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Background <p>Brain connectivity abnormalities may underlie affective psychosis which may be influenced by sex. Using diffusion magnetic resonance imaging (dMRI) tractography, we assessed frontostriatal brain wiring connectivity patterns in 46 early psychosis affective and 56 healthy control young adult, male and female participants.</p> Methods <p>We collected harmonized whole brain tractography dMRI data from three sites and applied our novel fiber clustering methodology to identify 17 white matter fiber clusters connecting the frontal cortex and caudate per hemisphere in each group. By comparing cortical and caudate inter-cluster endpoint distances between groups, we assessed their patterns of frontostriatal connectivity.</p> Results <p>1) In both males and females in early affective psychosis and healthy controls, bilaterally, the frontal cortex to caudate wiring pattern deviated from a topographic organization. 2) in a right hemisphere frontal pole fiber cluster, independent of sex, we found a significant interaction effect of diagnosis on the connectivity pattern between frontal cortex and caudate, (<i>p</i> = 0.013); 3) in a left hemisphere inferior frontal gyrus, pars triangularis, fiber cluster, we found sex influenced the significant interaction effect of diagnosis on the connectivity pattern between frontal cortex and caudate, (<i>p</i> = 0.0085), with the effect much greater in females (<i>p</i> &lt; 0.00001) than in males (<i>p</i> = 0.97); and, 4) post-hoc tests showed a significant effect of diagnosis on the pattern of frontal cortex to caudate connectivity in specific subregions (ps ≤0.04).</p> Conclusions <p>Importantly, while the frontostriatal wiring pattern in both early affective psychosis and healthy controls deviated from a topographic organization, we found in a right hemisphere fiber cluster, independent of sex, that a significant interaction effect of diagnosis was observed on the frontal cortex to caudate connectivity pattern, whereas, in a left hemisphere fiber cluster, the effect of diagnosis on connectivity pattern was influenced by sex, showing the importance of the role of sex in brain wiring patterns in early affective psychosis.</p>

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Diagnostic and sex effects on frontostriatal brain wiring structural organization in early psychosis affective subjects compared to healthy controls

  • 期刊论文

  • 发表日期：

    2026年7月4日

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  • J. J. Levitt,
  • F. Zhang,
  • M. Vangel,
  • P. G. Nestor,
  • Y. Rathi,
  • S. Cetin-Karayumak,
  • M. Kubicki,
  • O. Pasternak,
  • M. J. Coleman,
  • K. E. Lewandowski,
  • D. J. Holt,
  • M. Keshavan,
  • S. Bouix,
  • D. Öngür,
  • A. Breier,
  • M. E. Shenton,
  • L. J. O’Donnell

摘要

Background

Brain connectivity abnormalities may underlie affective psychosis which may be influenced by sex. Using diffusion magnetic resonance imaging (dMRI) tractography, we assessed frontostriatal brain wiring connectivity patterns in 46 early psychosis affective and 56 healthy control young adult, male and female participants.

Methods

We collected harmonized whole brain tractography dMRI data from three sites and applied our novel fiber clustering methodology to identify 17 white matter fiber clusters connecting the frontal cortex and caudate per hemisphere in each group. By comparing cortical and caudate inter-cluster endpoint distances between groups, we assessed their patterns of frontostriatal connectivity.

Results

1) In both males and females in early affective psychosis and healthy controls, bilaterally, the frontal cortex to caudate wiring pattern deviated from a topographic organization. 2) in a right hemisphere frontal pole fiber cluster, independent of sex, we found a significant interaction effect of diagnosis on the connectivity pattern between frontal cortex and caudate, (p = 0.013); 3) in a left hemisphere inferior frontal gyrus, pars triangularis, fiber cluster, we found sex influenced the significant interaction effect of diagnosis on the connectivity pattern between frontal cortex and caudate, (p = 0.0085), with the effect much greater in females (p < 0.00001) than in males (p = 0.97); and, 4) post-hoc tests showed a significant effect of diagnosis on the pattern of frontal cortex to caudate connectivity in specific subregions (ps ≤0.04).

Conclusions

Importantly, while the frontostriatal wiring pattern in both early affective psychosis and healthy controls deviated from a topographic organization, we found in a right hemisphere fiber cluster, independent of sex, that a significant interaction effect of diagnosis was observed on the frontal cortex to caudate connectivity pattern, whereas, in a left hemisphere fiber cluster, the effect of diagnosis on connectivity pattern was influenced by sex, showing the importance of the role of sex in brain wiring patterns in early affective psychosis.