The omnibus test statistic, Pillai’s Trace, indicated the presence of a significant group difference among the log lobe volumes (F = 2.886, df = 4,37; p = 0.040).

ID: 001
Value: log lobe vol
Variable: diagnosis
ModelID: Pillai's Trace
F: 2.886
DF: 4, 37
P: 0.040

Cerebellar white matter was significantly larger in the ALI group (28.2 cc) than in the SLI group (25.1 cc), F(3,38) = 3.0, p = 0.04, contrast t(38) = 2.96, p < 0.005.

ID: 002
Variable: cerebellar WM vol
Group: ALI
Cerebellar WM Vol: 28.2
Units: cc

ID: 003
Variable: cerebellar WM vol
Group: SLI
Cerebellar WM Vol: 25.1
Units: cc
ID: 004
Variable: cerebellar WM vol, diagnosis
Group: ALI, SLI
F: 3.0
DF: 3, 38
P: 0.04
ContrastDF: 38
ContrastT: 2.96
ContrastP: <0.005
*Break into test of all groups, then contrast is ALI SLI

Whole cerebellum and cerebellar cortex volumes did not differ among the four subject groups

ID: 001
Variable: whole cerebellum volume, cerebellar cortex volume, diagnosis
Interpretation: Whole cerebellum volume and cerebellar cortex volume did not vary across diagnostic groups NC, ALN, ALI, SLI

Cortical analyses vertexwise across the surface were performed with general linear models to investigate relations of birth weight to regional cortical area and thickness, controlling for variation in age, sex, household income, and GAF as well as scanner used. When a commonly used approach to correct for multiple comparisons was used [false discovery rate (FDR) < 5%], minute effects of birth weight were observed on cortical thickness. However, significant positive relationships between birth weight and area were observed across large parts of the cortical surface (Fig. 1). On the medial surface of the brain, effects were seen bilaterally in the rostral anterior cingulate, retrosplenial, paracentral, precuneus, superior frontal and medial orbitofrontal cortices, parahippocampal, and fusiform gyri. On the lateral brain surface, bilateral effects extended from parsorbitalis to cover parts of lateral orbitofrontal cortices, and there were also effects in the rostral middle frontal, inferior parietal, and superior and middle temporal cortices as well as in the pre- and postcentral gyri. A few somewhat more scattered unilateral effects were also seen. Medially, effects extended into the caudal anterior cingulate in the left but not right hemisphere, whereas superior and orbitofrontal effects were more pronounced in the right than left hemisphere. Lateral effects were also more pronounced in the left orbitofrontal cortex, but otherwise, lateral effects also seemed slightly more extensive in the right hemisphere, covering somewhat larger temporal and parietal areas. Because the use of FDR for correction for multiple comparisons may influence the detection of specific effect sites, the full range of effects uncorrected at P < 0.05 is also shown in Fig. S1. Uncorrected, effects were somewhat more extensive, but the general pattern described was similar. A scatter plot of the relationship between birth weight and anterior cingulate area (partial β = 0.19, P < 0.0001) is shown in Fig. 2A. It appears from the plot that the low birth weight cases were not disproportionately influencing the relationship and that the relationship between cortical area and birth weight was also monotonous. The relationship between birth weight and anterior cingulate area remained virtually identical when excluding the low birth weight (1,500–2,499 g) cases (partial β = 0.18, P < 0.0001).

No significant effects were observed for the striatal volumes, with only a marginal effect observed for putamen (P = 0.062) when congruent reaction time was included as covariate.

ID: 020
Variable: Flanker performance, striatal vol
Interpretation: no relationship found

ID: 021
Variable: Flanker performance, putamen vol
Model: ? (includes congruent RT)
P: 0.062
Interpretation: slight cognitive control effect observed for putamen volume

There were no significant effects of birth weight on Flanker performance

ID: 019
Variable: incongruent condition Flanker performance, birth weight
Interpretation: no relationship found

Birth weight was positively related to total anterior cingulate area in this subsample (partial β = 0.14, P < 0.001, df = 20, 502).

