Abstract
Neural Effects of Ziprasidone Monotherapy in First-Episode Schizophrenia: A Longitudinal Study using fMRI and a Procedural Learning Paradigm
Author(s): Veena Kumari , Anantha P. P. Anilkumar , Dominic H. ffytche ,Ravi Mehrotra , Martina T. Mitterschiffthaler , Tonmoy SharmaIntroduction: Deficient procedural learning (PL) and lack of striato-thalamic-cortical activity in chronic schizophrenia patients on typical antipsychotics, compared to healthy people, has been previously demonstrated. There is also evidence of striatal dysfunctioning with normal or near-normal performance in schizophrenia patients treated mostly or predominantly with atypical antipsychotics. The purpose of this study was to examine procedural learning and its neural correlates, as well as the effect of ziprasidone monotherapy on neural responses using functional magnetic resonance imaging (fMRI) and a relatively simple non-verbal, sequence-learning task in a longitudinal design in firstepisode patientswith schizophrenia. Methods:Acohort of patientswhowere experiencing their first psychotic episode and had no or minimum exposure to antipsychotic medication underwent blood oxygenation level-dependent fMRI during a blocked, periodic procedural learning task at baseline (pretreatment) and again after six-week ziprasidone monotherapy. Behavioral data were recorded online. Results: We found 1) procedural learning in patients, but with a different pattern to that normally seen in healthy people, and abnormal,ratherthan absent, activity in the striatalregion in patients at baseline; and 2) changestowards normalization ofthe procedural learning pattern and increased neural activity in a number ofregions, including cingulate gyrus, caudate nucleus, thalamus and temporal lobe, following ziprasidonemonotherapy.Conclusions:First-episode schizophreniapatients are characterizedby aberrant,ratherthanabsent, procedural learning and brain activity, which change towards normalization with six-week ziprasidone monotherapy