Psychotic Disorders PDF

11 Psychotic Disorders This chapter deals with the group of disorders referred to as “psychotic disorders.” The definition of the term psychotic has evolved over the course of previous DSM revisions. In the DSM-5, the meaning of psychotic refers to the presence o...

11 Psychotic Disorders This chapter deals with the group of disorders referred to as “psychotic disorders.” The definition of the term psychotic has evolved over the course of previous DSM revisions. In the DSM-5, the meaning of psychotic refers to the presence of specific symptoms that vary depending on the condition. In general, though, these symptoms include false beliefs (delusions), seriously impaired perceptions (hallucinations) without awareness of their pathological nature, and disorganized thinking, as evidenced in speech and behavior. In addition to noting the presence of these symptoms, it is important to observe their content; for example, delusions may be paranoid (“I am being followed by the FBI”), and hallucinations may be self-deprecatory (“I hear a voice telling me I am bad”). Psychosis, per se, is not a diagnosis but a symptom. There are a number of types of psychotic disorders, which have traditionally been classified into two broad groups: functional psychoses and organic psychoses. The term functional refers to those psychoses with a presumed psychological etiology, and organic refers to those with a presumed biological etiology. Schizophrenia was traditionally classified as a functional psychosis; however, more recent research findings strongly suggest that schizophrenia has a biological basis; that is, it is an endogenous mental disorder. The distinction, however, is still important, but now different terminology is used. The functional disorders are referred to as “primary psychiatric disorders,” and the organic disorders are referred to as “due to a general medical condition.” 152  Differential Diagnosis Psychotic Disorder Due to Another Medical Condition The term “psychotic disorder due to another medical condition” is used when delusions and/or hallucinations are present that are judged to be due to another medical condition and are not better explained by another mental disorder. Substance/medication-induced psychotic disorder is a separate diagnostic category. Substance-related disorders that can be associated with psychotic symptoms can be produced by all classes of substances, that is, alcohol, hallucinogens, opioids, phencyclidine, sedative-hypnotics, and stimulants. Sometimes psychotic symptoms are more often associated with intoxication and, sometimes, more with withdrawal. Many medical conditions can produce psychotic symptoms, but the most common can be grouped into the following categories: Psychotic Disorder Facts 1 percent of the population has schizophrenia. 1 to 4 percent of psychiatric admissions have delusional disorder. 10 to 15 percent of medical-surgical patients in a general hospital have delirium. 15 percent of patients diagnosed with dementia have a treatable condition. Delirium is most common in the very young and the elderly. Medical Conditions That Can Cause Psychosis MetabolicOrgan failure, such as renal failureHypoxiaHypoglycemiaVitamin deficiencyEndocrinopathy, such as hyperthyroidismFluid or electrolyte imbalancePorphyria Drug or alcohol intoxication or withdrawal Infections Epilepsy Head injury Vascular diseases, such as lupus 153  Intracranial tumor Cerebral degenerative diseasesDementia, such as Alzheimer’s diseaseMultiple sclerosisHuntington’s choreaParkinson’s disease Primary Psychoses The primary psychoses can be divided into the following diagnoses: Brief psychotic disorder Delusional disorder Schizophrenia Schizophreniform disorder Schizoaffective disorder Other specified and unspecified schizophrenia spectrum and other psychotic disorders Major depression with psychotic features Bipolar disorder, manic Brief psychotic disorder refers to a condition in which a person has psychotic symptoms lasting from one day to a month. There usually is some identifiable stressor that has precipitated the psychosis, and the person demonstrates significant emotional turmoil. The symptoms may be identical to those seen in schizophrenia, but they remit in a fairly brief period of time (less than one month). Delusional disorder refers to a disorder with persistent nonbizarre delusions without bizarre behavior or prominent hallucinations. Thus, if someone has the delusion that he or she is under surveillance by the FBI, they may meet the criteria. But if delusions are bizarre—for example, if a patient thinks she is under surveillance by Martians—she does not meet the criteria. The disorder is classified by type of delusion: erotomanic, grandiose, jealous, persecutory, or somatic. Schizophrenia refers to a disorder of longer than six months’ duration with prominent psychotic symptoms. This disorder is discussed in detail below. Schizophreniform disorder has the same criteria as schizophrenia but is of less than six months’ duration. Schizoaffective disorder refers to a condition in which the person has not only schizophrenia but also significant episodes of mood disorder, either manic or depressive. (Psychotic symptoms seen in severe affective disorders and mania and depressive psychoses are covered in chapters 7 and 8.) Now let’s discuss schizophrenia in more detail, using it as the prototype of primary psychosis. 