Three-dimensional mapping of hippocampal anatomy in adolescents with bipolar disorder.
OBJECTIVE
Early-onset bipolar disorder is thought to be a particularly severe variant of the illness. Continuity with the adult form of illness remains unresolved, but preliminary evidence suggests similar biological underpinnings. Recently, we observed localized hippocampal decreases in unmedicated adults with bipolar disorder that were not detectable with conventional volumetric measures. Using the same three-dimensional mapping methods, we sought to investigate whether a similar pattern exists in adolescents with bipolar disorder.


METHODS
High-resolution brain magnetic resonance images were acquired from 16 adolescents meeting DSM-IV criteria for bipolar disorder (mean age 15.5 +/- 3.4 years, 50% female) and 20 demographically matched, typically developing control subjects. Three-dimensional parametric mesh models of the hippocampus were created from manual tracings of the hippocampal formation.


RESULTS
Controlling for total brain volume, total hippocampal volume was significantly smaller in adolescent patients with bipolar disorder relative to controls (by 9.2%). Statistical mapping results, confirmed by permutation testing, revealed significant localized deformations in the head and tail of the left hippocampus in adolescents with bipolar disorder, relative to normal controls. In addition, there was a significant positive correlation between hippocampal size and age in patients with bipolar disorder, whereas healthy controls showed an inverse relation.


CONCLUSIONS
Localized hippocampal deficits in adolescent patients with bipolar disorder suggest a possible neural correlate for memory deficits observed in this illness. Moreover, age-related increases in hippocampal size in patients with bipolar disorder, not observed in healthy controls, may reflect abnormal developmental mechanisms in bipolar disorder. This possibility must be confirmed by longitudinal studies.
Bearden
Carrie E
CE
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.. Electronic address: cbearden@mednet.ucla.edu.
Soares
Jair C
JC
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Klunder
Andrea D
AD
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Nicoletti
Mark
M
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Dierschke
Nicole
N
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Hayashi
Kiralee M
KM
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Narr
Katherine L
KL
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Brambilla
Paolo
P
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Sassi
Roberto B
RB
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Axelson
David
D
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Ryan
Neal
N
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Birmaher
Boris
B
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
Thompson
Paul M
PM
Dr. Bearden is with the Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California, Los Angeles; Dr. Soares and Mr. Nicoletti are with the Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine; Ms. Klunder, Ms. Hayashi, and Drs. Narr and Thompson are with the Laboratory of NeuroImaging, UCLA School of Medicine; Ms. Dierschke is with the Department of Psychiatry, University of Texas Health Science Center at San Antonio; Dr. Brambilla is with the Scientific Institute IRCCS; Dr. Sassi is with the Department of Psychiatry, University of Sao Paulo School of Medicine; Drs. Axelson, Ryan, and Birmaher are with the Department of Psychiatry, University of Pittsburgh School of Medicine.
D000293:Adolescent; D000679:Amygdala / Q000473:pathology; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000503:physiopathology; D001931:Brain Mapping; D004292:Dominance, Cerebral / Q000502:physiology; D004644:Emotions / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000502:physiology; D009415:Nerve Net / Q000473:pathology; D009483:Neuropsychological Tests; D012016:Reference Values