Empirical Validation of Primary Negative Symptoms: Independence From Effects of Medication and Psychosis

OBJECTIVE: Recent studies of negative symptoms in schizophrenia—specifically, those involving the deficit syndrome—have focused on uncovering the symptoms that are primary to the disease rather than secondary to the psychotic process. One of the foremost concerns in this effort is establishing whether the negative symptoms observed are the result of medication effects. METHOD: This study used negative symptom ratings obtained in a drug withdrawal paradigm to compare symptom profiles in the same schizophrenic patients when they were on and off antipsychotic drug treatment. The study group consisted of 93 physically healthy male patients with DSM-III-R-defined schizophrenia. Principal components analysis was performed on negative symptom data obtained separately during haloperidol treatment and again when the patients were drug free to determine whether there were meaningful factor scores that were consistent across medication conditions. Drug withdrawal effects on negative symptom factors were then tested for associations with secondary sources of variance including extrapyramidal side effects, anxiety/depression, and psychosis. RESULTS: Two factors, termed affective flattening and diminished motivation, exhibited similar loadings when the patients were both on and off medication. Changes in motivation were associated with changes in anxiety/depression and psychosis, while changes in affective flattening were associated with changes in extrapyramidal side effects. CONCLUSIONS: The documented secondary sources of negative symptoms are related to different and distinct aspects of negative symptoms; this finding will aid in the identification of primary negative symptoms. (Am J Psychiatry 1999; 156:406–411)