What is Schizophrenia?
Schizophrenia is a neurological disorder with abnormal social behaviour and difficulty understanding reality (delusions with hallucinations)
It is characterised by positive and negative symptoms.
The positive symptoms are additions to the person and negative symptoms are subtractions to the person so to speak.
The positive symptoms are
- reality distortion
- wild trains of thought
- Irrational conclusions
- Disorganised behaviour These are thought to be from increased tonic dopamine release in the nucleus accumbens
The Negative symptoms are
- Thought disorder
- Poor social functioning
- Flattening of emotional response
- Decreased cognitive function
- Decreased salience
- This is that your brain does not filter what information is important and what is not. a schizophrenic person may think everything around them in important and pertaining to them. (This is the result of excessive tonic dopamine signalling of the salience network) And thought to be from decreased release into the prefrontal cortex
The chemical basis of schizophrenia
There are 3 dopaminergic pathways in the brain. These are:
- The Mesocortical pathway
- The Nigrostriatal pathway
- And the Mesolimbic pathway.
The 2 meso pathways originate in the ventral tegmental area and deal with cognition and emotion (mesocortical and the PFC), and reward and addiction (mesolimbic and the nucleus accumbens).
The nigrostriatal pathway foes to the striatum and are relevant in movement disorders like parkinsons and huntingtons.
Schizophrenia and the dopaminergic pathways
Schizophrenia is characterised by too much tonic dopamine release in the mesolimbic pathway (nucleus accumbens) , leading to the positive effects of schizophrenia and too little release in the PFC leading to the negative symptoms of schizophrenia
Dubious trials
Some trials of interesting ethics have figured out some of the pathways possibly implicated in schizophrenia.
Deliriants cause frightening hallucinations which you think are real, psychedelics cause hallucinations which you know are fake, and can cause ego death
Drugs which emulate “schizophrenic” symptoms are implied to cause alterationin the brain which those with schizophrenia have naturally. Over the years, some medications used are:
- Hyoscine butylbromide, found a in witches “flying ointment”, which is a deliriant, and is an ACh muscinaric antagonist. Mimics select positive and negative symptoms of schizophrenia
- Sernyl (PCP) → causes ego death and disassociation & disorganisation of thought. Acts on glutamate NMDA receptors. Mimics select positive and negative symptoms of schizophrenia
- LSD - agonises Serotonin 5-HT2A receptors. Is a psychedelic. not super like schizophrenia
- Methamphetamine. Abuse is very very much like schizophrenia.
From the drug which cause schizophrenia like effects, we can try to get something that does the opposite to treat schizophrenia.
Additionally, as glutamate NMDA antagonists have similar symptoms (positive and negative) to schizophrenia there is a theory that hypoglutamatic states could be a component of schizophrenia.
The mechanism for this is specifcally listed as not to be memorised but follows as this. The prefrontal cortex uses glutamate to signal to the VTA to realease dopamine into the PFC and to inhibit release of dopamine into the nucleus accumbens. Lack of glutamate leads to diminished dopamine in the PFC and extra in the Nucleus accumbens.
The drug classes used are:
- Dopamine antagonists
- 5-HT2A antagonists
- Muscarinic agonists
These are covered in Anti-psychotics
Diagnosis of schizophrenia
A: 2 or more of the following much be present for a significant portion of time during a 1-month period. At least 1 must be of the first 3
- Delusions
- Hallucinations
- Disorganised speech
- Drossly disorganised or catatonic behaviour
- Negative symptoms (Diminished emotional expression or avolition)
B: For a significant portion of the time since the onset functioning must be below expected C: continuous signs of disturbance persist for at least 6 months. Active phase symptoms (A.)must be at least 1 month but only a single symptom is needed for the other months. D: All other disorders have been excluded as a cause E: It isn’t a substance or other drug F: If there is history of autism there must be prominent delusions or hallucinations