Pediatric Bipolar Disorder Patients Research Articles

Structural and functional disruption of subcortical limbic structures related with executive function in pediatric bipolar disorder

BackgroundImpaired cognition has been demonstrated in pediatric bipolar disorder (PBD). The subcortical limbic structures play a key role in PBD. However, alternations of anatomical and functional characteristics of subcortical limbic structures and their relationship with neurocognition of PBD remain unclear. MethodsThirty-six PBD type I (PBD-I) (15.36 ± 0.32 years old), twenty PBD type II (PBD-II) (14.80 ± 0.32 years old) and nineteen age-gender matched healthy controls (HCs) (14.16 ± 0.36 years old) were enlisted. Primarily, the volumes of the subcortical limbic structures were obtained and differences in the volumes were evaluated. Then, these structures served as seeds of regions of interest to calculate the voxel-wised functional connectivity (FC). After that, correlation analysis was completed between volumes and FC of brain regions showing significant differences and neuropsychological tests. ResultsCompared to HCs, both PBD-I and PBD-II patients showed a decrease in the Stroop color word test (SCWT) and digit span backward test scores. Compared with HCs, PBD-II patients exhibited a significantly increased volume of right septal nuclei, and PBD-I patients presented increased FC of right nucleus accumbens and bilateral pallidum, of right basal forebrain with right putamen and left pallidum. Both the significantly altered volumes and FC were negatively correlated with SCWT scores. SignificanceThe study revealed the role of subcortical limbic structural and functional abnormalities on cognitive impairments in PBD patients. These may have far-reaching significance for the etiology of PBD and provide neuroimaging clues for the differential diagnosis of PBD subtypes. ConclusionsDistinctive features of neural structure and function in PBD subtypes may contribute to better comprehending the potential mechanisms of PBD.

Distinct functional patterns in child and adolescent bipolar and unipolar depression during emotional processing.

Accumulating evidence from functional magnetic resonance imaging studies supported brain dysfunction during emotional processing in bipolar disorder (BD) and major depressive disorder (MDD). However, child and adolescent BD and MDD could display different activation patterns, which have not been fully understood. This study aimed to investigate common and distinct activation patterns of pediatric BD (PBD) and MDD (p-MDD) during emotion processing using meta-analytic approaches. Literature search identified 25 studies, contrasting 252 PBD patients, and 253 healthy controls (HCs) as well as 311 p-MDD patients and 263 HCs. A total of nine meta-analyses were conducted pulling PBD and p-MDD experiments together and separately. The results revealed that PBD and p-MDD showed distinct patterns during negative processing. PBD patients exhibited activity changes in bilateral precuneus, left inferior parietal gyrus, left angular gyrus, and right posterior cingulate cortex while p-MDD patients showed functional disruptions in the left rectus, left triangular part of the inferior frontal gyrus, left orbital frontal cortex, left insula, and left putamen. In conclusion, the activity changes in PBD patients were mainly in regions correlated with emotion perception while the dysfunction among p-MDD patients was in the fronto-limbic circuit and reward-related regions in charge of emotion appraisal and regulation.

Increased regional Hurst exponent reflects response inhibition related neural complexity alterations in pediatric bipolar disorder patients during an emotional Go-Nogo task.

Fractal patterns have been shown to change in resting- and task-state blood oxygen level-dependent signals in bipolar disorder patients. However, fractal characteristics of brain blood oxygen level-dependent signals when responding to external emotional stimuli in pediatric bipolar disorder remain unclear. Blood oxygen level-dependent signals of 20 PBD-I patients and 17 age- and sex-matched healthy controls were extracted while performing an emotional Go-Nogo task. Neural responses relevant to the task and Hurst exponent of the blood oxygen level-dependent signals were assessed. Correlations between clinical indices and Hurst exponent were estimated. Significantly increased activations were found in regions covering the frontal lobe, parietal lobe, temporal lobe, insula, and subcortical nuclei in PBD-I patients compared to healthy controls in contrast of emotional versus neutral distractors. PBD-I patients exhibited higher Hurst exponent in regions that involved in action control, such as superior frontal gyrus, inferior frontal gyrus, inferior temporal gyrus, and insula, with Hurst exponent of frontal orbital gyrus correlated with onset age. The present study exhibited overactivation, increased self-similarity and decreased complexity in cortical regions during emotional Go-Nogo task in patients relative to healthy controls, which provides evidence of an altered emotional modulation of cognitive control in pediatric bipolar disorder patients. Hurst exponent may be a fractal biomarker of neural activity in pediatric bipolar disorder.

