Dopamine hypothesis of schizophrenia

The dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model attributing symptoms of schizophrenia (like psychoses) to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have dopamine-receptor antagonistic effects. The theory, however, does not posit dopamine overabundance as a complete explanation for schizophrenia.
Some researchers have suggested that dopamine systems in the mesolimbic pathway may contribute to the 'positive symptoms' of schizophrenia (whereas problems with dopamine function in the mesocortical pathway may be responsible for the 'negative symptoms', such as avolition and alogia.)

Evidence for the dopamine hypothesis

Amphetamine, cocain and similar drugs increase levels of dopamine in the brain and can cause symptoms which resemble those present in psychosis, particularly after large doses or prolonged use. This is often referred to as "amphetamine psychosis" or "cocaine psychosis," but may produce experiences virtually indistinguishable from the positive symptoms associated with schizophrenia. Similarly, those treated with dopamine enhancing levodopa for Parkinson's disease can experience psychotic side effects mimicking the symptoms of schizophrenia. Up to 75% of patients with schizophrenia have increased signs and symptoms of their psychosis upon challenge with moderate doses of methylphenidate or amphetamine or other dopamine-like compounds, all given at doses at which control normal volunteers do not have any psychologically disturbing effects.

Genetic

Estimates of heritability vary because of the difficulty in separating the effects of genetics and the environment. The greatest risk for developing schizophrenia is having a first-degree relative with the disease (risk is 6.5%); more than 40% of monozygotic twins of those with schizophrenia are also affected. It is likely that many genes are involved, each of small effect. Many possible candidates have been proposed, including specific copy number variations, NOTCH4 and histone protein loci. A number of genome-wide associations such as zinc finger protein 804A have also been linked. There appears to be significant overlap in the genetics of schizophrenia and bipolar disorder.

Enviormental

Environmental factors associated with the development of schizophrenia include the living environment, drug use and prenatal stressors. Parenting style seems to have no effect, although people with supportive parents do better than those with critical parents. Living in an urban environment during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two, even after taking into account drug use, ethnic group, and size of social group. Other factors that play an important role include social isolation and immigration related to social adversity, racial discrimination, family dysfunction, unemployment, and poor housing conditions. Childhood experiences of abuse or trauma are risk factors for a diagnosis of schizophrenia later in life.