Anxiety disorders and obsessive-compulsive disorder (OCD) affect millions of people worldwide. OCD currently affects approximately 1 in 40 adults and 1 in 100 children in the United States. Anxiety disorders are the most common mental illness in the United States, affecting 40 million adults. While both may commonly occur together and are closely related to stress, their shared neurobiological substrates and therapeutic targets remain unclear. In a new study, researchers from Nanjing University report that a common neuronal circuit is responsible for the co-occurrence of anxiety- and obsessive-compulsive-like behaviors.

Their study, “Targeting presynaptic H3 heteroreceptor in nucleus accumbens to improve anxiety and obsessive-compulsive-like behaviors,” is published in Proceedings of the National Academy of Sciences.

“Anxiety commonly co‐occurs with OCD. Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core, a vital node in the limbic loop,” the researchers wrote.

The NAc is a region in the basal forebrain and is comprised of two parts: the core and shell. It plays a role in motivation and cognitive processing of aversion. The NAc, particularly the core compartment, holds a key position in motivation, emotion, and cognition and it has been strongly implicated in the psychopathology and treatment of anxiety and OCD. Deep brain stimulation (DBS) targeting the NAc core has been shown to improve obsessive-compulsive symptoms and decrease ratings of anxiety in patients suffering from treatment-resistant OCD or depression.

The researchers have previously reported that DBS can induce an increase in histamine release to alleviate Parkinsonian motor deficits. In the current study, they created a new transgenic rat strain expressing Cre recombinase in the histamine-producing neurons, restrictedly localized in the tuberomammillary nucleus of the hypothalamus, and observed that selective optogenetic activation of histaminergic afferent inputs in the NAc core remarkably improves anxiety as well as obsessive-compulsive-like behaviors induced by restraint stress.

“Here we reveal the PrL–NAc core glutamatergic circuitry as a common pathway for the comorbidity of anxiety disorders and OCD. By activating the presynaptic H3 heteroreceptor localized in the NAc core glutamatergic terminals from the PrL, histaminergic afferent inputs may actively modulate the encoding information by glutamatergic inputs, especially the affective and cognitive signals from the PrL, and effectively regulate anxiogenic and obsessive-compulsive-like behaviors,” noted the researchers.

The researchers’ strategy may lead to new clinical treatments of anxiety disorders and OCD.