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

Negative symptoms have been associated with poor response to neuroleptics, enlarged ventricles, cognitive impairment, and poor outcome in schizophreni a. These associations appear, however, to be dependent on the phase of stud y, suggesting that acute-phase (phasic) negative symptoms may be pathophysi ologically distinct from enduring negative symptoms that persist through th e residual phase. To compare correlates of enduring and phasic negative sym ptoms, we studied 60 drug-free schizophrenic patients (DSM-III-R and SADS/R DC) at baseline, 4 weeks after neuroleptic treatment, and assessed the 1 ye ar outcome. We rated positive and negative symptoms at baseline and 4 weeks after treatment. At baseline, premorbid function, neuropsychological funct ion, ventricle-brain ratio (VBR) and symptom response to an anticholinergic agent were assessed, and a two-night sleep EEG and 1 mg dexamethasone supp ression test (DST) were conducted. Phasic negative symptoms were defined as the change in negative symptoms (baseline to 4 weeks) and enduring negativ e symptoms as severity of negative symptoms at 4 weeks. Patients had varyin g proportions of phasic and enduring symptoms; the two did not define disti nct 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, VER, poor performan ce 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 pathoph ysiological mechanisms. (C) 2000 Elsevier Science B.V. All rights reserved.