Altered cerebellar effective connectivity in first-episode schizophrenia and long-term changes after treatment

Cerebello-cortical functional dysconnectivity plays a key role in the pathology of schizophrenia (SZ). We aimed to investigate the changes in cerebello-cortical directional connectivity in patients with SZ.

A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom.

We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission.

These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait.