Abstract Background Schizophrenia is often a persistent mental illness characterized by cognitive deficits and altered brain network dynamics especially affecting the cortico-subcortical salience processing system. Childhood trauma has been implicated in mechanisms contributing to schizophrenia, but the role of genetic vulnerability remains unclear. Methods A total of 164 schizophrenia patients and 114 healthy controls were included. First, a matched subsample of 117 patients (76 with and 41 without childhood trauma), and 59 healthy controls were compared on polygenic risk scores for schizophrenia (SczPRS). SczPRS was then correlated with neurocognitive performance using a comprehensive cognitive battery (n = 147 patients) and brain-wide static and dynamic functional connectivity (sFC and dFC) using resting-state fMRI (n = 117 patients). Patients were also stratified into high-SczPRS and low-SczPRS (n = 25 each) subgroups. Results Patients with childhood trauma had significantly lower SczPRS than those without. Higher Childhood Trauma Questionnaire (CTQ) scores related to lower cognitive PC score (r = −0.282, p < 0.001), but CTQ did not affect brain-wide dysconnectivity or subcortical/salience system among patients. Patients with the highest SczPRS showed lower dFC between the cingulo-opercular network and subcortical networks (F = 7.949, p = 0.007), but SczPRS did not affect cognitive performance. Conclusions Our findings reveal distinct effects of childhood trauma and polygenic risk in the neural and cognitive substrates of schizophrenia. Childhood trauma relates to poor cognitive function, while polygenic risk primarily affects salience/subcortical network dynamics. These patterns indicate that in genetically predisposed individuals who experience childhood trauma, a “double mechanistic hit” may influence the schizophrenia phenotype.
Danqing Huang, Yicheng Long, Zhening Liu et al.· European psychiatry· 0 citations
BACKGROUND
The neuropathological mechanisms of schizophrenia remain unclear. Intrinsic neural timescale (INT) reflects the temporal organization of neural activity. This study aimed to characterize INT alterations in patients with first-episode schizophrenia who were drug-naïve or minimally treated, while minimizing confounding effects of chronic illness and medication exposure.
METHODS
Resting-state fMRI data were collected from 123 first-episode, drug-naïve or minimally treated schizophrenia patients and 102 matched healthy controls. INT values were derived from the autocorrelation function of the fMRI signal. Group differences in INT were assessed using analysis of covariance (ANCOVA), controlling for age, gender and scanner site. Additional analyses included correlation analyses, gene annotation and enrichment analyses, and spatial correlation analyses.
RESULTS
Patients exhibited a divergent cortical-subcortical pattern, characterized by reduced cortical INT and prolonged subcortical INT. Compared with healthy controls, patients showed significant INT alterations in 13 regions of interest (p-fdr < 0.05), predominantly involving the default mode network (5 regions) and subcortical network (4 regions), as well as the sensorimotor network, memory retrieval network, salience network, and ventral attention network. Regions with altered INT were enriched for synapse-related genes, and their spatial distribution was correlated with cerebral blood flow.
CONCLUSIONS
Our findings show that first-episode drug-naïve or minimally treated schizophrenia patients are characterized by disrupted intrinsic neural timescales with distinct cortical-subcortical alterations. These abnormalities may be related to cerebral perfusion, synaptic function and symptom severity. The distinct cortical-subcortical alterations of INTs may represent a candidate neurobiological marker of early-stage schizophrenia.
Xiawei Liu, Feiwen Wang, Yiju Wang et al.· Asian Journal of Psychiatry· 0 citations
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