Three-Dimensional Mapping of Hippocampal Anatomy in Adolescents With Bipolar Disorder

Abstract

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.Method-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.Discussion-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.Correspondence to Dr. Carrie E. Bearden, Department of Psychiatry and Biobehavioral Sciences, UCLA, 300 Building Medical Plaza, Suite 2265, Los Angeles, CA 90095; e-mail: cbearden@mednet.ucla.edu. This article is the subject of an editorial by Dr. Hilary P. Blumberg in this issue.Disclosure: Dr. Birmaher has participated in forums sponsored by Solvay Pharmaceuticals and Abcomm, and has received royalties from Random House.The other authors report no conflicts of interest. Much less is known about the neurobiological underpinnings of juvenile-onset bipolar disorder, although it is thought to be a particularly severe variant of the illness, 9,10 potentially with a higher genetic loading. 11 Its continuity with the adult form of the illness remains unresolved, but neuroanatomical findings to date in early-onset bipolar disorder appear similar to those for adults, with most studies finding no differences in global hippocampal volume between children with bipolar disorder and controls. [12][13][14] In contrast, two studies have identified hippocampal volume decreases in young patients with bipolar disorder. 15,16 In particular, in a sample of adolescents...

Decreased Right Hippocampal Volumes and Neuroprogression Markers in Adolescents with Bipolar Disorder

“…Decreased HCV may be more prominent in cases of pediatric as opposed to adult BP [9,11,15,32,33]. On the other hand, some studies found no structural differences for HCVs in youths with BP, similar to our results [12,13,14].…”

“…In fact, the HC may be one of the earliest structures to be negatively impacted by the disorder [34]. A recent study using three-dimensional modeling found significant volume reductions in HCV among youths with BP and alterations in the volumetric changes associated with age [15]. Nevertheless, the findings of cross-sectional structural MRI studies in children and youths have been controversial.…”

“…In contrast, some of these studies found no differences in global HCV between children with BP and controls [12,13,14]. A significant positive correlation was found between hippocampal size and age in patients with bipolar disorder, whereas healthy controls showed an inverse relation [15]. …”

612. Hippocampal Subfield Volumes in Mood Disorders

“…33 However, these findings were consistent with previous studies using surface-based method. 29 It is worth mentioning that our study was able to consider for two important variables in the study of hippocampus changes in patients with BD, such as the lithium effect on the hippocampus (Supplementary Materials) and the effect of BD types. Indeed, several important studies, including meta-analyses reported the neuroprotective effect of lithium in the hippocampus.…”

“…Previous studies have made great advancement in understanding the morphometric and volumetric changes in the hippocampus in mood disorders using surface-based shape analyses 14,28,29 or an automated method of labeling the subfields based on an in vivo atlas. 30,31 However, the surface-based shape analysis could not reach deep structures of the hippocampus.…”