, however, or they experience unpleasant side effects. Fortunately, some people respond well to newer medications; the most common are clozapine, risperidone, and olanzapine. First marketed in 1990, clozapine is now used widely, and risperidone and other newer drugs hold promise for helping patients who were previously unresponsive to medications (American Psychiatric Association, 2000b; Iskedjian et al., 1998; Malla et al., 2001; Wahlbeck et al., 1999). These newer antipsy- chotics are now prescribed to more than three-quarters of patients with schizophrenia in Canada (Smith et al., 2006). They tend to have fewer serious side effects than the conventional antipsychot- ics (Black & Andreasen, 1999; Levy et al., 2004). In fact, evidence from Howard Margo- lese and colleagues at McGill University shows that treatment with these newer antipsychotics can reduce the severity of long- standing tardive dyskinesia, discussed more below (Margo- lese et al., 2005). Some limited evidence also suggests that these newer antipsychotics may be more effective than conventional anti- psychotics in reducing both negative and positive symptoms (e.g., Chouinard et al., 1993). For example, University of Montréal researcher Emmanuel Stip and his colleagues have recently shown that the newer antipsychotic quetiapine may be effective in treating the nega- tive symptom of flat affect (Stip et al., 2005). Moreover, research by Kimberly Good and her colleagues at Dalhousie University provided evidence that these newer medications may be helpful in improving cognitive functioning, at least among patients experi- encing their first episode of psychosis (Good et al., 2002; Kopala et al., 2006). Despite the optimism generated by the effectiveness of anti- psychotics, they work only when they are taken properly, and many people with schizophrenia do not routinely take their medi- cation. David frequently “cheeked” the Haldol pills that were helpful in reducing his hallucinations, holding them in his mouth until he was alone, then spitting them out. Approximately, 7 percent of the people prescribed antipsychotic medication refuse to take it at all (Hoge et al., 1990). Research on the prevalence of occasional noncompliance suggests that a majority of people with schizophrenia stop taking their medication periodically. A follow- up study, for example, found that over a two-year period, three out of four patients studied refused to take their antipsychotic medica- tion for at least one week (Weiden et al., 1991). Several factors seem to be related to patients’ noncompliance with a medication regimen, including negative doctor–patient relationships, cost of the medication, stigma, and poor social support (Haddad, Brain, and Scott, 2014). Not surprisingly, nega- tive side effects are a major factor in patient refusal. Antipsychot- ics can produce a number of unwanted physical symptoms, such as grogginess, blurred vision, and dryness of the mouth. Because the drugs affect neurotransmitter systems, more serious side effects, called extrapyramidal symptoms, can also result (Cunning- ham Owens & Johnstone, 2012). These symptoms include the motor difficulties similar to those experienced by people with Parkinson’s disease, sometimes called parkinsonian symptoms (Levy et al., 2004). Akinesia is one of the most common; it includes an expressionless face, slow motor activity, and monoto- nous speech (Blanchard & Neale, 1992). Another extrapyramidal symptom is tardive dyskinesia, which involves involuntary move- ments of the tongue, face, mouth, or jaw, and can include protru- sions of the tongue, puffing of the cheeks, puckering of the mouth, and chewing movements. Tardive dyskinesia seems to result from long-term use of high doses of antipsychotic medica- tion and is often irreversible. Studies have shown that 20 to 50 percent of all patients treated with antipsychotics develop tardive dyskinesia, with lower risk for younger people: only 3 to 5 percent of young people taking this medication display tardive dyskinesia, with the risk increasing over time (Waln & Jankovic, 2013). These serious negative side effects have justifiably concerned people who otherwise benefit from the drugs. To learn what patients themselves say, Windgassen (1992) questioned 61 people who had had recent onsets of schizophrenia. About half reported the feeling of sedation or grogginess as an unpleasant side effect: “I always have to fight to keep my eyes open,” “I felt as though I was on drugs . . . drowsy, and yet really wound up” (p. 407). Other complaints included deterioration in the ability to think or concentrate (18 percent), problems with salivation (16 percent), and blurred vision (16 percent). Although a third of the patients felt the medications were beneficial, about 25 percent had a negative attitude toward them. A significant number of people who could benefit from antipsychotic medica- tions find them unacceptable as a treatment, which may explain the relatively high rates of refusal and noncompliance (Sendt et al., 2015; Yamada et al., 2006). Researchers have made this a major treatment issue in schizo- phrenia, realizing that medications can’t be successful if they aren’t taken regularly. Clinicians hoped that the new antipsychot- ics such as clozapine, which produce fewer negative side effects, would allay some legitimate patient concerns. However, even clozapine produces undesirable effects, and its use must be moni- tored closely to avoid rare effects that are potentially life threaten- ing (Umbricht & Kane, 1996). Researchers hoped that compliance rates would improve with the introduction of injectable medica- tions. Instead of taking an oral antipsychotic every day, patients can