The ventral portion of the CA1 region of the hippocampus and the prefrontal cortex as candidate regions for neuromodulation in schizophrenia

Existing antipsychotic drugs are most effective in the treatment of the positive symptoms of schizophrenia. However, they are associated with considerable side effects and have relatively low efficacy. Diminished inhibitory control in the hippocampus has been suggested to lead to hyperactivation of the dopamine system thus underpinning the dopamine-dependent psychosis associated with schizophrenia. Similarly, diminished inhibitory control is thought to underpin the cortical disruption associated with the cognitive dysfunctions. Impairment of a specific class of parvalbumin-positive inhibitory interneuron has been consistently identified in the prefrontal cortex and hippocampus of schizophrenics. Thus, this impairment common to both regions, may subserve these distinct symptom domains. Deep brain stimulation has been suggested to act, at least in part, through the modulation of interneuron function and here we propose the prefrontal cortex and hippocampus as potential targets for neuromodulatory intervention in the treatment of schizophrenia. Further, we specifically consider whether multiple targets and multiple neuromodulatory approaches may be necessary in the treatment of this multi-faceted disease. Finally we propose that deep brain stimulation of the ventral protion of the CA1 region of the hippocampus may be the most promising single target for neuromodulation in schizophrenia.