- Graded reduction in striatal grey matter volume across groups, with bvFTD showing greatest atrophy, then schizophrenia.
- Both disorders show similar RSFC in right nucleus accumbens and bilateral dorsolateral putamen, but bvFTD shows unique intra-striatal functional connectivity abnormalities.
- bvFTD exhibits lower RSFC correlations with 5-HT6, α4β2, M1, mGluR5 and D2 receptor density maps than schizophrenia, implying divergent neurotransmitter involvement.
Int Psychogeriatr. 2026 Sep 10:100273. doi: 10.1016/j.inpsyc.2026.100273. Online ahead of print.
ABSTRACT
OBJECTIVE: Behavioral variant frontotemporal dementia (bvFTD) and schizophrenia share similar clinical manifestations, cognitive profiles and overlapping brain lesions. The striatal subregions play critical roles in both disorders, yet relevant comparative investigations remain limited. This study aimed to explore the distinct neural mechanisms between bvFTD and late-life schizophrenia by comparing striatal subregional structure, function and spatial correlations of neurotransmitters.
METHODS: A total of 36 patients with bvFTD, 21 patients with late-life schizophrenia and 56 healthy comparison group were enrolled. All participants underwent neurocognitive assessment, behavioral evaluation and magnetic resonance imaging (MRI). Voxel-Based Morphometry and Resting-state functional connectivity (RSFC) analyses based on the Human Brainnetome Atlas. Partial correlation analysis was performed to evaluate the associations of imaging metrics with neuropsychological and behavioral measures. JuSpace was used to compare RSFC-neurotransmitter spatial correlation differences between bvFTD and schizophrenia groups.
RESULTS: A graded reduction in gray matter volume was observed across most striatal subregions: the bvFTD group showed the smallest volume, then the schizophrenia group. Both bvFTD and schizophrenia groups exhibited similar RSFC in the right nucleus accumbens and bilateral dorsolateral putamen. Specifically, the bvFTD group presented unique aberrant intra-striatal functional connectivity, including connections between the left nucleus accumbens and right putamen, as well as between the left dorsal caudate nucleus and left ventral caudate. Significant partial correlations were detected: Hamilton Depression Rating Scale scores negatively correlated with bilateral dorsal caudate volume in the schizophrenia group. Additionally, the bvFTD group exhibited lower spatial correlations between RSFC and the density maps of 5-HT₆, α4β2, M1, mGluR5 and D₂ receptors, compared with the schizophrenia group.
CONCLUSIONS: These findings suggest similar striatal impairment patterns but divergent underlying neural mechanisms in bvFTD and schizophrenia, offering new insights into the neural circuits of clinical phenotypes and the pathophysiological basis of the two disorders.
PMID:42722600 | DOI:10.1016/j.inpsyc.2026.100273
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