Phasic and enduring negative symptoms in schizophrenia: biological markers and relationship to outcome.

Negative symptoms have been associated with poor response to neuroleptics, enlarged ventricles, cognitive impairment, and poor outcome in schizophrenia. These associations appear, however, to be dependent on the phase of study, suggesting that acute-phase (phasic) negative symptoms may be pathophysiologically distinct from enduring negative symptoms that persist through the residual phase. To compare correlates of enduring and phasic negative symptoms, we studied 60 drug-free schizophrenic patients (DSM-III-R and SADS/RDC) at baseline, 4 weeks after neuroleptic treatment, and assessed the 1 year outcome. We rated positive and negative symptoms at baseline and 4 weeks after treatment. At baseline, premorbid function, neuropsychological function, ventricle-brain ratio (VBR) and symptom response to an anticholinergic agent were assessed, and a two-night sleep EEG and 1mg dexamethasone suppression test (DST) were conducted. Phasic negative symptoms were defined as the change in negative symptoms (baseline to 4 weeks) and enduring negative symptoms as severity of negative symptoms at 4 weeks. Patients had varying proportions of phasic and enduring symptoms; the two did not define distinct subgroups. Phasic negative symptoms were significantly correlated with global treatment response, positive symptom treatment response, response to anticholinergic agent, baseline post-dexamethasone cortisol, and shortened REM latency. Enduring negative symptoms were significantly correlated with residual positive symptoms and global psychopathology, VBR, poor performance on neuropsychological testing, decreased slow-wave sleep, poor premorbid function, and poor 1 year outcome. These data suggest that phasic negative symptoms and enduring negative symptoms may be caused by different pathophysiological mechanisms.