Schizophrenia Spectrum Disorders by Deanna M. Barch is licensed under a Creative Commons AttributionNonCommercial-ShareAlike 4.0 International license. © 2015, Diener Education Fund.
Schizophrenia Spectrum Disorders
By Deanna M. Barch
Washington University in St. Louis
Schizophrenia and the other psychotic disorders are some of the most impairing forms of
psychopathology, frequently associated with a profound negative effect on the individual’s educational,
occupational, and social function. Sadly, these disorders often manifest right at time of the transition
from adolescence to adulthood, just as young people should be evolving into independent young adults.
The spectrum of psychotic disorders includes schizophrenia, schizoaffective disorder, delusional disorder,
schizotypal personality disorder, schizophreniform disorder, brief psychotic disorder, as well as psychosis
associated with substance use or medical conditions. In this module, we summarize the primary clinical
features of these disorders, describe the known cognitive and neurobiological changes associated with
schizophrenia, describe potential risk factors and/or causes for the development of schizophrenia, and
describe currently available treatments for schizophrenia.
Learning Objectives
•
Describe the signs and symptoms of schizophrenia and related psychotic disorders.
•
Describe the most well-replicated cognitive and neurobiological changes associated with
schizophrenia.
•
Describe the potential risk factors for the development of schizophrenia.
•
Describe the controversies associated with “clinical high risk” approaches to identifying
individuals at risk for the development of schizophrenia.
•
Describe the treatments that work for some of the symptoms of schizophrenia.
The phenomenology of schizophrenia and related psychotic disorders
Most of you have probably had the experience of walking down the street in a city and seeing a person
you thought was acting oddly. They may have been dressed in an unusual way, perhaps disheveled or
wearing an unusual collection of clothes, makeup, or jewelry that did not seem to fit any particular
group or subculture. They may have been talking to themselves or yelling at someone you could not see.
If you tried to speak to them, they may have been difficult to follow or understand, or they may have
acted paranoid or started telling a bizarre story about the people who were plotting against them. If so,
chances are that you have encountered an individual with schizophrenia or another type of psychotic
disorder. If you have watched the movie A Beautiful Mind or The Fisher King, you have also seen a
portrayal of someone thought to have schizophrenia. Sadly, a few of the individuals who have committed
some of the recently highly publicized mass murders may have had schizophrenia, though most people
who commit such crimes do not have schizophrenia. It is also likely that you have met people with
schizophrenia without ever knowing it, as they may suffer in silence or stay isolated to protect
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themselves from the horrors they see, hear, or believe are operating in the outside world. As these
examples begin to illustrate, psychotic disorders involve many different types of symptoms, including
delusions, hallucinations, disorganized speech and behavior, abnormal motor behavior (including
catatonia), and negative symptoms such anhedonia/amotivation and blunted affect/reduced speech.
Delusions are false beliefs that are often fixed, hard to change even when the person is presented with
conflicting information, and are often culturally influenced in their content (e.g., delusions involving
Jesus in Judeo-Christian cultures, delusions involving Allah in Muslim cultures). They can be terrifying for
the person, who may remain convinced that they are true even when loved ones and friends present
them with clear information that they cannot be true. There are many different types or themes to
delusions.
The most common delusions are persecutory and involve the belief that individuals or groups are trying
to hurt, harm, or plot against the person in some way. These can be people that the person knows
(people at work, the neighbors, family members), or more abstract groups (the FBI, the CIA, aliens, etc.).
Other types of delusions include grandiose delusions, where the person believes that they have some
special power or ability (e.g., I am the new Buddha, I am a rock star); referential delusions, where the
person believes that events or objects in the environment have special meaning for them (e.g., that song
on the radio is being played specifically for me); or other types of delusions where the person may believe
that others are controlling their thoughts and actions, their thoughts are being broadcast aloud, or that
others can read their mind (or they can read other people’s minds).
