Euthymic Pediatric Bipolar Disorder Research Articles

Shared and specific patterns of structural and functional thalamo-frontal disturbances in manic and euthymic pediatric bipolar disorder

Bipolar disorder (BD) is clinically defined by alternating depressive and manic episodes with a separated period of euthymia. Thalamo-frontal loop plays vital role in psychotic symptoms, altered motor control and executive difficulties in BD. It remains unclear that structural and functional alterations of thalamo-frontal loop among the different mood states in BD, especially in pediatric BD(PBD).Twenty manic PBD (mPBD), 20 euthymic PBD (ePBD) and 19 healthy controls (HCs) were included in the study. By analyzing the T1 images and fMRI signals, thalamus volume and frontal grey matter cortical thickness were tested, and functional connectivity (FC) between bilateral thalamus and frontal cortex was calculated. Relationship between clinical indices and thalamo-frontal FC was also evaluated in mPBD and ePBD adolescents.Compared to HCs, the cortical thickness of left middle frontal gyrus (MFG), bilateral superior frontal gyrus (SFG) was significantly decreased in both mPBD and ePBD patients, and volume of left thalamus and cortical thickness of right MFG significantly decreased in mPBD patients. Compared to that of the HCs and ePBD subjects, thalamo-frontal hyperconnectivity with MFG was found in mPBD, and compared with that of HCs, thalamo-frontal hypoconnectivity with precentral gyrus/SFG was found in ePBD. In ePBD patients, episode times positively correlated with FC values between thalamus and precentral gyrus.The findings of the present study demonstrate detailed knowledge regarding shared and specific structural and functional disruption in thalamo-frontal loop in mPBD and ePBD subjects. Thalamo-frontal abnormalities reported in adult BD subjects were also observed in adolescent BD patients, and thalamo-frontal dysfunction may be a crucial treatment target in BD.

Children with euthymic bipolar disorder during an emotional go/nogo task: Insights into the neural circuits of cognitive-emotional regulation

Background: Pediatric bipolar disorder (PBD), manifested by alternating episodes of depression and mania, is more likely to relapse than adult BD and develop into chronic BD. Although it can be asymptomatic during the remission of PBD, subtle changes in the brain neural response can still exist. Abnormal activities in the neural circuits of cognitive-emotional regulation have been found in adult BD patients using fMRI. However, few fMRI studies focus on emotional regulation on cognitive function in euthymic PBD, especially during an emotional go/nogo task. Therefore, this study aims to compare differences in the activities of both emotional and cognitive circuits between euthymic BD children and healthy controls. Methods: 18 euthymic PBD and 17 healthy subjects from 12 to 17 years of age were enrolled in our study. Simultaneous neural activity was recorded during the overall task and the effect of emotional factors on task performances was assessed. Results: There were no significant differences in behavioral performances between the PBD group and the control group. During a task with emotional versus neutral distractors, euthymic PBD patients showed increased activities in the DLPFC, inferior parietal lobule, superior/middle frontal gyrus, superior/middle temporal gyrus, insula, posterior cingulate gyrus and posterior cerebellum lobe relative to healthy controls. The insula and DLPFC activities in response to emotional versus neutral distractors were positively associated with the differences in false response errors. Conclusions: This study confirms the enhanced neural activities in euthymic PBD during a task with emotional versus control distractors. These brain regions supporting the cognitive and emotional dysregulation of PBD mainly coincide with the salience and executive control networks. As neural responses are more sensitive than behavioral manifestations in euthymic PBD, our findings will inspire more clinical studies to unveil the characteristic neuromechanism of PBD.

Manic and euthymic states in pediatric bipolar disorder patients during an emotional Go/Nogo task: A functional magnetic resonance imaging study

BackgroundNeural abnormalities in emotional response inhibition still exist in the euthymic phase of bipolar disorder (BD). Few studies on comparisons of functional magnetic resonance imaging (fMRI) manifestations between different mood phases of pediatric bipolar disorder (PBD) have ever been published. The goal of this study was to explore the differences in neural activities between manic and euthymic PBD during emotional response inhibition. MethodsSimultaneous imaging of neural activity was recorded during an emotional Go/Nogo paradigm and the effect of emotional response inhibition was analyzed. Neural activities were compared between the three groups. ResultsIn the presence of emotional versus neutral distractors, both manic and euthymic PBD subjects similarly showed widespreadly increased activities in the cognitive and emotional regulation circuits compared with healthy individuals. Compared with euthymic PBD patients, those with manic PBD exhibited increased activities in the left superior frontal gyrus. Hyperactivity in the left superior frontal, left middle frontal and right inferior frontal gyrus in manic PBD was positively associated with false response errors. ConclusionIncreased activity in the left superior frontal gyrus may be characteristic of manic episodes in PBD patients, and such a disparity between manic and euthymic phrases may attribute to more severe emotional dysregulation.

Alterations of Cognition and Cerebral Ventricle Volume in Manic and Euthymic Pediatric Bipolar Disorder.