154 Schizophrenia Schizophrenia as a syndrome has been recognized for thousands of years. As long ago as the Hippocratic school, a syndrome called dementia (with behaviors and symptoms akin to schizophrenia) was recognized as distinct from mania and melancholia. Kraepelin (1921) described a syndrome he called “dementia praecox.” This referred to a psychotic disorder with progressive debilitation leading to severe impairment of social and intellectual functioning. In his view, this syndrome was invariably progressive, with a very poor prognosis, although more recent research questions the progressive nature of all schizophrenic disorders. The clinical picture of schizophrenia varies depending on the particular phase of the disorder. DSM-5 divides the course of schizophrenia into three phases: prodromal, active, and residual. During the prodromal phase, patients show a deterioration in their level of functioning, without being actively psychotic. In this phase, the patient may show mostly “negative” symptoms (discussed below), such as isolativeness, blunted or flat affect, and lack of initiative. There may also be a disruption of sleep patterns. Often there is a deterioration of performance (at work or school), and sometimes in personal hygiene. There may be an abrupt change in behavior or lifestyle, such as a career change. In the active phase, the person is floridly psychotic, with disorganized thinking, delusions, and hallucinations. In the following residual phase, the patient continues to be impaired but without severe psychotic symptoms. Social isolation and peculiar affect and thinking may persist, to a degree. Schneiderian First-Rank Symptoms Thought broadcasting—belief that one’s thoughts are escaping aloud into the external world Experiences of alienation—belief that one’s thoughts, feelings, and actions are not one’s own Experiences of influence—belief that one’s thoughts, feelings, and actions are being controlled by some external agent Complete auditory hallucinations—hallucinations of voices coming from outside one’s head Delusional perceptions—a real, normal perception to which one attaches a private meaning For a diagnosis of schizophrenia, these three phases must last longer than six months and must not be due to a mood disorder. The presence of catatonia, a prominent movement disorder, is considered a subtype of schizophrenia. 155 CASE 16 George A. was a nineteen-year-old college student who was brought to the student health clinic by his roommate. It was difficult to get a clear history from George because he kept changing the subject and making odd and disconnected statements. His roommate reported that George had been progressively more isolative the past four months. For the past month he had been staying up late at night and had become somewhat secretive. He wrote notes to himself in a special notebook and made odd comments about God and Christ and about something “coming soon.” His personal hygiene had deteriorated, and he sometimes went several days without bathing or changing clothes. George reported that he felt he was on a special mission to prepare for the second coming of Christ and that he sometimes heard God or the devil speaking to him. He thought it was necessary that he die or suffer in order to atone for his sins and the sins of the world. He admitted he was doing poorly in school, but explained that doing God’s work was more important. His roommate, who had known him in high school, described him as quiet, shy, and somewhat of a loner. He had never dated. George was treated with antipsychotic medication, and the delusions and hallucinations resolved. But he continued to have difficulty in college and eventually dropped out of school and returned home to stay with his family. This case illustrates the prodromal, active, and residual phases. George A. is described as having a somewhat schizoid premorbid personality, as is classically described (although some studies have shown that this is present in only about 50 percent of those diagnosed with schizophrenia). This case also illustrates what are