have their medications injected every few weeks. Unfortu- nately, noncompliance remains an issue, primarily because patients do not return to the hospital or clinic for repeated doses (Kane et al., 2009). Psychosocial interventions are now used not only to treat schizophrenia but also to increase medication-taking compliance by helping patients communicate better with profes- sionals about their concerns. An interesting treatment for the hallucinations experienced by many persons with schizophrenia involves exposing the individ- ual to magnetic fields. Called transcranial magnetic stimulation (TMS), this technique uses wire coils to repeatedly generate magnetic fields—up to 50 times per second—that pass through the skull to the brain (see review by Daskalakis et al., 2002). This input seems to interrupt the normal communication temporarily to that part of the brain. Hoffman and colleagues (2000) used this technique to stimulate the area of the brain involved in hallucina- tions for 12 individuals with schizophrenia who experienced auditory hallucinations. They found that many of the individuals experienced improvement following TMS. A more recent study by Jeff Daskalakis at the Centre for Addiction and Mental Health in Toronto and his colleagues produced less promising results. They investigated whether TMS could help individuals with treatment-resistant auditory hallucinations. Unfortunately, TMS was generally ineffective in treating the auditory hallucinations except in decreasing their loudness (Fitzgerald et al., 2005). Subsequent studies have shown that TMS can modestly improve auditory hallucinations, but that its effects last less than one month (e.g., Slotema et al., 2012).

Answer 22

Historically, a number of psychosocial treatments have been tried for schizophrenia, reflecting the belief that the disorder results from problems in adapting to the world because of early experi- ences (Cunningham Owens & Johnstone, 2012). Many therapists have thought that individuals who could achieve insight into the presumed role of their personal histories could be safely led to deal with their existing situations. Although clinicians who take a psychodynamic or psychoanalytic approach to therapy continue to use this type of treatment, research suggests that their efforts at best may not be beneficial and at worst may be harmful (Mueser & Berenbaum, 1990; Scott & Dixon, 1995b). Today, few believe that psychological factors cause people to have schizophrenia or that traditional psychotherapeutic approaches will cure them. We will see, however, that psychological methods do have an important role. Despite the great promise of drug treat- ment, the problems with ineffectiveness, inconsistent use, and relapse suggest that, by themselves, drugs may not be effective with many people. As with several other disorders discussed in this text, recent work in the area of psychosocial intervention has suggested the value of an approach that uses both kinds of treat- ment (Mueser & Marcello, 2010; Tarrier et al., 1999, 2000). Until relatively recently, most people with severe and chronic cases of schizophrenia were treated in hospital settings. During the 19th century, inpatient care involved “moral treatment,” which emphasized improving patients’ socialization, helping them establish routines for self-control, and showing them the value of work and religion (Tenhula et al., 2009). Various types of such Radius Images/Jupiter Images milieu treatment have been popular but, with one important exception, none seems to have helped people with schizophrenia (Tucker et al., 1984). In the 1970s, Gordon Paul and Robert Lentz (1977) conducted pioneering work that borrowed from the behavioural approaches used by Ted Ayllon and Nate Azrin (1968). Paul and Lentz designed an environment for inpatients that encouraged appropri- ate socialization, participation in group sessions, and self-care, such as bed-making, while discouraging violent outbursts. They set up an elaborate token economy, in which residents could earn access to meals and small luxuries by behaving appropriately. A patient could, for example, buy cigarettes with the tokens earned for keeping his or her room neat. Conversely, a patient would be fined (lose tokens) for being disruptive or otherwise acting inappropriately. This incentive system was combined with a full schedule of daily activities. Paul and Lentz compared the effectiveness of applied behavioural (or social learning) principles with traditional inpatient envi- ronments. In general, they found that patients who went through their program did better than others on social, self- care, and vocational skills, and more of them could be discharged from the hospital. This study was one of the first to show that people experiencing the debilitating effects of schizophrenia can learn to perform some of the skills they need to live more independently. Since 1955, many efforts have combined to halt the routine institutionalization of people with schizophrenia in both Canada and the United States (Bachrach, 1994; Barnes & Toews, 1983; Talbott, 1990). This trend has occurred in part because of court rulings that limit involuntary hospitalization (as we saw in Arthur’s case), in part because of the relative success of antipsy- chotic medication and in part because of fiscal crisis and ensuing cutbacks in health care (Hanna, 2001). In Canada, provincial psychiatric hospitals released thousands of patients and closed down more than 32 500 beds between 1960 and 1976, and this trend continues today (Nichols, 1995; Sealy & Whitehead, 2004). The bad news is that policies of deinstitutionalization have often been ill conceived so that the process has sometimes