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, Δ 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 (ΔAUC = 0.018, p BH = .083). In exploratory subgroup analyses, higher SN network-rest density was observed only in SZ+A with high delusion severity (ΔAUC = 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.