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).

ObservationID: 001
ObservationDepVar: Diagnostic Groups
ObervationIndVar: Left Cerebral volume
ObservationStat: what test was run? Pointer to StatisticMethod
ObservationStatP: 0.04
ObservationStatF: 3.1
ObservationStatFDOF: 3
ObservationStatFN: 93
LinktoSourcedata: ???
LinktoStatExec: ???

ObservationID: 002
ObservationDepVar: Diagnostic Groups
ObervationIndVar: Right Cerebral volume
ObservationStat: what test was run? Pointer to StatisticMethod
ObservationStatP: 0.04
ObservationStatF: 2.9
ObservationStatFDOF: 3
ObservationStatFN: 93

Significant effects for TCV (F=18.1, p<0.01) and for age group-by-diagnosis interaction term (F=6.97, p<0.01) for the CC4 volumetric measurements were found

Significant effects of TCV (F=19.4, p<0.01) and for age group-by-diagnosis interaction term (F=4.60, p=0.01) for the volumetric measurements of total CC were found

ObsID: 002
MeasureID: CC vol
GroupID: HC_young, HC_old, BPD_young, BPD_old
CovariateID: TCV
StatID: ANOVA
F: 19.4
P: <0.01

ObsID:003
MeasureID: CC vol
GroupID: HC, BPD
CovariateID: age group-by-diagnosis interaction term
StatID: ANOVA
F: 4.60
P: 0.01

For CC2, significant effects were found for TCV in CC2 volume (F=12.64, p<0.01) and area (F=5.18, p=0.03) measurements, respectively

ObsID: 014
MeasureID: CC2 vol
GroupID: HC, BPD
CovariateID: TCV
StatID: ANOVA
F: 12.64
P: <0.01

ObsID: 015
MeasureID: CC2 area
GroupID: HC, BPD
CovariateID: TCV
StatID: ANOVA
F: 5.18
P: 0.03

For CC1, area measurement found age (F=5.28, p=0.03) to be a significant covariate.

ObsID: 013
MeasureID: CC1 area
GroupID: HC, BPD
CovariateID: age
StatID: ANOVA
F: 5.28
P: 0.03

There was no significant difference between the younger BPD the younger HC.

ObsID: 012
ObsType: GroupComparison
GroupID: BPD_young, HC_young
MeasureID: CC Vol
StatID: TTEST
P: not significant

Volumetric and area measurements found that the older HC (15.5 cc) had significantly larger total CC than the younger HC group (13.1 cc), whereas there was not a significant difference among the BPD age groups (13.6 and 13.7 cc).

ObsID: 006
MeasureID: CC vol
GroupID: HC_old, HC_young
CovariateID: Group
StatID: TTEST
P: significant

ObsID: 007
MeasureID: CC vol
GroupID: HC_old
MeanValue: 15.5
Units: cc

ObsID: 008
MeasureID: CC vol
GroupID: HC_young
MeanValue: 13.1
Units: cc

ObsID: 009
MeasureID: CC Vol
GroupID: BPD_old, BPD_young
CovariateID: Group
StatID: TTEST
P: not significant

ObsID: 010
MeasureID: CC area
GroupID: BPD_old
MeanValue: 13.6
Units: cc

ObsID: 011
MeasureID: CC vol
GroupID: BPD_young
MeanValue: 13.7
Units: cc

The youths with BPD had a mean MRS score of 20.8±9.5 (range 0–38)

ObsID: 001
GroupID: BPD
MeasureID: MRS
StatID: Descriptive
Mean: 20.8
Std: 9.5
RangeMin: 0
RangeMax: 38

Data from 66 participants (44 children with DSM-IV BPD, age 10.6±3.0 years (mean ± SD) and 22 HC, age 10.5±3.1 years (mean ± SD) are included in this report

GroupID: BPD
N: 44
AgeMean: 10.6
AgeStd: 3.0

GroupID: HC
N: 22
AgeMean: 10.5
AgeStd: 3.1

The linear mixed model for total volumes of structures in the limbic system indicated significant diagnosis by region effects (F[9, 105] = 3.5, p = 0.001) as well as significant covariate effects of age (F[3, 105] = 4.3, p = 0.007) and TCV (F[3, 105] = 16.2, p < 0.001)

In youths with BP, the amygdala was negatively correlated with MRS score (r = − 0.44, p = 0.03; rho = − 0.41, p = 0.05). For youths with BP + ADHD, the nucleus accumbens negatively correlated with number of medications (r = − 0.62, p ≤ 0.01; rho = − 0.64, p ≤ 0.01). Finally for HC, the putamen (r = 0.49, p ≤ 0.01; rho = 0.50, p ≤ 0.01) and the thalamus (r = 0.37, p = 0.05; rho = 0.42, p = 0.02) positively correlated with age.

Youths with ADHD have leftward symmetry, while all other groups have rightward symmetry (BP + ADHD, − 0.8%; BPD, − 0.9; HC, − 1.4%; all Q[8, 96] > 4.0, all p < 0.03).

