Cortical microcircuits in schizophrenia--the dopamine hypothesis revisited.
Strong evidence exists for disturbed functional connectivity of cortical microcircuits--particularly of prefrontal cortex. Dopamine, long implicated in antipsychotic drug effects, is crucially involved in optimizing signal-to-noise ratio of local cortical micro-circuits. This action of dopamine is achieved by means of D1- and D2-receptor-mediated effects on pyramidal and local circuit neurons, which mediate recurrent inhibition and thus contribute to the stability of cortical representations of external and internal stimuli. In schizophrenia, a diminished cortical dopamine D1/D2 activation ratio--in concert with altered GABAergic and glutamatergic transmission--appear to critically interfere with this process.
Winterer
G
G
Department of Psychiatry, Heinrich-Heine University Hospital Duesseldorf, Germany. georg.winterer@uni-duesseldorf.de
D002540:Cerebral Cortex / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D007389:Internal-External Control; D009415:Nerve Net / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology; D017397:Prefrontal Cortex / Q000503:physiopathology; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004298:Dopamine