Psychosis and schizophrenia
Psychosis is a difficult term to define and is frequently misused, not only in the
media but unfortunately among mental health professionals as well. Stigma and fear
surround the concept of psychosis, and sometimes the pejorative term “crazy” is used
for psychosis. This chapter is not intended to list the diagnostic criteria for all
the different mental disorders in which psychosis is either a defining feature or
an associated feature. The reader is referred to standard reference sources such as
the DSM (Diagnostic and Statistical Manual) of the American Psychiatric Association and the ICD (International Classification of Diseases) for that information. Although schizophrenia is emphasized here, we will approach
psychosis as a syndrome associated with a variety of illnesses that are all targets
for antipsychotic drug treatment.
Symptom dimensions in schizophrenia
Clinical description of psychosis
Psychosis is a syndrome – that is, a mixture of symptoms – that can be associated
with many different psychiatric disorders, but is not a specific disorder itself in
diagnostic schemes such as the DSM or ICD. At a minimum, psychosis means delusions and hallucinations. It generally also
includes symptoms such as disorganized speech, disorganized behavior, and gross distortions
of reality.
Therefore, psychosis can be considered to be a set of symptoms in which a person’s
mental capacity, affective response, and capacity to recognize reality, communicate,
and relate to others is impaired. Psychotic disorders have psychotic symptoms as their
defining features; there are other disorders in which psychotic symptoms may be present,
but are not necessary for the diagnosis.
Those disorders that require the presence of psychosis as a defining feature of the diagnosis include schizophrenia, substance-induced (i.e., drug-induced)
psychotic disorders, schizophreniform disorder, schizoaffective disorder, delusional
disorder, brief psychotic disorder, and psychotic disorder due to a general medical
condition (Table 4-1). Disorders that may or may not have psychotic symptoms as associated features include mania and depression as well as several cognitive disorders such
as Alzheimer’s dementia (Table 4-2).
Psychosis itself can be paranoid, disorganized/excited, or depressive. Perceptual distortions and motor disturbances can be associated with any type of psychosis.
Perceptual distortions include being distressed by hallucinatory voices; hearing voices that accuse, blame,
or threaten punishment; seeing visions;
Table 4-1 Disorders in which psychosis is a defining feature

reporting hallucinations of touch, taste or odor; or reporting that familiar things
and people seem changed.
Motor disturbances are peculiar, rigid postures; overt signs of tension; inappropriate grins or giggles;
peculiar repetitive gestures; talking, muttering, or mumbling to oneself; or glancing
around as if hearing
voices.
In paranoid psychosis, the patient has paranoid projections, hostile belligerence and grandiose expansiveness.
Paranoid projection includes preoccupation with delusional beliefs; believing that people are talking
about oneself; believing one is being persecuted or being conspired against; and believing
people or external forces control one’s actions. Hostile belligerence is verbal expression of feelings of hostility; expressing an attitude of disdain;
manifesting a hostile, sullen attitude; manifesting irritability and grouchiness;
tending to blame others for problems; expressing feelings of resentment; complaining
and finding fault; as well as expressing suspicion of people. Grandiose expansiveness is exhibiting an attitude of superiority; hearing voices that praise and extol; believing
one has unusual powers or is a well-known personality, or that one has a divine mission.
In a disorganized/excited psychosis there is conceptual disorganization, disorientation, and excitement. Conceptual disorganization can be characterized by giving answers that are irrelevant or incoherent, drifting
off the subject, using neologisms, or repeating certain words or phrases. Disorientation is not knowing where one is, the season of the year, the calendar year, or one’s
own age. Excitement is expressing feelings without restraint; manifesting speech that is hurried; exhibiting
an elevated mood; an attitude of superiority;
Table 4-2 Disorders in which psychosis is an associated feature

dramatizing oneself or one’s symptoms; manifesting loud and boisterous speech; exhibiting
overactivity or restlessness; and exhibiting excess of
speech.
