Chapter 9
Schizophrenia = A disorder characterized by disordered thinking, in which ideas are not logically related; faulty
perception and attention; a lack of emotional expressiveness; and disturbances in behavior, such as a disheveled
appearance.
- People with schizophrenia may withdraw from other people and from everyday reality, often into a life
of odd beliefs (delusions) and hallucinations.
- Substance use rates are high among people with schizophrenia, perhaps reflecting shared genetic
vulnerability between substance use disorder and schizophrenia or an attempt to achieve some relief
from the symptoms.
- The suicide rate among people with schizophrenia is 12 times higher than people in the general
population.
- The lifetime prevalence of schizophrenia is around 1% and it affects men slightly more than women.
Schizophrenia is diagnosed more frequently among some groups, such as African Americans and
Latino Americans, though this appears to reflect a bias among those making the diagnosis
- Schizophrenia rarely begins in childhood; it usually appears in late adolescence or early adulthood and
usually somewhat earlier in men than in women.
- People with schizophrenia typically have several acute episodes of their symptoms and less severe but
still debilitating symptoms between episodes.
Major symptoms
1. Positive symptoms = Comprise excesses and distortions and include hallucinations and delusions. For
the most part, acute episodes of schizophrenia are characterized by positive symptoms. These
symptoms are also referred to as psychotic symptoms.
a) Delusions = Beliefs contrary to reality and firmly held despite disconfirming evidence.
b) Hallucinations = Sensory experiences in the absence of any relevant stimulation from the
environment. They are more often auditory than visual.
2. Negative symptoms = Deficits in motivation, pleasure, social closeness and emotion expression. These
symptoms tend to endure beyond an acute episode. The presence of many negative symptoms is a
strong predictor of a poor quality of life.
- Research suggests that these symptoms can be understood more simply as representing two
domains. The first domain, involving motivation, emotional experience, and sociality, is
sometimes referred to as the motivation and pleasure domain. The second domain,
involving outward expression of emotion and vocalization, is referred to as the expression
domain.
a) Avolition = The diminished motivation and a seeming absence of interest or persistence in
what are usually routine activities, including work or school, hobbies or social activities. It
appears that people with schizophrenia may have trouble with motivation for certain life areas
but not for others. More motivated by goals that had to do with reducing boredom, less
motivated by goals associated with autonomy or gaining new knowledge.
b) Asociality = People with this symptom may interact only superficially and briefly and may
appear aloof or indifferent to the social interaction. They may have few friends, poor social
skills, and very little interest in being with other people. They may not desire close
relationships with family, friends or romantic partners. (less common)
c) Anhedonia = A loss of interest in or a reported lessening of the experience of pleasure (less
common)
- Consummatory pleasure = The amount of pleasure experienced in the moment or in
the presence of something pleasurable.
- Anticipatory pleasure = The amount of expected or anticipated pleasure from future
events or activities.
1
, People with schizophrenia appear to have a deficit in anticipatory pleasure but not
consummatory pleasure.
d) Blunted affect = A lack of outward expression of emotion. A person with this symptom may
stare vacantly, the muscles of the face motionless, the eyes lifeless. The concept refers only to
the outward expression of emotion, not to the patient's inner experience, which is not
impoverished at all.
e) Alogia = A significant reduction in the amount of speech. A person may answer a question
with one or two words and is not likely to elaborate on an answer with additional detail (less
common).
3. Disorganized symptoms
a) Disorganized speech = Problems in organizing ideas and in speaking so that a listener can
understand. Also known as formal thought disorder.
- Loose associations (derailment) = The person may be more successful in
communicating with a listener but has difficulty sticking to one topic.
b) Disorganized behavior = May go into inexplicable bouts of agitation, dress in usual clothes,
act in a silly manner, wander with no particular destination or collect garbage.
- Catatonia = People with this symptom may gesture repeatedly, using peculiar and
sometimes complex sequences of finger, hand and arm movement, which often seem
to be purposeful. Some people manifest an unusual increase in their overall level of
activity, including much excitement, flailing of the limbs and great expenditure of
energy similar to that seen in mania. Catatonia is seldom seen today in people with
schizophrenia, perhaps because medications work effectively on these disturbed
movements or postures.
Types delusions
Most common
- Persecutory
- Referential
Less often
- Somatic (body experiences, e.g.
bugs under the skin)
- Grandiosity
- Erotomanic ('celebrity X is in
love with me')
- Nihilistic ('impending
catastrophe')
2
,History of Schizophrenia
Two European psychiatrists, Emil Kraepelin and Eugen Bleuler, initially formulated the concept of
schizophrenia. Kraepelin first described dementia praecox, which is an early-onset (praecox) and a progressive,
inevitable intellectual deterioration (dementia).
