Inhibitory deficit in schizophrenia is not necessarily a GABAergic deficit.
1. Current evidence strongly supports the idea of an inhibitory deficit as a central pathophysiological mechanism in schizophrenia. This deficit has been well documented in sensory gating and paired-pulse studies and may be related to decreases in inhibitory interneurons found in schizophrenic patients. 2. The GABAergic system has been repeatedly postulated to mediate this deficit, but the findings are controversial, at least in some areas, and mostly negative regarding treatment with drugs enhancing GABAergic activity. Therefore, the scope of mediators of this inhibitory deficit should be widened and the neuromodulator adenosine is proposed as a candidate to be further studied. 3. A state of adenosinergic hypoactivity in schizophrenia is compatible not only with the inhibitory deficit but also with symptoms, clinical response to antipsychotics, impaired sensory gating, deteriorating course, increased smoking, and sleep alterations reported in schizophrenia. 4. It is concluded that although the GABAergic system should be further studied, especially in sensory gating model in humans, emphasis on other inhibitory mechanisms may prove useful and provide more effective treatment.
Lara
Diogo R
DR
Departamento de Ciências Fisiológicas, Faculdade de Ciências Biológicas, PUCRS, Porto Alegre, Brazil. drlara@pucrs.br
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D006801:Humans; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000172:deficiency*
D018755:GABA Agonists; D018047:Receptors, Purinergic P1; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D004298:Dopamine