When you see a person on the street talking to themselves or shouting at other people, they are
experiencing hallucinations. These are perceptual experiences that occur even when there is no stimulus
in the outside world generating the experiences. They can be auditory, visual, olfactory (smell), gustatory
(taste), or somatic (touch). The most common hallucinations in psychosis (at least in adults) are auditory,
and can involve one or more voices talking about the person, commenting on the person’s behavior, or
giving them orders. The content of the hallucinations is frequently negative (“you are a loser,” “that
drawing is stupid,” “you should go kill yourself”) and can be the voice of someone the person knows or a
complete stranger. Sometimes the voices sound as if they are coming from outside the person’s head.
Other times the voices seem to be coming from inside the person’s head, but are not experienced the
same as the person’s inner thoughts or inner speech.
Talking to someone with schizophrenia is sometimes difficult, as their speech may be difficult to follow,
either because their answers do not clearly flow from your questions, or because one sentence does not
logically follow from another. This is referred to as disorganized speech, and it can be present even when
the person is writing. Disorganized behavior can include odd dress, odd makeup (e.g., lipstick outlining a
mouth for 1 inch), or unusual rituals (e.g., repetitive hand gestures). Abnormal motor behavior can include
catatonia, which refers to a variety of behaviors that seem to reflect a reduction in responsiveness to
the external environment. This can include holding unusual postures for long periods of time, failing to
respond to verbal or motor prompts from another person, or excessive and seemingly purposeless motor
activity.
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Some of the most debilitating symptoms of schizophrenia are difficult for others to see. These include
what people refer to as “negative symptoms” or the absence of certain things we typically expect most
people to have. For example, anhedonia or amotivation reflect a lack of apparent interest in or drive to
engage in social or recreational activities. These symptoms can manifest as a great amount of time spent
in physical immobility. Importantly, anhedonia and amotivation do not seem to reflect a lack of enjoyment
in pleasurable activities or events (Cohen & Minor, 2010; Kring & Moran, 2008;Llerena, Strauss, & Cohen,
2012) but rather a reduced drive or ability to take the steps necessary to obtain the potentially positive
outcomes (Barch & Dowd, 2010). Flat affect and reduced speech (alogia) reflect a lack of showing
emotions through facial expressions, gestures, and speech intonation, as well as a reduced amount of
speech and increased pause frequency and duration.
In many ways, the types of symptoms associated with psychosis are the most difficult for us to understand,
as they may seem far outside the range of our normal experiences. Unlike depression or anxiety, many
of us may not have had experiences that we think of as on the same continuum as psychosis. However,
just like many of the other forms of psychopathology described in this book, the types of psychotic
symptoms that characterize disorders like schizophrenia are on a continuum with “normal” mental
experiences. For example, work by Jim van Os in the Netherlands has shown that a surprisingly large
percentage of the general population (10%+) experience psychotic-like symptoms, though many fewer
have multiple experiences and most will not continue to experience these symptoms in the long run
(Verdoux & van Os, 2002). Similarly, work in a general population of adolescents and young adults in
Kenya has also shown that a relatively high percentage of individuals experience one or more psychoticlike experiences (~19%) at some point in their lives (Mamah et al., 2012; Ndetei et al., 2012), though
again most will not go on to develop a full-blown psychotic disorder.
Schizophrenia is the primary disorder that comes to mind when we discuss “psychotic” disorders (see
Table 1 for diagnostic criteria), though there are a number of other disorders that share one or more
features with schizophrenia. In the remainder of this module, we will use the terms “psychosis” and
“schizophrenia” somewhat interchangeably, given that most of the research has focused on schizophrenia.
In addition to schizophrenia (see Table 1), other psychotic disorders include schizophreniform disorder
(a briefer version of schizophrenia), schizoaffective disorder (a mixture of psychosis and depression/mania
symptoms), delusional disorder (the experience of only delusions), and brief psychotic disorder (psychotic
symptoms that last only a few days or weeks).
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Table 1: Types of Psychotic Disorders (Simplified from the Diagnostic and
Statistical Manual - 5th Edition (DSM-5) (APA, 2013)
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The Cognitive Neuroscience of Schizophrenia
As described above, when we think of the core symptoms of psychotic disorders such as schizophrenia,
we think of people who hear voices, see visions, and have false beliefs about reality (i.e., delusions).