Introduction: It remains unknown whether volumetric alterations of ventricles are similar or not in pediatric bipolar disorder (PBD) among different mood states. The present study aims to estimate ventricular volumetric alteration of PBD patients in manic and euthymic status, as well as the relationship between this alteration and cognitive changes.Methods: T1 magnetic resonance images were obtained from 20 manic PBD patients, 21 euthymic PBD patients, and 19 healthy controls (HCs). Ventricular volumes were automatically obtained via FreeSurfer 6.0 software. Ventricular volumes and cognitive indices were compared among the three groups, and the relationship between ventricular volumes and cognitive/clinical indices was analyzed.Results: In contrast to HCs, manic and euthymic PBD patients exhibited decreased cognitive scores of the Stroop color-word test and the digit span subtest. Manic PBD subjects presented enlarged volumes in the bilateral ventricles, third ventricle, and whole ventricles, and euthymic PBD participants displayed increased volumes in the third ventricle, fourth ventricle, and whole ventricles. No significant differences in cognitive performance and ventricular volumes were found between PBD groups. No significant correlation was discovered between ventricular volumes and cognitive/clinical indices in both manic and euthymic PBD patients.Conclusions: No significant differences in cognitive performance and ventricle volume were observed between euthymic and manic PBD groups, which may imply that the alterations are not specific to mood state. It may indicate structural and functional damage of corresponding brain circuits in euthymic PBD patients similar with that of manic PBD, which may provide clues to the diagnosis and treatment of euthymic PBD.

Altered Functional Integration in the Salience and Default Mode Networks in Euthymic Pediatric Bipolar Disorder.

Accumulating studies demonstrate emotional and cognitive dysregulation in the euthymic period of pediatric bipolar disorder (PBD). However, the relative contribution of functional integration in human brain to disturbed emotion and cognitive function in the euthymic PBD patients remains unclear. In this study, 16 euthymic PBD patients and 16 healthy controls underwent resting-state functional magnetic resonance imaging. A data-driven functional connectivity analysis was used to investigate functional connectivity changes of the euthymic PBD. Compared with healthy controls, the euthymic PBD exhibited greater global functional connectivity density in the left anterior insula and lower global functional connectivity density in the right temporoparietal junction, the left angular gyrus, and the bilateral occipital lobule. A distant functional connectivity analysis demonstrated altered integration within the salience and default mode networks in euthymic PBD. Correlation analysis found that altered functional connectivity of the salience network was related to the reduced performance in the backward digit span test, and altered functional connectivity of the default mode network was related to the Young Mania Rating Scale in euthymic PBD patients. Our findings indicated that disturbed functional integration in salience and default mode networks might shed light on the physiopathology associated with emotional and cognitive dysregulation in PBD.

Altered spatiotemporal consistency of corticolimbic circuitry in euthymic pediatric bipolar disorder.

Bipolar disorder (BD) is a life-threatening illness which clinically defined by an alternating pattern of depressive and manic episodes with a separated period of euthymia. It remains unknown about the consistency of temporal-spatial spontaneous brain activity in euthymic patients, especially in pediatric BD (PBD) patients.Resting-state fMRI signals of sixteen euthymic PBD patients and 16 healthy controls were processed and FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) and functional connectivity were calculated in the present study. Voxel-wised correlation between clinical and cognitive indices and FOCA in PBD was calculated.Compared with healthy subjects, euthymic PBD patients showed worse performance in tests of Stroop Color-Word Test, Digit Span Test and Trail Making Test. Euthymic PBD patients demonstrated increased FOCA in left inferior frontal gyrus, left anterior cingulate cortex and left superior frontal gyrus and decreased FOCA in right orbital frontal gyrus, bilateral precuneus, right superior occipital gyrus and bilateral superior parietal gyrus. Decreased functional connectivities were found between right orbital frontal gyrus and left amygdala, between left superior frontal gyrus and left putamen, and between left superior frontal gyrus and left insula. And increased functional connectivity was found between right superior occipital gyrus and right hippocampus. FOCA of parahippocampal gyrus was negatively correlated with the SCWT-B score in PBD patients.Abnormal spatiotemporal consistency of brain regions of corticolimbic circuitry is possible to contribute to an imbalance between emotional processing and cognitive control in euthymic PBD. The measurement of FOCA measure may provide important clues of understanding PBD.

Correlation Between Decreased Amygdala Subnuclei Volumes and Impaired Cognitive Functions in Pediatric Bipolar Disorder.

BackgroundThe amygdala has been proposed to be involved in the pathophysiology of pediatric and adult bipolar disorder (BD). The goal of this structural magnetic resonance imaging (sMRI) study was to investigate the morphometric characteristics of amygdala subnuclei in patients with pediatric bipolar disorder (PBD) compared to healthy controls (HCs). Simultaneously, we examined correlation between amygdala subnuclei volumes and cognitive dysfunction.Materials and MethodsWe assessed 40 adolescent outpatients, diagnosed with manic or euthymic PBD according to the DSM-5 criteria for BD and 19 HCs. Cognitive functions were evaluated using a Stroop color-word test (SCWT), trail making test (TMT), visual reproduction immediate recall subtest (VR I), and digit span subtest (DST). Amygdala and its subnuclei structures were automated segmented using FreeSurfer software and the volumes of them were compared between groups and correlation with clinical and cognitive outcomes was conducted.ResultsManic patients exhibited significantly decreased volumes in the bilateral whole amygdala and its basal nucleus, cortico-amygdaloid transition (CAT), and accessory basal nucleus (ABN) compared with HCs. Euthymic patients had decreased volume in the bilateral ABN and left CAT. In addition, we found significant positive associations between VR I scores and the right whole amygdala and its bilateral basal, right lateral, and ABN volumes in the manic group.ConclusionThese findings support previous reports of smaller amygdala volumes and cognitive dysfunctions in PBD, and further mapping abnormalities to specific amygdala subnuclei. Correlation between basolateral volume and VR I of PBD may expand our understanding of neural abnormalities that could be targeted by treatment.