The Different Impact of Depressive or Manic First-episode on Pediatric Bipolar Disorder Patients: Evidence From Resting-state fMRI

Bipolar disorder may begin as depression or mania, which can affect the treatment and prognosis of bipolar disorder. However, the physiological and pathological differences of pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The purpose of this study was to investigate the differences of clinical, cognitive function and intrinsic brain networks in PBD patients with first-episode depression and first-episode mania. A total of 63 participants, including 43 patients and 20 healthy controls, underwent resting-state fMRI scans. PBD patients were classified as first-episode depressive and first-episode manic based on their first-episode symptoms. Cognitive tests were used to measure attention and memory of all participants. Independent component analysis (ICA) was used to extract the salience network (SN), default-mode network (DMN), central executive network (ECN) and limbic network (LN) for each participant. Spearman rank correlation analysis was performed between abnormal activation and clinical and cognitive measures. The results showed that there were differences in cognitive functions such as attention and visual memory between first-episode depression and mania, as well as differences activation in anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), precuneus, inferior parietal cortex and parahippocampus. And significant associations of brain activity with clinical assessments or cognition were found in different patients. In conclusion, we found differential impairments in cognitive and brain network activation in first-episode depressive and first-episode manic PBD patients, and correlations were found between these impairments. These evidences may shed light on the different developmental paths of bipolar disorder.

Fourteen‐year trends in the prescribing patterns of pediatric bipolar patients discharged from two public mental hospitals in Taiwan

The management of pediatric bipolar disorder (PBD) requires pharmacotherapy to control acute symptoms, reduce relapse, prevent suicide, and improve psychosocial functioning. The purpose of this study was to investigate prescribing patterns among PBD patients discharged from two public mental hospitals in Taiwan, from 2006 to 2019. PBD patients discharged from the two study hospitals, from 1 January 2006 to 31 December 2019 (n=420), were included in the analysis. Prescribed drugs at discharge, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), antipsychotics (i.e., second- and first-generation antipsychotics, SGAs and FGAs), and antidepressants, were explored. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Time trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. The most commonly prescribed psychotropic agents were SGAs (76.0%), followed by valproate (65.7%) and FGAs (24.8%). The prescription rates of SGAs, antidepressants, antidepressant plus antipsychotic, and antidepressant without mood stabilizer significantly increased over time, whereas the prescription rates of mood stabilizers, lithium, and FGAs significantly decreased. Prescribing patterns changed greatly for PBD patients over time. However, much more evidence supporting the effectiveness of psychotropic agents in PBD patients is required.

Machine learning algorithm performance evaluation in structural magnetic resonance imaging-based classification of pediatric bipolar disorders type I patients.

The diagnosis based on clinical assessment of pediatric bipolar disorder (PBD) may sometimes lead to misdiagnosis in clinical practice. For the past several years, machine learning (ML) methods were introduced for the classification of bipolar disorder (BD), which were helpful in the diagnosis of BD. In this study, brain cortical thickness and subcortical volume of 33 PBD-I patients and 19 age-sex matched healthy controls (HCs) were extracted from the magnetic resonance imaging (MRI) data and set as features for classification. The dimensionality reduced feature subset, which was filtered by Lasso or f_classif, was sent to the six classifiers (logistic regression (LR), support vector machine (SVM), random forest classifier, naïve Bayes, k-nearest neighbor, and AdaBoost algorithm), and the classifiers were trained and tested. Among all the classifiers, the top two classifiers with the highest accuracy were LR (84.19%) and SVM (82.80%). Feature selection was performed in the six algorithms to obtain the most important variables including the right middle temporal gyrus and bilateral pallidum, which is consistent with structural and functional anomalous changes in these brain regions in PBD patients. These findings take the computer-aided diagnosis of BD a step forward.

Altered spatiotemporal consistency in pediatric bipolar disorder patients with and without psychotic symptoms

ObjectivePsychotic symptoms are quite common in patients with pediatric bipolar disorder (PBD) and may affect the symptom severity and prognosis of PBD. However, the potential mechanisms are less well elucidated until now. Thus, the purpose of this study was to investigate the brain functional differences between PBD patients with and without psychotic symptoms.MethodA total of 71 individuals including: 27 psychotic PBD (P-PBD), 25 nonpsychotic PBD (NP-PBD), and 19 healthy controls were recruited in the present study. Each subject underwent 3.0 Tesla functional magnetic resonance imaging scan. Four-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was employed to detect the local brain activity changes. Analyses of variance (ANOVA) were used to reveal brain regions with significant differences among three groups groups of individuals, and inter-group comparisons were assessed using post hoc tests.ResultsThe ANOVA obtained significant among-group FOCA differences in the left triangular inferior frontal gyrus, left supplementary motor area, left precentral gyrus, right postcentral gyrus, right superior occipital gyrus, and right superior frontal gyrus. Compared with the control group, the P-PBD group showed decreased FOCA in the left supplementary motor area and bilateral superior frontal gyrus and showed increased FOCA in the left triangular inferior frontal gyrus. In contrast, the NP-PBD group exhibited decreased FOCA in the right superior occipital gyrus and right postcentral gyrus and showed increased FOCA in the left orbital inferior frontal gyrus. Compared to the NP-PBD group, the P-PBD group showed decreased FOCA in the right superior frontal gyrus.ConclusionThe present findings demonstrated that the two groups of PBD patients exhibited segregated brain functional patterns, providing empirical evidence for the biological basis of different clinical outcomes between PBD patients with and without psychotic symptoms.

