SCHIZOPRHENIA - 1 A. Early description/diagnosis of schizophrenia 1. Emil Kraepelin: a. Combined catatonic (i.e., alternating immobility and excited

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1 SCHIZOPRHENIA - 1 II. A. Early description/diagnosis of schizophrenia 1. Emil Kraepelin: a. Combined catatonic (i.e., alternating immobility and excited agitation), hebephrenia (i.e., silly and immature emotionality), and paranoia (i.e., delusions of grandeur and persecution) and labeled them as falling under the heading dementia praecox. b. Distinguished dementia praecox from manic-depressive illness by emphasizing onset and outcome. (Schiz. Onset early, poor prognosis.) 2. Eugen Bleuler, a Swiss psychiatrist a. First to introduce the term schizophrenia; a term derived from the Greek words for split (skhizen) and mind (phren). b. Bleuler believed that the core of schizophrenia rests in an associative splitting of basic personality functions. This concept emphasized the following: i. "Breaking of associative threads," or the breakdown of forces that connect one function to the next. ii. Bleuler also believed that an inability to keep a constant train of thought was the cause of all schizophrenic symptoms. B. Schizophrenic symptoms are heterogeneous--number of symptoms and behaviors that are not shared by all persons with the diagnosis. Clinical Description, Symptoms, and Subtypes A. The term psychotic refers to either delusions or hallucinations. B. Positive symptoms: 1. Delusions refer to a belief that would be seen by most members of society as a misrepresentation of reality; often referred to as a disorder of thought content. Delusions often are called the basic characteristic of madness. Some research suggests that delusions give some patients a sense of meaning and purpose in life and result in less depression. Thus, delusions may serve an adaptive function. Types of delusions include: a. Delusions of grandeur, or the belief that one is particularly famous or important. b. Delusions of persecution, or the belief that other people are out to get or harm the person. c. More unusual delusions include Capgras syndrome, or the belief that someone a person knows has been replaced by a double, and Cotard s syndrome, where the person believes that a part of the body (e.g., brain) has changed in some impossible way.

2 SCHIZOPRHENIA Hallucinations can involve any of the senses; though auditory hallucinations are most common in persons with schizophrenia. C. Negative: a. Single photon emission tomography (SPECT) has been used to study cerebral blood flow in schizophrenic patients during their auditory hallucinations. The part of the brain most active during auditory hallucinations is Broca s area (i.e., the area involved in speech production), not Wernicke's area (i.e., the area involved in understanding and language comprehension). This research supports the idea that auditory hallucinations do not involve hearing voices of others, but rather listening to one s own thoughts or voices, and a failure to recognize the difference. 1. Avolition (inc. show little interest in performing even the most basic daily functions, such as personal hygiene) 2. Alogia (inc. brief replies to questions with little content, delayed comments or slowed responses to questions, or as disinterest in conversation) 3. Anhedonia 4. Affective flattening, or flat affect (inc. little change in facial expression, but not the experience of appropriate emotions) D. Disorganized symptoms: 1. Disorganized speech: a. Cognitive slippage often manifests as illogical and incoherent speech where the person jumps from one topic to the next. b. Tangentiality manifests as "going off on a tangent" rather than answering a question directly. c. Loose associations or derailment 2. Other disorganized symptoms: a. Inappropriate affect b. Disorganized behavior (e.g., hoarding objects or acting in unusual ways in public). Including: i. Catatonia (inc. catatonic immobility and/or waxy flexibility).

