Rhesus monkeys exhibiting spontaneous ritualistic behaviors resembling obsessive-compulsive disorder

Area of Science:

• Neuroscience
• Genetics
• Primatology

Background:

• Obsessive-compulsive disorder (OCD) is a prevalent psychiatric condition impacting 2-3% globally.
• Understanding OCD's origins requires studying spontaneous behaviors in animal models.
• Rhesus monkeys offer a potential model for investigating OCD pathogenesis.

Purpose of the Study:

• To investigate spontaneous obsessive-compulsive disorder (OCD)-like behaviors in rhesus monkeys.
• To identify genetic and neurobiological underpinnings of these behaviors.
• To evaluate the effects of stress and medication on OCD-like behaviors.

Main Methods:

• Observation of rhesus monkey colonies to identify spontaneous sequential motor behaviors (SMBs).
• Genetic analysis of monkeys exhibiting SMBs to identify mutations in OCD-risk genes.
• Brain imaging (MRI) to assess gray matter volume and white matter integrity.
• Behavioral testing involving stressor exposure and fluoxetine administration.

Main Results:

• Ten monkeys spontaneously developed persistent, repetitive, and individual-specific SMBs.
• Severely damaging mutations in human OCD-risk genes were found in affected monkeys.
• Monkeys with SMBs showed increased left caudate nucleus gray matter volume and reduced corpus callosum fractional anisotropy.
• SMB duration correlated with left caudate nucleus gray matter volume.
• Stress significantly increased SMBs, while fluoxetine treatment decreased them.

Conclusions:

• Spontaneous OCD-like behaviors in rhesus monkeys provide a valuable model for human OCD.
• Genetic and neurobiological findings in these monkeys mirror aspects of human OCD.
• Stress exacerbates and fluoxetine ameliorates these behaviors, suggesting conserved therapeutic targets.