Depressive psychosis is characterized by psychomotor retardation, apathy, and anxious self-punishment
and blame. Psychomotor retardation and apathy are manifested by slowed speech; indifference to one’s future; fixed facial expression;
slowed movements; deficiencies in recent memory; blocking in speech; apathy toward
oneself or one’s problems; slovenly appearance; low or whispered speech; and failure
to answer questions. Anxious self-punishment and blame is the tendency to blame or condemn oneself; anxiety about specific matters; apprehensiveness
regarding vague future events; an attitude of self-deprecation, manifesting as a depressed
mood; expressing feelings of guilt and remorse; preoccupation with suicidal thoughts,
unwanted ideas, and specific fears; and feeling unworthy or sinful.
This discussion of clusters of psychotic symptoms does not constitute diagnostic criteria
for any psychotic disorder. It is given merely as a description of several types of
symptoms in psychosis to give the reader an overview of the nature of behavioral disturbances
associated with the various psychotic illnesses.
Schizophrenia is more than a psychosis
Although schizophrenia is the commonest and best-known psychotic illness, it is not
synonymous with psychosis, but is just one of many causes of psychosis. Schizophrenia
affects 1% of the population, and in the US there are over 300 000 acute schizophrenic
episodes annually. Between 25% and 50% of schizophrenia patients attempt suicide, and 10% eventually
succeed, contributing to a mortality rate eight times greater than that of the general
population. Life expectancy of a patient with schizophrenia may be 20–30 years shorter
than the general population, not only due to suicide, but in particular due to premature
cardiovascular disease. Accelerated mortality from premature cardiovascular disease in patients with schizophrenia is caused not
only by genetic and lifestyle factors, such as smoking, unhealthy diet, and lack of
exercise leading to obesity and diabetes, but also – sorrily – from treatment with
some antipsychotic drugs which themselves cause an increased incidence of obesity
and diabetes, and thus increase cardiac risk. In the US, over 20% of all social security benefits are used for the care of
patients with schizophrenia. The direct and indirect costs of schizophrenia in the
US alone are estimated to be in the tens of billions of dollars every year.
Schizophrenia by definition is a disturbance that must last for six months or longer,
including at least one month of delusions, hallucinations, disorganized speech, grossly
disorganized or catatonic behavior, or negative symptoms. Positive symptoms are listed in Table 4-3 and shown in Figure 4-1. These symptoms
Table 4-3 Positive symptoms of psychosis and schizophrenia

of schizophrenia are often emphasized, since they can be dramatic, can erupt suddenly
when a patient decompensates into a psychotic episode (often called a psychotic “break,”
as in break from reality), and are the symptoms most effectively treated by antipsychotic
medications.
Delusions are one type of positive symptom, and these usually involve a misinterpretation of
perceptions or experiences. The most common content of a delusion in schizophrenia
is persecutory, but it may include a variety of other themes including referential
(i.e., erroneously thinking that something refers to oneself), somatic, religious,
or
grandiose.
Hallucinations are also a type of positive symptom (
Table 4-3) and may occur in any sensory modality (e.g., auditory, visual, olfactory, gustatory,
and tactile), but auditory hallucinations are by far the most common and characteristic
hallucinations in
schizophrenia. Positive symptoms generally reflect an
excess of normal functions, and in addition to delusions and hallucinations may also include
distortions or exaggerations in language and communication (disorganized speech),
as well as in behavioral monitoring (grossly disorganized or catatonic or agitated
behavior). Positive symptoms are well known because they are dramatic, are often the
cause of bringing a patient to the attention of medical professionals and law enforcement,
and are the major target of antipsychotic drug treatments.
