div class=”ChapterContextInformation”>
7. Natural History of Schizophrenia
Keywords
Natural historyCourseOnsetChildhood-onset schizophrenia (COS)Late-onset schizophrenia (LOS)Very late-onset schizophrenia-like psychosisPostpartum psychosisPremorbid phaseProdromeFirst episode of psychosisConrad stages of beginning psychosisChronic schizophreniaPsychotic relapseLong-term outcomePrognosisCultureEssential Concepts
Schizophrenia is a clinical diagnosis based on a combination of characteristic symptoms of sufficient duration and severity (in the absence of other factors that would account for them) that typically begin in late adolescence or early adulthood. Female patients have a later illness onset, including a second peak around menopause.
In some patients, the onset of schizophrenia is already in childhood (childhood-onset schizophrenia) or later in life (late-onset schizophrenia and very late-onset schizophrenia-like psychosis).
Patients who develop schizophrenia undergo a transition through several phases: from a premorbid phase (clinically silent) to a prodromal phase (unspecific symptoms) before they enter their first episode of psychosis (frank psychosis).
An unspecific prodromal phase of several months or years precedes the onset of psychosis. Poor concentration, depression, social withdrawal, and role failure characterize the prodrome. Attenuated psychotic symptoms begin to appear at the end of the prodromal period, heralding the emergence of full psychosis.
At the beginning of schizophrenia, patients may first experience delusional mood (“something is up”) that is followed by delusional perceptions and self-referential delusions.
Once a first episode of schizophrenia is successfully treated, there is a high-risk of recurrence of psychotic symptoms. For most patients, schizophrenia is a relapsing-remitting illness, with periods of acute psychotic against a background of chronic negative and cognitive symptoms that are stable.
Psychotic relapse in a chronic patient is usually preceded by a several-week period of nonpsychotic symptoms that follows a predictable course and symptom development unique to this patient.
We are not very good at predicting the eventual outcome of schizophrenia-spectrum disorders, with outcomes ranging from full recovery to severe, unremitting illness requiring institutionalization. In most cohorts, about one quarter of patients does well, regardless of treatment received.
The sociocultural context of care impacts prognosis greatly, particularly if treatment is available or not. The reported better clinical outcomes in developing countries may be overstated.
“It’s tough to make predictions, especially about the future.” [1]
Often (mis-)attributed to Yogi Berra, baseball Hall of Famer, 1972
The father of psychiatric nosology, Emil Kraepelin, divided severe psychiatric disorder into the episodic mood disorders (i.e., manic-depressive illness or bipolar disorder) and non-episodic psychotic disorders (i.e., dementia praecox or schizophrenia) [2]. Now, 100 years later, we still use this fundamental dichotomy. In his scheme, schizophrenia is the prototypical psychotic illness marked by prominent psychosis in the absence of psychiatric or medical disorders that would explain psychosis; patients who have this disease suffer from some degree of social impairment. In the real world of clinical cases, patients do not always fit the syndrome of schizophrenia: some patients experience short periods of illness without obvious impairment; others display rather significant admixtures of mood symptoms (see previous chapter). In this chapter, I provide a clinical description of the schizophrenia that focuses on its “natural history” or the progression through several illness phases (prodrome, acute psychosis, chronic phase) as the correct diagnosis of schizophrenia hinges on knowledge about the longitudinal history. How to make a clinical diagnosis of schizophrenia using current diagnostic criteria is discussed in the next chapter.
Natural History
Modern and narrowly defined schizophrenia follows a rather prototypical longitudinal illness course. The natural history of schizophrenia can be divided into four clinical phases [3]. A clinically asymptomatic premorbid phase gives way to a prodromal period with progressive yet unspecific symptoms until frank psychosis develops and a patient experiences his first psychotic episode of psychosis. Finally, patients enter a relatively stable chronic phase.
