The Relationship Between Schizophrenia And Glutamate

Schizophrenia is a complex disorder that affects approximately 1% of the world’s population. It is one of the leading causes of chronic disability. There seems to be a link between schizophrenia and glutamate.

Based on this association, a new approach has emerged that seeks to explain the cause and possible treatment of this disorder. This approach has been referred to as the “glutamate hypothesis of schizophrenia.”

This hypothesis highlights the deficiency in the activity of a neurotransmitter called glutamate. In the brain there is a process that we call the hypofunction of glutamate.

To better understand the mechanism of this neurotransmitter in schizophrenia, we need to know exactly how glutamate works and what schizophrenia entails.

What is glutamate?

Glutamate is one of the most important neurotransmitters in the nervous system. It is responsible for 80% of the energy used by our brains. In addition, it is part of some metabolic processes, the production of antioxidants, the motor and sensory systems and emotions and behavior.

This neurotransmitter mediates between excitatory responses and intervenes in neuroplasticity processes. This refers to the brain’s ability to adapt as a result of an experience. Glutamate also intervenes in learning processes and is related to other neurotransmitters, such as GABA and dopamine.

When the synaptic vesicles release glutamate, it activates several pathways. In addition, this neurotransmitter is linked to its precursor GABA. GABA deactivates the pathways that glutamate has activated. GABA therefore acts as the antagonist of glutamate.

In addition , glutamate intervenes in cognitive, motor, sensory, emotional and memory information. That’s the main reason why people have started looking for a connection between schizophrenia and glutamate, given the function this neurotransmitter has at the cognitive and behavioral levels.

What is schizophrenia?

Schizophrenia is a serious mental disorder. It has a huge impact on a person’s quality of life. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) it usually manifests with the following symptoms:

• Hallucinations: The person sees visual or auditory manifestations that do not exist.
• Delusions: The person is convinced of something that is not true. In other words, he falsely believes in something he upholds with great conviction.
• Disorganized Language: Confusing language, such as often wandering or speaking inconsistently.
• Negative symptoms: apathy (a lack of energy to move) or decreased emotional expression.
• Disorganized or Catatonic Behavior.

To be diagnosed with schizophrenia, you must have two or more of the above symptoms for at least a month. In addition, there should be continuous signs of change for at least six months. In addition, the symptoms must affect the life of the person experiencing them.

On the other hand, the disease is not diagnosed when the symptoms are caused by the effects of a certain substance. And if the patient has a history of autism spectrum disorder, schizophrenia is only diagnosed if the hallucinations and delusions are very severe.

The link between schizophrenia and glutamate

The association between schizophrenia and glutamate has been looked at in response to the growing need for a theory that explains schizophrenia. The existing theories did not allow people to fully understand the mechanisms of this disease.

It was initially believed that schizophrenia might be caused by a problem with dopamine. Subsequently, however, researchers realized that in addition to dopamine, glutamate also played a key role and that it could be related to this disease. This is how the glutamate hypothesis of schizophrenia arose.

This hypothesis proposed that schizophrenia was caused by a hypofunction of glutamate in the cortical projections. In other words, if there is a deficiency of this neurotransmitter in the cortical region of the brain.

Now the glutamate hypothesis of schizophrenia does not rule out the link between schizophrenia and dopamine. Rather, it proposes that a hypofunction of glutamate causes an increase in dopamine. In other words, this hypothesis complements the dopamine theory.

The glutamate receptors generate activity in the GABAergic interneurons, which in turn inhibit the glutamate receptors. Then they prevent hyperactivation. That way no excess glutamate can be formed. This process causes more neurons to die. In the case of schizophrenia, this system is negatively affected.

Receptors involved in the link between schizophrenia and glutamate

As we mentioned above, the glutamate hypothesis refers to a dysfunction in glutamate receptors. In schizophrenia, they generate less cortical activity, which leads to the manifestation of certain symptoms. In other words, when the glutamate receptors do not function correctly, this disorder manifests.

Scientists discovered the importance of these receptors when they administered intravenous substances that blocked these receptors. Instead, cognitive and behavioral symptoms similar to those of schizophrenia manifested themselves.

In addition , scientists have also studied the following glutamate receptors related to schizophrenia:

• Ionotropic receptors: These receptors act on ions such as calcium and magnesium. They include the NMDA, AMPA, and kainate receptors. In addition, they send fast signals.
• Metabotropic receptors: These receptors bind to G proteins and have a characteristically slow transmission.

While there are some accurate results, there are also other conflicting results. The ionotropic NMDA receptor has been widely studied. The action of the AMPA and kainate receptors has also been studied, but the results are inconclusive.

In addition, when NMDA receptors malfunction, they cause neurons to die. This, in turn, exhibits behavioral dysfunctions characteristic of schizophrenia. Concerning the AMPA and kainate receptors, consistent data from different authors is needed for the data to be considered relevant.

Metabotropic receptors, on the other hand, are associated with neuronal protection. With change, the amount of glutamate in these receptors decreases. As a result, they cause behavioral problems that are characteristic of schizophrenia.

Therapeutic possibilities arising from the glutamate hypothesis

The glutamate hypothesis has allowed scientists to create certain pharmacological substances. The utility of these substances is to mimic the role of glutamate receptors and they have yielded fairly good results so far.

However, this does not mean that the process is easy or that the treatment is effective. It is not easy to control the activation of receptors. In addition, hyperactivation can also be harmful.

Since studies have only shown general symptoms, most of the experiments have been performed on animals. We cannot therefore be sure of the exact relationship between a symptom and brain localization in humans.

Yet the glutamate hypothesis represents a great advance. However, we should not forget that environmental factors also play a role in schizophrenia. Future research could combine several aspects to better understand this disorder. Perhaps an integrated approach can help to understand all the factors associated with it.