Psychoses are major psychiatric disorders, in which the patient has no insight of his illness. They are associated with gross disturbance of thought (e.g. delusions) and/or mood, & abnormal perception. There is familial link in many of them.
They comprise :
1. Schizophrenia : this is largely a gross disorder of thought,
perception, and behaviour
2. Affective disorders: these are emotional disorders in which mood may be either excessively and persistently low (depression) or high (mania). They are associated usually with thought disturbance

As a general rule, psychotic illness requires drug therapy as first-line treatment.

Psychotherapy has an adjunctive role helping drug compliance, improving family relations, and helping patient to cope with his distressing symptoms.



I. Schizophrenia : The underlying cause is unknown but is associated with positive symptoms (such as delusions and hallucinations (esp. auditory), paranoid ideas, thought insertion, and sometimes agitation with hostility) as well as negative symptoms (such as social withdrawal and apathy).

Symptoms pathogenesis may be explained by :

A/ Dopamine hypothesis : positive schizophrenia symptoms may result from overactive DA neurotransmission in mesolimbic pathways.


Note : DA2 receptors are found in striatum, as well as cerebral cortex, and limbic structures.

The following favour DA hypothesis :

1. Most conventional antipsychotic drugs
block DA2 receptors, and there is an excellent correlation between their clinical potency and their
in-vitro affinity for these DA2 receptors.

2. Drugs that increase DA in CNS synapses by increasing its synthesis ( e.g. L-DOPA), or its release (e.g. amphetamines) or block its reuptake (e.g. cocaine) can induce psychotic behavior in overdose



B/. Linked dopamine and hypofrontality
hypothesis :

This theory states that dysfunction in mesocortical
pathways accounts for negative symptoms.

Consequently, the loss of cortical inhibition leads to
increase dopaminergic neurotransmission in
mesolimbic pathways, thus resulting in the positive
symptoms of schizophrenia.



This is consistent with the following facts :

1. Conventional antipsychotics , which are DA2 receptor antagonists , relieve positive symptoms of schizophrenia but have little or no effect on negative symptoms.

2. The new antipsychotics , which have more affinity to block 5-HT2 receptors in frontal lobe ( and thus increase DA release mesocortical pathway) , relieve negative symptoms of schizophrenia ,
and also relieve the positive symptoms by restoring the inhibition exerted by frontal cortex on
mesolimbic system



This is consistent with the following facts :

1. Conventional antipsychotics , which are DA2 receptor antagonists , relieve positive symptoms of schizophrenia but have little or no effect on negative symptoms.

2. The new antipsychotics , which have more affinity to block 5-HT2 receptors in frontal lobe ( and thus increase DA release mesocortical pathway) , relieve negative symptoms of schizophrenia ,
and also relieve the positive symptoms by restoring the inhibition exerted by frontal cortex on
mesolimbic system



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