However, problems in cognitive function are also a critical aspect of psychotic disorders and of
schizophrenia in particular. This emphasis on cognition in schizophrenia is in part due to the growing
body of research suggesting that cognitive problems in schizophrenia are a major source of disability
and loss of functional capacity (Green, 2006; Nuechterlein et al., 2011). The cognitive deficits that are
present in schizophrenia are widespread and can include problems with episodic memory (the ability to
learn and retrieve new information or episodes in one’s life), working memory (the ability to maintain
information over a short period of time, such as 30 seconds), and other tasks that require one to “control”
or regulate one’s behavior (Barch & Ceaser, 2012; Bora, Yucel, & Pantelis, 2009a; Fioravanti, Carlone,
Vitale, Cinti, & Clare, 2005; Forbes, Carrick, McIntosh, & Lawrie, 2009; Mesholam-Gately, Giuliano, Goff,
Faraone, & Seidman, 2009). Individuals with schizophrenia also have difficulty with what is referred to as
“processing speed” and are frequently slower than healthy individuals on almost all tasks. Importantly,
these cognitive deficits are present prior to the onset of the illness (Fusar-Poli et al., 2007) and are also
present, albeit in a milder form, in the first-degree relatives of people with schizophrenia (Snitz,
Macdonald, & Carter, 2006). This suggests that cognitive impairments in schizophrenia reflect part of the
risk for the development of psychosis, rather than being an outcome of developing psychosis. Further,
people with schizophrenia who have more severe cognitive problems also tend to have more severe
negative symptoms and more disorganized speech and behavior (Barch, Carter, & Cohen, 2003;Barch et
al., 1999; Dominguez Mde, Viechtbauer, Simons, van Os, & Krabbendam, 2009; Ventura, Hellemann,
Thames, Koellner, & Nuechterlein, 2009; Ventura, Thames, Wood, Guzik, & Hellemann, 2010). In addition,
people with more cognitive problems have worse function in everyday life (Bowie et al., 2008; Bowie,
Reichenberg, Patterson, Heaton, & Harvey, 2006; Fett et al., 2011).
Some people with schizophrenia also show deficits in what is referred to as social cognition, though it is
not clear whether such problems are separate from the cognitive problems described above or the
result of them (Hoe, Nakagami, Green, & Brekke, 2012; Kerr & Neale, 1993; van Hooren et al., 2008).
This includes problems with the recognition of emotional expressions on the faces of other individuals
(Kohler, Walker, Martin, Healey, & Moberg, 2010) and problems inferring the intentions of other people
(theory of mind) (Bora, Yucel, & Pantelis, 2009b). Individuals with schizophrenia who have more problems
with social cognition also tend to have more negative and disorganized symptoms (Ventura, Wood, &
Hellemann, 2011), as well as worse community function (Fett et al., 2011).
The advent of neuroimaging techniques such as structural and functional magnetic resonance imaging
and positron emission tomography opened up the ability to try to understand the brain mechanisms of
the symptoms of schizophrenia as well as the cognitive impairments found in psychosis. For example, a
number of studies have suggested that delusions in psychosis may be associated with problems in
“salience” detection mechanisms supported by the ventral striatum (Jensen & Kapur, 2009; Jensen et
al., 2008; Kapur, 2003; Kapur, Mizrahi, & Li, 2005; Murray et al., 2008) and the anterior prefrontal cortex
(Corlett et al., 2006; Corlett, Honey, & Fletcher, 2007; Corlett, Murray, et al., 2007a, 2007b). These are
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regions of the brain that normally increase their activity when something important (aka “salient”)
happens in the environment. If these brain regions misfire, it may lead individuals with psychosis to
mistakenly attribute importance to irrelevant or unconnected events. Further, there is good evidence
that problems in working memory and cognitive control in schizophrenia are related to problems in the
function of a region of the brain called the dorsolateral prefrontal cortex (DLPFC) (Minzenberg, Laird,
Thelen, Carter, & Glahn, 2009;Ragland et al., 2009). These problems include changes in how the DLPFC
works when people are doing working-memory or cognitive-control tasks, and problems with how this
brain region is connected to other brain regions important for working memory and cognitive control,
including the posterior parietal cortex (e.g., Karlsgodt et al., 2008; J. J. Kim et al., 2003; Schlosser et al.,
2003), the anterior cingulate (Repovs & Barch, 2012), and temporal cortex (e.g., Fletcher et al., 1995;
Meyer-Lindenberg et al., 2001). In terms of understanding episodic memory problems in schizophrenia,
many researchers have focused on medial temporal lobe deficits, with a specific focus on the hippocampus
(e.g., Heckers & Konradi, 2010). This is because there is much data from humans and animals showing
that the hippocampus is important for the creation of new memories (Squire, 1992). However, it has
become increasingly clear that problems with the DLPFC also make important contributions to episodic
memory deficits in schizophrenia (Ragland et al., 2009), probably because this part of the brain is
important for controlling our use of memory.
