Delayed Visual NA Potential in Remitted Schizophrenia: A New Vulnerability Marker for Psychotic Relapse under Low-Dose Medication Hiroo Matsuoka, Kazunori Matsumoto, Hisato Yamazaki, Sumiko Yoshida, Yohtaro Numachi, Hidemitsu Saito, Takashi Ueno, and Mitsumoto Sato Background: Lasting cognitive dysfunction throughout remission has been regarded as a biological vulnerability in schizophrenia, which may produce psychotic relapses with characteristic symptoms. Our hypothesis was that an abnormality in event-related potentials (ERPs) may be a neurophysiological marker of vulnerability to psychotic relapse in remitted schizophrenia. We conducted a 2-year follow-up study after evaluating ERP abnormalities to find a new ERP marker for schizophrenic relapse. Methods: Visual ERPs were recorded from outpatients with remitted schizophrenia under maintenance pharma- cotherapy (n = 44) and normal controls (n = 20) during a letter discrimination task. Based on the prospective study, the patients were divided into a relapse group (n = 20) and a nonrelapse group (n = 24). ERP findings that related to psychotic relapse within 2 years were analyzed. Results: Compared with controls, the relapsers showed ERP abnormalities in the NA, N2, and P3 components, and the nonrelapsers in the P3 component. The peak latency of the NA potential was delayed significantly in the relapse group relative to the nonrelapse group, and predicted a psychotic relapse with about 90% prob- ability. Conclusions: The delayed NA, which reflects early per- ceptual disorganization, may be a promising neurophysi- ological predictor of psychotic relapse in remitted schizo- phrenia under maintenance pharmacotherapy. Biol Psychiatry 1999;45:107–115 © 1999 Society of Biologi- cal Psychiatry Key Words: Schizophrenia, psychotic relapse, vulnerabil- ity, event-related potential, NA potential Introduction D iscontinuation of maintenance pharmacotherapy may produce psychotic relapse in about 75% of schizophrenic patients even after a long remission period (Kane 1987; Kissling 1992), suggesting a lasting vulnerability to psychotic relapse in schizophrenia. While many double-blind, placebo-controlled clinical trials have demonstrated a significant prophylactic ef- fect of maintenance pharmacotherapy on psychotic relapse in schizophrenia (Davis 1975; Kane 1987; Kissling 1992), long-term pharmacotherapy, even in combination with psychosocial therapy, cannot com- pletely prevent psychotic relapse (Hogarty et al 1974) and may induce neuroleptic-induced tardive dyskinesia or tardive dystonia. In addition, several long-term follow-up studies on schizophrenia have demonstrated a variety of clinical courses and outcomes (Bleuler 1978; Ciompi and Mu ¨ller 1976; Harding et al 1987a, 1987b; Huber et al 1975, 1980; Shepherd et al 1989; Tsuang et al 1979), which may depend upon the vulnerability to psychotic decompensation (Ciompi and Mu ¨ller 1976). Although various neurophysiological deviations indi- cating attention deficits, abnormal pursuit eye move- ments, and abnormal P3 components of event-related potentials (ERPs) have been found in schizophrenia, their relationships to psychotic relapse have not been fully examined. A new reliable vulnerability marker that enables us to predict the possibility of psychotic relapse is needed for improving current prophylactic treatments after recovery from schizophrenic episodes. Recently we reported a conspicuous information- processing deficit in remitted schizophrenia assessed by endogenous ERPs in an attention-dependent, geometri- cal-figure discrimination task (Matsuoka et al 1996). In this study, we evaluated the endogenous ERPs of remitted schizophrenic subjects in a letter discrimina- tion task, and examined the correlation between the ERP findings and psychotic relapse in a 2-year fol- low-up period. From the Department of Psychiatry, Tohoku University School of Medicine (HM, KM, HY, SY, YN, MS), and Department of Educational Psychology, Tohoku University Faculty of Education (TU), Sendai, Japan; and Minami-Hanamaki National Hospital, Hanamaki, Japan (HS). Address reprint requests to H. Matsuoka, MD, Department of Psychiatry, Tohoku University School of Medicine, Sendai 980-8574, Japan. Received February 24, 1997; revised August 25, 1997; accepted November 12, 1997. © 1999 Society of Biological Psychiatry 0006-3223/99/$19.00 PII S0006-3223(97)00526-X