ID: 018
Variable: birth weight, total anterior cingulate area
PartialBeta: 0.14
P: <0.001
DF: 20, 502

no relationship was observed in the congruent condition

ID: 017
Variable: incongruent condition Flanker performance, total anterior cingulate area
Interpretation: no relationship found

alid Flanker data were available for 522 participants, and we used reaction time in the incongruent condition, related to cognitive control, as the measure of interest. With GAF, MR site, sex, socioeconomic status, and age as covariates, better Flanker performance was significantly related to larger total anterior cingulate area [partial β = −0.092, P = 0.011, degrees of freedom (df) = 20, 502]. This effect was specific to cognitive control, because the relationship survived adding congruent reaction time as an additional covariate area (partial β = −0.064, P = 0.006, df = 21, 501);

ID: 015
Variable: Flanker performance, total anterior cingulate area
Model:
PartialBeta: -0.092
P: 0.011
DF: 20, 502

ID: 016
Variable: Flanker performance, total anterior cingulate area
Model: ? (includes congruent RT)
PartialBeta: -0.064
P: 0.006
DF: 21, 501

Although there did seem to be somewhat stronger effects of birth weight on pallidum and caudate volumes within the low birth weight group, none of the differences among effects in this group and the others reached significance (P > 0.10).

ID: 013
Variable: birth weight, pallidum vol
Group: low birth rate
Low Birth Weight: 1500-2499 g
P: >0.10
Interpretation: birth weight effects observed on pallidum volume

ID: 014
Variable: birth weight, caudate vol
Group: low birth rate
Low Birth Weight: 1500-2499 g
P: >0.10
Interpretation: birth weight effects observed on caudate volume

palladium,

For selected ROIs showing a significant relationship to birth weight, putamen, palladium, caudate, TBV, and rostral anterior cingulate cortex area, regression analyses were also repeated, including (i) a quadratic birth weight term to investigate possible differential effects in select ranges of birth weight and (ii) an interaction term of birth weight and age to investigate possible differential effects of birth weight at different ages. In no case did the quadratic term or the interaction term exert a significant effect (P > 0.10).

an effect of method of delivery on rostral anterior cingulate area, where larger area was observed with cesarean section (standardized β = 0.09, P = 0.018). This finding did not, however, attenuate the relationship with birth weight, for which the effect size remained virtually identical (standardized β = 0.185 vs. 0.193, both P values < 0.0001) when method of delivery was included or not included in the analysis, respectively.

ID: 010
Variable: rostral anterior cingulate area, birth method
Group: c section
ModelID: ?
StandardizedBeta: 0.09
P: 0.018

ID: 011
Variable: birth weight, birth method
Group: c section
ModelID: ?
StandardizesBeta: 0.193
P: <0.0001
ID: 012
Variable: birth weight, birth method
Group: vaginal birth
ModelID: ?
StandardizesBeta: 0.185
P: <0.0001
*Assumption made about which beta corresponds to which birth method

a unique relationship between birth weight and caudate volume remained (partial β = 0.11, P = 0.002)

ID: 009
Variable: birth weight, caudate vol
Model: ? (include TBV as regressor)
PartialBeta: 0.11
P: 0.002

These relationships also remained largely similar when excluding the low (1,500–2,499 g) birth weight cases (partial β for putamen: 0.09, P = 0.022; pallidum: 0.11, P = 0.004; caudate: 0.19, P < 0.001; TBV: 0.17, P < 0.001)

ID: 005
Variable: birth weight, putamen vol
Group: birth weight >2499g
PartialBeta: 0.09
P: 0.022
Interpretation: birth weight positively associated with putamen volume

ID: 006
Variable: birth weight, pallidum vol
Group: birth weight >2499g
PartialBeta: 0.11
P: 0.004
Interpretation: birth weight positively associated with pallidum volume
ID: 007
Variable: birth weight, caudate vol
Group: birth weight >2499g
PartialBeta: 0.19
P: <0.001
ID: 008
Variable: birth weight, TBV vol
Group: birth weight >2499g
PartialBeta: 0.17
P: <0.001
Interpretation: birth weight positively associated with TBV vol

Birth weight was uniquely and positively associated with each volume (partial β for putamen: 0.11, P = 0.006; pallidum: 0.12, P = 0.002; caudate: 0.20, P < 0.001; TBV: 0.16, P < 0.001)

ID: 001
Variable: birth weight, putamen vol
PartialBeta: 0.11
P: 0.006
Interpretation: birth weight positively associated with putamen volume

