The Prevalence of Negative Symptoms in Schizophrenia and Their Impact on Patient Functioning and Course of Illness
Christoph U. Correll, MD
Recognition and Prevention Program (RAP), The Zucker Hillside Hospital, Glen Oaks; the Department of Psychiatry and Molecular Medicine, Hofstra-North Shore-Long Island Jewish School of Medicine, Hempstead; and the Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York
AV 1. The Illness Course of Schizophrenia Over Time (00:28)
Negative symptoms are key characteristics of schizophrenia, yet they have been neglected as core illness features and treatment targets. In early descriptions of schizophrenia, psychiatrists like Emil Kraepelin and Eugen Bleuler recognized problems such as avolition and anhedonia in patients,1,2 but through the years, positive symptoms (eg, hallucinations and delusions) have typically received more treatment focus than negative symptoms. It now appears that positive symptoms actually occur rather late in the illness progression and are generally preceded by negative symptoms ().3
Not only do negative symptoms appear earlier in the illness, but the extent of these symptoms also predicts long-term patient outcomes better than the presence of positive symptoms.4 Understanding the structure, prevalence, diagnosis, and impact of negative symptoms will help clinicians focus on this often overlooked area.
Structure of Negative Symptoms
In patients with schizophrenia, factor analyses of rating scale results have consistently separated negative symptoms from other illness characteristics like positive symptoms, affective symptoms (depression and anxiety), and disorganized thought, speech, and behavior.5 The 5 SANS-based negative symptom domains—affective flattening, inattention, alogia, avolition-apathy, and anhedonia-asociality—are partially intercorrelated and may be consolidated to 3 main factors: (1) diminished expression (affective flattening), (2) inattention-alogia, and (3) social amotivation.6
Within the domain of negative symptoms, researchers have tried to identify the core dysfunction. For example, Foussias and Remington2 proposed that avolition may be the driving force behind all negative symptoms. That is, because patients with schizophrenia may have reward system deficits, they have reduced goal-directed behavior.
In addition to avolition, anhedonia may be a core dysfunction of negative symptoms and an inherent feature of schizophrenia, but this idea has been debated since patients with schizophrenia have been shown to experience pleasure.2 According to a meta-analysis,7 although many patients with schizophrenia report the inability to experience pleasure, their ratings of pleasant stimuli are similar to those of controls—a discrepancy termed the anhedonia paradox.1 These patients do not seem to be able to envision, fully appreciate, or anticipate satisfaction from certain activities, which is why they do not engage in them. But, when they do participate in enjoyable activities, they rate the hedonic value as being almost equal to that of people without schizophrenia. Rather than anticipating something in the future, patients feel consummatory pleasure for something in the moment. These explanations are tempered by the possibility that the patients’ assessment and recollection of pleasure may be altered.
Prevalence of Negative Symptoms
AV 2. Ranges of Prevalence Rates of Negative Symptoms in Patients With Schizophrenia (00:26)
According to 3 studies,8–10 social amotivation is the most prevalent negative symptom, followed by diminished expression, and then inattention-alogia (). The prevalence of negative symptoms, even in patients taking antipsychotics, is a relevant problem that must be addressed.
Using the PANSS, an analysis11 of patients with treated schizophrenia spectrum disorders revealed that 50% had at least 1 negative symptom and 18% had all 5 negative symptoms (the most frequent being social or emotional withdrawal). Compared with patients with schizophreniform and schizoaffective disorders, those with schizophrenia had significantly higher average negative symptom scores (P < .05). The prevalence of negative symptoms was also higher in men who were single and unemployed, had reduced functioning, and were taking a higher antipsychotic dosage.