resulted in problems. For example, as a consequence of deinstitutionaliza- tion, many people who have schizophrenia or other serious psychological disorders are homeless (e.g., Stuart & Arboleda- Florez, 2000). As another example, women (and other family members) are increasingly expected to bear the burden of caring for a family member who has a mental illness (Chan & O’Brian, 2011). The good news is that more attention is being focused on supporting these people in their communities, among their friends and families (Richman & Harris, 1982–1983; Uditsky, 1994). In fact, when adequate community support is provided, these people fare no worse and sometimes fare better in the community than in institutions (Barnes & Toews, 1983). Thus, the trend is away from creating better hospital environments and toward the perhaps more difficult task of addressing complex problems in the less predictable and insecure world outside. So far, only a small frac- tion of the growing number of homeless individuals with mental disorders are being helped. One of the more insidious effects of schizophrenia is its nega- tive impact on a person’s ability to relate to other people. Although not as dramatic as hallucinations and delusions, this problem can be the most visible impairment displayed by people with schizophrenia and can prevent them from getting and keep- ing jobs and making friends. Clinicians attempt to reteach social skills, such as basic conversation, assertiveness, and relationship building, to people with schizophrenia. Therapists divide complex social skills into their component parts, which they model. Then the clients role-play and ultimately practise their new skills in the real world, all the while receiving feedback and encouragement at signs of progress. This isn’t as easy as it may sound. For example, how would you teach someone to make a friend? Many skills are involved, such as maintaining eye contact when you talk to someone and providing the prospec- tive friend with some (but not too much!) positive feedback on his or her own behaviour (“I really enjoy talking to you”). Such indi- vidual skills are practised and then combined until they can be used naturally (Swartz et al., 2006). Basic skills can be taught to people with schizophrenia, but there is some disagreement about how ultimately successful the treatment is (Bellack & Mueser, 1992; Hogarty et al., 1992). The problem is that the positive results of social skills training may fade after the training is over (Scott & Dixon, 1995b). The challenge of teaching social skills, as with all therapies, is to maintain the effects over a long time. In addition to social skills, programs often teach a range of ways that people can adapt to their disorder yet still live in the community. In the Independent Living Skills Program developed by Eckman and colleagues (1992), the focus is on helping people take charge of their own care by such methods as identifying signs that warn of a relapse and learning how to manage their medica- tion (Corrigan et al., 1994; Eckman et al., 1992). Preliminary evidence indicates that this type of training may help prevent the relapses of people with schizophrenia. For example, Ross Norman and his colleagues at the University of Western Ontario added a stress-management intervention to an existing medical and psycho- social treatment program for individuals with schizophrenia. Patients who participated in the stress-management program had fewer hospitalizations in the following year, particularly those who showed a high level of attendance at treatment sessions (Norman et al., 2002). Longer-term outcome research is needed to see how long these effects last (Cunningham Owens & Johnstone, 2012). To address some of the obstacles to this much- desired maintenance, such programs combine skills training with the support of a multidisciplinary team that provides services directly in the community, which seems to reduce hospitalization (Cunningham Owens & Johnstone, 2012; Scott & Dixon, 1995a). The more time and effort given to these services, the more likely the improvement (Brekke et al., 1997). In our discussion of the psychosocial influences on schizo- phrenia, we reviewed some of the work linking the person’s social and emotional environments to the recurrence of schizophrenic episodes (McNab et al., 2007). It is logical to ask whether fami- lies could be helped by learning to reduce their level of EE and whether this would result in fewer relapses and better overall functioning for people with schizophrenia. Several studies have addressed these issues in a variety of ways (Falloon et al., 1985; Hogarty et al., 1986, 1991), and behavioural family therapy has been used to teach the families of persons with schizophrenia to be more supportive (Dixon & Lehman, 1995; Mueser et al., 1990). Research on professionals who provide care for people who have schizophrenia, and who may also display high levels of EE, is also an active area of study (Barrowclough & Tarrier, 1998; Cunningham Owens & Johnstone, 2012; Tattan & Tarrier, 2000). In contrast to traditional therapy, behavioural family therapy resembles classroom education (Falloon, 2015; Lefley, 2009). Family members are informed about schizophrenia and its treat- ment, relieved of the myth that they caused the disorder, and taught practical facts about antipsychotic medications and their side effects. They are also helped with communication skills so they can become more empathic listeners, and they learn construc- tive ways of expressing negative feelings to replace the harsh criticism that characterizes some family interactions. In addition, they learn problem-solving skills to help them resolve conflicts that