Bleuler broke with Kraepelin's description on two major points: He believed that the disorder did not necessarily
have an early onset, and he believed that it did not inevitably progress toward dementia. In 1908 Bleuler
proposed his own term schizophrenia, from the greek words schizein ('to split') and phren ('mind'), capturing
what he viewed as the essential nature of the condition. Bleuler used the term 'the breaking of associative
threads'. For Bleuler, associative threads joined not only words but also thoughts. Thus, goal-directed, efficient
thinking and communication were possible only when these hypothetical structures were intact. The notion that
associative threads were disrupted in people with schizophrenia could then be used to account for the range of
other symptoms.
Two other psychotic disorders appearing in the chapter of schizophrenia spectrum are schizophreniform
disorder and brief psychotic disorder. The symptoms of schizophreniform disorder are the same as those of
schizophrenia but last only 1 to 6 months. For a diagnosis of schizophrenia, symptoms have to last for at least 6
months. Brief psychotic disorder lasts from 1 day to 1 month and is often brought on by extreme stress.
Schizoaffective disorder comprises a mixture of symptoms of schizophrenia and mood disorders. The DSM-5
requires either a depressive or a manic episode rather than simply mood disorder symptoms. A person with
delusional disorder is troubled by persistent delusions. These can be delusions of persecution or jealousy, such
as the unfounded conviction that a spouse or lover is unfaithful.
Genetic influences
The heritability estimate for schizophrenia based on behavior genetics studies is 0.77. Relatives of people with
schizophrenia are at higher risk, and the risk increases as the genetic relationship between the person with
schizophrenia and the relative becomes closer.
For people who had one parent admitted for schizophrenia and one parent admitted for bipolar disorder, the
incidence of schizophrenia was higher than for those people who had just one parent admitted for schizophrenia.
These findings suggest that there may be some shared genetic vulnerability between schizophrenia and bipolar
disorder; molecular genetics studies also suggest such a link.
Familial high-risk study = This type of family study begins with one or two biological parents with
schizophrenia and follows their children longitudinally to identify how many of them develop schizophrenia and
what types of childhood neurobiological and behavioral factors may predict the disorder's onset. The studies
show that having a parent with schizophrenia is associated with greater risk of developing not only
schizophrenia, but other disorders as well.
Although the risk for identical (MZ) twins of people with schizophrenia (44,3%) is greater than that for fraternal
(DZ) twins of people with schizophrenia (12,08%), it is still much less than 100%. The less-than-100%
concordance in MZ twins is important: if genetic transmission alone accounted for schizophrenia and one
identical twin had schizophrenia, the other twin would also have schizophrenia.
Studying children whose biological mothers had schizophrenia but who were reared from early infancy by
adoptive parents without schizophrenia is another useful behavior genetics research method. The follow-up
assessment of an adoption study revealed that not one of the controls were diagnosed with schizophrenia versus
10,6% (five) of the offspring of women with schizophrenia.
3
, Molecular genetics research
Research has found that there are multiple common genes associated with both schizophrenia and bipolar
disorder, suggesting that the genetic vulnerability is not likely even specific to schizophrenia.
An older approach in schizophrenia genetics research was to identify specific candidate genes associated with
schizophrenia. This is accomplished by establishing how often specific genes and a particular trait or behavior
co-occur. Approximately 25 candidate genes have been identified for schizophrenia over the years. One such
candidate gene is called DRD2. This gene encodes a specific type of dopamine receptor called D2.
Consistent with evidence that genetic vulnerability is common across different disorders, many CNVs observed
in schizophrenia are also observed in other disorders, including autism spectrum disorder and intellectual
disability, suggesting that these CNVs are not specific to schizophrenia. SNP studies, like the familial high-risk
and CNV studies, suggest that there may be a common genetic vulnerability for schizophrenia and bipolar
disorder.
Three important points about GWAS findings:
a) Observed mutations are rare - CNVs account for less than 1% of genetic variance, and SNPs account
for less than 25% of genetic variance.
b) Only some people with these rare mutations have schizophrenia
c) The mutations are not specific to schizophrenia
Dopamine theory = The theory that schizophrenia is related to excess activity of the neurotransmitter dopamine
is based principally on the knowledge that drugs effective in treating schizophrenia reduce dopamine activity.
Antipsychotic drugs fit into and thereby block a type of postsynaptic dopamine receptor called the D2 receptor.
