Structural aging of human neurons is the opposite of the changes in schizophrenia

• Published in: arXiv.org 2022-11
• Main Authors: Mizutani, Ryuta, Saiga, Rino, Yamamoto, Yoshiro, Uesugi, Masayuki, Takeuchi, Akihisa, Uesugi, Kentaro, Terada, Yasuko, Suzuki, Yoshio, De Andrade, Vincent, De Carlo, Francesco, Takekoshi, Susumu, Inomoto, Chie, Nakamura, Naoya, Torii, Youta, Kushima, Itaru, Iritani, Shuji, Ozaki, Norio, Oshima, Kenichi, Itokawa, Masanari, Arai, Makoto
• Format: Article
• Language: English
• Subjects: Age; Brain; Curvature; Hallucinations; Schizophrenia; Three dimensional analysis
• ISSN: 2331-8422
• DOI: 10.48550/arxiv.2211.07024

Human mentality develops with age and is altered in psychiatric disorders, though their underlying mechanism is unknown. In this study, we analyzed nanometer-scale three-dimensional structures of brain tissues of the anterior cingulate cortex from eight schizophrenia and eight control cases. The distribution profiles of neurite curvature of the control cases showed a trend depending on their age, resulting in an age-correlated decrease in the standard deviation of neurite curvature (Pearson's r = -0.80, p = 0.018). In contrast to the control cases, the schizophrenia cases deviate upward from this correlation, exhibiting a 60% higher neurite curvature compared with the controls (p = 7.8 x 10^(-4)). The neurite curvature also showed a correlation with a hallucination score (Pearson's r = 0.80, p = 1.8 x 10^(-4)), indicating that neurite structure is relevant to brain function. We suggest that neurite curvature plays a pivotal role in brain aging and can be used as a hallmark to exploit a novel treatment of schizophrenia. This nano-CT paper is the result of our decade-long analysis and is unprecedented in terms of number of cases.