Causes of schizophrenia

The causes of schizophrenia that underlie the development of schizophrenia, a psychiatric disorder, are complex and not clearly understood. A number of hypotheses including the dopamine hypothesis, and the glutamate hypothesis have been put forward in an attempt to explain the link between altered brain function and the symptoms and development of schizophrenia. The exact pathophysiology of schizophrenia remains poorly understood. The most commonly supported theories are the dopamine hypothesis and the glutamate hypothesis. Other theories include the specific dysfunction of interneurons, abnormalities in the immune system, abnormalities in myelination, and oxidative stress. Dopamine hypothesis of schizophrenia The first formulations of the dopamine hypothesis of schizophrenia came from post-mortem studies finding increased numbers of D2/D3 receptors in the striatum, and elevated cerebrospinal fluid levels of dopamine metabolites. Subsequently, most antipsychotics were found to have affinity for D2 receptors. Later investigations have suggested a link between striatal dopamine synthesis and positive symptoms, as well as increased dopamine transmission in subcortical regions, and decreased transmission in cortical regions. A meta-analysis of molecular imaging studies observed increased presynaptic indicators of dopamine function, but no difference in the availability of dopamine transporters or dopamine D2/D3 receptors. Both studies using radio labeled L-DOPA, an indicator of dopamine synthesis, and studies using amphetamine release challenges observed significant differences between those with schizophrenia and control. These findings were interpreted as increased synthesis of dopamine, and increased release of dopamine respectively. These findings were localized to the striatum, and were noted to be limited by the quality of studies used. A large degree of inconsistency has been observed in D2/D3 receptor binding, although a small but nonsignificant reduction in thalamic availability has been found.