Primary and secondary alterations of white matter connectivity in schizophrenia: A study on first-episode and chronic patients using whole-brain tractography-based analysis

Schizophrenia is a debilitating mental disorder that is associated with an impaired connection of cerebral white matter. Studies on patients with chronic and first-episode schizophrenia have found widespread white matter abnormalities. However, it is unclear whether the altered connections are inherent in or secondary to the disease. Here, we sought to identify white matter tracts with altered connections and to distinguish primary or secondary alterations among 74 fiber tracts across the whole brain using an automatic tractography-based analysis method. Thirty-one chronic, 25 first-episode patients with schizophrenia and 31 healthy controls were recruited to receive diffusion spectrum magnetic resonance imaging at 3T. Seven tracts were found to exhibit significant differences between the groups; they included the right arcuate fasciculus, bilateral fornices, left superior longitudinal fasciculus I, and fibers of the corpus callosum to the bilateral dorsolateral prefrontal cortices (DLPFC), bilateral temporal poles, and bilateral hippocampi. Post-hoc between-group analyses revealed that the connection of the callosal fibers to the bilateral DLPFC was significantly decreased in chronic patients but not in first-episode patients. In a stepwise regression analysis, the decline of the tract connection was significantly predicted by the duration of illness. In contrast, the remaining six tracts showed significant alterations in both first-episode and chronic patients and did not associate with clinical variables. In conclusion, reduced white matter connectivity of the callosal fibers to the bilateral DLPFC may be a secondary change that degrades progressively in the chronic stage, whereas alterations in the other six tracts may be inherent in the disease.