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This large-scale study of 2,260 schizophrenia patients and 3,058 healthy controls examined brain network organization in relation to aggressive behavior. Contrary to expectations, patients with schizophrenia who displayed aggression showed fewer brain network abnormalities than non-aggressive patients, with only modest differences from healthy controls. The most notable finding was increased connectivity of the salience network in aggressive patients with severe delusions, suggesting abnormal salience processing may contribute to aggression in this subgroup.
Why it matters
These findings suggest that aggressive behavior in schizophrenia may have distinct neurobiological underpinnings from the disorder itself, reflecting etiological heterogeneity rather than simply more severe brain pathology. The identified salience network alterations in patients with delusions could potentially inform targeted prevention strategies for aggression in high-risk individuals.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Background: Although most individuals with schizophrenia do not show aggressive behavior, rates are higher than in the general population. Identifying the neurobiological correlates of aggression may inform prevention. Methods: We included 2260 individuals with schizophrenia spectrum disorders and 3058 healthy controls (HC) from 26 sites in the ENIGMA-Schizophrenia Working Group. The former were classified as showing at least moderate aggression (SZ+A; N = 231) or not (SZ-A; N = 2029) based on symptom rating scales. Structural covariance networks were constructed from cortical and subcortical volumes. We examined global and nodal network topology, as well as density within six large-scale brain networks and between each network and the rest of the brain. Metrics were summarized as the area under the curve (AUC) across a prespecified range of densities (K = 0.10-0.25, {Delta}K = 0.01). Group differences were assessed using pairwise permutation tests with Benjamini-Hochberg correction for multiple comparisons. Results: Global and nodal network topology did not differ significantly between SZ+A and HC. Network-rest density of the salience network (SN) was higher in SZ+A than in HC, although this difference did not survive multiple-comparison correction ({Delta}AUC = 0.018, pBH = .083). In exploratory subgroup analyses, higher SN network-rest density was observed only in SZ+A with high delusion severity ({Delta}AUC = 0.021, p = .007). By contrast, SZ-A demonstrated extensive alterations in global network topology compared with SZ+A and HC, alongside selective alterations in nodal topology and large-scale network density compared with HC. Results were broadly consistent across sensitivity analyses using alternative definitions of aggression and adjusting for current antipsychotic dose. Conclusions: SZ+A was characterized by fewer–not more–abnormalities in structural covariance network organization than SZ-A, which may reflect etiological heterogeneity. In SZ+A with high delusion severity, higher network-rest density of the SN may point to aberrant salience processing in aggressive behavior.