A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals

Abstract

AimsAntisocial 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.MethodsThe transcriptomic profiles of OFC samples from subjects with ASPD and/or CD were compared to those of unaffected age‐matched controls (n = 9/group).ResultsThe 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.ConclusionThese 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.

Altered Regional Brain Spontaneous Activity and Functional Connectivity in Patients of Non-Acute Subcortical Stroke With versus Without Cognitive Impairment: A Resting-State fMRI Study.

“…Studies on speci c species have demonstrated that different forms and degrees of cognitive impairment are displayed when the mPFC is damaged [26,27]. Among them, the OFC is involved in inhibitory control, and decision-making, emotion and social behavior control [28][29][30][31]. However, fewer studies have been conducted only for REC.…”

“Amity Seizures”: A previously unreported semiology localizing to a circuit between the right hippocampus and orbitofrontal area

“…Moreover, the orbitofrontal area plays a role in hedonic experience [14] and reward-driven learning behavior [15] , and direct electrical stimulation to the area has improved mood in patients with epilepsy [16] . Dysfunction of the orbitofrontal are well-established to correlate with antisocial behavior [17] , [18] , [19] .…”

CELSR3 deficiency leads to tic-related behaviors and dopaminergic alterations in the striatum

“…RNA was sequenced using a NovaSeq Reagent Kit v1.5_150x150 bp (100 M read-pairs) Sequencing (Illumina Inc, San Diego CA, USA) and sequencing libraries were prepared using Illumina TruSeq Stranded Total RNA Library Prep Ribo-Zero Gold kit (Illumina). Transcriptomic analyses on bulk tissues were performed as previously described 52 . For details, see Supplemental Methods.…”