Hippocampal neurogenesis as a target for the treatment of mental illness: a critical evaluation

Abstract

Over one-quarter of adult Americans are diagnosed with a mental illness like Major Depressive Disorder (MDD), Post-Traumatic Stress Disorder (PTSD), schizophrenia, and Alzheimer's Disease. In addition to the exceptional personal burden these disorders exert on patients and their families, they also have enormous cost to society. Although existing pharmacological and psychosocial treatments alleviate symptoms in many patients, the comorbidity, severity, and intractable nature of mental disorders strongly underscore the need for novel strategies. As the hippocampus is a site of structural and functional pathology in most mental illnesses, a hippocampal-based treatment approach has been proposed to counteract the cognitive deficits and mood dysregulation that are hallmarks of psychiatric disorders. In particular, preclinical and clinical research suggests that hippocampal neurogenesis, the generation of new neurons in the adult dentate gyrus, may be harnessed to treat mental illness. There are obvious applications and allures of this approach; for example, perhaps stimulating hippocampal neurogenesis would reverse the overt and noncontroversial hippocampal atrophy and functional deficits observed in Alzheimer's Disease and schizophrenia, or the more controversial hippocampal deficits seen in MDD and PTSD. However, critical examination suggests that neurogenesis may only correlate with mental illness and treatment, suggesting targeting neurogenesis alone is not a sufficient treatment strategy. Here we review the classic and causative links between adult hippocampal neurogenesis and mental disorders, and provide a critical evaluation of how (and if) our basic knowledge of new neurons in the adult hippocampus might eventually help combat or even prevent mental illness.