Psychiatric comorbidity is common in psychotic disorders, but the chronology of comorbid and principal diagnoses has not been closely examined. Understanding chronology may be important for identifying risk factors, or alternatively, prodromal syndromes, for some patients with psychosis. To address this issue, we examined the rates of antecedent comorbid syndromes in patients with first-episode psychoses. Patients aged > or = 12 years presenting with psychosis were recruited from inpatient and outpatient treatment sites. Patients were excluded if they had been previously hospitalized or if symptoms resulted entirely from substance abuse or medical illness. All diagnoses were made using the Structural Clinical Interview for DSM-III-R-Patient Version (SCID-P). Comorbidity was defined as antecedent if the age of onset of the comorbidity predated the age of the onset of the psychotic disorder by more than 1 year. Seventy-one patients were recruited during a 1-year period and included 39 with bipolar disorder, 18 with schizophrenia spectrum disorders, and 14 with psychotic depression. Comorbidity was present in 69% of patients. This comorbidity was antecedent in over 80% of the patients with concurrent syndromes. Patients with psychotic depression had the highest rates of comorbidity, in particular alcohol abuse and antecedent posttraumatic stress disorder (PTSD). Comorbidity is common in first-episode psychosis and is often antecedent to the psychotic disorder. These antecedent comorbidities may represent risk factors or prodromal syndromes for the psychotic disorder.