Compared with TD children, children with ASD exhibited increased structural covariation between adjacent regions, such as between the right globus pallidus and right putamen.

Both MCI and AD subjects exhibited smaller bilateral hippocampus volumes compared with CN individuals

The volumes of the bilateral hippocampus and the right putamen were also smaller in AD compared with MCI patients

In comparison to the control group, ADHD patients demonstrated a significantly lower GM volume in the cingulate gyrus, left middle temporal gyrus, right middle occipital gyrus, left fusiform gyrus

Suicidal patients had larger right amygdala volumes than non-suicidal patients

Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects

volumetric analysis that includes a library of MRI scans that has been used in prior studies (Frazier et al. 2005a; Frazier et al. 2005b; Frazier et al. 2008).

Healthy controls had no DSM-IV Axis I diagnosis based on structured and clinical interviews. Healthy controls had no first-degree family history of BP, ADHD, psychosis, or any other psychiatric family history

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

Pearson and Spearman (rank) correlations were performed on clinical variables (bipolar onset and duration, ADHD onset and duration, current GAF, and MRS mania and psychosis scores), the number of psychoactive medications (atypicals, stimulants, mood stabilizers, lithium, antidepressants, chlorpromazine equivalents), and age for only those structures that differed significantly between diagnostic groups and HC

Post hoc mean comparisons were made for significant main effects and interactions using Tukey's Honestly Significant Difference, with α = 0.05 to control for pairwise comparisons, and by the Student t-test to indicate modest (uncorrected) effects

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

analyses of variance for continuous variables and chi-squared tests for categorical variables.

For each set of regions, a general linear mixed model with an unstructured covariance matrix was run to estimate overall diagnosis effects while controlling the multicolinearity among the regions of interest. Given a significant region-by-diagnosis effect, a series of univariate analyses of covariance (ANCOVA) were performed with diagnosis (HC, ADHD, BP + ADHD, BP ) and sex (female, male), plus their interaction, as factors, and with age and TCV as covariates. TCV was excluded as a covariate in the analysis of symmetry coefficients (age was the only covariate)

Each dataset was segmented according to the anatomic boundaries described in detail in Filipek et al. (1994) and Frazier et al. (2005a, 2005b). In brief, structural scans 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

Exclusion criteria for all subjects and HC were: major sensorimotor handicaps (e.g., deafness, blindness, paralysis); full scale intelligence quotient (IQ) < 70 or learning disabilities; history of claustrophobia, autism, schizophrenia, anorexia nervosa or bulimia, drug or alcohol dependence/abuse (during 2 months prior to scan or total past history ≥12 months); active medical or neurological disease; history of electroconvulsive therapy (ECT); metal fragments or implants; and current pregnancy or lactation. History of learning disabilities was obtained via parental interview, and these youths were excluded due to the potential for confounding of neuroanatomical findings

Inclusion criteria for all subjects in this analysis were: age 6–19 years old, right-handedness

On the basis of the extant literature, we hypothesized that: (1) youths with ADHD would have smaller basal ganglia structures, including the caudate and putamen; (2) youths with BP would have reduced limbic structures, including hippocampal and amygdala volumes, and enlarged right nucleus accumbens volumes; (3) youths with co-morbid BP and ADHD would have limbic abnormalities similar to youths with BP alone and would have smaller basal ganglia structures similar to youths with ADHD

An emerging neuroimaging literature indicates that distinct subcortical brain structures may characterize ADHD and BP in youths.