1. 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.

2. 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.

3. 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

4. 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).

5. 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.

6. 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