WHY IS PSYCHOSIS BAD FOR YOUR BRAIN?What is Calcium Excitotoxicity?N-methyl-D-aspartate receptors in the brain mediateglutamatergic neurotransmission. Binding of glutamate andglycine to the NMDA receptor opens the door for Calcium toenter the neuron. Magnesium also has to be removed fromthe 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 excessiveamounts of Calcium enter the neurons, leading to thedestruction of the organelles and the activation of cell deathcascade (apoptosis). This process is called excitotoxicity. During normal neurotransmission small amounts ofCalcium enter the neuron via NMDA receptors. ThisCalcium entry into the neuron is beneficial, it is part ofglutamate neurotransmission and it forms the basis of longterm potentiation, which is essential for the memory.
Intracellular Calcium HomeostasisExcessively high levels of Calcium in the neuron causedamage by activating the cell death cascade (apoptosis). Thisis what happens during psychotic episodes.For this reason the neurons, developed diverse homeostaticmechanisms to regulate intracellular Calcium level veryprecisely. Thus extracellular Calcium level is approximately2 mM, while the resting intracellular Calcium level is in therange of 100nM (20,000 times less).In order to keep tight control of the intracellular Calcium,the neuron developed Calcium pumps (to eliminate it), andCalcium proteins to sequestrate it. Thus it is estimated that
Calcium ion can only diffuse 0.5 micrometers and is free forless than 50 microseconds before encountering a Calciumbinding protein to sequestrate it. This mechanism isnecessary due to the fact that free intacellular Calcium isdeadly 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, followedby the neuronal death is the reason for treatment resistancein schizophrenia late in the course of illness (burn outphase).
Neuronal death due to excitotoxicity isthe reason for treatment resistance inschizophrenia late in the course of illness (burn out phase).Enlargement of Lateral Ventricles is one of the mostconsistent radiologic findings in schizophrenia. It is due toneurodegeneration caused by neuronal death as a result ofexcitotoxicity caused by Calcium.
Enlarged lateral ventricles due to neurodegeneration at the expense of thetemporal lobe tissue(auditory cortex) might explain auditory hallucinations inschizophrenia.Psychosis is bad for the brain because it increases excessively intacellularCalcium which leads to neuronal death.ADONIS SFERA, MD