Negative symptoms are listed in Tables 4-4 and 4-5 and shown in Figure 4-1. Classically, there are at
least five types of negative symptoms all starting with the letter A (
Table 4-5):
-
alogia – dysfunction of communication; restrictions in the fluency and productivity of thought
and speech
-
affective blunting or flattening – restrictions in the range and intensity of emotional expression
-
asociality – reduced social drive and interaction
-
anhedonia – reduced ability to experience pleasure
-
avolition – reduced desire, motivation or persistence; restrictions in the initiation of goal-directed
behavior
Table 4-4 Negative symptoms of schizophrenia

Negative symptoms in schizophrenia, such as blunted affect, emotional withdrawal,
poor rapport, passivity and apathetic social withdrawal, difficulty in abstract thinking,
stereotyped thinking and lack of spontaneity, commonly are considered a reduction
in normal functions and are associated with long periods of hospitalization and poor
social functioning. Although this reduction in normal functioning may not be as dramatic
as positive symptoms, it is interesting to note that negative symptoms of schizophrenia
determine whether a patient ultimately functions well or has a poor outcome. Certainly,
patients will have disruptions in their ability to interact with others when their
positive symptoms are out of control, but their degree of negative symptoms will largely
determine whether patients with schizophrenia can live independently, maintain stable
social relationships, or re-enter the workplace.
Although formal rating scales can be used to measure negative symptoms in research
studies, in clinical practice it may be more practical to identify and monitor negative
symptoms quickly by observation alone (Figure 4-2) or by some simple questioning (Figure 4-3). Negative symptoms are not just part of the syndrome of schizophrenia – they can
also be part of a “prodrome” that begins with subsyndromal symptoms that do not meet
the diagnostic criteria of schizophrenia and occur before the onset of the full syndrome
of schizophrenia. Prodromal negative symptoms are important to detect and monitor
over time in high-risk patients so that treatment can be initiated at the first signs
of psychosis. Negative
Table 4-5 What are negative symptoms?

symptoms can also persist between psychotic episodes once schizophrenia has begun,
and reduce social and occupational functioning in the absence of positive symptoms.
Current antipsychotic drug treatments are limited in their ability to treat negative
symptoms, but psychosocial interventions along with antipsychotics can be helpful
in reducing negative symptoms. There is even the possibility that instituting treatment
for negative symptoms during the prodromal phase of schizophrenia may delay or prevent
the onset of the illness, but this is still a matter of current research.
Beyond positive and negative symptoms of schizophrenia
Although not recognized formally as part of the diagnostic criteria for schizophrenia,
numerous studies subcategorize the symptoms of this illness into five dimensions:
not just positive and negative symptoms, but also cognitive symptoms, aggressive symptoms,
and affective symptoms (Figure 4-4). This is perhaps a more sophisticated, if complicated, manner of describing the
symptoms of schizophrenia.
Aggressive symptoms such as assaultiveness, verbally abusive behaviors, and frank
violence can
occur with positive symptoms such as delusions and hallucinations, and be confused
with positive symptoms. Behavioral interventions may be particularly helpful to prevent
violence linked to poor impulsivity by reducing provocations from the environment.
Certain antipsychotic drugs such as
clozapine, or very high doses of standard antipsychotic drugs, or occasionally the
use of two antipsychotic drugs simultaneously, may also be useful for aggressive symptoms
and violence in some
patients.
It can also be difficult to separate the symptoms of formal cognitive dysfunction
from the symptoms of affective dysfunction and from negative symptoms, but research
is attempting to localize the specific areas of brain dysfunction for each symptom
domain in schizophrenia in the hope of developing better treatments for the often-neglected
negative, cognitive, and affective symptoms of schizophrenia. In particular, neuropsychological assessment batteries are being developed
to quantify cognitive symptoms, in order to detect cognitive improvement after treatment
with a number of novel psychotropic drugs currently being tested. Cognitive symptoms
of schizophrenia are impaired attention and impaired information processing manifested
as impaired verbal fluency (ability to produce spontaneous speech), problems with
serial learning (of a list of items or a sequence of events), and impairment in vigilance
for executive functioning (problems with sustaining and focusing attention, concentrating,
prioritizing, and modulating behavior based upon social cues).
Important cognitive symptoms of schizophrenia are listed in Table 4-6. These do not include symptoms of dementia and memory disturbance more characteristic
of Alzheimer’s disease, but cognitive symptoms of schizophrenia emphasize “executive
dysfunction,” which includes problems representing and maintaining goals, allocating
attentional resources, evaluating and monitoring performance, and utilizing these
skills to solve problems. Cognitive symptoms of schizophrenia are important to recognize
and monitor because they are the single strongest correlate of real-world functioning,
even stronger than negative symptoms.
