Schizophrenia

Schizophrenia is a severe, persistent mental illness associated with substantial disability. The pattern of inheritance is consistent with multiple genes, and genetic predisposition interacts with environmental factors. Several neurotransmitter systems, particularly the dopamine system, have been implicated. Antipsychotics work primarily by blocking dopamine D 2 receptors, but alterations in dopamine neurotransmission cannot explain the myriad symptoms of schizophrenia. Glutamate, γ-aminobutyric acid, and acetylcholine neurotransmitter systems play roles in the pathophysiology of schizophrenia, and alterations in glial function are implicated. Changes in astrocyte function lead to problems with energy metabolism, oligodendrocyte deficits to problems with myelination and lipid metabolism, and microglial activation to alterations in immune function and inflammation. Cortical neuronal atrophy, reduced dendritic complexity, and decreased spines indicate a substantial loss of cortical synaptic connectivity. This complex neuropathology concurs with the complex genetics of schizophrenia. Greater understanding of the pathogenesis and pathophysiology of schizophrenia should lead to improved treatment and prevention.