In addition to problems with regions such as the DLFPC and medial temporal lobes in schizophrenia
described above, magnitude resonance neuroimaging studies have also identified changes in cellular
architecture, white matter connectivity, and gray matter volume in a variety of regions that include the
prefrontal and temporal cortices (Bora et al., 2011). People with schizophrenia also show reduced
overall brain volume, and reductions in brain volume as people get older may be larger in those with
schizophrenia than in healthy people (Olabi et al., 2011). Taking antipsychotic medications or taking
drugs such as marijuana, alcohol, and tobacco may cause some of these structural changes. However,
these structural changes are not completely explained by medications or substance use alone. Further,
both functional and structural brain changes are seen, again to a milder degree, in the first-degree
relatives of people with schizophrenia (Boos, Aleman, Cahn, Pol, & Kahn, 2007; Brans et al., 2008; FusarPoli et al., 2007; MacDonald, Thermenos, Barch, & Seidman, 2009). This again suggests that that neural
changes associated with schizophrenia are related to a genetic risk for this illness.
Risk Factors for Developing Schizophrenia
It is clear that there are important genetic contributions to the likelihood that someone will develop
schizophrenia, with consistent evidence from family, twin, and adoption studies. (Sullivan, Kendler, &
Neale, 2003). However, there is no “schizophrenia gene” and it is likely that the genetic risk for
schizophrenia reflects the summation of many different genes that each contribute something to the
likelihood of developing psychosis (Gottesman & Shields, 1967; Owen, Craddock, & O'Donovan, 2010).
Further, schizophrenia is a very heterogeneous disorder, which means that two different people with
“schizophrenia” may each have very different symptoms (e.g., one has hallucinations and delusions, the
other has disorganized speech and negative symptoms). This makes it even more challenging to identify
specific genes associated with risk for psychosis. Importantly, many studies also now suggest that at
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least some of the genes potentially associated with schizophrenia are also associated with other mental
health conditions, including bipolar disorder, depression, and autism (Gejman, Sanders, & Kendler,
2011; Y. Kim, Zerwas, Trace, & Sullivan, 2011; Owen et al., 2010; Rutter, Kim-Cohen, & Maughan, 2006).
There are also a number of environmental factors that are associated with an increased risk of developing
schizophrenia. For example, problems during pregnancy such as increased stress, infection, malnutrition,
and/or diabetes have been associated with increased risk of schizophrenia. In addition, complications
that occur at the time of birth and which cause hypoxia (lack of oxygen) are also associated with an
increased risk for developing schizophrenia (M. Cannon, Jones, & Murray, 2002; Miller et al., 2011).
Children born to older fathers are also at a somewhat increased risk of developing schizophrenia.
