FACTORS INFLUENCING TREATMENT RESPONSE AND OUTCOME OF FIRST-EPISODE SCHIZOPHRENIA - IMPLICATIONS FOR UNDERSTANDING THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA

For the majority of patients, schizophrenia is a chronic recurrent dis ease that leads to significant residual morbidity which occurs through a process of behavioral deterioration. The factors that influence the course of schizophrenia after its onset and the ability of treatment to modify the effects of the patient's illness are not well understood . This article examines specific clinical and biological variables tha t are associated with treatment response and outcome. These variables, which are both trait and state dependent, include premorbid adjustmen t, age and mode of onset of illness, gender, duration of psychosis, sc hizophrenia subtype, primary negative symptoms, and extrapyramidal sig ns including tardive dyskinesia and plasma HVA and brain pathomorpholo gy. In addition, the chronic effects of antipsychotic drug treatment m ay influence illness course both favorably and adversely as well as po tentially altering the neurobiological substrates that mediate express ion of the illness and treatment response. Finally, the question of wh ether the active phase of the illness involves a pathologic process th at leads to illness progression is discussed. In light of this discuss ion, we can speculate that although certain aspects of the illness in terms of its severity and course may be, to an extent, predetermined, a number of factors can exert favorable and unfavorable effects on the course of the illness and its ultimate outcome. One question for the field is to develop therapeutic strategies that minimize the morbidity of the illness in a way that does not introduce iatrogenic consequenc es to the patient.