called positive and negative symptoms. For practical purposes, it is helpful to group schizophrenic symptoms into four categories, as outlined below. (Note that characterological features are not psychotic symptoms per se, but do often accompany the more core positive or negative symptoms.) The distinction between positive and negative symptoms appears to be significant because of both their differential responses to medication and their differing clinical course and probable differing etiology. Recently, a third symptom cluster has been identified, the disorganized cluster (Arndt, Alliger, and Andreasen 1991; Liddle et al. 1989). This symptom cluster, like negative symptoms, correlates with cognitive impairment and frontal lobe dysfunction but has different behavioral manifestations. There are now several theoretical models of the neurophysiological basis for these different types of symptoms and the course they follow in schizophrenia. They are discussed below: Schizophrenia Symptoms Positive symptoms:HallucinationsDelusionsAgitationFloridly bizarre behaviorFirst-rank symptoms (see sidebar on the opposite page) Negative symptoms:AnhedoniaApathyBlunted affectPoverty of thoughtFeelings of emptinessAmotivational states DisorganizationBehavioral disorganizationDistractibilityThought disorder 156 “Characterological” symptoms:Social isolation or alienationMarked feelings of inadequacyPoorly developed social skills 157  Etiology Over the centuries, there have been a multitude of theories about the etiology of schizophrenia. These have ranged from religious, social, and psychological theories to more recent biological theories. Early evidence of biological factors came from genetic studies. Twin studies showed that the rate of concordance was much higher for monozygotic (identical) than for dizygotic (fraternal) twins. Adoptive studies done by Kety et al. (1971) have shown that schizophrenia is much more prevalent in the biological relatives than in the adoptive families of those adopted at birth who are later diagnosed as schizophrenic. Since that study, many others have shown biological differences between schizophrenic subjects and controls: CT and MRI scans have demonstrated enlargement of the lateral ventricles and widened cortical sulci. This finding suggests that either there is brain atrophy or (more likely) that in some types of schizophrenia there has been abnormal brain development (Weinberger 1996). These abnormalities may increase over time. MRI scans have shown the presence of smaller anterior hippocampi (Weinberger et al. 1992) in schizophrenic subjects, which correlates with cognitive impairment (Nester et al. 1993). PET scan studies have shown decreased metabolic activity in the prefrontal cortex, which correlates with the severity of negative symptoms. Studies have found a positive correlation between levels of HVA (a dopamine metabolite) in plasma and clinical severity. Also, many studies have found an increase in the number of D2 receptors in the striatum and nucleus acumbens of schizophrenics (Bochus and Kleinman 1996; Lieberman et al. 1996; Gur et al. 1998; Knoll et al. 1998). The Dopamine Model The dopamine model was the predominant theory of biological causation during the late twentieth century. This theory hypothesized that schizophrenia is caused by abnormal dopaminergic activity in the brain. Dopamine neurons are located in a number of different brain regions. In the basal ganglia, these nerve cells help to regulate motor functioning. In areas of the limbic and reticular systems, dopamine neurons appear to play an important role in emotional control and the screening of stimuli. The dopamine model holds that the basic physiological pathology involves primarily overactive or hyper- reactive dopamine neurons. The excessive dopamine activity can lead to behavioral agitation, a failure to adequately screen stimuli, and disorganization of perception and thought. This theory is supported by two observations: The first is that the potency of antipsychotic drugs has correlated closely with their ability to bind to and block the postsynaptic dopamine (D2) receptors in the mesolimbic system (see figure 11-A). The second observation is that drugs that increase dopamine activity (such as amphetamines) can produce a paranoid psychosis similar to paranoid schizophrenia and, if given to schizophrenic patients, amphetamines may exacerbate psychotic symptoms. 