Diagnosis of Negative Symptoms
Negative symptoms may be primary or secondary to other symptoms or disorders. To make a differential diagnosis in a patient with schizophrenia, clinicians need to rule out a number of presentations that are caused by different underlying psychiatric conditions including depression, anxiety, and pronounced paranoia. For example, paranoid or persecutory delusions (which are positive symptoms) might cause the patient to be socially withdrawn. Also, medication-induced side effects, like sedation and EPS, as well as chronic pain or environmental deprivation/understimulation, may also present as secondary negative symptoms.
Secondary negative symptoms usually respond to treatment of the underlying cause, but no intervention is currently available to treat primary negative symptoms.12 Primary or secondary negative symptoms that do not resolve are called persistent or enduring negative symptoms.13 Persistent negative symptoms continue even during clinically stable periods, impede the patient’s normal role functions, and remain an unmet therapeutic need.14 Buchanan13 proposed criteria for defining persistent negative symptoms, which must be at least moderately severe on an accepted rating scale such as the PANSS or SANS.
When considering negative symptoms as persistent, clinicians should differentiate continued symptomatic presentation of negative symptoms from schizophrenia with deficit syndrome. This form of psychosis may present predominantly with negative symptoms (diminished expression, amotivation, asociality, alogia), but deficit syndrome symptoms last longer and are more severe than persistent negative symptoms, resulting in a different course of illness and treatment response.13
Impact of Negative Symptoms
Although often overlooked, negative symptoms greatly affect patients’ functioning and predict real-world behavior. For example, a long-term study15 found that negative symptoms increased in severity over the first 5 years for patients with deficit syndrome. After 19 years, almost 70% of deficit patients spent more time hospitalized, less time working, and less time socializing than those without deficit syndrome.
AV 3. The Effect of High and Low Levels of Negative Symptoms in Schizophrenia on Long-term Outcome (00:25)
Physical and social anhedonia are also associated with poor health-related quality of life.16 One study17 of patients with schizophrenia found that those who had more mixed and ambivalent emotional responses to positive stimuli than healthy controls had significantly higher anhedonia (P = .01) and PANSS negative subscale scores (P = .01) in addition to a lower quality of life (P = .05) and reduced interpersonal relations (P = .02) than patients who showed emotional responses similar to those of healthy controls. Another analysis4 showed that patients with high levels of negative symptoms had an insidious illness onset, a more continuous illness course, poorer long-term functioning, and poorer premorbid functioning, including acquiring less occupational skills and avocational interests and having a lower IQ, than those with low levels of negative symptions (). Predictors of long-term outcome included anhedonia, acquisition of skills and interests, and affective flattening.
Another early indicator of poor outcome in patients with schizophrenia is cognitive dysfunction. Cognitive performance appears to affect patients’ ability to perform everyday living skills (functional capacity), while negative symptoms affect patients’ likelihood of performing these skills (functional performance).18
To lessen the potentially severe impact of negative symptoms on patients’ functioning, clinicians must include these symptoms in the treatment plan. The current treatment options for schizophrenia are more effective for alleviating positive rather than negative and cognitive symptoms. While first- and second-generation antipsychotics treat psychotic positive symptoms very well, cognitive and negative symptoms are largely areas of unmet therapeutic need, requiring clinicians to consider combinations of antipsychotics with other medications or therapy.
Negative symptoms of schizophrenia are categorized in the domains of diminished expression, inattention and alogia, and social amotivation. Negative symptoms are prevalent and greatly affect patients’ functioning, long-term outcomes, and quality of life, and therefore require attention as core features and treatment targets in schizophrenia. As research into the pathophysiology and effective treatment of negative symptoms continues, clinicians may be able to better address these issues and improve the often seriously impaired social and occupational functioning of their patients.
For Clinical Use
- Recognize the negative symptoms related to the primary symptom domains of diminished expression, inattention-alogia, and social amotivation in patients with schizophrenia
- Differentiate persistent negative symptoms and the deficit syndrome
EPS = extrapyramidal side effects
PANSS = Positive and Negative Syndrome Scale
SANS = Scale for the Assessment of Negative Symptoms
Take the online posttest.
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