Further, using cannabis increases risk for developing psychosis, especially if you have other risk factors
(Casadio, Fernandes, Murray, & Di Forti, 2011; Luzi, Morrison, Powell, di Forti, & Murray, 2008). The
likelihood of developing schizophrenia is also higher for kids who grow up in urban settings (March et
al., 2008) and for some minority ethnic groups (Bourque, van der Ven, & Malla, 2011). Both of these
factors may reflect higher social and environmental stress in these settings. Unfortunately, none of
these risk factors is specific enough to be particularly useful in a clinical setting, and most people with
these “risk” factors do not develop schizophrenia. However, together they are beginning to give us clues
as the neurodevelopmental factors that may lead someone to be at an increased risk for developing this
disease.
An important research area on risk for psychosis has been work with individuals who may be at “clinical
high risk.” These are individuals who are showing attenuated (milder) symptoms of psychosis that have
developed recently and who are experiencing some distress or disability associated with these symptoms.
When people with these types of symptoms are followed over time, about 35% of them develop a
psychotic disorder (T. D. Cannon et al., 2008), most frequently schizophrenia (Fusar-Poli, McGuire, &
Borgwardt, 2012). In order to identify these individuals, a new category of diagnosis, called “Attenuated
Psychotic Syndrome,” was added to Section III (the section for disorders in need of further study) of the
DSM-V (see Table 1 for symptoms) (APA, 2013). However, adding this diagnostic category to the DSM-V
created a good deal of controversy (Batstra & Frances, 2012; Fusar-Poli & Yung, 2012). Many scientists
and clinicians have been worried that including “risk” states in the DSM-V would create mental disorders
where none exist, that these individuals are often already seeking treatment for other problems, and
that it is not clear that we have good treatments to stop these individuals from developing to psychosis.
However, the counterarguments have been that there is evidence that individuals with high-risk symptoms
develop psychosis at a much higher rate than individuals with other types of psychiatric symptoms, and
that the inclusion of Attenuated Psychotic Syndrome in Section III will spur important research that
might have clinical benefits. Further, there is some evidence that non-invasive treatments such as
omega-3 fatty acids and intensive family intervention may help reduce the development of full-blown
psychosis (Preti & Cella, 2010) in people who have high-risk symptoms.
Treatment of Schizophrenia
The currently available treatments for schizophrenia leave much to be desired, and the search for more
effective treatments for both the psychotic symptoms of schizophrenia (e.g., hallucinations and
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delusions) as well as cognitive deficits and negative symptoms is a highly active area of research. The
first line of treatment for schizophrenia and other psychotic disorders is the use of antipsychotic
medications. There are two primary types of antipsychotic medications, referred to as “typical” and
“atypical.” The fact that “typical” antipsychotics helped some symptoms of schizophrenia was discovered
serendipitously more than 60 years ago (Carpenter & Davis, 2012; Lopez-Munoz et al., 2005). These are
drugs that all share a common feature of being a strong block of the D2 type dopamine receptor. Although
these drugs can help reduce hallucinations, delusions, and disorganized speech, they do little to improve
cognitive deficits or negative symptoms and can be associated with distressing motor side effects. The
newer generation of antipsychotics is referred to as “atypical” antipsychotics. These drugs have more
mixed mechanisms of action in terms of the receptor types that they influence, though most of them
also influence D2 receptors. These newer antipsychotics are not necessarily more helpful for schizophrenia
but have fewer motor side effects. However, many of the atypical antipsychotics are associated with
side effects referred to as the “metabolic syndrome,” which includes weight gain and increased risk for
cardiovascular illness, Type-2 diabetes, and mortality (Lieberman et al., 2005).
The evidence that cognitive deficits also contribute to functional impairment in schizophrenia has led to
an increased search for treatments that might enhance cognitive function in schizophrenia. Unfortunately,
as of yet, there are no pharmacological treatments that work consistently to improve cognition in
schizophrenia, though many new types of drugs are currently under exploration. However, there is a
type of psychological intervention, referred to as cognitive remediation, which has shown some evidence
of helping cognition and function in schizophrenia. In particular, a version of this treatment called
Cognitive Enhancement Therapy (CET) has been shown to improve cognition, functional outcome, social
cognition, and to protect against gray matter loss (Eack et al., 2009; Eack, Greenwald, Hogarty, &
Keshavan, 2010; Eack et al., 2010; Eack, Pogue-Geile, Greenwald, Hogarty, & Keshavan, 2010; Hogarty,
Greenwald, & Eack, 2006) in young individuals with schizophrenia. The development of new treatments
such as Cognitive Enhancement Therapy provides some hope that we will be able to develop new and
better approaches to improving the lives of individuals with this serious mental health condition and
potentially even prevent it some day.
