Chemical imbalance in forebrain behind OCD, research finds

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 has been found in people with obsessive-compulsive disorder, or OCD.

Glutamate is an "excitatory" neurochemical allowing electrical impulses to send information across brain networks, whereas GABA is the "inhibitory" one, dampening neural excitation and thereby, creating and maintaining a balance.

In OCD sufferers, 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, the University of Cambridge (UK) research showed.

Using magnetic resonance spectroscopy, the researchers found heightened glutamate and lowered GABA levels in one of these cerebral cortical regions, the anterior cingulate cortex, of people with OCD than in those without.

Further, enhanced glutamate levels in the other cerebral cortical region, the supplementary motor region, 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", the scientists said.

Publishing their study in the journal Nature Communications, the neuroscientists said it will open up new avenues for treating a potentially disabling OCD, a psychiatric disorder characterised by recurrent and persistent thoughts and feelings and repetitive, ritualised behaviours.

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

" For some sufferers, severe OCD is a mental health disorder causing untold misery and leading to loss of work and relationships, and social isolation.

"Symptoms of intrusive thoughts and repetitive rituals can confine patients to their homes for months on end," said Robbins. In extreme cases, the lack of control and sense of hopelessness caused by OCD can even result in thoughts of suicide.

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 anterior cingulate cortex entirely.

The researchers say that raised glutamate levels may prove to be an OCD "biomarker" guiding new therapies, including medication.

"The results suggest new strategies for medication in OCD based on available drugs that regulate glutamate. In particular, drugs that inhibit presynaptic glutamate receptors," said Robbins. A presynaptic receptor is the part of a nerve cell that controls release of neurotransmitter chemicals.

Along with scans, the researchers conducted tests and questionnaires with all participants to gauge obsessive-compulsive and habitual tendencies, which checked for their behavioural adaptability to better pursue goals, rather than repeating responses out of habit.

"Compulsions and habits are not the same, but impaired regulation of habits can be the basis of compulsions and shift people away from their goal-directed behaviour," said Robbins.