Chemical imbalance in forebrain behind OCD, research finds

Chemical imbalance in forebrain behind OCD, research finds

Chemical imbalance in forebrain behind OCD, research finds

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterised by recurrent and persistent thoughts and feelings and repetitive, ritualised behaviours. For some sufferers, severe OCD can cause untold misery and lead to loss of work and relationships, and social isolation. In extreme cases, the lack of control and sense of hopelessness caused by OCD can even result in thoughts of suicide.

Understanding the causes and mechanisms of OCD is a central question for psychiatry. A new study by scientists at the University of Cambridge (UK) has shed light on one of the possible factors behind OCD: an imbalance in the neurotransmitters, or chemicals in the brain, in the brain's frontal regions responsible for maintaining the excitation-inhibition equilibrium in these regions.

What are neurotransmitters and how do they affect OCD?

Neurotransmitters are molecules that allow electrical impulses to send information across brain networks. There are two main types of neurotransmitters: excitatory and inhibitory. Excitatory neurotransmitters, such as glutamate, increase the activity of neurons, while inhibitory neurotransmitters, such as gamma-aminobutyric acid (GABA), decrease the activity of neurons. The balance between these two types of neurotransmitters is crucial for normal brain functioning.

In OCD sufferers, the researchers found that the glutamate-GABA balance was disrupted in two regions of the brain's cerebral cortex, both fundamentally involved in deciding the balance between our conscious goals and more automatic habits. These regions are the anterior cingulate cortex (ACC) and the supplementary motor area (SMA).

The ACC is involved in monitoring conflicts between our actions and our intentions, as well as regulating emotions and impulses. The SMA is involved in planning and executing movements, as well as learning from feedback and errors. Both regions are part of a larger network called the cortico-striatal-thalamic-cortical (CSTC) circuit, which is known to be implicated in OCD.

Using magnetic resonance spectroscopy, a non-invasive technique that measures the levels of different chemicals in the brain, the researchers found heightened glutamate and lowered GABA levels in the ACC of people with OCD than in those without. This means that the ACC is overactive and less able to inhibit unwanted thoughts and impulses.

Further, enhanced glutamate levels in the SMA were linked to severity of OCD symptoms, along with a tendency towards habitual and compulsive behaviour. The researchers found this to be the case in both OCD patients as well as healthy participants with milder compulsive tendencies.

The research, thus, suggested that compulsions arise from a dysregulated brain system for controlling habits, which is driven by excess glutamate and reduced GABA in key regions of the OCD brain.

What are the implications of this study?

The study, published in the journal Nature Communications, is one of the first to show definitive changes in these key neurotransmitters in OCD sufferers. It also provides a potential biomarker for diagnosing and monitoring OCD, as well as a target for developing new therapies.

"Excess glutamate and reduced GABA is disrupting the neural circuitry in key regions of the OCD brain," said senior author Trevor Robbins from Cambridge's Department of Psychology. "We have now shown definitive changes in these key neurotransmitters in OCD sufferers."

In terms of treatment, while people with milder symptoms can benefit from some anti-depressants, fewer and extreme options exist for those with severe OCD, such as deep-brain stimulation and even a neurosurgical removal of the ACC entirely. The researchers say that modulating glutamate levels may prove to be an effective alternative strategy for treating OCD.

"We hope that our findings will stimulate further research into novel pharmacological interventions that can normalise glutamate-GABA balance in OCD," said lead author Claire Gillan from Cambridge's Department of Psychology. "This could potentially offer more effective and less invasive options for patients with this debilitating condition.



What brain chemical is associated with OCD?

Research suggests that OCD involves problems in communication between the front part of the brain and deeper structures of the brain. These brain structures use a neurotransmitter (basically, a chemical messenger) called serotonin.

What neurotransmitters are unbalanced in OCD?

Glutamatergic neurotransmission is the principal neurotransmitter implicated in the CSTC model of OCD. Hyperactivity in the CSTC loop implies a high level of glutamate in the cortical-striatal pathways as well as a dysregulation of GABAergic transmission, and could represent the pathophysiology of OCD.

Is OCD associated with brain abnormalities?

The bottom line for patients "We know that OCD is a brain-based disorder, and we are gaining a better understanding of the potential brain mechanisms that underlie symptoms, and that cause patients to struggle to control their compulsive behaviors," says Norman.

What is the root cause of OCD?

Ongoing anxiety or stress, or being part of a stressful event like a car accident or starting a new job, could trigger OCD or make it worse. Pregnancy or giving birth can sometimes trigger perinatal OCD.

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