Study Links GABA and Glutamate Balance to Anxiety in Adolescent Girls

Adolescence can be hell, without question. Rising expectations, surging hormones and a brain that seems to break down and rebuild itself like a caterpillar inside a neurological cocoon all make the teenage years difficult.

For young women, these developmental years seem to be emotionally tougher than they are for many young men. Studies have found increases in generalised and social anxiety that are not mirrored among adolescent males.

One possible contributor is an “overactive braking system” that disrupts the kind of reasoning that would usually help someone work through stressful circumstances.

GABA, glutamate and anxiety in adolescent girls

A recent study by University of Surrey psychologist Nicola Johnstone and cognitive neuroscientist Kathrin Cohen Kadosh examined how the levels of two important metabolites in female brains rise and fall with age.

The findings lend support to the neural over-inhibition hypothesis of anxiety. This hypothesis suggests that anxiety disorders may result from an imbalance between the excitation and inhibition of brain circuits responsible for regulating emotional responses.

Much of neurology relies on a contest between chemicals that activate nerve cells and molecules that obstruct their activity.

Glutamate and gamma-aminobutyric acid (GABA) are two neurochemicals competing over various switches in parts of the brain: glutamate pushes for them to remain on, while GABA argues for switching them off.

Understanding how either chemical influences behaviour is not as straightforward as identifying one as inhibitory and the other as excitatory. Shutting down one circuit can, in some situations, simply allow another to become more active.

Examining changes in the female brain

Higher GABA levels in crucial brain regions have long been regarded as a way of keeping anxiety under control. More recent research, however, has challenged that view. It suggests that excessive GABA in brain areas involved in higher-order processes, including planning and decision-making, could regulate activity too strongly and instead allow anxiety to arise.

With that distinction in mind, Johnstone and Kadosh recruited 49 girls aged 10 to 12 and 32 young adult women aged 18 to 25. Before their brain activity was assessed with an MRI scanner, each participant completed a survey covering their history of mood disorders.

Using the scans, the researchers estimated the fluctuations of GABA and glutamate in regions associated with reasoning and emotional processing. They then compared those differences with anxiety measures across the age groups.

Although the study did not investigate changes in activity or function caused by shifting GABA levels relative to glutamate, the researchers contend that their measurements, considered alongside earlier studies, support the idea that anxiety emerges when neurochemistry suppresses efforts to reason through a problem. This appeared especially relevant among the older participants.

An overactive brain braking system

“Our research indicates that the equilibrium between GABA and glutamate in the dorsolateral prefrontal cortex serves as a vital indicator of anxiety levels,” says Johnstone.

“While glutamate propels brain activity, GABA acts as a brake. Our findings suggest that anxiety, often characterized by impaired rational thought, is intricately linked to the overactive braking system in the brain.”

This does not mean that anxiety is determined by sex. Viewed alongside other studies of male brains led by Cohen Kadosh, the neural circuits involved in stress generally differ between the brains of different sexes. Male neurology appears able to manage the additional GABA loads affecting the prefrontal cortex.

“Grasping how key brain chemicals, GABA and glutamate, fluctuate during important growth stages like adolescence is vital for spotting and stopping anxiety disorders early,” says Cohen Kadosh.

“This study shines a light on the possibility of focusing on these brain chemicals for new treatments, particularly in young women.”

The research was published in Developmental Cognitive Neuroscience.