Schizophrenia is typically a disease of late adolescence or early adulthood. About 50% of patients will become ill between ages 15 and 25 and about 80% between ages 15 and 35. However, earlier illness onset during childhood and much later onset during late adulthood are possible (see below). Gender differences exist: more males than females are affected, and females have a later onset (by about 3–4 years) and a less virulent disease, with fewer negative symptoms [4]. Females also have a second peak around menopause. The typical male patient experiences his first psychotic episode in college.
Typical course of schizophrenia. Note the following features: excellent and quick recovery after first episode (V-shaped). Increasing difficulties to achieve prior level of function with each relapse. Eventual plateau at patient’s own level of disability (no progressive decline)
You may rightly criticize the term “natural history” of schizophrenia as it assumes a disease process that relentlessly drives an outcome that is completely independent from any external factors. Paul Farmer has pointed out that there is no such thing as a “natural history” of disease as all disease takes place in a particular time and place [8]. The “natural” history of tuberculosis in the twenty-first century in Boston is going to be one of early identification through screening and treatment which is not the same natural history for an inmate in a Russian prison who will die from tuberculosis. Even if we stipulate that “natural” means no treatment, we recognize that the availability of clean water, for example, may make a difference in surviving a diarrheal infection – there is always a context, and isolating a disease from its context is only possible in the most abstract way. As an abstraction, however, the natural history of schizophrenia remains a useful idea as we can create a blueprint for a prototypical illness course that allows us to diagnose schizophrenia and devise treatments to change disease trajectories.
Key Point
The longitudinal history is critical for a diagnosis of schizophrenia. Without understanding the course of the illness, you will not be able to differentiate schizophrenia from other disorders, particularly good-prognosis atypical psychotic disorders or episodic mood disorders.
Childhood-Onset Schizophrenia
Childhood-onset schizophrenia (COS), arbitrarily (and inconsistently) defined as onset by age 12, is very rare but not impossible [9]; it is extremely rare before age 10. Its prognosis is ominous. Many children have problems that are apparent long before the onset of psychosis: premorbid function is poor, and children are developmentally delayed in language, motor development, and social skills. The younger a child, the more difficult the diagnosis; normal development (e.g., imaginary friends) must be taken into account to avoid overdiagnosing schizophrenia in childhood.
The symptoms of COS are similar to the symptoms seen in adults, with the obvious adjustment for age-appropriate themes (e.g., “monsters”). Multiple domains of perception are usually affected (auditory hallucinations, visual hallucinations, tactile hallucination). The more persistent symptoms suggestive of psychosis are, the more one should worry about the possibility of a psychotic disorder; the more fleeting or unclear the psychotic symptoms, the more one should consider other diagnoses, e.g., dissociative disorders or autism-spectrum disorder (see Chap. 6). Family history can help, as genetic loading is more common in COS. One important developmental task of childhood is schooling; every effort should be made to successfully complete the afflicted child’s education.
Late-Onset Schizophrenia
Schizophrenia is generally not considered a disorder of middle or old age, but a significant minority of patients (around 10%) has late-onset schizophrenia (LOS) [10]. Dilip Jeste, a researcher specializing in LOS, has argued that age of onset between 40 and 60 years should be considered LOS [11]. What if psychosis develops after 60 or 65? For this age bracket, the term “very late-onset schizophrenia-like psychosis” has been proposed to indicate the somewhat different clinical features and probably risk factors vis-à-vis LOS [12].
Most patients with LOS are female, with better-preserved cognition, less prominent or no affective blunting, and no formal thought disorder. The positive symptom presentation is often paranoid. To me, late-onset paranoid schizophrenia in females with no blunting or thought disorder starts to look very much like delusional disorder. British authors in particular use the term “late paraphrenia” for cases of late-life psychosis [13]: lonely, never-married, elderly “spinsters” with problems hearing who develop a paranoid psychosis with few other symptoms. For some patients with LOS, the onset of psychosis represent the prodrome of what will later turn out to be a dementing illness [14].
Tip
I would suggest that you look very hard for medical disorders in any elderly person presenting with psychosis, including early dementia, subclinical delirium, unrecognized alcohol use, or psychotic depression before diagnosing schizophrenia or delusional disorder. Make sure patients are not sensory deprived, and get them eye glasses and hearing aids [15].