Discussion Questions
1. Describe the major differences between the major psychotic disorders.
2. How would one be able to tell when an individual is “delusional” versus having non-delusional
beliefs that differ from the societal normal? How should cultural and sub-cultural variation been
taken into account when assessing psychotic symptoms?
3. Why are cognitive impairments important to understanding schizophrenia?
4. Why has the inclusion of a new diagnosis (Attenuated Psychotic Syndrome) in Section III of the
DSM-V created controversy?
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5. What are some of the factors associated with increased risk for developing schizophrenia? If we
know whether or not someone has these risk factors, how well can we tell whether they will
develop schizophrenia?
6. What brain changes are most consistent in schizophrenia?
7. Do antipsychotic medications work well for all symptoms of schizophrenia? If not, which
symptoms respond better to antipsychotic medications?
8. Are there any treatments besides antipsychotic medications that help any of the symptoms of
schizophrenia? If so, what are they?
Vocabulary
Alogia
A reduction in the amount of speech and/or increased pausing before the initiation of speech.
Anhedonia/amotivation
A reduction in the drive or ability to take the steps or engage in actions necessary to obtain the
potentially positive outcome.
Catatonia
Behaviors that seem to reflect a reduction in responsiveness to the external environment. This can
include holding unusual postures for long periods of time, failing to respond to verbal or motor prompts
from another person, or excessive and seemingly purposeless motor activity.
Delusions
False beliefs that are often fixed, hard to change even in the presence of conflicting information, and
often culturally influenced in their content.
Diagnostic criteria
The specific criteria used to determine whether an individual has a specific type of psychiatric disorder.
Commonly used diagnostic criteria are included in the Diagnostic and Statistical Manual of Mental
Disorder, 5th Edition (DSM-V) and the Internal Classification of Disorders, Version 9 (ICD-9).
Disorganized behavior
Behavior or dress that is outside the norm for almost all subcultures. This would include odd dress, odd
makeup (e.g., lipstick outlining a mouth for 1 inch), or unusual rituals (e.g., repetitive hand gestures).
9
Disorganized speech
Speech that is difficult to follow, either because answers do not clearly follow questions or because one
sentence does not logically follow from another.
Dopamine
A neurotransmitter in the brain that is thought to play an important role in regulating the function of
other neurotransmitters.
Episodic memory
The ability to learn and retrieve new information or episodes in one’s life.
Flat affect
A reduction in the display of emotions through facial expressions, gestures, and speech intonation.
Functional capacity
The ability to engage in self-care (cook, clean, bathe), work, attend school, and/or engage in social
relationships.
Hallucinations
Perceptual experiences that occur even when there is no stimulus in the outside world generating the
experiences. They can be auditory, visual, olfactory (smell), gustatory (taste), or somatic (touch).
Magnetic resonance imaging
A set of techniques that uses strong magnets to measure either the structure of the brain (e.g., gray
matter and white matter) or how the brain functions when a person performs cognitive tasks (e.g.,
working memory or episodic memory) or other types of tasks.
Neurodevelopmental
Processes that influence how the brain develops either in utero or as the child is growing up.
Positron emission tomography
A technique that uses radio-labelled ligands to measure the distribution of different neurotransmitter
receptors in the brain or to measure how much of a certain type of neurotransmitter is released when a
person is given a specific type of drug or does a particularly cognitive task.
Processing speed
The speed with which an individual can perceive auditory or visual information and respond to it.
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Psychopathology
Illnesses or disorders that involve psychological or psychiatric symptoms.
Working memory
The ability to maintain information over a short period of time, such as 30 seconds or less.
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