158  Action of Antipsychotic Drugs on Dopamine Receptors Figure 11-A Although the dopamine model has merit, the basic theory has been modified to help explain some clinical data (Davis et al. 1991). One of the strongest stimuli has been the finding that clozapine, although effective in the treatment of schizophrenia, is only a weak D2 blocker, because it is a reversible blocker. On the other hand, it is a fairly potent 5-HT2A and 5-HT2C antagonist. The 5-HT blocking ability appears to correlate with its effectiveness against negative symptoms. This has also been the case with second-generation antipsychotics (discussed in detail in chapter 19). (Note that second-generation antipsychotics were formerly called atypical antipsychotics.) Also, it has been shown that clozapine does significantly decrease dopaminergic activity in the mesolimbic area (despite the lack of D2 blockade) but not in the nigrostriatal tracts (thus the lack of extrapyramidal effects). What emerges is the following picture: In schizophrenia, there is hyperdopaminergic activity in the mesolimbic tracts that is associated with positive symptoms. In addition, there is decreased activity in the prefrontal cortex associated with negative symptoms. The exact relationship between these phenomena is not fully understood at this time. It has been suggested (Bochus and Kleinman 1996) that hypofunction of the glutamate neurons, which interconnect the four main areas shown to be abnormal in schizophrenia (prefrontal cortex, mesolimbic, striatum/nucleus acumbens, and medial temporal lobe), may be the underlying pathophysiology. The different neurochemical basis dictates alternative treatment approaches: the use of second-generation antipsychotics (discussed in detail in chapter 19). The Glutamate Model 159  Another theory was proposed over fifty years ago (Luby et al. 1962) as the phencyclidine (PCP) model of schizophrenia. This was based on the discovery that PCP exerts its effect by blocking the action of glutamate at the N-methyl-D-aspartate (NMDA) receptor in the brain. The advantage of this model is that PCP, unlike amphetamines, induces negativism and apathy in addition to disorganized thinking. It is hypothesized that in schizophrenia there is a primary dysregulation of the glutamate system resulting in cognitive deficits and that the dopaminergic hyperactivity, and resultant positive symptoms, are secondary phenomena (Goff and Coyle 2001). The Neurodevelopmental/Neurodegenerative Model The neurodevelopmental model proposes that in schizophrenia there is a defect, possibly genetically determined or from an event (e.g., a viral infection) during intrauterine or early infantile development, that leads to abnormal development later in life, especially during the synaptic “pruning” during adolescence (Hoffman and McGlashan 1997). This model suggests that the pathophysiological processes of schizophrenia develop over time until they produce overt symptomatology. Treatment would then be directed, not just at the final psychotic symptoms, but toward correcting the abnormal development. Some evidence suggests that schizophrenia is a neurodegenerative disorder leading to poorer functioning and progressively diminished cognitive functioning after each psychotic episode (Lieberman 1999; Tsuang, Stone, and Faraone 2000). A number of studies using MRI imaging to measure brain and ventricular volume have shown progressive enlargement of the lateral ventricles, and corresponding loss of brain tissue. Furthermore, these changes correlate with deterioration in condition, and precede the first psychotic episode. Other studies have shown elevation of both dopamine and glutamate. Taken together, this evidence suggests that in some cases schizophrenia is a progressive neurodegenerative disorder with progressive loss of neurons and cognitive function. Newer evidence (Harvey and Keefe 2001) suggests that the second-generation antipsychotics may greatly reduce, or possibly eliminate, this deterioration. The evidence suggests that early intervention and treatment may lead to marked improvement in the overall course of the illness. On the other hand, older studies (Bleuler 1968) have suggested that almost half of schizophrenic patients substantially improved or recovered. Whatever the precise neurophysiological pathogenesis of schizophrenia may turn out to be, several things are clear: There is not just one type of schizophrenia. Different people with schizophrenia may have very differing courses, for example, good-prognosis versus poor-prognosis schizophrenia. These have differing neuroanatomical findings and, presumably, differing pathogeneses. The etiology of schizophrenia is complex. A simple theory like the dopamine model cannot fully explain the disorder. A full understanding will take into account factors at the intracellular, synaptic, and neural network levels. The genetic factors are complex. They are certainly polygenic and seem to overlap with other disorders. 