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Updated: Jul 28, 2025
Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia
Published on: December 2, 2015
A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals
Ignazio S Piras1, Giulia Braccagni2, Matthew J Huentelman1
1Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, Arizona, USA.
Aims:
Antisocial personality disorder (ASPD) and conduct disorder (CD) are characterized by a persistent pattern of violations of societal norms and others' rights. Ample evidence shows that the pathophysiology of these disorders is contributed by orbitofrontal cortex (OFC) alterations, yet the underlying molecular mechanisms remain elusive. To address this knowledge gap, we performed the first-ever RNA sequencing study of postmortem OFC samples from subjects with a lifetime diagnosis of ASPD and/or CD.
Methods:
The transcriptomic profiles of OFC samples from subjects with ASPD and/or CD were compared to those of unaffected age-matched controls (n = 9/group).
Results:
The OFC of ASPD/CD-affected subjects displayed significant differences in the expression of 328 genes. Further gene-ontology analyses revealed an extensive downregulation of excitatory neuron transcripts and upregulation of astrocyte transcripts. These alterations were paralleled by significant modifications in synaptic regulation and glutamatergic neurotransmission pathways.
Conclusion:
These preliminary findings suggest that ASPD and CD feature a complex array of functional deficits in the pyramidal neurons and astrocytes of the OFC. In turn, these aberrances may contribute to the reduced OFC connectivity observed in antisocial subjects. Future analyses on larger cohorts are needed to validate these results.
