Valence processing alterations in SAPAP3 knockout mice and human OCD

Area of Science:

• Neuroscience
• Behavioral Science
• Translational Psychiatry

Background:

• Abnormalities in processing aversive or appetitive stimuli (valence processing) may be underrecognized in obsessive-compulsive disorder (OCD).
• Preclinical rodent models are crucial for understanding OCD pathophysiology, but few examine valence system alterations in compulsive behavior models.

Purpose of the Study:

• To assess valence processing in the SAPAP3 knockout (KO) mouse model of compulsive behavior.
• To compare preclinical findings in SAPAP3 KO mice with behavioral phenomena in human OCD patients.
• To investigate potential therapeutic targets for valence processing alterations in OCD.

Main Methods:

• SAPAP3 KO mice underwent auditory fear conditioning/extinction (negative valence) and operant conditioning (positive valence).
• OCD patients completed behavioral tests assessing explicit and implicit processing of fear (negative) and happy (positive) facial expressions.
• Preclinical and clinical data were analyzed to identify congruent valence processing abnormalities.

Main Results:

• SAPAP3 KO mice exhibited heightened negative valence processing (enhanced fear learning, impaired extinction) and impaired positive valence processing (deficits in reward acquisition, goal-directed behavior).
• OCD patients showed similar trends towards enhanced negative and impaired positive valence processing.
• Valence processing abnormalities were observed in both the mouse model and human patients.

Conclusions:

• The SAPAP3 KO mouse model displays valence processing abnormalities mirroring those in OCD patients.
• These findings highlight the role of valence processing in OCD pathophysiology.
• Valence processing alterations represent a promising area for novel therapeutic development in OCD.