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Orbitofrontal sulcogyral morphology in patients with cocaine use disorder.

ABSTRACT: Orbitofrontal cortex (OFC) is thought to be involved in appropriate processing of rewarding stimuli, and abnormal OFC structure and function has been found in patients with substance use disorders. Atypical patterns of the H-sulcus in the OFC have been primarily identified with schizophrenia, but also with bipolar disorder, both of which are associated with comorbid substance use. Given the high rates of substance use within Axis I psychiatric disorders, it is reasonable to consider how frequencies of OFC patterns in populations with only substance use compare to controls. This information is crucial to disentangle whether atypical frequencies of H-sulcus sulcogyral patterns within psychopathology are associated with the psychiatric or substance use phenotype. Here, we present the first analysis of H-sulcus sulcogyral patterns in a population of adult black men with (n = 84) and without (n = 24) cocaine use disorder (CUD). We find that OFC sulcogyral patterns are not significantly different from the control group, indicating that OFC sulcogyral patterns are not disrupted in patients with CUD. As exploratory analyses, we describe OFC sulcogyral pattern subtypes in this cohort as well as an additional control group (n = 52), in order to add to the growing body of literature on OFC sulcogyral pattern characterization.

SUBMITTER: Patti MA

PROVIDER: S-EPMC8126989 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Orbitofrontal sulcogyral morphology is a transdiagnostic indicator of brain dysfunction.

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Project description:Alcohol use disorder (AUD) is a life-threatening disease characterized by compulsive drinking, cognitive deficits, and social impairment that continue despite negative consequences, which are driven by dysfunction of cortical areas, such as the orbitofrontal cortex (OFC), that normally balances decisions related to reward and risk. In this study, proteomics and machine learning analysis of post-mortem OFC brain samples collected from individuals with AUD revealed dysregulation of presynaptic (e.g., AP2A1) and mitochondrial proteins that predicted the occurrence and severity of AUD. Alcohol-sensitive OFC proteins also mapped to abnormal social behaviors and interactions. Validation using reverse genetics, we found that prefrontal Ap2a1 regulates alcohol drinking in genetically diverse mouse strains. Furthermore, we demonstrated sexual dimorphism in human OFC proteins that regulate extracellular matrix structure and signaling. Together, these findings highlight the impact of excessive alcohol consumption on the human OFC proteome and identify important cross-species cortical mechanisms underlying AUD.

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2023-08-08 | GSE235818 | GEO

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