Computer-assisted cognitive remediation therapy increases hippocampal volume in patients with schizophrenia: a randomized controlled trial

Tsubasa Morimoto, Yasuhiro Matsuda, Kiwamu Matsuoka, Fumihiko Yasuno, Emi Ikebuchi, Hiroyuki Kameda, Toshiaki Taoka, Toshiteru Miyasaka, Kimihiko Kichikawa, Toshifumi Kishimoto

Cognitive remediation therapy (CRT) effectively reduces neurocognitive impairment in patients with schizophrenia, but few studies have used structural neuroimaging methods to assess its neuroanatomical effects. We investigated these effects, as well as the association between changes in cortical volume and neurocognitive performance. Between August 2013 and September 2016, we performed a randomized controlled study comprising a CRT group (16 individuals) and a treatment-as-usual (TAU) group (15 individuals) of patients with schizophrenia. CRT participants engaged in twice-weekly computer-assisted CRT sessions and weekly group meetings for 12 weeks. T1-weighted magnetic resonance imaging was performed before and after the intervention period, and whole-brain voxel-based morphometric analysis was used to detect significant cortical gray matter volume changes. We also assessed the correlation between cortical volume changes and CRT-derived neurocognitive improvements. The CRT group exhibited significantly greater improvements than the TAU group in verbal fluency (P = 0.012) and global cognitive scores (P = 0.049). The CRT group also exhibited significantly greater increases in right hippocampal volume than the TAU group (P < 0.001). Changes in verbal fluency scores and right hippocampal volumes were positively correlated (r = 0.53, P = 0.001). We found that CRT significantly increased right hippocampal volumes and that these enhancements were positively correlated with changes in verbal fluency scores. Our results indicate that CRT induces cognitive improvement through hippocampal plasticity. Registration number: UMIN000026146 , 2017/02/15, retrospectively registered.