Schizoaffective Disorder

The set of symptoms called schizoaffective disorder represents both a theoretical puzzle and a practical problem for psychiatry. The disorder looks like an amalgam of two kinds of major mental illness that are usually thought to run in different families, involve different brain mechanisms, develop in different ways, and respond to different treatments: mood (affective) disorders and schizophrenia.

The two major mood disorders are unipolar depression and bipolar or manic-depressive illness. Seriously depressed people feel constantly sad and fatigued. They have lost interest in everyday activities and are indecisive and unable to concentrate. They sleep and eat too little or too much and complain of various physical symptoms. They may have recurrent thoughts of death and suicide. Patients in an expansive, manic mood are cheerful, sleepless, compulsively talkative, agitated, and distractible, with racing thoughts and an inflated sense of their own importance. They are susceptible to buying sprees, indiscreet sexual advances, and foolish investments. Their cheerfulness can also turn to irritability, paranoia, and rage.

Patients with chronic schizophrenia appear apathetic and emotionally unresponsive. Their speech is limited and their thinking confused. They suffer from hallucinations and delusions, and they perplex others with their strange behavior and inappropriate emotional reactions. People with affective disorders usually appear normal between episodes of illness and do not become more seriously disabled with time. Schizophrenic patients rarely seem normal, and their condition tends to deteriorate, at least in the early years of the illness.

This distinction is not always as obvious as the description suggests. Emotion and behavior are more fluid and less easy to classify than physical symptoms. Seriously depressed and manic patients often have hallucinations and delusions. Mania can be impossible to distinguish from an acute schizophrenic reaction, and psychotic or delusional depression is important enough to rate its own classification by some psychiatrists. Mood changes occur both as symptoms of schizophrenia and as reactions to its devastating effects; for example, depression after a schizophrenic episode (post-psychotic depression) is common and often severe, and it is during this time that a schizophrenic patient is most likely to commit suicide. Schizophrenic apathy and an incapacity for pleasure can also be mistaken for depression.

Often a diagnosis has to be changed from one kind of major mental disorder to the other. In a recent study of more than 936 psychiatric patients hospitalized at least four times in a seven year period, investigators found that about 25% of those originally thought to be schizophrenic ended with a diagnosis of bipolar disorder and 33% of those originally given other diagnoses (including bipolar disorder) had a final diagnosis of schizophrenia.

One cause of these ambiguities and difficulties is a puzzling mixture of symptoms, like the following:

A 40-year-old widowed mother of two was admitted to a clinic complaining that “the neighbors are trying to strangle my mind.” She said she had heard them breathing down her neck at night for about a month, since her husband died in an automobile accident. Her memory and orientation were normal, but her thoughts were somewhat disorganized. Two weeks later she began to say that she was “tired and dirty, like a tramp, and might be better off dead.” She ate poorly and awoke early in the morning. For the next two months these symptoms continued while she remained afraid of her neighbors and still heard strange breathing noises in bed. Then her sleep and appetite improved and she no longer claimed to feel tired or dirty, but she still thought that the neighbors were out to get her and occasionally heard them whispering in her ear when she was alone. These fears persisted for another month, then started to fade away.

A 30-year-old man began to hear voices threatening to kill him and became convinced that his thoughts were being broadcast for others to hear. For three weeks he stayed in his apartment, kept awake by the voices, unable to eat, and avoiding everyone but his immediate family. He says he was “terrified” but not depressed. He was persuaded to enter a hospital and given an antipsychotic drug. After six weeks the voices stopped and he left the hospital, but two weeks later he became depressed. He lost his energy and appetite, woke at four o’clock every morning, and could not concentrate sufficiently to read a newspaper or watch television. When his doctors stopped the antipsychotic drug, the hallucinations did not return, but he was able to do little more than sit in his apartment and stare dejectedly at the wall. A year after the original hospitalization, he was readmitted and given an antidepressant drug.

A fluid definition

The idea of a schizoaffective psychosis is supposed to clarify such situations, but its usefulness is still disputed, partly because its definition and description have fluctuated so much that research findings are difficult to interpret. One study of eight more or less accepted definitions found that on the average, only 20% of patients designated as schizoaffective by one of these definitions would be schizoaffective according to all of them. The disorder has been regarded as a form of schizophrenia, a type of mood disorder, a transitional stage between the two, a combination of the two, a distinct illness, or even a label misleadingly applied to various collections of symptoms that have little in common.

