Negative symptoms undermine social, vocational, and recreational functioning in people with schizophrenia, according to results from a study evaluating a large patient sample.
The study, published recently (Eur. Psychiatry 2014 [doi: 10.1016/j.eurpsy.2014.01.007]), is one of few that have looked at the relationship between primary negative symptoms and functional outcomes while also controlling for potential secondary sources of negative symptoms, such as drug-related akinesia.
Distinguishing between primary and secondary negative symptoms is difficult but important in clinical practice, the study’s authors noted, because underlying pathophysiology and treatment strategies can differ between the two.
The researchers, led by Gagan Fervaha of the Centre for Addiction and Mental Health and the University of Toronto, hypothesized that a higher burden or severity of primary negative symptoms – including blunted affect, emotional withdrawal, poor rapport, motor retardation, and active social avoidance – would have a significant effect on functional outcomes.
Mr. Fervaha and his colleagues examined 1,427 records from patients enrolled in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) Schizophrenia Trial, a large randomized, controlled trial comparing various antipsychotic medications. All patients in the trial were evaluated before randomization and treatment initiation using validated scores: the Positive and Negative Syndrome Scale (PANSS); the Calgary Depression Scale for Schizophrenia (CDSS); the Simpson-Angus Scale (SAS), which measures extrapyramidal side effects; and the Heinrichs-Carpenter Quality of Life Scale.
Negative symptoms at baseline, Mr. Fervaha and his colleagues found, were significantly correlated with poorer scores in interpersonal relations (r = –0.42; P less than .001), instrumental role functioning (r = –0.24; P less than .001) and use of common objects and activities (r = –0.30; P less than .001). Greater negative symptom burden was associated with worse functioning.
Primary negative symptoms were significantly and inversely related to functioning even after potential sources of secondary negative symptoms – such as psychosis, depression, anxiety, and extrapyramidal symptoms – were controlled for, the researchers found. After further controlling for sociodemographic and clinical variables such as age, sex, substance abuse, and obesity, primary negative symptoms "still held a significant and inverse relationship with each facet of functioning evaluated," they wrote.
"Negative symptoms were found to be a significant contributor to the functional impairment seen in patients with schizophrenia," the authors concluded. "While many studies have noted this relationship, the present study extends these findings and confirms that primary idiopathic negative symptoms serve as an impediment to functional recovery."
Treatments aimed at primary negative symptoms should promote functional recovery, they said, and investigations into the underlying pathobiology of negative symptoms "should take into account the potential for these symptoms to co-vary with other clinical factors."
The researchers noted that the limitations of their study included the fact that subjects were entering into a treatment trial, meaning that the findings might not be generalizable to patients stabilized on their medications. Also, the list of factors included to control for secondary sources of negative symptoms was not exhaustive, "and it is thus possible that some of the variance ascribed to primary negative symptoms is in fact due to nonidiopathic influences (e.g., environmental deprivation)," they said.
The study was funded by the Centre for Addiction and Mental Health. Mr. Fervaha’s three coauthors disclosed financial relationships with Medicure, Neurocrine Biosciences, and several other companies.