Schizophrenia is linked to over a dozen genes that regulate neuronal connectivity, synaptogenesis, NMDA glutamate receptors, and neuronal migration. It is also regulated by four genes: BDNF, Dysbindin, DISC1, and neuregulin. Schizophrenia is postulated to have four stages: stage 1 from birth to 15 with full functioning; stage 2 from 15-20 with subtle symptoms; stage 3 from 20-40 with acute positive symptoms and relapses; and stage 4 from 40-60 with prominent negative and cognitive symptoms and continuing disability.

2. Researchers agree that schizophrenia is both
a neuro-developmental and a neuro-
degenerative

3.  More than a dozen genes have been
identified and linked to the risk of
schizophrenia.
Genes regulate:
 Neuronal connectivity
 Synaptogenesis
 NMDA glutamate receptors
 Neuronal migration

4.  Is regulated by four genes: BDNF, Dysbindin,
DISC 1 and neuregulin.

12.  It is postulated that the clinical course of schizophrenia has four stages.
 Stage 1- birth to 15 patient has full functioning early in life and is
virtually asymptomatic.
 Stage 2 – 15-20 prodromal phase that starts in the teens, there may be
odd behaviors and subtle negative symptoms.
 Stage 3 – 20 – 40 the acute stage of the illness usually announces itself
fairly dramatically in the twenties with positive symptoms, remissions,
and relapses. But the patient never quite returns to previous level of
functioning. This is often a chaotic stage of illness with a progressive
downhill course.
 Stage 4 40 – 60 the final phase of the illness may begin in the forties or
latter, with prominent negative and cognitive symptoms. Although there
is some waxing and waning, this is more of a “burnout” phase of
continuing disability. The illness may not necessarily take a continual
and relentless downhill course, but the patient may become
progressively resistant to treatment with antipsychotic medications
during this stage.

13. Presymptomatic/Prodromal Treatment of
Schizophrenia
presymptomatic
treatment
prodromal second episode
treatment first episode treatment and
maintenance
100% treatment
50%
0
15 20 40 60
onset of full schizophrenia syndrome
onset of negative symptoms,
asocial features, subsyndromal
asymptomatic but genetically and
biologically endophenotypically at risk AGE

14.  During a psychotic episode calcium continuously
enters the neurons through activated NMDA
receptors.
 Too much calcium inside the neuron causes
activation of the lysosomal enzymes.
 This leads to the formation of free radicals that
damage the organelles in the neuron and ultimately
cause cell death.
 The more psychotic episodes an individual has
throughout lifetime the more damage to the cells.
 The more the cellular pathways are damaged the
less responsive the individual becomes to the
effects of antipsychotic medications.