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.

we predicted that there would be diagnosis-by-sex interactions in subcortical structures rich in sex hormone receptors, particularly in the amygdala and hippocampus.

we predicted, based on previous reports, that youths with BPD would have abnormal NA volumes22,23 and that youths with SZ would have reduced thalamic volumes.24,33 We also predicted that the BPD with psychosis group would share features with the BPD without psychosis and the primary psychotic disorder groups

there were diagnosis-by-sex interactions in the amygdala and hippocampus,

There were no limbic volumetric differences between BPD and SZ

SZ showed reduced thalamic volumes bilaterally and both BPD groups had larger right nucleus accumbens (NA) volumes relative to HC

girls with BPD had the smallest left hippocampal volumes

boys with SZ had smallest left amygdala

two-way (diagnosis, sex) univariate analyses covarying for total cerebral volume and age

brain volumes

Structural magnetic resonance images (MRIs) were acquired on a 1.5 Tesla, General Electric Signa Scanner.

29 healthy controls (HC)

20 with SZ

we hypothesized that reduced amygdala volume would more reliably be associated with BPD and reduced hippocampal volume with SZ.

we set out to compare youths with early-onset BPD without psychosis and BPD with psychosis to those with SZ to discern if there would be findings in the amygdala and the hippocampus that would differentiate these disorders.

the increased NA in both the BPD without psychosis and the BPD with psychosis and not in the group with SZ suggests that this finding may be relatively specific to bipolar illness processes.

Our finding of a reduced thalamic volume in SZ and not BPD suggests that the thalamus may be more intimately involved in the SZ phenotype

we did find that amygdala volumes in the BPD without psychosis group correlated inversely with the MRS, which suggests the involvement of this structure in the clinical phenotype.

the most consistently reported finding in early-onset BPD is a reduced amygdala volume16 and in early-onset SZ, a decreased hippocampal volume.

we found that youths with SZ had the smallest thalamic volumes bilaterally, with at least a moderate effect size when compared with the other 3 groups

We found that there were no volumetric differences between SZ and BPD in the amygdala and the hippocampus, which was not consistent with our a priori hypothesis.

This study investigated the volumetric differences in subcortical gray matter volumes, particularly the amygdala and the hippocampus, in early-onset BPD without psychosis, BPD with psychosis, and SZ in order to elucidate the diagnostic specificity of patterns of subcortical neural abnormality. In addition, this study evaluated diagnosis-by-sex interactions to understand the influence of sexual dimorphism on the limbic structures.

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)

smaller thalamus was associated with SZ while larger right NA volumes were most related to BPD

19 with BPD with psychosis

Thirty-five youths with DSM-IV BPD without psychosis

youths with BPD with and without psychosis had increased right and left NA volumes, with a moderate effect size compared with the other groups

We found that males with SZ had smaller left amygdala volumes relative to other groups and that females with BPD had the smallest left hippocampus.

we found that the right amygdala volume correlated with GAF scores in the SZ group.

we did find that amygdala volumes in the BPD without psychosis group correlated inversely with the MRS

When diagnosis-by-sex interactions were evaluated, males with SZ had the smallest left amygdala and females with BPD had the smallest left hippocampus.

these data suggest that specific subcortical brain regions are differentially affected in early-onset BPD and SZ, perhaps suggesting that these are disease-specific abnormalities.

We also found that the youths with BPD with psychosis only shared findings with the BPD without psychosis and not with the primary psychotic disorder group

Both the thalamic finding and the right NA finding were independent of sex effects.

all other subcortical structures included in an exploratory

neurological examination, and cognitive testing

This article has been corrected.

structured and clinical interviews

Diagnostic and Sex Effects on Limbic Volumes in Early-Onset Bipolar Disorder and Schizophrenia

Neurotypical Group473013R46Inferior Frontal Gyrus49832R9Inferior Frontal Gyrus−431033L9Middle Frontal Gyrus35153R6Middle Frontal Gyrus32144R8Cingulate gyrus71830R8Medial Frontal Gyrus33−6445R7Superior Parietal Lobule−29−5945L7Superior Parietal LobuleAutism Group422823R46Middle Fontal Gyrus40240R47Inferior Frontal Gyrus50727R9Inferior Frontal Gyrus−31 265L45Inferior Frontal Gyrus102241R32Cingulate Gyrus29−7142R19Precuneus−23−6143L7Superior Parietal Lobule31−78−2R18Inferior Occipital Gyrus36−3942R40Inferior Parietal Lobule−33−65−3L19Fusiform Gyrus

Application Due Date(s)

three years

Budgets are limited to $300,000 Direct Costs

November 20, 2015; June 14, 2016; November 21, 2016; June 14, 2017

pip install numpy scipy && pip install nipype nibabel nitime pyyaml pandas

python setup.py install

cd /qap

Neurotypical group473013R46Inferior frontal gyrus49832R9Inferior frontal gyrus− 43033L9Middle frontal gyrus35153R6Middle frontal gyrus32144R8Cingulate gyrus71830R8Medial frontal gyrus33− 6445R7Superior parietal lobule− 29− 5945L7Superior parietal lobuleAutism group422823R46Middle frontal gyrus40240R47Inferior frontal gyrus50727R9Inferior frontal gyrus− 31265L45Inferior frontal gyrus102241R32Cingulate gyrus29− 7142R19Precuneus− 23− 6143L7Superior parietal lobule31− 78− 2R18Inferior occipital gyrus36− 3942R40Inferior parietal lobule− 33− 65− 3L19Fusiform gyrus

Social stimuli interfere with cognitive control in autism

1000 Functional Connectomes (“Classic”)a1288, age 18–80 years 24 Str/RS niit1:5ABIDEb1112, age 6–64 years 17 Str/RS niit1:6ADHD-200c973, age 7–26 years 8 Str/RS niit1:7Beijing Enhancedd180, age 17–28 years 1 Str/RS/Diff niit1:8Beijing Eyes Open Eyes Closede48, age 18–30 years 1 Str/RS/Diff niit1:9Beijing

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