Astrocyte Dysfunctions in Obsessive Compulsive Disorder: Rethinking Neurobiology and Therapeutic Targets

Area of Science:

• Neuroscience
• Glial Biology
• Psychiatry

Background:

• Obsessive-compulsive disorder (OCD) traditionally viewed as a neuronal circuit disorder.
• Emerging evidence highlights the critical role of astrocytes in OCD.
• Astrocytes regulate key neurotransmitters and synaptic functions implicated in OCD.

Purpose of the Study:

• To reframe OCD pathophysiology by emphasizing the role of astrocytes.
• To explore how astrocyte dysfunction contributes to cortico-striato-thalamo-cortical (CSTC) circuit dysregulation in OCD.
• To propose novel therapeutic strategies targeting glial cells in OCD.

Main Methods:

• Review of recent molecular and proteomic studies.
• Integration of human and animal data.
• Analysis of astrocyte subpopulations and their functions.

Main Results:

• Specific astrocyte subpopulations modulate excitatory/inhibitory balance and behavior.
• Astrocytic dysfunctions in neurotransmitter clearance and dopamine metabolism exacerbate CSTC hyperactivity.
• Astrocytes are identified as key players in perseverative behaviors associated with OCD.

Conclusions:

• OCD should be viewed as a disorder involving neuro-glial dysfunction.
• Targeting astrocytic signaling, metabolism, and plasticity presents a promising therapeutic approach.
• A glial-centric model enhances understanding and opens new avenues for precision OCD treatment.