arise. Like the research on social skills training, outcome research suggests that the effects of behavioural family therapy are significant during the first year but less robust two years after intervention (Cunningham Owens & Johnstone, 2012). This type of therapy, therefore, must be ongoing if patients and their fami- lies are to benefit from it. Adults with schizophrenia face great obstacles to maintaining gainful employment. Their social skills deficits make reliable job performance and adequate employee relationships a struggle. To address these difficulties, some programs focus on vocational rehabilitation, such as supportive employment (Bustillo et al., 2001). Providing coaches who give on-the-job training may help some people with schizophrenia maintain meaningful jobs (Bond et al., 1997; Drake et al., 1996; Lehman, 1995). Social skills train- ing, family intervention, and vocational rehabilitation may be helpful additions to biological treatments for schizophrenia, in terms of avoiding or delaying relapse. A general trend in the treatment of schizophrenia today is toward early intervention. It is increasingly becoming recognized that intervening early can be important in affecting the course of the disorder over time. Getting help in the early stages of the illness is critical. In fact, research has shown that getting patients onto the right medications and into effective psychotherapy as soon as possible, and providing information and support to affected families right away, can actually reduce the severity of future relapses (e.g., Drury et al., 1996). The key elements of early intervention are outlined in Table 14.1. Early psychosis clinical programs have now been developed at several sites across Canada (e.g., Halifax, Toronto, London, Hamilton, and Calgary; Lines, 2001). The first such centre, the First Episode Psychosis Clinic/ Early Psychosis Unit, was developed at the Centre for Addiction and Mental Health in Toronto (Nichols, 1995). It is designed to meet the needs of individuals experiencing a first episode of psychosis and assists such individuals and their families with the initial period of adjustment and recovery. The clinic provides a full assessment and psychosocial intervention to help such patients on an outpatient basis; inpatient services are also available. Prior- ity is given to adults (aged 18 to 45) who have not yet received any antipsychotic treatment. For an example of early intervention in British Columbia see http://www.earlypsychosis.ca. A relatively newer approach to the treatment of schizophrenia that has been applied over the past 20 years is cognitive-behav- ioural therapy (CBT; see reviews by Bouchard et al., 1996; Norman & Townsend, 1999; Rector & Beck, 2001). For example, British researchers David Kingdon and Douglas Turkington (1994) argued that people with schizophrenia are not inherently irrational but instead have a set of irrational beliefs that are amenable to intervention with cognitive and behavioural tech- niques. CBT has usually been applied to auditory hallucinations and delusions (i.e., positive symptoms; Birchwood et al., 1994; Norman & Townsend, 1999), although CBT strategies have been developed to treat both positive and negative symptoms (Beck & Rector, 2000). CBT strategies developed to treat symptoms of schizophrenia are essentially adaptations of CBT strategies successfully used in the treatment of depression and anxiety (Beck et al., 2001). Take the case example of Thomas described by clinical psychologist Neil Rector—a case that was treated by Aaron Beck over 50 years ago, in the first application of CBT to the treatment of delusions (Rector & Beck, 2002). In the following excerpt, a patient from the Royal Ottawa Hospital, J. P. Lee, who has been living with schizophrenia for 20 years, describes how he learned to use CBT to effectively challenge his delusional paranoid thoughts. He attempts to describe a scenario where he used CBT to modify the sequence of his reactions: Despite a good deal of initial skepticism as to whether symp- toms of a such a severe disorder could be amenable to “talk ther- apy,” more recent reviews of the literature are unanimous in supporting the potential of this approach in the treatment of patients with schizophrenia. For example, in a review of the litera- ture conducted with CBT developer Aaron Beck, University of Toronto psychologist Neil Rector found that CBT produces large clinical effects on both positive and negative symptoms of schizo- phrenia (Rector & Beck, 2001). In one such study, 42 patients with schizophrenia were randomly assigned to either a treatment-as- usual control condition (i.e., specialized schizophrenia treatment services) or to treatment as usual with an additional 20 sessions of CBT. For patients in the experimental group receiving adjunctive CBT, significant benefits of treatment were observed at a six-month follow-up for positive symptoms, negative symptoms, and overall severity of the disorder. The most pronounced effect of the addition of CBT relative to the treatment-as-usual control group was in the reduction of negative symptoms at follow-up (Rector et al., 2003). In another example, Garety and colleagues at the Institute of Psychiatry in London, England, reported excellent outcome of a controlled trial of CBT for patients with schizophrenia who had not responded well to drug treat- ment in the past. They found that the treatment group improved more than the controls on the degree of conviction in their delusional beliefs, the severity of their overall symptoms, and their depression levels (Garety et al., 1994). Results such as these suggest promise for the impact of CBT in the treatment of schizophrenia.

