Despite the fact that cognitive function is the best predictor of functional outcome and quality of life in schizophrenia (1), cognitive symptoms remain poorly treated in the illness. A myriad of cognitive domains are affected, including selective and sustained attention, working memory, episodic memory, processing speed, executive function, and social cognition (2). Patients consequently suffer from high unemployment rates (80%) and most are unable to live independently (30%) (3). Clearly, new treatments are needed.
One strategy for developing new interventions for these symptoms is to focus on treatments that may target biological indicators (ābiomarkersā) of cognitive dysfunction. Recently, our laboratory found that resting-state hyperactivity of the hippocampus (as examined by functional magnetic resonance imaging) was strongly predictive of poor cognition in schizophrenia patients (4). This finding, along with previous studies that have demonstrated increased hippocampal blood flow (5), blood volume (6, 7), and hyperactivity during sensory processing (8, 9) in the disease suggests that hippocampal hyperactivity may be a biomarker for cognitive dysfunction in the illness (10). Loss of inhibitory signaling in the hippocampus is also hypothesized to play a role in sensory filtering deficits in schizophrenia (11), one of the most prominent electrophysiological features of the disease. This loss is thought to be conveyed through reduced nicotinic (12, 13) and/or GABAergic (14) signaling. It follows that interventions that reduce hippocampal hyperactivity may have therapeutic benefit in schizophrenia.