The effects of chronic antipsychotic administration on the human brain are debated. In particular, first-generation (FGAs) and second-generation antipsychotics (SGAs) seem to have different impacts on brain function and structure in subjects with schizophrenia. Few studies have investigated the effect of chronic administration of FGAs and SGAs on indices of brain function, such as event-related potentials (ERP) or neuropsychological performance.

Within the Italian Network for Research on Psychoses study, subjects stabilized on FGAs or SGAs were compared on P300, an ERP component, thought to reflect attention, working memory and context integration and on neurocognitive indices.

ERPs were recorded in 110 chronic, stabilized patients with Schizophrenia (28 used FGAs) during a standard auditory oddball task. P300 latency and amplitude were assessed at Pz channel. MATRICS Consensus Cognitive Battery (MCCB) was used for cognitive assessment.

Compared with the SGAs group, patients on FGAs showed significant increased P300 latency (P = 0.003; Cohen's d = 0.67) and significant decreased P300 amplitudes (P = 0.023; Cohen's d = 0.38). The two groups did not differ on psychopathology and MCCB scores. Multiple linear regressions revealed that “FGAs vs. SGAs” (β = 0.298, P = 0.002) and MCCB neurocognitive composite T-score (β = –0.273, P = 0.004) were independent predictors of P300 latency, whereas only age (β = –0.220, P = 0.027) was an independent predictor of P300 amplitude.

FGAs seem to affect the functional brain activity more than SGAs, particularly slowing cortical processing. Our results suggest that discrepant findings concerning P300 latency in schizophrenia might be related to the type of antipsychotic treatment used. Longitudinal studies are needed to further address this issue.

The authors have not supplied their declaration of competing interest.