The Bipolar Hippocampus

aavanGogh_1888_PontLAngloisA Vanderbilt University study just published in the Archives of General Psychiatry reveals that hippocampal interneurons are modified by bipolar depression. The hippocampus is an important component of the limbic system that acts as the switching center through which incoming sensory signals are retransmitted and initiate behavioral reactions for different purposes. Its importance has been demonstrated empirically: experimental artificial stimulation of the hippocampus can induce a wide variety of behavioral patterns such as pleasure, rage, passivity, or excessive sexual drive. Because of its central function in the modulation of emotions, the hippocampus is believed to have a role in mood disorders such as depression. Numerous postmortem studies conducted on the brain of individuals who were affected by bipolar disorder have shown a decreased density and decreased gene expression of hippocampal interneurons. These findings, however, had not been confirmed by neuroimaging studies of hippocampal volume and function in live subjects—until now.

hippocampal_anatomyTo assess hippocampal volume, neuron number, and interneurons the Vanderbilt study examined sample brain specimens of hippocampi from 14 individuals with bipolar disorder and compared them to those taken from 18 healthy control subjects. The specimens, provided by the Harvard Brain Tissue Resource Center at McLean Hospital, were cut at 2.5-mm intervals and sections from each tissue slice were either Nissl-stained or stained with antibodies against somatostatin or parvalbumin. Messenger RNA was extracted from fixed tissue and real-time quantitative polymerase chain reaction was performed.

The researchers analyzed each sample by measuring the volume of pyramidal and nonpyramidal cell layers, overall neuron number and size, number of somatostatin- and parvalbumin-positive interneurons, and messenger RNA levels of somatostatin, parvalbumin, and glutamic acid decarboxylase 1.

After comparing healthy and unhealthy hippocampal samples, the study showed that the 2 groups did not differ in the total number of hippocampal neurons, but the bipolar disorder group showed reduced volume of the nonpyramidal cell layers, reduced somal volume in cornu ammonis sector 2/3, reduced number of somatostatin- and parvalbumin-positive neurons, and reduced messenger RNA levels for somatostatin, parvalbumin, and glutamic acid decarboxylase 1.

According to the researchers, these results indicate a specific alteration of hippocampal interneurons in bipolar disorder, which is likely to produce a hippocampal dysfunction that can have, among other manifestations, an effect on the onset and severity of bipolar depression.