Postpartum Psychosis
While postpartum depression is common, mild, and self-limited, the perinatal period also increases the risk for serious psychiatric disorders [16]. Postpartum psychosis (puerperal psychosis) which occurs within 1 month of childbirth is rare, occurring in 1 out of 1000 births [17]. In most cases, postpartum psychosis is the expression of bipolar illness (psychotic mania) and not of schizophrenia [18]. In future pregnancies, prophylactic treatment is necessary since the recurrence risk is high (around 30%) [19]. Postpartum psychosis is a psychiatric emergency, and a mother who develops postpartum psychosis needs to be hospitalized. There is a risk of maternal infanticide which, if it occurs, leads in the United States to draconian punishment of the mother [20].
Premorbid Phase
This phase is clinically silent, at least on the surface. If one looks more closely, one can find clues in some children that hint at a brewing neurodevelopmental disorder. In birth cohort studies, antecedents of schizophrenia include motor delays and language deficits [21]. Academic underachievement in schizophrenia compared to their peers and siblings is another well-established finding [22]. However, childhood precursors of schizophrenia are non-specific and also only present in a subgroup of children who will later be diagnosed with schizophrenia. Most clumsy children will not go on to develop schizophrenia, whereas, conversely, the star athlete in high school may. Nevertheless, the group-level finding of cognitive changes that translate into educational difficulties in middle school or even earlier is important if we want to develop effective interventions to prevent schizophrenia [23]. The neurodevelopmental origin of schizophrenia challenges us to answer the question when schizophrenia begins.
Schizophrenia Prodrome
In medicine, many illnesses are preceded by an unspecific prodromal state during which no diagnosis can be made (e.g., erythema infectiosum or fifth disease) until certain characteristic symptoms (telltale rash in this case) appear. Similarly, the full syndrome of schizophrenia with frank psychosis is preceded in most cases by a prodrome that varies in length from several weeks to years. The ABC Schizophrenia Study was an influential cohort study conducted in the Heidelberg-Mannheim area, Germany, that retrospectively collected detailed information about the period before admission for a first episode of psychosis [24]. Lessons learned from this study gave rise to attempts to identify putatively prodromal patients prospectively in order to prevent schizophrenia (see Chap. 9 on prevention and clinical staging and Chap. 11 on first-episode psychosis).
Key Point
A prodromal period of 2–4 years with unspecific symptoms and social difficulties is often present before acute psychosis declares the presence of schizophrenia [24]. Given its non-specific nature per definitionem, a prodrome can only be determined retrospectively. About 20% of patients experience no prodrome but have a rather abrupt onset of psychosis.
Prodromal symptoms of schizophrenia
Change in thinking and feeling |
Unspecific (early): anxiety, depression, difficulties concentrating, difficulties sleeping |
Attenuated psychotic symptoms (late): ideas of reference, paranoia, “odd,” unusual perceptions, difficulties communicating, preoccupation with new ideas |
Impaired function |
Role failure (drop in grades or job performance) |
Decline in self-care |
Social withdrawal |
Not only are prodromal symptoms unspecific, but they are also prevalent in normal populations. In one survey of 657 normal 16-year-old high school students, individual prodromal symptoms were endorsed at rates reaching 50% [28]. The prodromal phase of schizophrenia has received much attention, as there is hope that treatment during the prodrome might prevent schizophrenia or change its “natural” course if treated earlier (see Chap. 9 on prevention and clinical staging).
Tip
As you are reviewing a person’s longitudinal history, see if you can identify a “Knick in der Lebenslinie” (a “bend in the life line”) which is when the person began to deviate from a projected trajectory. In many patients, families are able in hindsight to pinpoint to a period when their son or daughter changed in very significant ways and started doing things out of character for them and inconsistent with their upbringing and interests. A well-adjusted college student, with friends and sports activities who had planned to go to medical school but instead takes off to go to India to study “the nature of being,” is an example where a psychotic process explains his behavior better than some adolescent rebellion. The more “normal” a person was prior to illness onset, the more obvious this “Knick” will be.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