Table 4-6 Cognitive symptoms of schizophrenia

Symptoms of schizophrenia are not necessarily unique to schizophrenia
It is important to recognize that several illnesses other than schizophrenia can share
some of the same five symptom dimensions as described here for schizophrenia and shown
in Figure 4-4. Thus, disorders in addition to schizophrenia that can have positive symptoms include bipolar disorder, schizoaffective disorder, psychotic depression, Alzheimer’s disease and other organic dementias, childhood psychotic illnesses, drug-induced psychoses, and others. Negative symptoms can also occur in other disorders and can also overlap with cognitive and affective
symptoms that occur in these other disorders. However, as a primary deficit state,
negative symptoms are fairly unique to schizophrenia. Schizophrenia is certainly not
the only disorder with cognitive symptoms. Autism, post-stroke (vascular or multi-infarct) dementia, Alzheimer’s disease, and many other organic dementias (Parkinsonian/Lewy body dementia, frontotemporal/Pick’s dementia, etc.) can also be associated with cognitive dysfunctions similar to those
seen in schizophrenia.
Affective symptoms are frequently associated with schizophrenia but this does not necessarily mean that
they fulfill the diagnostic criteria for a comorbid anxiety or affective disorder.
Nevertheless, depressed mood, anxious mood, guilt, tension, irritability, and worry
frequently accompany schizophrenia. These various symptoms are also prominent features
of major depressive disorder, psychotic depression, bipolar disorder, schizoaffective disorder, organic dementias, childhood psychotic disorders, and treatment-resistant cases of depression, bipolar disorder, and schizophrenia, among others. Finally, aggressive and hostile symptoms occur in numerous other disorders, especially those with problems of impulse control.
Symptoms include overt hostility, such as verbal or physical abusiveness or assault,
self-injurious behaviors including suicide, and arson or other property damage. Other types of impulsiveness such as sexual acting
out are also in this category of aggressive and hostile symptoms. These same symptoms
are frequently associated with bipolar disorder, childhood psychosis, borderline personality
disorder, antisocial personality disorder, drug abuse, Alzheimer’s and other dementias,
attention deficit hyperactivity disorder, conduct disorders in children, and many
others.
Brain circuits and symptom dimensions in schizophrenia
The various symptoms of schizophrenia are hypothesized to be localized in unique brain
regions (Figure 4-4). Specifically, the positive symptoms of schizophrenia have long been hypothesized
to be localized to malfunctioning mesolimbic circuits, especially involving the nucleus
accumbens. The nucleus accumbens is considered to be part of the brain’s reward circuitry,
so it is not surprising that problems with reward and motivation in schizophrenia,
symptoms that can overlap with negative symptoms and lead to smoking, drug and alcohol
abuse, may be linked to this brain area as well. The prefrontal cortex is considered
to be a key node in the nexus of malfunctioning cerebral circuitry responsible for
each of the remaining symptoms of schizophrenia: specifically, the mesocortical and
ventromedial prefrontal cortex with negative symptoms and affective symptoms, the
dorsolateral prefrontal cortex with cognitive symptoms, and the orbitofrontal cortex
and its connections to amygdala with aggressive, impulsive symptoms (Figure 4-4).
This model is obviously oversimplified and reductionistic, because every brain area
has several functions, and every function is certainly distributed to more than one
brain area. Nevertheless, allocating specific symptom dimensions to unique brain areas
not only assists research studies, but has both heuristic and clinical value. Specifically, every patient has unique symptoms, and
unique responses to medication. In order to optimize and individualize treatment,
it can be useful to consider which specific symptoms any given patient is expressing,
and therefore which areas of that particular patient’s brain are hypothetically malfunctioning
(Figure 4-4). Each brain area has unique neurotransmitters, receptors, enzymes, and genes that
regulate it, with some overlap, but also with some unique regional differences, and
knowing this can assist the clinician in choosing medications and in monitoring the
effectiveness of treatment.