In the early 1930's, when the term “schizoaffective” was introduced, it was meant to describe a form of schizophrenia, but today many would say that the original cases were actually bipolar disorder or psychotic major depression. For years the label continued to be applied in this way to patients who would today be called depressed or manic. Mental health professionals eventually became concerned about overusing the diagnosis of schizophrenia, and this change of attitude was reflected in the third edition of the American Psychiatric Association’s diagnostic manual (DSM-III), published in 1980: the definition of schizophrenia was narrowed, the definition of affective disorder was broadened, and schizoaffective disorder was identified as a distinct illness for the first time.

The definition was changed once again in DSM-III-R, the 1987 revision of the manual. There schizoaffective disorder is described as an episode of major depression or mania punctuated by a period of delusions and hallucinations without prominent (as opposed to transient or mild) mood symptoms. Most of the symptoms listed are usually regarded as typical of schizophrenia: incoherent or loose associations, flat affect (apparent lack of emotion, lack of normal feeling tone), and hallucinatory voices carrying on a conversation or giving a running commentary on the patient’s actions. This description narrowed the definition of schizoaffective disorder and made it appear more like schizophrenia.

In DSM-III, “mood-incongruent” delusions or hallucinations in a depressed or manic person were regarded as a sign of schizoaffective disorder. (A severely depressed patient’s belief that she is dying of an incurable disease is mood-congruent; if she believes that creatures on another planet have chosen her as a vehicle for delivering messages to humanity, that would be mood-incongruent.) In DSM-III R, “bizarre “ delusions are also mentioned. (A delusion that someone is in love with you or plotting against you is not bizarre; a belief that your mind is controlled through electrodes planted by the CIA is.)

In the latest APA manual, DSM-IV (1994), the definition of schizoaffective disorder does not refer to the bizarre quality of hallucinations and delusions. The disorder is again defined more broadly, as an illness during which the patient has symptoms of both schizophrenia and a major mood disorder at the same time. Major depression, mania or a mixture or alternation of depressive and manic symptoms must last for at least two weeks along with two of the following, for at least a month: delusions, hallucinations, disorganized speech, disorganized behavior, and negative schizophrenic symptoms (apathy, limited speech, lack of normal feeling tone). The psychotic symptoms (delusions or hallucinations) must persist for at least two weeks without prominent mood symptoms; otherwise the correct diagnosis would be a mood disorder with psychotic features. A final stipulation is that neither the psychotic nor the mood symptoms can be the effect of drugs or of a medical condition such as temporal lobe epilepsy or hyperthyroidism.

This current official American definition is only one of several that have expert support. There are also proposals to divide schizoaffective disorder into subtypes depending on whether the symptoms more closely resemble schizophrenia or affective disorder; whether the patient is normal between episodes; whether the symptoms include both mania and depression , only mania, or only depression (bipolar and depressive subtypes); whether hallucinations and delusions fade and leave mood symptoms or the other way around; and whether all episodes of illness are the same or some are dominated by mood changes and others by psychotic symptoms.

Difficulties in diagnosis

It is not surprising that people often change their minds about this diagnosis. In the study referred to earlier, 48 of the 936 patients were originally diagnosed as schizoaffective, but only 13 of them eventually retained the diagnosis. Some 17 (35 %) had a final diagnosis of bipolar disorder and 18 (38%) a final diagnosis of schizophrenia. About the same number of patients had their diagnoses switched from schizophrenia, bipolar disorder, and other psychoses to schizoaffective disorder, and in the end 51 patients were given that diagnosis.

To improve the reliability and usefulness of schizoaffective disorder as a diagnosis, researchers have looked beyond the symptoms for ways in which it might resemble or differ from schizophrenia and mood disorders. Its prevalence in the general population, about a fifth to a tenth the rate of schizophrenia, is probably compatible with the idea that it is nothing more than the coincidence of schizophrenia and a mood disorder in the same person. Like schizophrenia, it usually begins in early adulthood (generally earlier than mood disorders), but like mood disorders, it is much more common in women than in men, and women are much more likely than men to have their diagnosis switched from schizophrenia to schizoaffective disorder.