There is a significant main effect of diagnosis in the symmetry of the thalamus (F[3, 96] = 5.3, p = 0.002), but not a significant effect of sex (F[1, 96] = 0.1, p = 0.8).

Males with ADHD have moderately smaller volumes than males with BP or BP + ADHD (mean differences 0.9 and 1.0 mL, respectively, t[95] = 2.4 and 2.9, both p < 0.05 uncorrected, d = 0.9 and 1.0)

There were no significant main effects of diagnosis (F[3, 95] = 1.6, p = 0.2) or sex (F[1, 95] = 3.2, p = 0.07) in the total volumes of the thalamus

The linear mixed model for symmetry of structures in the basal ganglia system showed no significant diagnosis by region effects (F[9, 105] = 0.3, p = 0.9), nor a significant covariate effect of age (F[3, 105] = 0.8, p = 0.5). No trend effects were noted

Youths with ADHD had moderately smaller volumes than those with BP + ADHD (mean difference 0.35 mL, t[95] = 2.6, p < 0.05 uncorrected, d = 0.8). There was no significant interaction between diagnosis and sex (F[3, 95] = 0.4, p = 0.7).

There were no significant effects of diagnosis (F[3, 95] = 2.3, p = 0.08) or sex (F[1, 95] = 2.4, p = 0.13) for the total volumes of the pallidum.

females had significantly smaller volumes than males (mean difference 0.64 mL, statistic cited above). There was no significant interaction between diagnosis and sex (F[3, 95] = 0.7, p = 0.5).

Youths with ADHD had smaller volumes than those with BP + ADHD (mean difference 1.21 mL, Q[4, 95] = 4.6, p = 0.008). Similarly, youths with ADHD had moderately smaller volumes than those with BP alone (mean difference 0.84 mL, t[95] = 2.6, p < 0.05 uncorrected, d = 0.7) and HC (mean difference 0.72 mL, t[95] = 2.1, p < 0.05 uncorrected, d = 0.6)

There were significant main effects of diagnosis (F[3, 95] = 3.9, p = 0.01) and sex (F[1, 95] = 4.9, p = 0.03) in total volumes of the putamen

Youths with ADHD had smaller caudate volumes than BP + ADHD (mean difference 0.95 mL, Q[4, 95] = 4.4, p = 0.013), as well as BP (mean difference 0.97 mL, Q[4, 95] = 5.0, p = 0.004), and HC (mean difference 0.71 mL, t[95] = 2.5, p < 0.05, uncorrected, d = 0.7). There was no significant main effect of sex (F[1, 95] = 0.1, p = 0.8) or an interaction between diagnosis and sex (F[3, 95] = 1.0, p = 0.4)

There was also a significant main effect of diagnosis for total volumes of the caudate (F[3, 95] = 4.8, p = 0.004)

The linear mixed model for total volumes of structures in the basal ganglia system indicated significant diagnosis by region effects (F[9, 105] = 2.5, p = 0.01) as well as significant covariate effects of age (F[3, 105] = 3.0, p = 0.035) and TCV (F[3, 105] = 9.7, p < 0.001)

Youths with BP + ADHD had moderately larger volumes than HC (mean difference 0.17 mL, t[95] = 2.1, p < 0.05 uncorrected, d = 0.6) and there was a trend for BP to have larger nucleus accumbens volumes than HC (mean difference = 0.14 mL, T[95] = 1.9, P = 0.06, D = 0.5)

males with ADHD were rightward asymmetric (−3.6%), whereas HC males and females with ADHD were leftward asymmetric (12.7% and 13%, respectively, t(95) = 3.2 and 2.5, both p < 0.05, uncorrected, d = 1.1 and 1.1).

The linear mixed model for symmetry of structures in the limbic system showed no significant diagnosis by region effects (F[9, 103] = 1.3, p = 0.2), but a significant covariate effect for the symmetries to become more leftward with age (F[3, 103] = 4.7, p = 0.004)

There were no significant effects for the total volumes of the nucleus accumbens

There was no significant main effect of sex (F[1, 95] = 1.0, p = 0.3) or an interaction between diagnosis and sex (F[3, 95] = 1.1, p = 0.3)

Youths with ADHD had smaller amygdala volumes than BP + ADHD (mean difference 0.48 mL, t[95] = 2.5, p < 0.05 uncorrected, d = 0.7), as well as BP (mean difference 0.45 mL, t[95] = 2.6, p < 0.05 uncorrected, d = 0.7) and HC (mean difference 0.41 mL, t[95] = 2.3, p < 0.05 uncorrected, d  = 0.6)

There was also a significant main effect of diagnosis for total volumes of the amygdala (F[3, 95] = 2.9, p = 0.04)

moderate interaction effect (F[3, 95] = 2.6, p = 0.06) indicated that females with BP or BP + ADHD were significantly smaller than female HC (mean differences 0.7 and 1 mL, respectively, t[95] = 2.5 and 2.9, both p < 0.05 uncorrrected, d = 0.9 and 1.4) or females with ADHD (mean differences 0.7 and 1 mL, respectively, t[95] = 2.1 and 2.7, both p < 0.05 uncorrrected, d = 0.9 and 1.4)

Youths with BP + ADHD had smaller volumes than those with ADHD (mean difference 0.7 mL, Q[4, 95] = 4.1, p = 0.02) or HC (mean difference 0.6 mL, Q[4, 95] = 4.0, p = 0.03), while not significantly different from BP (0.4 mL smaller).