However, as other studies progressed, this assumption turned out to be too simple to account for schizophrenia's
wide range of symptoms. An excess of dopamine activity appears to be related mainly to positive and
disorganization symptoms. Later revisions to the theory suggest that interactions between stress and other parts
of the brain, including the hippocampus and HPA axis, may trigger the excess release of dopamine. Because
schizophrenia is a disorder with widespread symptoms covering perception, emotion, cognition, and social
behavior, it is unlikely that a single neurotransmitter could account for all of them.
- Newer drugs used in treating schizophrenia implicate other neurotransmitters, such as serotonin, in the
disorder. These newer drugs partially block D2 receptors, but they also work by blocking the serotonin
receptor 5HT2.
- Another neurotransmitter that has been studied in schizophrenia is glutamate. Low levels of glutamate
have been found in the cerebrospinal fluid of people with schizophrenia, and postmortem studies have
revealed low levels of the enzyme needed to produce glutamate.
- The drugs PCP and ketamine can induce both positive and negative symptoms in people without
schizophrenia by interfering with NMDA receptors that are part of the glutamate system.
Among the most well-replicated findings of brain abnormalities in schizophrenia are enlargement of the
ventricles and dysfunction in the prefrontal cortex and temporal cortex, as well as surrounding brain regions.
- The brain has four ventricles, which are spaces in the brain filled with cerebrospinal fluid. Having
larger fluid-filled spaces implies a loss of brain cells. Studies have revealed that some people with
schizophrenia, even very early in the course of the illness and across the course of the illness, have
enlarged ventricles.
Evidence that the prefrontal cortex is impacted in schizophrenia:
- The prefrontal cortex is known to play a role in behaviors such as speech, decision making, emotion,
and goal-directed behavior, which are disrupted in schizophrenia.
- MRI studies have shown reductions in gray matter and overall volume (size) in the prefrontal cortex.
Unfortunately, antipsychotic medications may contribute to some of this loss.
- People with schizophrenia perform more poorly than people without schizophrenia on
neuropsychological tests designed to tap functions supported by the prefrontal region, including
working memory, or the ability to hold bits of information in memory.
Despite the reduced volume of the gray matter in the prefrontal cortex, the number of neurons in this area does
not appear to be reduced. More detailed studies indicate that what is lost may be what are called dendritic
spines, which are small projections on the shaft of dendrites where nerve impulses are received from other
neurons at the synapse.
4
Schizophrenia = A disorder characterized by disordered thinking, in which ideas are not logically related; faulty
perception and attention; a lack of emotional expressiveness; and disturbances in behavior, such as a disheveled
appearance.
- People with schizophrenia may withdraw from other people and from everyday reality, often into a life
of odd beliefs (delusions) and hallucinations.
- Substance use rates are high among people with schizophrenia, perhaps reflecting shared genetic
vulnerability between substance use disorder and schizophrenia or an attempt to achieve some relief
from the symptoms.
- The suicide rate among people with schizophrenia is 12 times higher than people in the general
population.
- The lifetime prevalence of schizophrenia is around 1% and it affects men slightly more than women.
Schizophrenia is diagnosed more frequently among some groups, such as African Americans and
Latino Americans, though this appears to reflect a bias among those making the diagnosis
- Schizophrenia rarely begins in childhood; it usually appears in late adolescence or early adulthood and
usually somewhat earlier in men than in women.
- People with schizophrenia typically have several acute episodes of their symptoms and less severe but
still debilitating symptoms between episodes.
Major symptoms
1. Positive symptoms = Comprise excesses and distortions and include hallucinations and delusions. For
the most part, acute episodes of schizophrenia are characterized by positive symptoms. These
symptoms are also referred to as psychotic symptoms.
a) Delusions = Beliefs contrary to reality and firmly held despite disconfirming evidence.
b) Hallucinations = Sensory experiences in the absence of any relevant stimulation from the
environment. They are more often auditory than visual.
2. Negative symptoms = Deficits in motivation, pleasure, social closeness and emotion expression. These
symptoms tend to endure beyond an acute episode. The presence of many negative symptoms is a
strong predictor of a poor quality of life.
- Research suggests that these symptoms can be understood more simply as representing two
domains. The first domain, involving motivation, emotional experience, and sociality, is
sometimes referred to as the motivation and pleasure domain. The second domain,
involving outward expression of emotion and vocalization, is referred to as the expression
domain.
a) Avolition = The diminished motivation and a seeming absence of interest or persistence in
what are usually routine activities, including work or school, hobbies or social activities. It
appears that people with schizophrenia may have trouble with motivation for certain life areas
but not for others. More motivated by goals that had to do with reducing boredom, less
motivated by goals associated with autonomy or gaining new knowledge.
b) Asociality = People with this symptom may interact only superficially and briefly and may
appear aloof or indifferent to the social interaction. They may have few friends, poor social
skills, and very little interest in being with other people. They may not desire close
relationships with family, friends or romantic partners. (less common)
c) Anhedonia = A loss of interest in or a reported lessening of the experience of pleasure (less
common)
- Consummatory pleasure = The amount of pleasure experienced in the moment or in
the presence of something pleasurable.
