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

TL;DR

This study reveals that human neuronal structures undergo age-related changes that are opposite to the structural alterations observed in schizophrenia, highlighting neurite curvature as a potential biomarker and therapeutic target.

Contribution

It provides the first detailed nano-CT analysis of human brain tissue across multiple cases, linking neurite curvature to aging and schizophrenia.

Findings

Neurite curvature decreases with age in controls

Schizophrenia cases show increased neurite curvature

Neurite curvature correlates with hallucination severity

Abstract

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.