The biological basis of schizophrenia: new directions.
The desire to understand the pathophysiology of schizophrenia has inspired an explosion in research over the past decade. This review highlights some key studies that have led to fundamental changes in our understanding of this disorder, focusing on the search for genes in schizophrenia, as well as several recent alternatives to the original dopamine hypothesis of schizophrenia. Advances in genetic methodology have allowed schizophrenia researchers to conduct genome-wide searches for susceptibility genes. Although these studies have identified several regions that demonstrate potential linkage with schizophrenia, a definitive genetic cause has not yet been proved. Recent neurochemical hypotheses have focused on the cortical amino acid neurotransmitter systems (i.e., glutamate and GABA), while anatomical studies suggesting abnormal brain development and premorbid functional deficits have led some researchers to propose a neurodevelopmental origin for schizophrenia. A sizable database can be marshaled in support of each of these ideas, but none as yet fully explain the biological basis of schizophrenia.
Weinberger
D R
DR
Clinical Brain Disorders Branch, NIMH, NIH, NIMH Neuroscience Center at St. Elizabeth's Hospital, Washington, DC 20032, USA.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000473:pathology; D002766:Cholecystokinin / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D018728:Entorhinal Cortex / Q000378:metabolism; D008040:Genetic Linkage; D005819:Genetic Markers; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D012377:Rodentia; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005819:Genetic Markers; D012333:RNA, Messenger; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; C000179:N-acetylaspartate; D004298:Dopamine