In medicine the understanding of a disease, and therefore its diagnosis, is ultimately based on identification of (1) etiological factors (such as microbes, toxins, or genetic risks) and (2) pathogenesis (mechanisms by which etiologic agents produce disease). Unfortunately, the etiology and pathogenesis of most mental disorders have not been determined. As a result, psychiatric diagnoses still rely on the patient's description of symptoms, the examiner's observations, a detailed natural history (the course of the illness over time), and the response to treatment.
This approach to psychiatric diagnosis began at the turn of the 20th century with the work of Emil Kraepelin in Germany. Influenced by Rudolf Virchow, the German pioneer of cellular pathology, and by Thomas Sydenham, the English clinician who focused attention on the natural history of medical diseases, Kraepelin studied mental disorders as specific disease processes. Even without knowledge about the etiology and pathogenesis, of diseases affecting thought, emotion, and behavior, he argued, such diseases could still be distinguished on the basis of signs, symptoms, and natural history.
Of course, the presentation of a single sign or symptom is not in itself evidence for disease because it may occur in healthy people. But when certain signs and symptoms occur together they form a syndrome, a condition that can be distinguished from normal behavior or from other clusters of signs and symptoms. The natural history of a disease is studied by tracing the onset of signs and symptoms in patients' lives and how they change with time. Thus a syndrome can emerge at a characteristic age or it can follow a characteristic clinical course. For example, Kraepelin recognized that most patients with schizophrenia (which he called dementia praecox) do not recover the level of functioning they had prior to the onset of the disease, whereas most patients with mood disorders experience cycles of relapse and at least partial recovery.
Since the 1980s the diagnosis of psychiatric disorders has been based on standardized criteria that have made diagnosis more reliable. Two different clinicians applying standardized criteria for schizophrenia are very likely to arrive at the same diagnosis. Nevertheless, without etiological or pathophysiological data and lacking objective tests, current diagnostic systems such as the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) of the American Psychiatric Association cannot define disease states in scientifically verifiable terms. With progress in such areas as genetics and neuroimaging, it eventually should be possible to arrive at objectively verifiable and thus valid diagnostic criteria for mental disorders.
The Symptoms of Schizophrenia Can Be Grouped into Positive, Negative, and Cognitive
It is useful to subdivide the symptoms of schizophrenia into three clusters because each may reflect different aspects of the pathophysiology and because each responds differently to the medications presently used. Positive or psychotic symptoms include mental phenomena that do not occur in healthy people, such as hallucinations and delusions. Negative (or "deficit") symptoms result from impairment of normal functions and can include blunted emotional responses, withdrawal from social interactions, impoverished content of thought and speech (Box 62–1), and a lack of motivation.
Box 62–1 Schizophrenic Speech
Language disturbance is a central feature of schizophrenia and one of the primary behaviors by which it is diagnosed. Grammar is reasonably intact, but content can wander or be incoherent, a symptom that is commonly referred to as "loosening of associations." More bizarre but less common patterns of speech include neologisms (idiosyncratically invented words), blocking (sudden spontaneous interruptions), or clanging (associations based on the sounds rather than the meanings of words, such as "If you can make sense out of nonsense, well, have fun. I'm trying to make cents out of sense. I'm not making cents anymore. I have to make dollars.")
Examples of loosening of associations are:
"I'm supposed to be making a film, but I don't know what is going to be the end of it. Jesus Christ is writing a book about me."
"I don't think they care for me because two million camels … 10 million taxis … Father Christmas on the rebound."
Question: "How does your head feel?" Answer: "My head, well that's the hardest part of the job. My memory is just as good as the next working man's. I tell you what my trouble is, I can't read. You can't learn anything if you can't read or write properly. You can't pick up a nice book, I don't just mean a sex book, a book about literature or about history or something like that. You can't pick up and read it and find things out for yourself."
Several different types of loosening of associations have been proposed (such as derailment, incoherence, tangentiality, or loss of goal). However, it remains unclear whether these reflect disturbances in fundamentally different mechanisms or different manifestations of a common underlying disturbance, such as the inability to represent a "speech plan" to guide coherent speech. A disturbance of such a mechanism would be consistent with, and may parallel, impairment of control of other cognitive functions in schizophrenia, such as deficits in working memory.
A third symptom cluster includes cognitive abnormalities—sometimes described as "disorganization symptoms." These symptoms impair working memory and executive functions—the ability to organize one's life. These cognitive symptoms typically persist even during otherwise successful treatment with medication and are thought to be significant contributors to long-term disability. Interestingly, cognitive symptoms can be found to some degree in persons at very high risk of developing schizophrenia but who have not yet experienced hallucinations or delusions, and in otherwise healthy relatives of patients with schizophrenia, suggesting that cognitive symptoms reflect genetic predispositions to schizophrenia.
The medications used to treat schizophrenia are called antipsychotic drugs and are most effective at diminishing the positive symptoms as well as psychotic symptoms that occur in mood disorders. None of the medications reliably benefits the cognitive symptoms.
Schizophrenia Is Characterized by Psychotic Episodes
The most dramatic manifestations of schizophrenia are psychotic symptoms, including hallucinations and delusions. Hallucinations are percepts that occur in the absence of appropriate sensory stimuli and can occur in any sensory modality. In schizophrenia the most common hallucinations are auditory. Typically, a patient hears voices, but noises or music are also common. Sometimes the voices will carry on a dialog and frequently are experienced as bullying and derogatory. Occasionally, voices will issue commands to the patient that can create a high risk of harm, including suicide. Neuroimaging studies of subjects experiencing auditory hallucinations suggest that areas normally involved in the processing of language are recruited during hallucinations. These include Broca's area in the frontal lobe and Wernicke's area in the superior temporal lobe of the cerebral cortex (see Chapter 60).
Delusions are firm beliefs that are not realistic and not explained by the patient's culture. They can be so powerful that sufferers cannot (or refuse to) compare their beliefs to what is actually happening in the world. Delusions can be quite varied in form. For some patients reality is distorted: The world is full of hidden signs meant only for them (delusions of reference), or they are being closely watched or persecuted (paranoid delusions). Others experience bizarre delusions, for example that some entity is inserting or extracting thoughts from their brain or that their dental fillings are radio transmitters broadcasting what they say to nefarious groups. Psychotic symptoms can also occur in mood disorders and drug-induced delirium, but the other symptoms and clinical course of those states are not consistent with schizophrenia.
The full emergence of schizophrenia is often preceded by a period of early symptoms. In this prodromal period the patient can behave eccentrically, become socially isolated, exhibit blunted affect, poverty of speech, a poor attention span, and lack of motivation. Once the disease is fully manifest, periods of florid psychosis typically occur, accompanied by markedly disordered thinking and abnormalities in the regulation of emotion. These periods of overt psychosis are interspersed with periods of residual symptoms. After the first few episodes the patient rarely returns to full normal functioning.