Hippocampus

The hippocampus is an area of the brain that plays an important role in learning and memory. Several studies have shown that alterations occur in the hippocampus following exposure to stress. Other brain areas involved in memory, including the amygdala and prefrontal cortex, are involved in the mediation of the stress response. The severe stress of exposure to a traumatic event may result in posttraumatic stress disorder (PTSD); patients show evidence of memory disturbance, including intrusive thoughts, flashbacks, nightmares, and problems with memory and concentration. Alterations in these brain areas provide a biological basis for the memory-related symptoms of PTSD. This entry focuses on the hippocampus.

Exposure to stress has been associated with damage to neurons in the hippocampus. Numerous studies in animals have demonstrated biological changes in hippocampal neurons following exposure to stress. Stress may affect hippocampal neurons through elevations in the stress hormone cortisol, decreased brain-derived neurotrophic factor (a trophic factor that promotes nerve growth in the brain), elevated glutamate concentrations (an excitatory amino acid neurotransmitter that can have toxic effects on the brain at high concentrations), and/or inhibition of new nerve growth, or neurogenesis. Treatments for depression including antidepressant medications, enrichment of the environment, and exercise have been shown to block or reverse the effects of stress on the hippocampus.

Studies of patients with PTSD have shown changes in memory and cognition that are consistent with dysfunction of the hippocampus. PTSD patients often have problems with what is known as verbal declarative memory, or the recall of facts or lists. Patients with PTSD secondary to combat, childhood abuse, and other traumas have been found to have deficits in verbal declarative memory function based on a variety of measures of neuro-psychological function.

Neuroimaging studies are also consistent with dysfunction of the hippocampus in PTSD. Multiple structural magnetic resonance imaging (MRI) studies have shown evidence that people with PTSD have smaller hippocampal volumes than do similar people who do not have PTSD. These include studies of combat veterans and adults with childhood abuse-related PTSD, which showed smaller hippocampal volume based on structural imaging with MRI relative to healthy comparison subjects. Other studies in PTSD have found reductions of N-acetylaspartate (NAA), a marker of neuronal integrity, in the hippocampus using magnetic resonance spectroscopy. One study found smaller hippocampal volume in PTSD subjects compared with trauma-exposed non-PTSD subjects, although another study did not. Therefore, it is not clear whether exposure to psychological trauma or the presence of PTSD is associated with a smaller hippocampus. One study indicated that there is a genetic contribution to smaller hippocampal volume in PTSD, but studies in children with PTSD did not find hippocampal volume reduction. To attempt to resolve these divergent results, recent meta-analyses pooled data from all of the published studies and found smaller hippocampal volume for both the left and the right hippocampal sides, equally in adult men and women with chronic PTSD, and no change in children.

Both hippocampal atrophy and hippocampal-based memory deficits have been found to be successfully reversed with treatment with the selective serotonergic reuptake inhibitor and antidepressant medication paroxetine, which has been shown to promote neurogenesis in the hippocampus in animal studies. Phenytoin, an anticonvulsant (antisei-zure) medication, also has been shown to increase hippocampal volume in PTSD patients. Therefore, medications that have been shown to be effective for the treatment of PTSD also increase hippocampal volume and improve memory function. This suggests that medications may act in part through the hippocampus to promote recovery from PTSD.

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