Hippocampal interneurons in bipolar disorder.
BACKGROUND
Postmortem studies have reported decreased density and decreased gene expression of hippocampal interneurons in bipolar disorder, but neuroimaging studies of hippocampal volume and function have been inconclusive.


OBJECTIVE
To assess hippocampal volume, neuron number, and interneurons in the same specimens of subjects with bipolar disorder and healthy control subjects.


METHODS
Whole human hippocampi of 14 subjects with bipolar disorder and 18 healthy control subjects were cut at 2.5-mm intervals and sections from each tissue block 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.


METHODS
Basic research laboratories at Vanderbilt University and McLean Hospital.


METHODS
Brain specimens from the Harvard Brain Tissue Resource Center at McLean Hospital.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our results indicate a specific alteration of hippocampal interneurons in bipolar disorder, likely resulting in hippocampal dysfunction.
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-8548, USA. christine.konradi@vanderbilt.edu
Christine
C
Konradi
Eric I
EI
Zimmerman
C Kevin
CK
Yang
Kathryn M
KM
Lohmann
Paul
P
Gresch
Harry
H
Pantazopoulos
Sabina
S
Berretta
Stephan
S
Heckers
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000473:pathology; D001714:Bipolar Disorder / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count / Q000706:statistics & numerical data; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007395:Interneurons / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010320:Parvalbumins / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism
D010320:Parvalbumins; D013004:Somatostatin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1