Increased saccadic distractibility in tardive dyskinesia: functional evidence for subcortical GABA dysfunction.
In mammals, GABAergic projections from the substantia nigra reticulata to the superior colliculus provide tonic inhibition to tectal neurons involved in the generation of saccades. Dysfunction of this pathway has been shown to produce saccadic "distractibility" in the experimental monkey. In two oculomotor paradigms, control of saccadic eye movements was tested in chronic schizophrenic patients with (n = 18) and without (n = 16) tardive dyskinesia (TD) and normal controls (n = 8). The three groups were matched by mean age; the TD and non-TD patient groups had similar duration of illness, benztropine and chlorpromazine equivalent doses and educational levels. A twofold increase in saccadic distractibility was observed in TD compared to non-TD schizophrenic patients, and both patient groups demonstrated a greater saccadic distractibility than normals. Furthermore, schizophrenic patients (both with and without TD) showed significantly increased latency for "volitional" saccades compared to the normal controls. These findings may provide further evidence for basal ganglia GABA dysfunction in tardive dyskinesia, as well as demonstrate oculomotor abnormalities in schizophrenic individuals.
Thaker
G K
GK
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, Baltimore 21228.
Nguyen
J A
JA
Tamminga
C A
CA
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001288:Attention / Q000187:drug effects*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D004525:Efferent Pathways / Q000187:drug effects / Q000503:physiopathology; D005133:Eye Movements / Q000187:drug effects*; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D012438:Saccades / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy*; D013378:Substantia Nigra / Q000187:drug effects* / Q000503:physiopathology
D014150:Antipsychotic Agents; D011963:Receptors, GABA-A