WHY IS PSYCHOSIS BAD FOR YOUR BRAIN?

What is Calcium Excitotoxicity?

N-methyl-D-aspartate receptors in the brain mediate

glutamatergic neurotransmission. Binding of glutamate and

glycine to the NMDA receptor opens the door for Calcium to

enter the neuron. Magnesium also has to be removed from

the NMDA receptor in open the Calcium gates.

Three things have to happen so that Calcium can enter the neuron:

-glutamate binding

-glycine binding

-removal of Magnesium from the NMDA channel.

Studies have shown that during psychotic episodes excessive

amounts of Calcium enter the neurons, leading to the

destruction of the organelles and the activation of cell death

cascade (apoptosis). This process is called excitotoxicity.

During normal neurotransmission small amounts of

Calcium enter the neuron via NMDA receptors. This

Calcium entry into the neuron is beneficial, it is part of

glutamate neurotransmission and it forms the basis of long

term potentiation, which is essential for the memory.

Intracellular Calcium Homeostasis

Excessively high levels of Calcium in the neuron cause

damage by activating the cell death cascade (apoptosis). This

is what happens during psychotic episodes.

For this reason the neurons, developed diverse homeostatic

mechanisms to regulate intracellular Calcium level very

precisely. Thus extracellular Calcium level is approximately

2 mM, while the resting intracellular Calcium level is in the

range of 100nM (20,000 times less).

In order to keep tight control of the intracellular Calcium,

the neuron developed Calcium pumps (to eliminate it), and

Calcium proteins to sequestrate it. Thus it is estimated that

Calcium ion can only diffuse 0.5 micrometers and is free for

less than 50 microseconds before encountering a Calcium

binding protein to sequestrate it. This mechanism is

necessary due to the fact that free intacellular Calcium is

deadly for the cell because it activates apoptosis

(programmed cell death).

Entry of Calcium into the neuron is very thightly controlled.

Excitotoxicity due to excess Calcium in the neuron, followed

by the neuronal death is the reason for treatment resistance

in schizophrenia late in the course of illness (burn out

phase).

Neuronal death due to excitotoxicity isthe reason for treatment resistance in

schizophrenia late in the course of illness (burn out phase).

Enlargement of Lateral Ventricles is one of the most

consistent radiologic findings in schizophrenia. It is due to

neurodegeneration caused by neuronal death as a result of

excitotoxicity caused by Calcium.

Enlarged lateral ventricles due to neurodegeneration at the expense of the

temporal lobe tissue(auditory cortex) might explain auditory hallucinations in

schizophrenia.

Psychosis is bad for the brain because it increases excessively intacellular

Calcium which leads to neuronal death.

ADONIS SFERA, MD