Dataset Information

A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals.

ABSTRACT:

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.

SUBMITTER: Piras IS

PROVIDER: S-EPMC10580340 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals.

Piras Ignazio S IS Braccagni Giulia G Huentelman Matthew J MJ Bortolato Marco M

CNS neuroscience & therapeutics 20230602 11

<h4>Aims</h4>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 ...[more]

PMID: 37269073

Similar Datasets

Project description:The orbitofrontal cortex (OFC) and hippocampus share striking cognitive and functional similarities. As a result, both structures have been proposed to encode "cognitive maps" that provide useful scaffolds for planning complex behaviors. However, while this function has been exemplified by spatial coding in neurons of hippocampal regions-particularly place and grid cells-spatial representations in the OFC have been investigated far less. Here we sought to address this by recording OFC neurons from male rats engaged in an open-field foraging task like that originally developed to characterize place fields in rodent hippocampal neurons. Single-unit activity was recorded as rats searched for food pellets scattered randomly throughout a large enclosure. In some sessions, particular flavors of food occurred more frequently in particular parts of the enclosure; in others, only a single flavor was used. OFC neurons showed spatially localized firing fields in both conditions, and representations changed between flavored and unflavored foraging periods in a manner reminiscent of remapping in the hippocampus. Compared with hippocampal recordings taken under similar behavioral conditions, OFC spatial representations were less temporally reliable, and there was no significant evidence of grid tuning in OFC neurons. These data confirm that OFC neurons show spatial firing fields in a large, two-dimensional environment in a manner similar to hippocampus. Consistent with the focus of the OFC on biological meaning and goals, spatial coding was weaker than in hippocampus and influenced by outcome identity.SIGNIFICANCE STATEMENT The orbitofrontal cortex (OFC) and hippocampus have both been proposed to encode "cognitive maps" that provide useful scaffolds for planning complex behaviors. This function is exemplified by place and grid cells identified in hippocampus, the activity of which maps spatial environments. The current study directly demonstrates very similar, though not identical, spatial representatives in OFC neurons, confirming that OFC-like hippocampus-can represent a spatial map under the appropriate experimental conditions.

Dataset Information

A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals.

Aims

Methods

Results

Conclusion

Publications

A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals.

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