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 disease 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 that are associated with treatment response and outcome. These variables, which are both trait and state dependent, include premorbid adjustment, age and mode of onset of illness, gender, duration of psychosis, schizophrenia subtype, primary negative symptoms, and extrapyramidal signs including tardive dyskinesia and plasma HVA and brain pathomorphology. In addition, the chronic effects of antipsychotic drug treatment may influence illness course both favorably and adversely as well as potentially altering the neurobiological substrates that mediate expression of the illness and treatment response. Finally, the question of whether the active phase of the illness involves a pathologic process that leads to illness progression is discussed. In light of this discussion, 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 consequences to the patient.