Fractional Anisotropic Changes of Corpus Callosum Associated with Antipsychotic Treatment in First-Episode Antipsychotic Drug-Naive Patients with Schizophrenia

Abstract

Objective: Schizophrenia involves white matter abnormalities that might have a central role in the pathophysiology. Abnormal brain connectivity especially in prefrontal and temporal heteromodal cortex has been suggested as the leading structural impairment in patients with schizophrenia. In this study we examined the relationship between potential white matter changes and clinical response, as well as associations with antipsychotic treatment follow-up. Methods: 18 first-episode schizophrenia (FES) patients were recruited from the outpatient unit of the GATA (Gulhane Military Medical Academy) Haydarpasa Research and Training Hospital, between June 2009-February 2010. Fourteen patients with FES were recruited, and 16 healthy control subjects were recruited from the community. Diffusion tensor MRI (DT-MRI) was obtained from participants at baseline and after 4 weeks of standard antipsychotic treatment. A color-coded fractional anisotropy map for each 11 patient was extracted from the 4-week follow-up and the baseline splenium and genu FA measurements. According to Basser and others major eigenvector linear maps were transformed into the color-coded maps. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Brief Psychiatric Rating Scale (BPRS) scores between baseline and follow up were also evaluated. Results: In this study; in the FES patients, both genu FA (p=0.001) and the splenium FA (p=0.013) values were statistically significantly lower than the healthy control group. There were mild FA increases respectively genu and splenium (p=0.533, p=0.318) in the FES patients after the treatment. But the FA changes did not correlate with the changes in clinical symptoms. A negative, moderate, statistically significant correlation (Pearson's r=-0.569, p=0.034) was found between baseline splenium FA values and BPRS scores. The duration of illness prior to treatment was negatively, weak, statistically non-significantly correlated (r=-0.066; p=0.846) between baseline and follow-up splenium FA changes. Conclusions: The reduced mean Callosal FA (CFA) values might indicate myelination defects and problems in axonal transport. The existence of white matter changes even in first episode drug-naive schizophrenia patients supports the view that these problems occurs in earlier stages of development. Although the callosal FA changes did not correlate with symptom improvement or the dose of antipsychotic medication, there was a mild increase in follow-up FA measurements. These findings show that CC which is the main conduit of interhemispheric connection is affected distinctly in patients with schizophrenia. Further collaborative studies are needed to clarify the potential long-term effects of antipsychotics on white matter microstructure and also its reversibility.