Impact of Antipsychotic Treatment on Attention and Motor Learning Systems in First-Episode Schizophrenia

Abstract

Background: Antipsychotic medications have established clinical benefit, but there are few neuroimaging studies before and after initiating antipsychotic medication to assess drug influence on brain circuitry. Attention and motor learning tasks are promising approaches for examining treatmentrelated changes in frontostriatal systems. Methods: Twentyone unmedicated first-episode schizophrenia patients (14 antipsychotic-naïve) participated in functional imaging studies while performing visual attention (prosaccades) and motor learning tasks (predictive saccades). Posttreatment testing was completed in 14 patients after 4-6 weeks of antipsychotic treatment. Matched healthy controls were studied in parallel. Results: Pretreatment, patients had reduced activation in the dorsal neocortical visual attention network. Activation deficits were significantly reduced posttreatment. Higher medication dose was associated with greater caudate activation at follow-up. For the motor learning task, patients' dorsolateral prefrontal cortex (DLPFC) was unimpaired prior to treatment but showed significantly reduced activation after treatment. Conclusion: Impairments in dorsal cortical attention networks are present in untreated first-episode schizophrenia patients. These impairments are reduced after antipsychotic treatment, suggesting a beneficial effect on neural systems for attention. Treatmentemergent decreases in DLPFC activation observed for the motor learning task are consistent with other clinical and preclinical evidence suggesting that antipsychotics can have adverse effects on prefrontal function.

Translational Medicine in Psychiatry

“…Bertolino and colleagues (Bertolino et al, 2007) replicated this finding and provided additional evidence of a faster response to atypical antipsychotics in the met allele carriers. Similar restorative effects of antipsychotics on brain function in the visual attention network have been reported in a recent longitudinal study in first-episode schizophrenia patients (Keedy et al, 2014). On the neural systems level, several fMRI studies have provided evidence suggesting a favorable impact of atypical antipsychotics on previously "disturbed" functional brain patterns.…”

RETRACTED: The effects of perceptual load in processing emotional facial expression in psychotic disorders

“…All patients were medicated with antipsychotics at the time of evaluation; however, available evidence suggests a positive influence of atypical antipsychotics in attentional processes, improving deficits already present in untreated first-episode patients (e.g., Keedy et al, 2015;Kucharska-Pietura et al, 2012). Further studies should also control for effects of medication.…”

Disease and drug effects on internally-generated and externally-elicited responses in first episode schizophrenia and psychotic bipolar disorder

“…Frontostriatal circuitry provides key support for such functions, including dorsolateral prefrontal cortex (DLPFC), premotor cortex, anterior cingulate and striatum (Simo et al, 2005). Of these cortical regions, DLPFC has shown reduced activation after 4–6 weeks of second generation antipsychotic treatment in first-episode schizophrenia patients performing a prosaccade task (Keedy et al, 2009) and a predictive saccade task (Keedy et al, in press). Such observations are also in line with reports of reduced accuracy of internally-generated saccades needed to perform an oculomotor delayed response task after initiation of antipsychotic treatment in first-episode schizophrenia patients (Reilly et al, 2006; Reilly et al, 2007), an effect also seen in non-human primates exposed to antipsychotics (Castner et al, 2000).…”