160 161  Treatment We can consider the positive and negative symptoms listed earlier as target symptoms for antipsychotic medication treatment. Antipsychotic medications are now considered an important, if not essential, component in the treatment of schizophrenia. The focus of treatment is not only the resolution of psychotic symptoms but also relapse prevention. Unfortunately, schizophrenia is a disorder in which relapse is extremely common. It is estimated that following a psychotic episode and subsequent recovery, 70 percent of patients will relapse within a year if treated with either placebo or no medication at all. With continued antipsychotic treatment the relapse rate can drop to 30 to 40 percent. Studies have shown that low-dose and intermittent treatment are associated with poorer outcome, as measured by number of hospitalizations (Carpenter et al. 1990; Kane 1990). In addition, there is now evidence to support the notion that being psychotic is damaging to the brain (Loebel et al. 1992). It is as if the more the dopamine circuits are used, the more the psychotic pathways become etched into the brain. Loebel and associates studied the relationship between duration of illness and clinical outcome in a group of untreated, first-episode schizophrenic patients. The study showed that patients who had been psychotic longer prior to treatment tended to have a poorer treatment response. This is consistent with the observation that prolonged hallucinogen or stimulant abuse is associated with incomplete clearing of mental status. It also suggests some type of kindling phenomena or toxic effect of psychosis and supports the need for prompt treatment with antipsychotic medications. As is said, “neurons that fire together, wire together.” Besides antipsychotic medications, both typical and atypical, other medications may be useful in the treatment of schizophrenia. These include lithium, carbamazepine, benzodiazepines, reserpine, propranolol, antidepressants, and antiparkinsonian drugs. Most of these are used to treat associated features of schizophrenia and are used in addition to, not instead of, antipsychotic medication. Lithium may be helpful to reduce psychotic and affective symptoms. It was once thought that lithium would benefit only those patients who were actually bipolar or schizoaffective, but even some patients without apparent affective symptoms can benefit from lithium. Benzodiazepines (minor tranquilizers) may be helpful in relieving some of the negative symptoms, in addition to anxiety and agitation. Antiparkinsonian medications are usually effective for the extrapyramidal side effects of antipsychotic medications. Antidepressants may be helpful when there are significant comorbid depressive symptoms. Propranolol (a beta blocker) is often helpful for akathisia (a common side effect of antipsychotic medications) and can sometimes reduce agitation. The goal of medication treatment is to reduce symptoms so that the person can function better and benefit more from other forms of treatment, such as individual, group, or family therapy, and social or vocational rehabilitation. An important part of such therapy involves educating the patient about prodromal symptoms and effects and side effects of medications. It is also important to address patients’ beliefs that taking medications means they are sick (and conversely, that not taking medications means they aren’t). Especially with paranoid patients, the belief that medications are a means of being controlled by others must be worked through. Sometimes people with schizophrenia feel better when not taking antipsychotic medications because they 162 are able to entertain more grandiose notions about themselves and thereby lift their moods. Even more commonly, premature discontinuation occurs because patients are plagued by very unpleasant medication side effects. Appropriate education of patients regarding side effects and medical intervention (many side effects can be controlled with other medications) can improve the quality of life and greatly enhance compliance. It may be helpful to present medications as a tool for people to use to help them control their illness, as a diabetic uses insulin. Any of the psychotic disorders, regardless of etiology, may respond to antipsychotic medications. Where there is an underlying medical illness causing the psychosis, it is crucial to treat the underlying disorder. However, even in that case, antipsychotic medication may help reduce symptomatology. In the case of drug- induced and brief reactive psychosis, it may be appropriate not to use antipsychotic medications initially and instead to await the resolution of the psychotic symptoms using only supportive treatments. In the cases of the other psychoses, it is usually best to treat with antipsychotic medications for at least six months. 163