In this review we explore several illustrative examples of this theme. The disruption of mnemonic processes can contribute to pathology in a variety of ways. The most obvious is the case in which fundamental mechanisms of memory formation are disrupted, either at the cellular or systemic level. This leads to conditions in which a memory deficit is the cardinal and defining symptom. For example, in Alzheimer’s disease, which is covered in detail elsewhere in this volume (p 445), cellular pathology affects

both the Inhibitors,research,lifescience,medical integrity of the hippocampus-centered explicit memory system and the cellular processes within it whereby information is stored, leading to prominent explicit memory deficits early in the disease course.1 In amnesia secondary to ischemic, infectious, or physical damage to medial temporal lobe structures, dense deficits in episodic memory may be observed in the context of otherwise

normal brain function.2 Abnormalities in mnemonic processes Inhibitors,research,lifescience,medical can contribute to psychopathology in a variety of more subtle ways. Disruption of explicit memory capacity is seen in a number of stress-associated disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD); chronic stress produces a number of abnormalities Inhibitors,research,lifescience,medical in brain circuitries that are required for explicit memory function, such as the hippocampus and dorsolateral prefrontal cortex, which provides a probable mechanism for these effects.3 Pathologically enhanced

memories contribute to acute stress disorder and PTSD, in which Inhibitors,research,lifescience,medical excessively strong associations with traumatic events lead to their disruptive recall and generalization. Pharmacological treatments that directly manipulate synaptic plasticity have shown promise in the treatment of such pathological memories.4 Pathologically enhanced memories also contribute to substance abuse, in which drug-associated cues take on enhanced IOX1 concentration salience, to the Inhibitors,research,lifescience,medical exclusion of other cues and natural rewards5; the interaction of drugs of abuse with plasticity-related molecular processes is addressed in detail elsewhere in this volume (p 431). Finally, disruption of the balance or interplay between parallel memory systems may contribute to psychopathology in some conditions; this idea has been about particularly well developed in the study of drug addiction,6 but recent data suggest that it may also be the case in obsessive-compulsive disorder (OCD)7 and other conditions. Stress, depression, and neuroplasticity Cognitive impairment is a core endophenotype of MDD8; difficulty with concentration is one of the defining criteria of the disorder.9 In addition to these deficits in concentration and attention, patients with major depression can exhibit difficulties with explicit memory, especially recollection memory.