Answer 23

Treatment of schizophrenia and its delivery differ from one country to another and across cultures within countries. In China, for example, the most frequently used treatment is anti- psychotic medication, although 7 to 9 percent of patients also receive traditional herbal medi- cine and acupuncture (Mingdao & Zhenyi, 1990). For financial and cultural reasons, more people in China are treated outside the hospital than are in Western societies. The vast majority of the Xhosa people of South Africa who have schizophrenia report using traditional healers who sometimes recommend the use of oral treatments to induce vomiting, enemas, and the slaughter of cattle to appease the spirits (Koen et al., 2008). In one interesting study, beliefs about symptoms and treatments were compared between British and Chinese populations (Furnham & Wong, 2007). Native Chinese hold more religious beliefs about both the causes and the treatments of schizophrenia than those living in England—for example, endorsing statements such as “Schizophrenia is due to evil done in a previous life,” and “Ancestor worship (burning candles and joss sticks) will help treat schizo- phrenia.” These different beliefs translate into practice—with the British using more biological, psychological, and community treat- ments and the Chinese relying more on alternative medicine (Furn- ham & Wong, 2007). Supernatural beliefs about the cause of schizophrenia among family members in Bali lead to limited use of antipsychotic medication in treatment (Kurihara et al., 2006). In many countries in Africa, people with schizophrenia are kept in prisons, primarily because of the lack of adequate alternatives (Mustafa, 1990). In general, the movement from housing people in large institutional settings to community care is ongoing in most Western countries.

Answer 24

One strategy for preventing a disorder such as schizophrenia— which typically first shows itself in early adulthood—is to iden- tify and treat children who may be at risk for getting the disorder later in life. In our discussion of genetics, we noted that approxi- mately 13 percent of the children born to parents who have schizophrenia are likely themselves to develop the disorder. These high-risk children have been the focus of several studies, both prospective (before and during an expected situation) and longitudinal (over long periods). A classic at-risk study was initiated in the 1960s by Mednick and Schulsinger (1965, 1968) in Denmark. They identified 207 Danish children of mothers who had severe cases of schizophrenia and 104 comparison children born to mothers who had no history of the disorder. The average age of these children was about 15 when they were first identified, and the researchers followed them for 25 years to determine whether any factors had predicted who would and would not develop schizophrenia. The children of mothers with schizophrenia were at much greater risk to develop schizophrenia (16 percent) or personality disorders (21 percent) than children of non- affected mothers (2 and 5 percent; Parnas et al., 1993). We have already discussed pregnancy and delivery-related complica- tions as predictors of schizophrenia. Mednick and Schulsinger also identified instability of the early family-rearing environ- ment, which suggests that environmental influences may trig- ger the onset of schizophrenia (Carter et al., 2002). Poor parenting may place additional strain on a vulnerable person who is already at risk. One approach to prevention of schizophrenia receiving increased attention is the treatment of persons in the prodromal stages of the disorder. Here, the individual is beginning to show early mild signs of schizophrenia (e.g., hallucinations, delu- sions) but is aware of these changes. Efforts to intervene with these individuals are being investigated as a means of either stopping the progression of the disorder or preventing relapses (Cunningham Owens & Johnstone, 2012).

Chapter 14 Flashcards

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