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The establishment of criteria for the definition of first-episode psychosis is complex. The literature on this topic is controversial in terms of the limits of duration of symptoms and the inclusion of prodromal symptoms, together with symptoms of the acute phase. Defining first-episode psychosis and determining the diagnostic outcome in the short term for early recognition and intervention might contribute significantly toward reducing later morbidity and chance of recovery. The aim of the current study is to examine the clinical presentation both at baseline and at short-term follow-up (2 years) with determination of the diagnostic outcome on the basis of systemic and structured instruments and frequent follow-up.Ninety drug-naïve patients were recruited consecutively from among inpatients after the exclusion of patients with first-contact psychosis who had neurological or central nervous system problems, chronic medical conditions, a history of or current substance abuse or dependence and mental subnormality. Assessment at baseline and after 2 years by structured DSM-IV interviews (SCID), PANSS, HDRS, YMRS, and WAIS as well as WMS-III. Demographics and clinical characteristics were obtained, and a consensus diagnosis was made on the basis of structured instruments, medical records, collateral information, and face-to-face interviews.Patients with first-episode psychosis were divided into three diagnostic outcome groups: schizophrenia spectrum (n=49; 54.4%), bipolar psychosis (n=21; 23.3%), and depressive psychosis (n=20; 22.2%). Patients in the schizophrenia spectrum were predominantly men, single, and students with no educational differentiation and with no familial risk compared with patients with other two diagnoses. Younger age, early age of onset, long duration of untreated psychosis and short duration of untreated illness, and low rate of hospitalization, but with longer duration of stability and higher sensitivity for extrapyramidal side effects were reported more in the schizophrenia spectrum group than the affective spectrum group. Cognitive functions were better in bipolar and depressive psychosis both at baseline and at the short-term assessment (2 years later) compared with schizophrenia spectrum patients, who showed more improvement after 2 years of assessment on attention and executive function than effective ones. Higher severity of depression was recorded on depressive psychosis in both steps of assessment than that in patients with bipolar schizophrenia. The mean YMRS scores were higher in patients with bipolar psychoses, followed by schizophrenia patients than the depressive group. PANSS five-factor analysis showed that negative symptoms and cognitive disorganization were the highly significant differentiating aspect of the schizophrenia spectrum group than the affective spectrum patients.Overlap of symptoms and clinical presentation in patients of first-episode psychosis both at baseline and for short-term outcome is quite common. Interacting longitudinal and cross-sectional assessment may help to clarify this complexity of presentation at first-episode psychosis. Focus on the differentiation of primary and secondary symptoms in researches as well as biological findings is important to clarify this heterogeneity.