3 SCHIZOPRHENIA - 3 E. Schizophrenia subtypes 1. Paranoid type relatively intact cognitive skills and affect do not generally show disorganized speech or flat affect associated with the best prognosis. a. Delusions and hallucinations usually have a theme of grandeur or persecution. b. DSM-IV-TR criteria specify a preoccupation with one or more delusions or auditory hallucinations but without marked display of disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect. 2. Disorganized type (hebephrenia) marked disruptions in their speech and behavior, including flat or inappropriate affect, and self-absorption If hallucinations or delusions are present, they tend to be organized around a theme, but are quite fragmented. typically show problems early and their problems tend to be chronic, lacking periods of remissions that characterize other forms of this disorder. 3. Catatonic type unusual motor responses and odd mannerisms. often show echolalia (i.e., repeating or mimicking the words of others) echopraxia (i.e., imitating the movements of others). This subtype is relatively rare. 4. Undifferentiated type do not neatly fit into any of the other subtypes and include people with major symptoms of schizophrenia but who do not meet criteria for paranoid, disorganized, or catatonic types. 5. Residual type have had at least one episode of schizophrenia but are no longer displaying the major symptoms. Often display residual symptoms, such as negative beliefs, unusual or bizarre ideas, social withdrawal, inactivity, and/or flat affect.

4 SCHIZOPRHENIA - 4 F. Other disorders showing psychotic behaviors 1. Schizophreniform disorder have experienced symptoms of schizophrenia for a few months only and usually resume normal lives. There are few studies of this disorder, with a lifetime prevalence of 0.2%. a. DSM-IV-TR criteria for schizophreniform disorder include onset of psychotic symptoms within 4 weeks of the first noticeable change in usual behavior, confusion at the height of the psychotic episode, good premorbid social and occupational functioning, absence of blunted affect. 2. Schizoaffective disorder DSM-IV-TR criteria for schizoaffective disorder require the presence of a mood disorder and delusions or hallucinations for at least 2 weeks in the absence of prominent mood disorder symptoms. The prognosis is similar as for people with schizophrenia and such persons do not tend to get better on their own. 3. Delusional disorder (non-bizarre delusions) tend not to have flat affect, anhedonia, or other negative symptoms of schizophrenia. may, however, become socially isolated as a function of their delusions. a. The DSM-IV-TR recognizes the following delusional subtypes: i. erotomanic type is a delusion reflecting the irrational belief of being loved by another person, usually of higher status (e.g., celebrity stalkers). ii. iii. iv. grandiose type of delusion involves having beliefs of inflated self-worth, power, knowledge, identity, or special relationship to a deity or famous person. jealous type of delusion believe that a sexual partner is unfaithful. persecutory type involves believing that oneself (or someone close) is being malevolently treated in some way. v. somatic type that one has some physical defect or medical disorder. b. Delusional disorder is rare, affecting people out of every 100,000. Average age of onset is in middle adulthood, and the disorder is slightly more common in females than males. Prognosis is better than schizophrenia, and features of delusional disorder may have a genetic component.

5 SCHIZOPRHENIA Brief psychotic disorder one or more positive symptoms of schizophrenia (e.g., delusions, hallucinations, or disorganized speech or behavior) within a one-month period. This disorder is often precipitated by an extremely stressful situation and commonly dissipates on its own. 5. Shared psychotic disorder (folie a deux) develop delusions as a result of a close relationship with someone else who has delusions. Content of such delusions span the spectrum and little is known about this condition. 6. Schizotypal personality disorder (Chapter 11) is related to psychotic disorders. The characteristics of this personality disorder are similar to schizophrenia, but less severe.

6 SCHIZOPRHENIA - 6 I. Prevalence and causes of schizophrenia A. Prevalence of schizophrenia worldwide is 0.2% to 1.5%, it will affect about 1% of the population at some point. Life expectancy slightly less than average. Women have more favorable outcomes than men. Onset greatest in early adulthood Declines with age for males, Reverse for females. 1. A more widely accepted classification system, introduced in the mid- 1970s, emphasizes positive, negative, and more recently disorganized symptoms. Accordingly, schizophrenia can be dichotomized into Type I and Type II based on several characteristics, including symptoms, response to medication, outcome, and presence of intellectual impairment. a. Type I positive symptoms, good response to medication, optimistic prognosis, absence of intellectual impairment. b. Type II negative symptoms poor response to medication, pessimistic prognosis, intellectual impairments.

