Transcriptomes of higher order thalamic nuclei in obsessive compulsive disorder.

Area of Science:

• Neuroscience
• Psychiatric Genetics
• Molecular Psychiatry

Background:

• Obsessive-compulsive disorder (OCD) is linked to dysfunction in cortico-striatal-thalamo-cortical (CSTC) circuits.
• Previous research indicated widespread gene expression changes in the orbitofrontal cortex and striatum in OCD.

Purpose of the Study:

• To investigate differential RNA expression in specific thalamic nuclei in postmortem brain tissue from individuals with OCD.
• To explore the role of GABAergic, glutamatergic, and ion channel genes in OCD pathophysiology within the thalamus.

Main Methods:

• Postmortem thalamic tissue from 11 OCD subjects and 10 controls were dissected into specific nuclei (mediodorsal magnocellular, mediodorsal parvocellular, ventral anterior, and posterior ventrolateral).
• Quantitative PCR (qPCR) was used to analyze preselected genes.
• Exploratory RNA sequencing (RNAseq) was performed for differential gene expression analysis.

Main Results:

• Two genes involved in GABA synthesis and release (GAD1 and SLC32A1) were downregulated in OCD subjects across all analyzed nuclei.
• The potassium channel gene KCNN3 was upregulated in OCD subjects.
• RNAseq identified a small number of differentially expressed genes (DEGs) per nucleus, with no significant findings after multiple comparison correction. OCD diagnosis did not effectively model gene expression or co-expressed gene modules.

Conclusions:

• This pilot study found minimal evidence of significant differential RNA expression in the studied thalamic nuclei in obsessive-compulsive disorder.
• The findings suggest that thalamic gene expression alterations may not be a primary driver of OCD pathophysiology, contrasting with findings in other brain regions.