There was a significant main effect of diagnosis for total volumes of the hippocampus (F[3, 95] = 3.6, p = 0.017)

females with BP + ADHD were significantly smaller than HC females (mean difference = 149.1 mL, Q[8, 96] = 5.1, p = 0.01)

Investigation of the modest interaction effect (F[3, 96] = 2.3, p = 0.09) indicated no group effects in the males (least-squares mean volumes range 1190–1248 mL);

0 youths with BP alone, 6 were manic, 13 mixed, 4 depressed, and 7 were euthymic at the time of assessment. Of the 23 youths in the BP + ADHD group, 4 were manic, 10 mixed, 3 depressed, and 6 were euthymic at the time of assessment. Thirteen youths with BP (25%) had histories of psychosis (7 in the BP group and 6 in the BP + ADHD group). Clinical and treatment characteristics of the diagnostic groups are shown in Table 2. At the time of assessment, 22 (73.3%) of the youths with BP were on atypical antipsychotics, 5 (16.7%) were taking stimulants, 11 (36.7%) were on mood stabilizers, 6 (20.0%) were on antidepressants, 9 (30.0%) were on other medications including α- and β-adrenergic agents, and 2 (6.7%) were taking clonazepam. Of the youths with BP + ADHD, 17 (73.9%) were on atypical antipsychotics, 6 (26.1%) were taking stimulants, 11 (47.8%) were on mood stabilizers, 9 (39.1%) were on antidepressants, and 1 (4.3%) was taking other medications including α- and β-adrenergic agents. Twelve (52.2%) of the youths with ADHD were taking stimulants, 3 (13.0%) were on antidepressants, 2 (8.7%) were taking other medications including α- and β-adrenergic agents, and 2 (8.7%) were taking clonazepam

BP + ADHD and those without ADHD had a mean MRS score of 19.0 ± 8.6 and 22.5 ± 10.2

23 children with ADHD

53 children with DSM-IV BP (23 with ADHD, 30 without)

29 HC

ouths with BPD without psychosis had a significant inverse correlation between the MRS score and amygdala volumes (right: r = –0.411, P = .02; left: r = –0.379, P = .004). No significant correlations were found in the BPD with psychosis group.

In the youths with SZ, there was a significant inverse correlation between GAS score and left amygdala volume (r = –0.634, P = .011). Also, there was a significant correlation between MRS scores and the right NA (r = 0.634, P = .03).

HCs had increasing volumes with age in the thalamus (right: r = 0.38, P = .04; left: r = 0.36, P = .06). In addition, the right amygdala volume correlated with GAS scores in the HCs (r = 0.470, P = .01).

significant sex differences were observed in bilateral cerebrum and pallidum volumes across groups, with females having significantly smaller volumes than males.

The asymmetry indices for all structures also did not differ significantly between groups.

There were no between-group differences in the amygdala; however, there was significant diagnostic-by-sex interaction in the left amygdala (F3,93 = 3.0, P = .04). SZ males had the smallest left amygdala volume (effect size relative to other males = 0.65–1.23); this structure was actually enlarged relative to HC in the BPD groups

For the subcortical structures, the omnibus statistics showed no diagnostic differences in the hippocampus but did show a trend for diagnostic-by-sex differences in the left hippocampus (F3,93 = 2.3, P = .08); post hoc analyses showed that the diagnostic reduction was particularly marked in the female patient groups

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.

35 youths with BPD I without psychosis (mean age = 10.4 ± 3.0 years), 19 with BPD I with psychosis (mean age = 11.6 ± 2.6 years), 20 with SZ or schizoaffective disorder (mean age = 13.5 ± 2.9 years), and 29 HCs (mean age = 10.5 ± 2.9 years). The proportion of males in each group ranged from 47.4% to 58.8%

Effects sizes between the BPD groups and SZ were 0.38 (right) and 0.42 (left), suggesting that there is a bilateral diagnostic difference in this structure.

The right NA showed a significant diagnostic difference (F3,93 = 3.15, P = .03) and was found to be larger in both BPD groups relative to HC (effect sizes: 0.74–0.78);

The pairwise effect sizes for both hemispheres between the SZ group and the others were all moderate, suggesting overall diagnostic differences (Cohen d range: 0.64–0.74 [right]; 0.41–0.54 [left])

Exploratory analyses of other subcortical structures showed that youths with SZ had the smallest thalamic volumes, significantly so in the right (F3,93 = 3.1, P = .03)