7 SCHIZOPRHENIA - 7 B. Children who eventually develop schizophrenia tend to show early abnormal signs such as more negative affect and less positive affect. It may be that brain damage early in development causes schizophrenia. Research suggests that people with schizophrenia who demonstrate early signs of abnormality at birth and during early childhood tend to do better in the long run than those that do not. Brain plasticity allows the brain to compensate for such deficits over time, whereas this is more difficult in a fully developed brain later in life. Older adults display fewer positive symptoms and more negative symptoms, suggesting that schizophrenia may improve over time. Most persons with schizophrenia fluctuate between severe and moderate levels of impairment throughout their lives, and relapse is common. C. Schizophrenia appears to be a universal world-wide phenomenon; however, the course and outcome of schizophrenia varies from culture to culture. In the U.S., more African-Americans are diagnosed with schizophrenia than whites, this difference may reflect misdiagnosis due to bias against some minority groups.

8 SCHIZOPRHENIA - 8 D. Genetic influences are responsible for making some individuals vulnerable to schizophrenia. 1. Family studies have shown that the more severe the parent s schizophrenia, the more likely the children were to develop it also. All forms of schizophrenia were also seen within families with histories of schizophrenia, meaning that we do not inherit a specific type of schizophrenia, but a general predisposition for schizophrenia that may differ from one family member to the next. Family members of a person with schizophrenia are also at increased risk not just for schizophrenia, but a spectrum of psychotic disorders. a. Risk for schizophrenia is associated with degree of genetic relatedness to the person with schizophrenia. Having any family member with schizophrenia increases the risk of schizophrenia in other family members above what is expected in the general population. 2. Twin studies indicate a confluence of genetic and environmental factors. monozygotic twins - 48%. Fraternal twins - 17% Genain quadruplets who shared identical genes and were raised in the same household, but differed in terms of the onset of schizophrenia, the symptoms, diagnoses, course of the disorder, and outcomes. Genain comes from the Greek meaning "dreadful gene." This case reveals the concept of unshared environments, which may lead to different outcomes for the same disorder even within the same household. 3. Adoption studies: Children of biological mothers with schizophrenia have a much higher chance of developing schizophrenia themselves, even when raised away from their biological parents.

9 SCHIZOPRHENIA a. 17% chance of developing schizophrenia, regardless of whether the identical twin parent has schizophrenia or the parent s twin is unaffected. b. If the parent is a fraternal twin with schizophrenia, then their children have about a 17% chance of developing schizophrenia. If the fraternal twin parent does not have schizophrenia but their fraternal twin does, the risk in the children drops to about 2%. 5. Several potential markers for schizophrenia have been studied. Smooth-pursuit eye movement or eye-tracking refers to a procedure involving keeping one s head still while visually tracking a moving pendulum back and forth. This tracking ability is deficient in many persons with schizophrenia, including relatives of schizophrenic persons. This work suggests that eye-tracking may be a marker for schizophrenia.

10 SCHIZOPRHENIA - 10 E. Neurobiological influences with regard to brain functioning in schizophrenia dates back as far as Emil Kraepelin. Several hypotheses have been proposed since then and include: 1. The dopamine hypothesis of schizophrenia argues that schizophrenia is the result of an excess of dopamine in the brain. This hypothesis was popularized by several of the following findings showing that when drugs are administered that are known to increase dopamine (agonists), schizophrenic behavior increases, whereas with drugs that are known to decrease dopamine activity (antagonists), schizophrenia symptoms tend to diminish: a. Antipsychotic neuroleptic drugs (i.e., dopamine antagonists) are effective in treating schizophrenia. Such drugs work primarily by blocking the D2 dopamine receptors b. The negative side effects are similar to those seen in persons with Parkinson's disease; a disorder known to be due to insufficient levels of dopamine. c. The drug L-dopa (i.e., a dopamine agonist) that is used to treat people with Parkinson s disease, and can result in schizophrenialike symptoms. d. Amphetamines (i.e., drugs that activate dopamine) can make psychotic symptoms worse in people with schizophrenia. e. Such observations led to the view that schizophrenia was due to excessive dopamine activity involving the D2 dopamine receptors. 2. Arguments against the dopamine theory include the following: a. Many persons with schizophrenia are not helped with dopamine antagonists. b. Neuroleptics work to block dopamine quickly, but the relevant symptoms remit long after. c. Neuroleptics do little to help the negative symptoms. d. It is unclear whether people with schizophrenia have more D2 receptors than others. e. Genetic-linkage studies do not support a clear connection between schizophrenia and the gene region for the D2 receptors. f. The drug clozapine is effective for many persons not helped by traditional neuroleptic medication, and yet it is one of the weakest dopamine antagonists. 3. Recent work has focused on the relation between dopamine and serotonin in the context of schizophrenia symptoms. Two studies suggest that the dopamine-serotonin relation may better explain the effects of neuroleptic drugs than looking at dopamine alone.

