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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 ( ) of the American Psychiatric Association and theDiagnostic and Statistical Manual ICD ( ) for that information. Although schizophrenia isInternational Classification of Diseases 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 as a feature of the diagnosisdisorders that require the presence of psychosis defining 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

as features include mania and depression as well as severalpsychotic symptoms associated 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. includePerceptual distortions 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

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reporting hallucinations of touch, taste or odor; or reporting that familiar things and people seem changed. are peculiar, rigid postures; overt signs of tension; inappropriate grinsMotor disturbances or giggles; peculiar repetitive gestures; talking, muttering, or mumbling to oneself; or glancing around as if hearing voices.

In , the patient has paranoid projections, hostile belligerence and grandioseparanoid psychosis expansiveness. includes preoccupation with delusional beliefs; believing thatParanoid projection people are talking about oneself; believing one is being persecuted or being conspired against; and believing people or external forces control one’s actions. is verbal expression ofHostile belligerence 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

is exhibiting an attitude of superiority; hearing voices that praise and extol; believingexpansiveness one has unusual powers or is a well-known personality, or that one has a divine mission.

In a there is conceptual disorganization, disorientation, anddisorganized/excited psychosis excitement. can be characterized by giving answers that are irrelevant orConceptual disorganization incoherent, drifting off the subject, using neologisms, or repeating certain words or phrases.

is not knowing where one is, the season of the year, the calendar year, or one’s ownDisorientation age. is expressing feelings without restraint; manifesting speech that is hurried; exhibitingExcitement 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. and are manifested by slowed speech;Psychomotor retardation apathy 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. is theAnxious self-punishment and blame 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. are listed in and shown in Positive symptoms Table 4-3 Figure

. These symptoms4-1

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. areDelusions 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. are also a type of positive symptom (Hallucinations

) and may occur in any sensory modality (e.g., auditory, visual, olfactory, gustatory, andTable 4-3 tactile), but auditory hallucinations are by far the most common and characteristic hallucinations in schizophrenia. Positive symptoms generally reflect an of normal functions, and in addition toexcess 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 and and shown in . Classically, there areTables 4-4 4-5 Figure 4-1 at

Figure 4-1. . The syndrome of schizophrenia consists of aPositive and negative symptoms of schizophrenia mixture of symptoms that are commonly divided into two major categories, positive and negative. Positive symptoms, such as delusions and hallucinations, reflect the development of the symptoms of psychosis; they can be dramatic and may reflect loss of touch with reality. Negative symptoms reflect the loss of normal functions and feelings, such as losing interest in things and not being able to experience pleasure.

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 ( ) or by some simple questioning ( ). Negative symptoms areFigure 4-2 Figure 4-3 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?

Figure 4-2. . Some negative symptoms of schizophrenia – suchNegative symptoms identified by observation as reduced speech, poor grooming, and limited eye contact – can be identified solely by observing the patient.

Figure 4-3. . Other negative symptoms of schizophrenia can beNegative symptoms identified by questioning identified by simple questioning. For example, brief questioning can reveal the degree of emotional responsiveness, interest level in hobbies or pursuing life goals, and desire to initiate and maintain social contacts.

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

Figure 4-4. . The different symptom domains of schizophrenia areLocalization of symptom domains hypothesized to be regulated by unique brain regions. Positive symptoms of schizophrenia are hypothetically modulated by malfunctioning mesolimbic circuits, while negative symptoms are hypothetically linked to malfunctioning mesocortical circuits and may also involve mesolimbic regions such as the nucleus accumbens, which is part of the brain’s reward circuitry and thus plays a role in motivation. The nucleus accumbens may also be involved in the increased rate of substance use and abuse seen in patients with schizophrenia. Affective symptoms are associated with the ventromedial prefrontal cortex, while aggressive symptoms (related to impulse control) are associated with abnormal information processing in the orbitofrontal cortex and amygdala. Cognitive symptoms are associated with problematic information processing in the dorsolateral prefrontal cortex. Although there is overlap in function among different brain regions, understanding which brain regions may be predominantly involved in specific symptoms can aid in customization of treatment to the particular symptom profile of each individual patient with schizophrenia.

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 . These do not includeTable 4-6 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 . Thus,Figure 4-4 disorders in addition to schizophrenia that can have include bipolar disorder,positive symptoms schizoaffective disorder, psychotic depression, Alzheimer’s disease and other organic dementias, childhood psychotic illnesses, drug-induced psychoses, and others. can alsoNegative symptoms 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 . Autism,cognitive symptoms 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, occur in numerous otheraggressive and hostile symptoms 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 ( ). Specifically, the positive symptoms of schizophrenia have long been hypothesized to beFigure 4-4

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 ( ). Each brain area has uniqueFigure 4-4 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.

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