Disorders of memory and plasticity in psychiatric disease.
Plasticity is found throughout the nervous system and is thought to underlie key aspects of development, learning and memory, and repair. Neuropiastic processes include synaptic plasticity, cellular growth and remodeling, and neurogenesis. Dysregulation of these processes can contribute to a variety of neuropsychiatric diseases. In this review we explore three different ways in which dysregulation of neuropiastic and mnemonic processes can contribute to psychiatric illness. First, impairment of the mechanisms of plasticity can lead to cognitive deficits; this is most obvious in dementia and amnesia, but is also seen in more subtle forms in other conditions. We explore the relationship between stress, major depression, and impaired neuroplasticity in some detail. Second, enhanced memories can be pathogenic; we explore the example of post-traumatic stress disorder, in which intrusive trauma associated memories, accompanied by hyperactivity of the normal fear learning circuitry, are core aspects of the pathology. Third, impaired modulation of the relationship between parallel memory systems can contribute to maladaptive patterns of behavior; we explore the bias towards inflexible, habit-like behavior patterns in drug addiction and obsessive-compulsive disorder. Together, these examples illustrate how different abnormalities in the mechanisms of neuroplasticity and memory formation can contribute to various forms of psychopathology. It is hoped that a growing understanding of these relationships, and of the fundamental mechanisms underlying neuroplasticity in the normal brain, will pave the way for new understandings of the mechanisms of neuropsychiatric disease and the development of novel treatment strategies.
Yale OCD Research Clinic, Yale University School of Medicine, New Haven, Connecticut, USA.
Christopher
C
Pittenger
D001921:Brain / Q000503:physiopathology*; D006801:Humans; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000150:complications / Q000503:physiopathology*; D001523:Mental Disorders / Q000150:complications / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology*
LTP; drug addiction; major depressive disorder; memory; multiple memory systems; neurogenesis; obsessive-compulsive disorder; plasticity; post-traumatic stress disorder; stress