11 4. Evidence for neurological damage in persons with schizophrenia is partially derived from the fact that children at risk for the disorder often show abnormal reflexes and attentional problems. Such problems tend to persist into adulthood. a. Positive symptoms of schizophrenia may be related to excessive dopamine activity, but negative symptoms may be related to structural brain abnormalities such as enlarged lateral ventricles. However, many people without schizophrenia have such abnormalities. b. The frontal lobes of people with schizophrenia tend to be less active than in people without the disorder; a phenomenon known as hypofrontality. The deficits appear in a dorsolateral prefrontal cortex of the frontal lobes. This prefrontal area is also one site of a major dopamine pathway in the brain. 5. Some have hypothesized that schizophrenia is a recent phenomenon historically, appearing during the past 200 years, and may involve some recently introduced virus. There is evidence that a virus-like disease may account for some cases of schizophrenia, particularly prenatal exposure to influenza. a. Evidence for developmental problems during the second trimester of fetal development has led to an interest in fingertip dermal cells that migrate to the cortex of the brain and produce fingerprint ridges. Migration of such cells would be disrupted if a virus occurred during this critical period of development. The number of fingertip ridges in twins without schizophrenia differs little, but substantial differences are seen in one-third of twins discordant for the disorder. This work suggests that finger-tip ridge count may be a marker of potential brain damage. F. Psychological and social influences 1. Research on stress and schizophrenia suggests that extreme stress can produce psychotic-like symptoms in otherwise normal persons. Stress appears related to activation of a schizophrenia predisposition and risk for relapse. 2. Family interactions and their effect on schizophrenia has been the focus of a great deal of research. The term schizophrenogenic was used for a time to describe a mother whose cold, dominant, and rejecting nature was thought to cause schizophrenia in her children. The term double-bind was also used to portray a type of communication that produced conflicting messages (e.g., saying "I love you" coupled with a stiff/distant hug), resulting in schizophrenia. Both terms are no longer widely used. Recent work has focused on how family interactions contribute to relapse from schizophrenia, not in the onset of schizophrenia. a. Expressed emotion is a term describing a particular family communication style that is related to schizophrenic relapse. High expressed emotion characterized by criticism, hostility, and

12 G. Treatment of Schizophrenia emotional over-involvement is strongly related to risk for relapse. Persons with schizophrenia living in a family with high expressed emotion are 3.7 times more likely to relapse than if they lived in a family low in expressed emotion. A. Historically, the treatment of schizophrenia was highly medicalized. For instance, primitive brain surgeries were used as early as the 1500s, and similar, albeit more sophisticated, procedures were used in the 1950s (e.g., prefrontal lobotomies). Modern Westernized treatment of schizophrenia usually begins with neuroleptic drugs in combination with psychosocial treatments aimed at reducing relapse, compensating for skills deficits, and to improve compliance with medication regimens. B. Biological interventions 1. During the 1930s, persons with schizophrenia may have undergone one of several biological interventions, including: a. Insulin coma therapy involved injections of massive doses of insulin to induce a coma in persons suffering from schizophrenia. Though many thought this procedure was helpful, serious illness and death often occurred. b. Psychosurgery, including prefrontal lobotomies, was also introduced in the 1930s. Prefrontal lobotomies involved severing the frontal lobes from the lower portion of the brain, resulting in calmed behavior but severe cognitive and emotional deficits. Such procedures are still used in some primitive cultures. c. In the late 1930s, electroconvulsive therapy (ECT) was advanced as a treatment for schizophrenia, but was found to be of little help. 2. During the 1950s, several neuroleptic drugs were introduced to relieve the symptoms of schizophrenia. Such drugs affect the positive symptoms of schizophrenia (i.e., reduce or eliminate hallucinations and delusions), and help persons think more clearly. Such drugs are not equally effective for all persons and often involve a trial and error process to find a medication that works best. Many persons with schizophrenia stop taking their medications from time to time, mostly because of the negative side effects of such drugs. a. The earliest neuroleptic drugs, called conventional antipsychotics, work in about 60% of persons who try them, but include several unpleasant side effects. b. Newer medications, such as clozapine, risperidone, and olanzapine, have fewer serious side effects than conventional antipsychotics.

