Prefrontal lobe dysfunction predicts treatment response in medication-naive first-episode schizophrenia

Dysfunction of the frontal lobe is considered to be central to the pathology of schizophrenia. However, the nature of these abnormalities is unclear, in particular whether they are affected by treatment. In an earlier functional MRI study of our group we found dorsolateral prefrontal lobe (DLPFC) dysfunction to be present in medication-naive first-episode patients. In this follow-up study, we investigated whether treatment with atypical antipsychotics had an effect on DLPFC functioning, and whether (change in) DLPFC functioning was related to treatment response. Twenty-three medication-naive, first-episode male schizophrenia patients and 33 matched healthy controls were scanned at baseline and were re-scanned after 10 weeks, while performing a modified Sternberg working-memory task. We specifically investigated the effect of practice on brain activation, defined as the signal change between a novel and practiced working-memory task. After the baseline scan, patients were treated with atypical antipsychotics. Based on their symptom change after ten weeks, patients were divided into responders and non-responders We found DLPFC function did not change after 10 weeks in healthy controls or in patients who received treatment. However, while patients who responded to treatment did not differ from controls, non-responders showed a reduced practice effect in the DLPFC that was present already at baseline, which did not change after treatment. A reduced practice effect in the DLFPC at baseline was found to be predictive of poor treatment response at 10 weeks. These results suggest that prefrontal lobe dysfunction reflects a distinct neuropathological substrate in a subgroup of treatment non-responsive schizophrenia patients.