Structural and functional abnormalities of the amygdala in schizophrenia.
Schizophrenia is characterized by delusions and hallucinations, which tend to respond to treatment with dopamine receptor blockers, and a loss of motivation and affect, which do not. Structural magnetic resonance imaging (sMRI) has convincingly demonstrated reduced volumes of the amygdala-hippocampal complex (AHC) and other limbic and paralimbic structures, on both manual tracing and automated analyses. The Edinburgh High-Risk Study (EHRS) of initially healthy adolescents with at least two affected relatives has found that AHC volumes are reduced pre-morbidly but not to schizophrenic levels, suggesting that further volume reductions may be associated with the onset of schizophrenia. AHC volumes appear to be genetically mediated in families with a dominant pattern of transmission, whereas prefrontal lobe and basal ganglia volumes are related to genetic liability to schizophrenia in the generality of high-risk subjects. Temporal lobe volumes may fall as psychotic symptoms develop, in the context of drug abuse and stress. Neuropsychological testing has also demonstrated pre-morbid impairments and symptom-related deterioration. More detailed analyses of the temporal lobe changes on sMRI and fronto-temporal dysconnectivity on fMRI are in progress. These findings are discussed with reference to other indications of pre-morbid developmental disturbance in our high-risk subjects, animal models of schizophrenia, and reliable findings from neuropathological, neuropsychological, and functional imaging studies of patients with schizophrenia.
Lawrie
Stephen M
SM
Edinburgh University, Department of Psychiatry, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, Scotland, UK. s.lawrie@ed.ac.uk
Whalley
Heather C
HC
Job
Dominic E
DE
Johnstone
Eve C
EC
D000679:Amygdala / Q000033:anatomy & histology* / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000033:anatomy & histology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D011446:Prospective Studies; D018570:Risk Assessment; D012559:Schizophrenia / Q000175:diagnosis* / Q000235:genetics