13 3. Factors affecting noncompliance with medications include a negative patient-doctor relationship, cost of medication, poor social support, and unwanted negative side effects. Side effects of neuroleptics may include extrapyramidal or Parkinsonian symptoms. a. One such symptom is akinesia, which is characterized by an expressionless face, slowed motor activity, and monotonous speech. b. Another extrapyramidal symptom is tardive dyskinesia, which involves involuntary movements of the tongue, face, mouth, or jaw and can include protrusions of the tongue, puffing of the cheeks, puckering of the mouth, and chewing movements. Tardive dyskinesia results from high doses of antipsychotic medications administered over long periods of time. Tardive dyskinesia is often irreversible. 4. A newer, and not-as-yet validated, procedure for the treatment of hallucinations involves exposing the individual to magnetic fields. This procedure, called transcranial magnetic stimulation, uses wire coils to repeatedly generate magnetic fields that pass through the skull to the brain. One study has demonstrated reductions in hallucinations following this procedure. C. Psychosocial interventions 0. Today, few believe that psychological factors cause schizophrenia or that traditional psychotherapeutic approaches alone are curative; however, psychosocial approaches have an important role in treatment. 1. Behavioral approaches for inpatients are designed to encourage and foster appropriate socialization, participation in group sessions, and self-care, while discouraging violent outbursts. Such interventions rely on token economy systems, in which residents earn access to meals and small luxuries by behaving appropriately. Patients in such programs do better than those who are not part of them. 2. Clinicians also reduce the routine institutionalization of persons with schizophrenia by implementing community care programs. 3. The more insidious negative effects of schizophrenia are on social behavior, or the person s ability to relate to other people. Treatments here target and attempt to re-teach social skills such as how to have a basic conversation, assertiveness, and relationship building. Modeling, role-play, feedback, and practice are emphasized. Maintenance of these skills may be problematic, however. 4. Independent living skills programs focus on teaching a range of skills that persons with schizophrenia can use to better adapt to their disorder and the challenges of community living. Such a

14 program is often multidisciplinary and seems to help prevent relapse. 5. Behavioral family therapy has been used as a means to teach families of persons with schizophrenia to be more supportive, particularly families high in expressed emotion. Such procedures provide education about schizophrenia, teach communication skills, address more constructive ways of expressing negative feelings, and emphasize problem solving. This type of therapy seems to require ongoing work, as its effectiveness diminishes after 1 year. 6. Vocational rehabilitation is used to help persons with schizophrenia gain and maintain employment, and may include hands-on job coaches. D. Treatment across cultures and prevention efforts 0. Cultural factors seem to play a role in the treatment of schizophrenia. For example, Hispanics are less likely to seek help in institutional settings and rely instead on family support. In China, the preferred treatment for schizophrenia is antipsychotic medication and most are treated outside of hospitals. In Africa, persons with schizophrenia are kept in prisons. 1. Prevention of schizophrenia focuses on identifying and treating children who may be at risk for the disorder later in life. Instability of early family rearing environment seems related to subsequent risk for developing schizophrenia in at risk children. Preventive efforts may focus on birth complications and early illnesses, particularly among those who are genetically predisposed.