Structural imaging was performed at the McLean Hospital Brain Imaging Center on a 1.5 Tesla Scanner (Signa; GE Medical Systems, Milwaukee, WI).

For the area measurement of the total CC, significant effects were also found for TCV (F=5.15, p=0.03) and age group-by-diagnosis interaction term (F=3.08, p=0.05).

ObsID: 004
MeasureID: CC area
GroupID: HC, BPD
CovariateID: TCV
StatID: ANOVA
F: 5.15
P: 0.03

ObsID:005
MeasureID: CC area
GroupID: HC, BPD
CovariateID: age group-by-diagnosis interaction term
StatID: ANOVA
F: 3.08
P: 0.05

the CC is divided into seven subregions which include: rostrum (CC1), genu (CC2), anterior body (CC3), midbody (CC4), posterior body (CC5), isthmus (CC6) and splenium (CC7) using anterior and posterior definitions as described in Witelson

AnalysisMethodID: CC area
Inputs: MRI
Software: proc_cc
OutputVariables: CC area, CC1 area, CC2 area, CC3 area, CC4 area, CC5 area, CC6 area, CC7 area
MeasurementType: Regional area
MeasurementUnits: cm2 (square centimeters)

Volu-metric assessment of the CC is provided as a distinct subset of regions within this WM parcellation system.

AnalysisMethodID: CC Volume
Inputs: MRI
Software: WM_Parc
OutputVariables: CC Vol, CC1 Vol, CC2 Vol, CC3 Vol, CC4 Vol, CC5 Vol, CC6 Vol, CC7 Vol
MeasurementType: Regional Volume
MeasurementUnits: cc (cubic centimeters)

Measures of current psychopathology were obtained using the Mania Rating Scale (MRS) (Young et al. 1978) and Global Assessment of Functioning scale (GAF

MeasureID: MRS
MeasureDescription: Mania Rating Scale (MRS)
MeasureDomain: current psychopathology
MeasureReference: Young et al. 1978

MeasureID: GAF
MeasureDescription: Global Assessment of Functioning scale (GAF)
MeasureDomain: current psychopathology
MeasureReference: American Psychiatric Association 1994)

Individuals with BPD were diagnosed using DSM-IV criteria in semi-structured and clinical interviews; HC participants had no DSM-IV Axis I diagnoses or a family history of mood or psychotic disorders in first-degree relatives, based on parental interview.

GroupID: BPD
Dx: Bipolar Disorder
DxStandard: DSM-IV
DxMethod: semi-structured and clinical interviews

GroupID: HC
GroupCharacteristic: no DSM-IV Axis I diagnoses or a family history of mood or psychotic disorders in first-degree relatives, based on parental interview

McLean Hospital Brain Imaging Center on a 1.5 Tesla General Electric Signa Scanner

AcquisitionType: MRI
Location: McLean Hospital Brain Imaging Center
MRField: 1.5 Tesla
Manufacturer: General Electric 
Model: Signa

Differences in right and left subcortical brain volumes were evaluated using 2-way (diagnosis, sex) univariate analyses covarying for TCV and age. Similar models were also evaluated on the asymmetry index for each structure, which was calculated as (right volume−left volume)/(right volume + left volume)÷ 2. Post hoc between-group tests were corrected for multiple comparisons using the Tukey-Cramer honestly significant difference method. Differences in demographic and clinical variables between groups were assessed using analyses of variance for continuous variables and chi-square tests for categorical variables. In addition, within-group Pearson and Spearman correlations were performed on clinical variables and those structures which were found to be significantly different between diagnostic groups. These clinical variables included MRS and GAF scores, age at onset of illness, duration of illness, and chlorpromazine equivalents. In an effort to be conservative, we report only clinical correlations that reached significance on both Spearman and Pearson tests; the r and P value for the Pearson correlations are reported. Effect sizes were calculated and interpreted using Cohen d statistic. All statistical tests were 2 sided with alpha = .05. JMP 7 for Mac (SAS Institute, Cary, NC) was used for statistical analysis.

The caudate was measured in its entirety (head, body, tail superior to ventricular trigone, and ventral striatum), defined superomedially by the interface with the lateral ventricles, inferiorly by the interface with the adjacent rostral peduncle of the thalamus (when present), and otherwise by the interface with adjacent white matter; putamen was defined medially by the external medullary lamina of the globus pallidus, laterally by the external capsule, and otherwise by adjacent white matter; globus pallidus was defined superomedially by the interface with the internal capsule, inferiorly by the anterior commissure, ansa lenticularis, or nucleus basalis, when present, and laterally by the external medullary lamina.43 The NA was separated from putamen and caudate superiorly by a segmentation line that connects the inferiormost tip of the lateral ventricle to the most ventral point of the internal capsule at the level of the ventral putamen. From this last point, a vertical line is drawn to define the lateral border with the putamen.45

using Cardviews software.

segmentations were performed according to the anatomic boundaries described in Filipek et al43 and Frazier et al.12

regions of interest (ROIs) in this study consisted of the amygdala and hippocampus

structural acquisitions included a conventional T1-weighted sagittal scout series, a proton density/T2-weighted interleaved double-echo axial series, and a three-dimensional inversion recovery-prepped spoiled grass coronal series.

Drug Exposure In an effort to control for medication confounds, antipsychotic doses were converted to chlorpromazine equivalents following the equivalency estimates provided by both Woods41 and Stoll.42

Of the bipolar subjects (bipolar with and bipolar without psychosis n = 56), 43 were included in prior publications; of the 29 HCs, 20 were included in previous publications

Socioeconomic status was assessed using the Hollingshead Scale. Onset of the disorder, number of episodes, and duration of illness were also obtained. Measures of psychopathology were obtained using the Mania Rating Scale (MRS),37,38 including the psychosis items, and the Global Assessment of Functioning (GAF).

diagnosis of psychosis (either with BPD or SZ) was based on lifetime history

In the case of BPD, the diagnosis was made if full DSM-IV diagnostic criteria were met BPD I (lifetime) with all subjects having clear cycles and meeting duration criteria

All children, including the HCs, underwent diagnostic semistructured (Kiddie Schedule for Affective Disorders and Schizophrenia: Epidemiologic Version—KSADS-E)34 and clinical interviews by board-certified child psychiatrists. Each child received a physical and neurological examination (including Tanner Staging: a I–V scale of pubertal development).35,36 Additionally, parents were administered an indirect KSADS-E regarding their children (see Frazier et al12 for more detail).

Exclusion criteria in both groups included presence of major sensorimotor handicaps; full-scale IQ < 70; presence of documented learning disabilities; history of claustrophobia, autism, anorexia, bulimia nervosa, alcohol or drug dependence or abuse (in the 2 months prior to the scan or total past history of 12 months or greater); active medical or neurological disease; presence of metal fragments or implants; history of electroconvulsive therapy; and current pregnancy or lactation.

HCs, with no DSM-IV Axis-I diagnosis on semistructured and clinical interviews, were recruited through local advertisements.

Youths aged 6–17 years, both male and female, and inpatient and outpatient were recruited through the McLean Hospital and Cambridge Health Alliance programs and through professional and patient advocacy groups.