How Brain Chemical Imbalances May Contribute to OCD

New research looking at levels of two neurotransmitters, glutamate and GABA, in critical brain regions aimed to shed light on the intricate neural mechanisms at play in obsessive compulsive disorder (OCD).

Glutamate is like a cheerleader for neurons, promoting activity and stimulating brain networks. It encourages them to send electrical signals and pass information to other neurons in the brain. On the other hand, GABA plays a calming role, acting as an “inhibitory” neurotransmitter.

Together the two neurotransmitters work in a seesaw fashion to balance the brain’s activity. GABA pushes down on one end to reduce the excitability of neurons while glutamate pushes down on the other end to pump the brakes. But when an imbalance between the two occurs, it can contribute to the development of compulsive behaviors.

Late-Onset OCD With Religious Obsessions

Protective Effect of Fluvoxamine for COVID-19 in OCD

OCD and Chromosome 2 Duplication

Study Findings

To conduct the study, Cambridge University researchers used an enhanced MRI technique known as 7-Tesla proton magnetic resonance spectroscopy (1H-MRS). This method pinpoints the levels of specific neurotransmitters in the brain by capturing high resolution images. 

Volunteers, both with and without an OCD diagnosis, underwent scans so that the researchers could compare the differences in two specific brain regions: the SMA (supplementary motor area) and the ACC (anterior cingulate cortex). Both of these frontal brain regions are involved in motor control and decision-making processes, which are relevant to compulsive behavior.

The scans showed that individuals, whether they had OCD or not, had higher levels of glutamate in the SMA associated with compulsive behavior. They also found no significant differences in GABA levels in the SMA between the two groups. This suggested to the researchers that the dysregulation of glutamate in the SMA may be a key factor in driving even milder forms of compulsive behavior.

In the subjects with OCD, there was some relationship between glutamate and habitual control. Levels of glutamate were higher and the levels of GABA were lower in the ACC of individuals with OCD. These neurochemical changes in the ACC suggest that they too may contribute to compulsive behavior.

“Understanding obsessive-compulsive disorder is a central question for psychiatry. We have now shown definitive changes in these key neurotransmitters in OCD sufferers,” senior author Trevor Robbins of Cambridge’s Department of Psychology said in a media release. “Excess glutamate and reduced GABA is disrupting the neural circuitry in key regions of the OCD brain.”

Complex Causes

While these findings are interesting, it’s important to note that compulsive behavior is multifactorial. 

For example, numerous other brain regions make a contribution, including the orbitofrontal cortex (OFC), striatum, thalamus, and amygdala. The OFC is involved in decision-making and reward processing, and its dysfunction has been linked to compulsive behaviors such as addiction. The striatum plays a key role in habit formation and reward processing, while the thalamus is involved in sensory processing and the amygdala is involved in emotional processing and fear conditioning.

Environmental influences such as childhood trauma and stressful life events can also contribute to OCD symptoms. So can parental traits and cultural and social factors. Compulsion behavior can be a comorbidity in other psychiatric conditions including depression and anxiety disorders. 

OCD Treatments

According to CDC statistics, the estimated prevalence of OCD in the US is around 2.3 percent of the adult population. This translates to approximately 5 million adults.

Effective treatment options for the disorder are limited. They include cognitive behavioral therapy (CBT) to modify negative thoughts and behaviors. Deep brain and transcranial magnetic target specific brain regions. Mindfulness-based therapies address emotional processing. SSRIs regulate brain activity through increasing levels of serotonin. Often, clinicians use a combination of therapies for best results.

The Cambridge researchers suggested that elevated glutamate levels could serve as a “biomarker” for OCD, potentially guiding the development of new therapies. This could mean new medication courses or non-invasive scalp magnetic stimulation, which have shown some promise in treating OCD symptoms.

“Some treatments already target glutamate imbalance in a roundabout way,” noted Marjan Biria, MD, one of the study’s lead authors. “Now we have the evidence for why certain approaches seem to have some beneficial effects.”