- Anticipatory pleasure = The amount of expected or anticipated pleasure from future
events or activities.
1
, People with schizophrenia appear to have a deficit in anticipatory pleasure but not
consummatory pleasure.
d) Blunted affect = A lack of outward expression of emotion. A person with this symptom may
stare vacantly, the muscles of the face motionless, the eyes lifeless. The concept refers only to
the outward expression of emotion, not to the patient's inner experience, which is not
impoverished at all.
e) Alogia = A significant reduction in the amount of speech. A person may answer a question
with one or two words and is not likely to elaborate on an answer with additional detail (less
common).
3. Disorganized symptoms
a) Disorganized speech = Problems in organizing ideas and in speaking so that a listener can
understand. Also known as formal thought disorder.
- Loose associations (derailment) = The person may be more successful in
communicating with a listener but has difficulty sticking to one topic.
b) Disorganized behavior = May go into inexplicable bouts of agitation, dress in usual clothes,
act in a silly manner, wander with no particular destination or collect garbage.
- Catatonia = People with this symptom may gesture repeatedly, using peculiar and
sometimes complex sequences of finger, hand and arm movement, which often seem
to be purposeful. Some people manifest an unusual increase in their overall level of
activity, including much excitement, flailing of the limbs and great expenditure of
energy similar to that seen in mania. Catatonia is seldom seen today in people with
schizophrenia, perhaps because medications work effectively on these disturbed
movements or postures.
Types delusions
Most common
- Persecutory
- Referential
Less often
- Somatic (body experiences, e.g.
bugs under the skin)
- Grandiosity
- Erotomanic ('celebrity X is in
love with me')
- Nihilistic ('impending
catastrophe')
2
,History of Schizophrenia
Two European psychiatrists, Emil Kraepelin and Eugen Bleuler, initially formulated the concept of
schizophrenia. Kraepelin first described dementia praecox, which is an early-onset (praecox) and a progressive,
inevitable intellectual deterioration (dementia).
Bleuler broke with Kraepelin's description on two major points: He believed that the disorder did not necessarily
have an early onset, and he believed that it did not inevitably progress toward dementia. In 1908 Bleuler
proposed his own term schizophrenia, from the greek words schizein ('to split') and phren ('mind'), capturing
what he viewed as the essential nature of the condition. Bleuler used the term 'the breaking of associative
threads'. For Bleuler, associative threads joined not only words but also thoughts. Thus, goal-directed, efficient
thinking and communication were possible only when these hypothetical structures were intact. The notion that
associative threads were disrupted in people with schizophrenia could then be used to account for the range of
other symptoms.
Two other psychotic disorders appearing in the chapter of schizophrenia spectrum are schizophreniform
disorder and brief psychotic disorder. The symptoms of schizophreniform disorder are the same as those of
schizophrenia but last only 1 to 6 months. For a diagnosis of schizophrenia, symptoms have to last for at least 6
months. Brief psychotic disorder lasts from 1 day to 1 month and is often brought on by extreme stress.
Schizoaffective disorder comprises a mixture of symptoms of schizophrenia and mood disorders. The DSM-5
requires either a depressive or a manic episode rather than simply mood disorder symptoms. A person with
delusional disorder is troubled by persistent delusions. These can be delusions of persecution or jealousy, such
as the unfounded conviction that a spouse or lover is unfaithful.
Genetic influences
The heritability estimate for schizophrenia based on behavior genetics studies is 0.77. Relatives of people with
schizophrenia are at higher risk, and the risk increases as the genetic relationship between the person with
schizophrenia and the relative becomes closer.
For people who had one parent admitted for schizophrenia and one parent admitted for bipolar disorder, the
incidence of schizophrenia was higher than for those people who had just one parent admitted for schizophrenia.
These findings suggest that there may be some shared genetic vulnerability between schizophrenia and bipolar
disorder; molecular genetics studies also suggest such a link.
Familial high-risk study = This type of family study begins with one or two biological parents with
schizophrenia and follows their children longitudinally to identify how many of them develop schizophrenia and
what types of childhood neurobiological and behavioral factors may predict the disorder's onset. The studies
show that having a parent with schizophrenia is associated with greater risk of developing not only
schizophrenia, but other disorders as well.
