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<p>Alternations in intrinsic brain activity are increasingly recognized as transdiagnostic markers in major psychiatric disorders, however, the extent to which spontaneous functional abnormalities are shared or disorder-specific remain incompletely understood. In this study, we systematically compared whole-brain intrinsic activity alterations among individuals with schizophrenia (SCZ), bipolar disorder (BD), and attention-deficit/hyperactivity disorder (ADHD) relative to healthy controls (HC), utilizing the resting-state amplitude of low-frequency fluctuation (ALFF) metric. We further explored potential neurochemical and microstructural substrates underlying these alterations by integrating disorder-related ALFF maps with normative neurotransmitter system templates and a cortical myelin water fraction atlas. The results revealed widespread diagnosis effects on ALFF, with prominent changes concentrated in the sensorimotor, visual, and limbic networks. Each disorder exhibited distinct regional patterns of ALFF alterations. Specifically, both SCZ and BD showed increased ALFF in the fusiform gyrus accompanied by decreased ALFF in occipital and postcentral regions, whereas ADHD was mainly characterized by reduced ALFF in the cerebellum. Pairwise comparisons further delineated both overlapping and disorder-specific loci of dysfunction across the three conditions. Spatial correlation analyses demonstrated that ALFF alteration patterns were differentially associated with neurotransmitter distributions, with SCZ and BD were commonly linked to dopaminergic markers (D1, D2, and DAT), while serotonergic 5-HT1a distributions were selectively associated with ALFF changes in SCZ and ADHD. Notably, only in schizophrenia did regional ALFF alterations show a significant negative spatial correspondence with cortical myelin water fraction, suggesting a disorder-specific microstructural substrate. These findings highlight convergent and divergent intrinsic activity alterations across major psychiatric disorders and provide multilevel insights into their potential neurochemical and microstructural underpinnings, advancing our understanding of transdiagnostic brain dysfunction.</p>

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Transdiagnostic alterations of intrinsic brain activity in major psychiatric disorders

  • 期刊论文

  • 发表日期：

    2026年3月23日

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  • Dian-Ming Zhu,
  • Wenli Zhu,
  • Di Wu,
  • Muzhen Guan,
  • Anping Ouyang,
  • Tian Zhang,
  • Chenxi Li,
  • Qiang Hu,
  • Peng Fang,
  • Yuanjun Xie

摘要

Alternations in intrinsic brain activity are increasingly recognized as transdiagnostic markers in major psychiatric disorders, however, the extent to which spontaneous functional abnormalities are shared or disorder-specific remain incompletely understood. In this study, we systematically compared whole-brain intrinsic activity alterations among individuals with schizophrenia (SCZ), bipolar disorder (BD), and attention-deficit/hyperactivity disorder (ADHD) relative to healthy controls (HC), utilizing the resting-state amplitude of low-frequency fluctuation (ALFF) metric. We further explored potential neurochemical and microstructural substrates underlying these alterations by integrating disorder-related ALFF maps with normative neurotransmitter system templates and a cortical myelin water fraction atlas. The results revealed widespread diagnosis effects on ALFF, with prominent changes concentrated in the sensorimotor, visual, and limbic networks. Each disorder exhibited distinct regional patterns of ALFF alterations. Specifically, both SCZ and BD showed increased ALFF in the fusiform gyrus accompanied by decreased ALFF in occipital and postcentral regions, whereas ADHD was mainly characterized by reduced ALFF in the cerebellum. Pairwise comparisons further delineated both overlapping and disorder-specific loci of dysfunction across the three conditions. Spatial correlation analyses demonstrated that ALFF alteration patterns were differentially associated with neurotransmitter distributions, with SCZ and BD were commonly linked to dopaminergic markers (D1, D2, and DAT), while serotonergic 5-HT1a distributions were selectively associated with ALFF changes in SCZ and ADHD. Notably, only in schizophrenia did regional ALFF alterations show a significant negative spatial correspondence with cortical myelin water fraction, suggesting a disorder-specific microstructural substrate. These findings highlight convergent and divergent intrinsic activity alterations across major psychiatric disorders and provide multilevel insights into their potential neurochemical and microstructural underpinnings, advancing our understanding of transdiagnostic brain dysfunction.