Developmental theory of schizophrenia

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

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

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

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.

Presymptomatic/Prodromal Treatment of Schizophrenia

0

50%

100%

15 20 40 60

AGEasymptomatic but genetically and biologically endophenotypically at risk

presymptomatictreatment

onset of negative symptoms, asocial features, subsyndromal

prodromaltreatment

onset of full schizophrenia syndrome

first episodetreatment

second episodetreatment andmaintenance

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.