Schizophrenia is considered a neurodevelopmental and
neurodegenerative disorder.
Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of
parvalbumin (PV)-positive γ-
aminobutyric acid (
GABA) interneurons has been associated with the pathophysiology of
schizophrenia, in view of the link between the abnormality of GABA neurons and
cognitive impairments of the disease. It is assumed that an imbalance of excitatory and inhibitory (E-I) activity induced by low activity of glutamatergic projections and PV-positive
GABA interneurons in the prefrontal cortex resulted in sustained neural firing and gamma oscillation, leading to impaired cognitive function. Therefore, it is important to develop novel
pharmacotherapy targeting GABA neurons and their activities. Clinical evidence suggests
serotonin (5-HT) 1A receptor agonist improves cognitive disturbances of
schizophrenia, consistent with results from preclinical studies, through mechanism that corrects E-I imbalance via the suppression of
GABA neural function. On the other hand,
T-817MA, a novel neurotrophic agent, ameliorated loss of PV-positive GABA neurons in the medial prefrontal cortex and reduction of gamma-band activity, as well as
cognitive dysfunction in animal model of
schizophrenia. In conclusion, a
pharmacotherapy to alleviate abnormalities in GABA neurons through 5-HT1A agonists and
T-817MA is expected to prevent the onset and/or progression of
schizophrenia.