ID: 002
Variable: birth weight, pallidum vol
PartialBeta: 0.12
P: 0.002
Interpretation: birth weight positively associated with pallidum volume
ID: 003
Variable: birth weight, caudate vol
PartialBeta: 0.20
P: <0.001
ID: 004
Variable: birth weight, TBV vol
PartialBeta: 0.16
P: <0.001
Interpretation: birth weight positively associated with TBV vol

No associations were found between the lobes or individual PUs and the following clinical variables: antipsychotic dose in chlorpromazine equivalents, YMRS score, duration of illness, presence or absence of ADHD, and current mood state (manic, mixed, depressed, or euthymic)

ID: 015
Variable: lobe vol, antipsychotic dos in chlorpromazine equivalents, YMRS score, duration of illness, ADHD, current mood state
Interpretation: No associations were found between lobe volume and these clinical variables

ID: 016
Variable: PU vol, antipsychotic dos in chlorpromazine equivalents, YMRS score, duration of illness, ADHD, current mood state
Interpretation: No associations were found between PU volumes and these clinical variables

When we looked at the gyri in the BPD group, we found only that volumes of the left log POG were significantly and positively associated with scores on the GAF (B = 0.012; t = 2.22, p = 0.035).

ID: 014
Variable: left POG vol, GAF score
Group: BPD
B: 0.012
T: 2.22
P: 0.035
Interpretation: left POG vol positively associated with GAF score

The left log PL volumes in the BPD children decreased significantly in association with increasing numbers of psychoactive medications (B = −0.04; t = −2.138, p = 0.042) (when we examined the possible relationship between type of medication and change in PL volumes, we did not detect any significant or trend relationship between type of medication and PL volume).

ID: 012
Variable: left PL vol, quantity of medications
B: -0.04
T: -2.138
P: 0.042
Interpretation: left PL vol decreased with increased number of psychoactive medications

ID: 013
Variable: PL vol, type of medication
Interpretation: no relationship observed between PL vol and type of medication

Within the BPD group, those children with psychotic symptoms had smaller left log TL volumes (B = −0.092; t = −2.066, p = 0.048) than those without psychotic symptoms

ID: 011
Variable: left TL vol, diagnosis
Group: BPD_psych
B: -0.092
T: -2.066
P: 0.048

No significant group differences were found in the right or left FL

ID: 009
Variable: FL vol
Interpretation: no significant difference in FL vol observed

We did find significant group differences in the right MFG (B = −0.144; t = −2.289, p = 0.027

ID: 010
Variable: right MFG vol
Group: BPD
B: -0.144
T: -2.289
P: 0.027

The bipolar group had significantly smaller log left TL volumes compared with the control group (B = −0.050; t = −2.258, p = 0.029).

ID: 008
Variable: left TL vol
Group: BPD
B: -0.050
T: -2.258
P: 0.029

the BPD had significant reductions in the right and left POG (right: B = −0.116; t = −2.027, p = 0.049; left: B = −0.136; t = −2.592, p = 0.013).

ID: 006
Variable: right POG vol
Group: BPD
B: -0.116
T: -2.027
P: 0.049

ID: 007
Variable: left POG vol
Group: BPD
B: -0.136
T: -2.592
P: 0.013

Interestingly, both age and Verbal IQ for all children in this study (both BPD and HC combined) showed inverse relationships with PL volume, such that children with higher Verbal IQ scores were more likely to have smaller PL volumes, and older children were more likely to have smaller PL volumes.

ID: 004
Interpretation: Observed inverse relationship between age and PL volume

ID: 005
Interpretation: Observed inverse relationship between verbal IQ score and PL volume

The bipolar youth had significantly smaller log right and left PL volumes relative to the HC (right: B = −0.080, t = −2.154, p = 0.037; left: B = −0.102; t = −3.122, p = 0.003), after controlling for the significant effects of age, Verbal IQ, and log cerebral volume (see Table 4 for summary of regression models).

ID: 002
Variable: right PL vol
Group: BPD
B: -0.080
T: -2.154
P: 0.037
Interpretation: BPD youth had smaller right PL volumes than HC

ID: 003
Variable: left PL vol
Group: BPD
B: -0.102
T: -3.122
P: 0.003
Interpretation: BPD youth had smaller left PL volumes than HC

Cross-sectional and longitudinal abnormalities in brain structure in children with severe mood dysregulation or bipolar disorder

Aberrant amygdala intrinsic functional connectivity distinguishes youths with bipolar disorder from those with severe mood dysregulation

Image analysis was done on Sun Microsystems, Inc. (Mountainview, CA) workstations using Cardviews software (Caviness et al. 1996).