Many schizophrenic patients have difficulty following a moving object with their eyes. The rapid eye movement (dreaming) sleep of depressed patients begins unusually early in the night. There is some evidence that people with schizoaffective disorder resemble schizophrenic patients in their eye tracking ability and depressed patients in their dreaming patterns. But the research is inadequate, and the results are confused by varying definitions. There is also evidence that schizophrenic patients are more likely than those with schizoaffective disorder to suffer from lack of insight; that is, an awareness of having a mental disorder and of the common symptoms, social consequences, and treatments. But in one study schizophrenic and schizoaffective patients performed equally poorly on a neuropsychological test sensitive to malfunctioning of the frontal lobes of the cerebral cortex, which govern planning and willed action.

Are genetic factors involved?

Another approach to the problem of schizoaffective disorder is to look for genetic indications that distinguish it from other psychiatric disorders. Some studies have found that identical twins are much more highly correlated for the diagnosis than fraternal twins. Family members of patients turn out to be sometimes at high risk for mood disorders, and sometimes at high risk for both. Genetic conclusions about schizoaffective disorder may ultimately depend on whether schizophrenia and major mood disorders are genetically related. Most researchers believe they are not, but there is evidence both ways. One recent family study concluded that schizophrenia represented one end of a genetic spectrum, with psychotic depression and bipolar disorder at the other end. Schizoaffective disorder lay close to schizophrenia on this spectrum, which also included the personality disorders, of schizotypal and paranoid personality. All these sets of symptoms seemed to indicate the same underlying genetic vulnerability; their differences appeared to be a matter of degree.

But in this study the families of patients with schizoaffective disorder also had the same risk for mood disorders as the families of people with mood disorders and the same risk for schizophrenia as the families of schizophrenic patients --- a result suggesting that schizoaffective disorder is a distinct syndrome resulting from high genetic liability to both mood disorders and schizophrenia. Possibly several different genetic predispositions result in disorders with varying degrees or unusual patterns of mood and psychotic symptoms. An affective subtype of schizophrenia might run in the same families as mood disorders and a schizophrenic subtype in the same families as schizophrenia.

A choice of therapies

Observing patients’ responses to treatment has been no more successful than genetic analysis in clearing up the uncertainty surrounding schizoaffective disorder. All possible combinations of the therapies used for schizophrenia and mood disorders have been tested, with the mixed results that might be expected. In general, therapists treat psychotic symptoms without reference to possible causes and brain mechanisms, and often without reference to the diagnosis of schizoaffective disorder. If the patient first appears in a psychotic state, a neuroleptic (antipsychotic) drug is most often used, since antidepressants and lithium (used for bipolar disorder) take several weeks to start working. Antipsychotic drugs may cause tardive dyskinesia, a serious and sometimes irreversible disorder of body movement, so patients are asked to take them for long periods only when there is no alternative. After the psychosis has ended, the mood symptoms may be treated with antidepressants, lithium, anticonvulsants, or electroconvulsive therapy (ECT). Sometimes a neuroleptic is combined with lithium or an antidepressant and then gradually withdrawn, to be restored if necessary.

The few available studies on drug treatment of schizoaffective disorder suggest that antipsychotic drugs are most effective. The only controlled study of schizoaffective depression found that an antipsychotic drug alone worked as well as an antipsychotic drug taken with an antidepressant; ECT was the best treatment of all. Several preliminary studies suggest that the atypical antipsychotic drug clozapine is even more useful in schizoaffective disorder than in schizophrenia. One study found that elderly patients with schizoaffective disorder responded well to risperidone, another atypical antipsychotic drug that rarely causes tardive dyskinesia. The greater effectiveness of these new drugs may be partly due to their activity at receptors for the neurotransmitter serotonin, which is not influenced as strongly by standard antipsychotic drugs.

As matters stand today, the theoretical importance of understanding schizoaffective symptoms is greater than the practical significance of the diagnosis. The appearance of this syndrome --- a set of symptoms, not a disease --- repeatedly raises the question to what extent and in what ways mood and schizophrenic disorders are distinct. The term “schizoaffective” reflects uncertainty without resolving it, and perhaps remains in the psychiatric vocabulary partly for that reason. It serves as a reminder of the limitations of our knowledge and a way of keeping open for examination some of the most important issues in psychiatry.

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