Disrupted brain structural connectivity in Pediatric Bipolar Disorder with psychosis

Bipolar disorder (BD) has been linked to disrupted structural and functional connectivity between prefrontal networks and limbic brain regions. Studies of patients with pediatric bipolar disorder (PBD) can help elucidate the developmental origins of altered structural connectivity underlying BD and provide novel insights into the aetiology of BD. Here we compare the network properties of whole-brain structural connectomes of euthymic PBD patients with psychosis, a variant of PBD, and matched healthy controls. Our results show widespread changes in the structural connectivity of PBD patients with psychosis in both cortical and subcortical networks, notably affecting the orbitofrontal cortex, frontal gyrus, amygdala, hippocampus and basal ganglia. Graph theoretical analysis revealed that PBD connectomes have fewer hubs, weaker rich club organization, different modular fingerprint and inter-modular communication, compared to healthy participants. The relationship between network features and neurocognitive and psychotic scores was also assessed, revealing trends of association between patients’ IQ and affective psychotic symptoms with the local efficiency of the orbitofrontal cortex. Our findings reveal that PBD with psychosis is associated with significant widespread changes in structural network topology, thus strengthening the hypothesis of a reduced capacity for integrative processing of information across brain regions. Localised network changes involve core regions for emotional processing and regulation, as well as memory and executive function, some of which show trends of association with neurocognitive faculties and symptoms. Together, our findings provide the first comprehensive characterisation of the alterations in local and global structural brain connectivity and network topology, which may contribute to the deficits in cognition and emotion processing and regulation found in PBD.

Altered regional homogeneity in pediatric bipolar disorder during manic and euthymic state: a resting-state fMRI study.

Pediatric bipolar disorder (PBD) is a severely debilitating illness, which is characterized by episodes of mania and depression separated by periods of remission. Little is known about the abnormalities in PBD in resting state, especially comparing manic with euthymic state. Resting state brain activity measured by fMRI might help to explore neurobiological biomarkers of the disorder. Regional homogeneity (ReHo) was examined with resting-state fMRI on 22 manic PBD patients, 21 euthymic PBD patients and 19 healthy controls. Compared with control group, manic group presented reduced cortical ReHo signal in the superior temporal gyrus(STG), the superior parietal lobe (SPL), precentral gyrus and altered subcortical ReHo signal in the insula and cerebelum crus I. Compared with control group, euthymic group only presented reduced cortical ReHo signal in the STG and SPL. Compared with euthymic group, we found reduced ReHo signal in insula, the STG and increased ReHo signal in cerebelum crus I in the manic group. The neural regions we found to have altered ReHo signal in the PBD manic and euthymic group are parts of the cortical-limbic systems, which are important for affective and cognitive processing. Importantly, our findings suggested that there was a difference between manic and euthymic PBD in the insula, cerebelum crus I and the STG.

Attention Deficits in a Comorbidity-Free Sample of Euthymic Pediatric Bipolar Disorder.

Attention deficits are considered one of the potential endophenotypic markers of Bipolar Disorder (BD). Pediatric bipolar disorder (PBD) likely has stronger genetic underpinnings than adult onset BD; therefore, demonstrating attention deficits in PBD can be both strategic and convincing in attesting their status as one of the potential endophenotypic markers of BD. However, unlike adult literature, uncertainty exists regarding the magnitude of attention deficits in PBD. In this regard, one key unresolved question is the potential impact of attention deficit hyperactivity disorder (ADHD). The main goal of the study was to examine attention deficits in a comorbidity-free sample of euthymic PBD patients. Thirty (21 boys, 9 girls) remitted PBD patients without co-morbidity and thirty age (<17 years), sex, handedness, and Full-Scale IQ matched control subjects were compared on performance on attention tasks. Working memory (WM), which might potentially confound with the attention task performances, was also examined. Compared to controls, PBD patients performed poorly on various tests of attention, but not on any WM tasks. Further, it was found that observed attention deficits were independent of residual mood symptoms, medication effect or illness characteristics. Such attention deficits in this comorbidity-free PBD sample further endorses its status as an endophenotypic marker of bipolar disorders and establishes continuity with deficits found in adult bipolar patients.

Resting-State Functional Connectivity of Occipital Cortex in Euthymic Pediatric Bipolar Disorder Patients

Resting-State Functional Connectivity of Occipital Cortex in Euthymic Pediatric Bipolar Disorder Patients