Astroglia and Obsessive Compulsive Disorder

Obsessive compulsive disorder (OCD) has a prevalence rate of 1-3% in the general population and has been ranked as one of the top ten leading causes of illness-related disability (American Psychiatric Association 2013; Kessler et al. 2005). OCD is characterized by persistent intrusive thoughts (obsessions) and repetitive behaviors (compulsions) (Leckman et al. 1997). There are various OCD-related disorders, including Tourette syndrome (TS), grooming disorders (e.g., skin-picking, trichotillomania), and autism spectrum disorders (ASD) that share considerable overlapping features with OCD (Browne et al. 2014). Although the neurobiological basis of OCD still remains obscure, neuroimaging studies in patients with OCD and OCD-related disorders have consistently identified hyperactivity in orbitofrontal cortex and striatum (Cerliani et al. 2015; Hou et al. 2014; Jung et al. 2017; Neuner et al. 2014). However, the cellular and synaptic abnormalities underlying this hyperactivity are unclear. The most prominent theory regarding the underlying mechanisms of OCD and OCD-related disorders is an increased excitation to inhibition (E/I) ratio due to increased glutamatergic excitation or reduced GABAergic inhibition (Albin and Mink 2006; Rubenstein and Merzenich 2003; Wu et al. 2012). A proper E/I ratio is achieved by factors expressed in neuron and glia. In astrocytes, both the glutamate transporter GLT1 and GABA transporter GAT-3 are critical for regulating the E/I balance (Aida et al. 2015; Aizawa et al. 2020; Boddum et al. 2016; Cui et al. 2014; Kersanté et al. 2013; Kiryk et al. 2008; Matos et al. 2018; Scimemi 2014; Sugimoto et al. 2018; Sugiyama et al. 2017; Tanaka et al. 1997; Zhao et al. 2018). Although astrocyte dysfunction has not been directly explored in OCD patients, several animal studies have found that astrocytes are involved in the pathophysiology of OCD. In this chapter, I highlight recent studies in which astrocyte dysfunction contributed to E/I imbalance, leading to pathological repetitive behaviors shared between patients with OCD, TS, and ASD.