Pediatric bipolar disorder (PBD) is characterized by abnormal functional connectivity among distributed brain regions. Increasing evidence suggests a role for the limbic network (LN) and the triple network model in the pathophysiology of bipolar disorder (BD). However, the specific relationship between the LN and the triple network in PBD remains unclear. This study aimed to investigate the aberrant causal connections among these four core networks in PBD.

Resting-state functional MRI scans from 92 PBD patients and 40 healthy controls (HCs) were analyzed. Dynamic Causal Modeling (DCM) was employed to assess effective connectivity (EC) among the four core networks. Parametric empirical Bayes (PEB) analysis was conducted to identify ECs associated with group differences, as well as depression and mania severity. Leave-one-out cross-validation (LOOCV) was used to test predictive accuracy.

Compared to HCs, PBD patients exhibited primarily excitatory bottom-up connections from the LN to the salience network (SN) and bidirectional excitatory connections between the default mode network (DMN) and SN. In PBD, top-down connectivity from the triple network to the LN was excitatory in individuals with higher depression severity but inhibitory in those with higher mania severity. LOOCV identified dysconnectivity circuits involving the caudate and hippocampus as being associated with mania and depression severity, respectively.

Disrupted bottom-up connections from the LN to the triple network distinguish PBD patients from healthy controls, while top-down disruptions from the triple network to LN relate to mood state differences. These findings offer insight into the neural mechanisms of PBD.

We investigated affect recognition and the impact of emotional valence on working memory (using happy, angry, and neutral faces) in pediatric patients with bipolar disorder (BD) and healthy control (HC) subjects.

Subjects (N=70) consisted of unmedicated patients with BD type I (BD I, n=23) and type II (BD II, n=16) and matched HC subjects (n=31). All subjects completed tasks of emotion recognition (Chicago Pediatric Emotional Acuity Task; Chicago PEAT) and working memory for happy, angry, and neutral faces (Affective N-Back Memory Task; ANMT).

Compared to HC subjects, BD patients performed significantly more poorly when identifying the intensity of happy and angry expressions on the Chicago PEAT, and demonstrated working-memory impairments regardless of the type of facial emotional stimuli. Pediatric BD patients displayed the most impaired accuracy and reaction time performance with negative facial stimuli relative to neutral stimuli, but did not display this pattern with positive stimuli. Only BD I patients displayed working-memory deficits, while both BD I and BD II patients displayed emotion-identification impairments. Results remained significant after controlling for co-morbid ADHD and mood state.

Both BD I and BD II youth demonstrate emotion-identification deficits. BD youth also demonstrate working-memory impairments for facial stimuli irrespective of emotional valence; however, working-memory deficits were the most pronounced with negative emotional stimuli. These deficits appear to be specific to BD I patients, and suggest therefore that a more severe form of illness is characterized by more severe social-cognitive impairment.

There is growing evidence for the familiality of pediatric bipolar disorder (BPD) and its association with impairments on measures of processing speed, verbal learning and ‘executive’ functions. The current study investigated whether these neurocognitive impairments index the familial risk underlying the diagnosis.

Subjects were 170 youth with BPD (mean age 12.3 years), their 118 non-mood-disordered siblings and 79 non-mood-disordered controls. Groups were compared on a battery of neuropsychological tests from the Wechsler Intelligence Scales, the Stroop Color Word Test, the Wisconsin Card Sorting Test (WCST), the Rey–Osterrieth Complex Figure (ROCF), an auditory working memory Continuous Performance Test (CPT) and the California Verbal Learning Test – Children's Version (CVLT-C). Measures were factor analyzed for data reduction purposes. All analyses controlled for age, sex and attention-deficit/hyperactivity disorder (ADHD).

Principal components analyses with a promax rotation yielded three factors reflecting: (1) processing speed/verbal learning, (2) working memory/interference control and (3) abstract problem solving. The CPT working memory measure with interference filtering demands (WM INT) was only administered to subjects aged ⩾12 years and was therefore analyzed separately. BPD youth showed impairments versus controls and unaffected relatives on all three factors and on the WM INT. Unaffected relatives exhibited impairments versus controls on the abstract problem-solving factor and the WM INT. They also showed a statistical trend (p=0.07) towards worse performance on the working memory/interference control factor.

Neurocognitive impairments in executive functions may reflect the familial neurobiological risk mechanisms underlying pediatric BPD and may have utility as endophenotypes in molecular genetic studies of the condition.

Deficits in theory of mind (ToM), or the ability to infer what another person is thinking or feeling, have been reported in manic and euthymic adults with bipolar disorder. To date, there have been no investigations of ToM in pediatric bipolar disorder (PBD). The aim of the current study was to investigate this ability in PBD patients and healthy controls.

PBD patients (n=26) and intellectually and demographically similar healthy comparison subjects (n=20) were administered two ToM tasks. In the Affective Story Task, subjects were read positive-, negative- and neutral-valenced stories, and were assessed on their ability to recognize that a misleading series of events could lead one character to develop a false belief about another character. On the Hinting Task, subjects were required to infer the real intentions behind subtle hints.

The PBD group performed significantly more poorly than controls on the Hinting Task and the positive and negative conditions of the Affective Story Task. In the PBD group only, younger age, earlier illness onset and manic symptoms were associated with poorer ToM performance.

Consistent with past findings in adult bipolar disorder (BD), PBD youth performed more poorly than controls on ToM tasks. Data suggest that ToM ability may be more impaired in affectively charged contexts. Additionally, an earlier onset of illness among PBD youth may interfere with the development of social-cognitive skills. ToM disturbances may be a useful treatment target in PBD, with the aim of facilitating more accurate assessment of social cues and better interpersonal functioning.