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Research and treatment strategies in first-episode psychoses: the Pittsburgh experience.

Keshavan MS, Schooler NR, Sweeney JA, Haas GL, Pettegrew JW (1998).

British Journal of Psychiatry 172 (Suppl 33): 60-65.

Studies of individuals with first-episode schizophrenia help avoid the confounding influences of chronicity, medication effects, and institutionalization on neurobiological alterations, as well as on the course of illness. In this study, baseline neurobiological evaluations of first-episode patients revealed structural and functional brain abnormalities consistent with a neurodevelopmental model of schizophrenia. The authors conclude that such changes probably take place prior to the onset of illness; however, because such changes occur progressively over time, early intervention may halt some of the expected changes.

Preliminary data also supported the value of risperidone as an antipsychotic medication for individuals suffering from their first episode of schizophrenia. Until now, atypical antipsychotic medications have been used for predominantly chronic patients.

The authors begin by reviewing the often confusing findings regarding whether there are changes in the brains of individuals with schizophrenia and, if such changes exist, they occur before or after the onset of the illness. The authors’ review of the literature concludes that such changes do exist, and that they probably occur prior to illness onset.

This article then summarizes preliminary findings from ongoing magnetic resonance imaging (MRI) and spectroscopy studies of first-episode schizophrenia patients.Patients were studied for a period of two years. In this study, the authors focused on longitudinal changes in the structure of the basal ganglia. In a series of 16 patients with first-episode schizophrenia, baseline neurobiological evaluations revealed structural and functional brain abnormalities consistent with a neurodevelopmental model of schizophrenia. Significant reductions in caudate volume were seen prior to initiation of treatment, compared with people who had a non-schizophrenic psychosis and healthy controls. In a subset of 11 people with first-episode, treatment-naive schizophrenia treated with typical antipsychotic medications, follow-up MRI scans revealed a significant increase in caudate volume. Past studies have suggested that structural changes in basal ganglia related to antipsychotic medications may be confined to typical medications.

Because some studies have suggested that delay from onset of illness to first treatment is associated with more severe psychotic symptoms, poorer functioning, and less adequate response to antipsychotic medications, 19 patients who had previously untreated first-episode schizophrenia were also studied. An inverse relationship was found between illness duration and the volume of the left superior temporal gyrus. Other studies looking at the correlation between various brain abnormalities and duration of psychosis have produced mixed results.

During the two-year period, patients received treatment with either typical antipsychotic medications or the atypical antipsychotic medication risperidone. All 16 patients had not previously been treated with antipsychotic medications. Preliminary data support the value of risperidone as an antipsychotic medication for individuals suffering from their first episode of schizophrenia. Both groups showed significant improvement in negative and positive symptoms, as well as in global functioning. Furthermore, significantly fewer people taking risperidone needed concomitant administration of anticholinergic agents.

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