Although the risk for identical (MZ) twins of people with schizophrenia (44,3%) is greater than that for fraternal
(DZ) twins of people with schizophrenia (12,08%), it is still much less than 100%. The less-than-100%
concordance in MZ twins is important: if genetic transmission alone accounted for schizophrenia and one
identical twin had schizophrenia, the other twin would also have schizophrenia.
Studying children whose biological mothers had schizophrenia but who were reared from early infancy by
adoptive parents without schizophrenia is another useful behavior genetics research method. The follow-up
assessment of an adoption study revealed that not one of the controls were diagnosed with schizophrenia versus
10,6% (five) of the offspring of women with schizophrenia.
3
, Molecular genetics research
Research has found that there are multiple common genes associated with both schizophrenia and bipolar
disorder, suggesting that the genetic vulnerability is not likely even specific to schizophrenia.
An older approach in schizophrenia genetics research was to identify specific candidate genes associated with
schizophrenia. This is accomplished by establishing how often specific genes and a particular trait or behavior
co-occur. Approximately 25 candidate genes have been identified for schizophrenia over the years. One such
candidate gene is called DRD2. This gene encodes a specific type of dopamine receptor called D2.
Consistent with evidence that genetic vulnerability is common across different disorders, many CNVs observed
in schizophrenia are also observed in other disorders, including autism spectrum disorder and intellectual
disability, suggesting that these CNVs are not specific to schizophrenia. SNP studies, like the familial high-risk
and CNV studies, suggest that there may be a common genetic vulnerability for schizophrenia and bipolar
disorder.
Three important points about GWAS findings:
a) Observed mutations are rare - CNVs account for less than 1% of genetic variance, and SNPs account
for less than 25% of genetic variance.
b) Only some people with these rare mutations have schizophrenia
c) The mutations are not specific to schizophrenia
Dopamine theory = The theory that schizophrenia is related to excess activity of the neurotransmitter dopamine
is based principally on the knowledge that drugs effective in treating schizophrenia reduce dopamine activity.
Antipsychotic drugs fit into and thereby block a type of postsynaptic dopamine receptor called the D2 receptor.
However, as other studies progressed, this assumption turned out to be too simple to account for schizophrenia's
wide range of symptoms. An excess of dopamine activity appears to be related mainly to positive and
disorganization symptoms. Later revisions to the theory suggest that interactions between stress and other parts
of the brain, including the hippocampus and HPA axis, may trigger the excess release of dopamine. Because
schizophrenia is a disorder with widespread symptoms covering perception, emotion, cognition, and social
behavior, it is unlikely that a single neurotransmitter could account for all of them.
- Newer drugs used in treating schizophrenia implicate other neurotransmitters, such as serotonin, in the
disorder. These newer drugs partially block D2 receptors, but they also work by blocking the serotonin
receptor 5HT2.
- Another neurotransmitter that has been studied in schizophrenia is glutamate. Low levels of glutamate
have been found in the cerebrospinal fluid of people with schizophrenia, and postmortem studies have
revealed low levels of the enzyme needed to produce glutamate.
- The drugs PCP and ketamine can induce both positive and negative symptoms in people without
schizophrenia by interfering with NMDA receptors that are part of the glutamate system.
Among the most well-replicated findings of brain abnormalities in schizophrenia are enlargement of the
ventricles and dysfunction in the prefrontal cortex and temporal cortex, as well as surrounding brain regions.
- The brain has four ventricles, which are spaces in the brain filled with cerebrospinal fluid. Having
larger fluid-filled spaces implies a loss of brain cells. Studies have revealed that some people with
schizophrenia, even very early in the course of the illness and across the course of the illness, have
enlarged ventricles.
Evidence that the prefrontal cortex is impacted in schizophrenia:
- The prefrontal cortex is known to play a role in behaviors such as speech, decision making, emotion,
and goal-directed behavior, which are disrupted in schizophrenia.
- MRI studies have shown reductions in gray matter and overall volume (size) in the prefrontal cortex.
Unfortunately, antipsychotic medications may contribute to some of this loss.
- People with schizophrenia perform more poorly than people without schizophrenia on
neuropsychological tests designed to tap functions supported by the prefrontal region, including
working memory, or the ability to hold bits of information in memory.
Despite the reduced volume of the gray matter in the prefrontal cortex, the number of neurons in this area does
not appear to be reduced. More detailed studies indicate that what is lost may be what are called dendritic
spines, which are small projections on the shaft of dendrites where nerve impulses are received from other
neurons at the synapse.
4