19 with BPD I with psychosis (mean age = 11.6 ± 2.6 years),

Significant diagnostic differences were seen in the left and right cerebral volumes in interaction with sex (right: F3,93 = 2.9, P = .04; left: F3,93 = 3.1, P = .04). Post hoc comparisons showed that both bipolar groups (with and without psychosis) had significantly smaller left and right cerebral volumes than HCs; this difference was even more marked in the female BPD groups. The SZ group did not differ significantly from the other groups.

Significant diagnostic differences were seen in the left and right cerebral volumes in interaction with sex (right: F3,93 = 2.9, P = .04; left: F3,93 = 3.1, P = .04). Post hoc comparisons showed that both bipolar groups (with and without psychosis) had significantly smaller left and right cerebral volumes than HCs; this difference was even more marked in the female BPD groups. The SZ group did not differ significantly from the other groups.

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

The regions of interest (ROIs) in this study consisted of the amygdala and hippocampus with all other subcortical structures included in an exploratory way

Significant diagnostic differences were seen in the left and right cerebral volumes in interaction with sex (right: F3,93 = 2.9, P = .04; left: F3,93 = 3.1, P = .04).

Differences in right and left subcortical brain volumes

In brief, structural scans were transferred to the Center for Morphometric Analysis-Charlestown Massachusetts General Hospital and coded and catalogued for blind analysis. Imaging analysis was done by 2 raters on Sun Microsystems, Inc (Mountainview, CA) workstations using Cardviews software.44 The datasets were positionally normalized to overcome variations in head position and then segmented into gray, white, and cerebrospinal fluid (CSF) tissue classes. The segmentation method uses a semiautomated intensity contour algorithm for external border definition and signal intensity histogram distributions for delineation of gray-white borders. Total cerebral volume (TCV) was defined as all tissue in the cerebrum, including CSF, and excluded cerebellum and brain stem

three-dimensional inversion recovery-prepped spoiled grass coronal series

29 HCs (mean age = 10.5 ± 2.9 years).

20 with SZ or schizoaffective disorder (mean age = 13.5 ± 2.9 years),

35 youths with BPD I without psychosis (mean age = 10.4 ± 3.0 years),

2-way (diagnosis, sex) univariate analyses covarying for TCV and age

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

All statistical tests were 2 sided with alpha = .05. JMP 7 for Mac (SAS Institute, Cary, NC) was used for statistical analysis

A series of Analyses of Variance (ANOVA) were performed on CC1 through CC7 and total CC as dependent variables with sex, age, and TCV as covariates to compare CC volumes and CC midsagittal areas between youths with BPD and HC to determine if there were group differences.

Equality of groups on demographic and clinical variables was evaluated by t-tests for continuous variables and chi-square tests for categorical variables

Total cerebral volume (TCV) was defined as all gray and white matter in the cerebrum and did not include CSF, cerebellum or brainstem.

volumetric measures of the CC, we utilized a comprehensive white matter parcellation method to subdivide the cerebral WM into peripheral and deep divisions based upon a set of topographic relationships and geometric constraints related to cortical and subcortical structures as guided by known generalized white matter organizational principles (Makris et al. 1999; Meyer et al. 1999)

ID: CCvolumes 
Measure: CCvol, CC1vol, CC2vol, CC3vol, CC4vol, CC5vol, CC6vol, CC7vol 
AnalysisWorkflow: VolumeAnalysis 
Data:

cross-sectional area measurements were obtained for total CC and the seven subregions based on the subdivisions described by Witelson

SPSS 15.0 for Windows (SPSS, Inc., Chicago, IL) was used for statistical analysis.

ID: VolumeAnalysis
URL:
Software: SPSS 15.0 for Windows (SPSS, Inc., Chicago, IL)
Observation: CCVolumes 
Model: ANOVA 

The acquisitions included a 3-D inversion recovery-prepped spoiled gradient recalled echo coronal series, which was used for structural analysis (124 slices, prep=300 msec, TE=1 min, flip angle=25°, FOV= 24 cm2, slice thickness 1.5 mm, acquisition matrix 256×192, number of excitations=2).

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