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Neuroscience themes inform treatment planning for OCD

Darin D. Dougherty

Collectively understanding five neuroscience themes — phenomenology and symptom dimensions, extinction science, neurochemistry, genetics, and animal models and neurotherapeutics — is key to formulation and treatment planning for patients with obsessive-compulsive disorder, according to a review published in JAMA Psychiatry.

“Alongside ... therapeutic discoveries, advances in neuroimaging have characterized the neural circuitry underlying OCD, paving the way for state-of-the-art circuit-based neurotherapeutics,” Darin D. Dougherty, MD, from the division of neurotherapeutics at Massachusetts General Hospital, and the Obsessive-Compulsive Disorder Institute at McLean Hospital, and colleagues wrote. “However, while these advances have vastly improved the care of patients with OCD, many patients still experience substantial residual symptoms.”

In their review, the authors provided an integrated neuroscience perspective on OCD pathobiology and treatment organized around five key neuroscience themes most relevant for the disorder.

Dougherty and colleagues reported that an integrated neuroscience formulation of OCD is predicated by understanding:

• phenomenology and symptom dimensions;

• fear conditioning and extinction;

• neurochemistry;

• genetics and animal models; and

• neurocircuitry and neurotherapeutics.

Symptom dimensions allow clinicians and researchers to better understand the phenotypic heterogeneity within OCD while also leaving room to personalize treatments, the researchers wrote in their review. In OCD, abnormal fear extinction is key to the underlying therapeutic mechanism of exposure and response prevention, according to the authors. Evidence from genome-wide association studies and animal studies may implicate genes involved in glutamatergic neurotransmission and synaptic function, they wrote.

According to the authors, understanding the neurochemistry of OCD should focus on both traditional monoaminergic systems and more recent evidence of glutamatergic and -aminobutyric acidergic dysfunction. Though promising, further exploration to determine whether glutamatergic medications can be useful to treat OCD and on the potential role of -aminobutyric acid dysfunction in OCD are needed.

Because OCD is highly heritable, future work to understand how genes contribute to underlying pathophysiology is necessary. Dougherty and colleagues also recommend that future OCD research should focus on:

• biological differences between symptom subtypes using deep phenotyping, a Research Domain Criteria approach and advanced neuroimaging techniques;

• exploring novel glutamate-modulating interventions;

• continuing study of potential pharmacologic, neuromodulatory or behavioral approaches to augment exposure and response prevention therapy; and

• improving neurotherapeutic/neurostimulation approaches.

“Advances in understanding the genetic, molecular, and neural underpinnings of OCD have rivaled that of any other psychiatric disorder over the last 30 years,” the authors concluded. “Ultimately, advancement in these areas holds promise for treatment interventions that can be prescribed in a neuroscientifically informed manner using a precision medicine approach for patients with OCD on an individualized basis to enhance outcomes.” – by Savannah Demko

Disclosure: Dougherty reports research support from Cyberonics, Eli Lilly and Company, Medtronic and Roche; travel support from Roche; and consulting for/honoraria from Medtronic. Please see the study for all other authors’ relevant financial disclosures.