Investigation of endophenotype potential of decreased fractional anisotropy in pediatric bipolar disorder patients and unrelated offspring of bipolar disorder patients.

Bipolar disorder (BD) is a severe psychiatric disorder associated with structural and functional brain abnormalities, some of which have been found in unaffected relatives as well. In this study, we examined the potential role of decreased fractional anisotropy (FA) as a BD endophenotype, in adolescents at high risk for BD. We included 15 offspring of patients with BD, 16 pediatric BD patients, and 16 matched controls. Diffusion weighted scans were obtained on a 3T scanner using an echo-planar sequence. Scans were segmented using FreeSurfer. Our results showed significantly decreased FA in six brain areas of offspring group; left superior temporal gyrus (LSTG; P<.0001), left transverse temporal gyrus (LTTG; P=.002), left banks of the superior temporal sulcus (LBSTS; P=.002), left anterior cingulum (LAC; P=.003), right temporal pole (RTP; P=.004) and left frontal pole (LFP; P=.017). On analysis, LSTG, LAC, and RTP demonstrated a potential to be an endophenotype when comparing all three groups. FA values in three regions, LBSTS, LTTG, and LFP were increased only in controls. Our findings point at decreased FA as a possible endophenotype for BD, as they were found in children of patients with BD. Most of these areas were previously found to have morphological and functional changes in adult and pediatric BD, and are thought to play important roles in affected domains of functioning. Prospective follow up studies should be performed to detect reliability of decreased FA as an endophenotype and effects of treatment on FA.

Brain structural alterations in pediatric bipolar disorder patients with and without psychotic symptoms

BackgroundBipolar disorder (BD) with psychotic symptoms is a specific phenotype that presents greater risk of relapse and worse outcomes than nonpsychotic BD, however, the underlying mechanisms remain unknown and are less revealed in youth. Thus, the aims of the present study were to investigate brain structural alterations in pediatric bipolar disorder (PBD) patients with and without psychotic symptoms, and specifically to evaluate the impact of psychotic features on gray matter volume (GMV) in PBD patients. MethodA total of 73 individuals were recruited into three groups, n = 28, psychotic PBD, P-PBD; n = 26, nonpsychotic PBD, NP-PBD; and n = 19, healthy controls, HC. All participants underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry was used to investigate GMV alterations. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. ResultsThe ANOVA revealed significant GMV differences among three groups in the bilateral amygdala-hippocampus-parahippocampal complex (AMY-HIS-ParaHIS complex), left superior temporal gyrus (STG), left inferior frontal gyrus (IFG), bilateral putamen (PUT), left precentral gyrus (PG), left supramarginal gyrus (SMG), and right inferior parietal lobule (IPL). Compared with HCs, P-PBD patients showed decreased GMV in the bilateral AMY-HIS-ParaHIS complex, left STG, left IFG, bilateral PUT, and left PG; while NP-PBD patients exhibited decreased GMV in the left IFG, left PG, left SMG, and right IPL. Furthermore, P-PBD patients showed increased GMV in the right IPL when comparing to NP-PBD patients. LimitationThe present findings require replication in larger samples and verification in medication free subjects. ConclusionThe present findings suggested that psychotic features in PBD were associated with extensive brain structural lesions mainly located in the prefrontal-limbic-striatum circuit, which might represent the pathological basis of more sever symptoms in patients with psychotic PBD.

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.

Errors in identifying emotion in body postures and facial expressions among pediatric patients with bipolar disorder

ABSTRACT Introduction Facial emotion processing impairments have been consistently demonstrated among patients with pediatric bipolar disorder (PBD). However, less is known about other domains of nonverbal emotion recognition in this group. Therefore, the aim of the current study was to investigate emotion identification for body postures in addition to facial expressions among PBD patients and matched healthy comparison (HC) subjects. Method Youth with PBD (n = 25) and HC subjects (n = 25), equal on intellectual and demographic variables, completed the body postures and faces subtests of the Diagnostic Analysis of Nonverbal Accuracy-2 scale (DANVA-2) along with diagnostic and clinical assessments. Results Compared to HC, PBD patients made significantly more errors identifying emotion in both body postures and faces. Poorer performance on the faces subtest was associated with more problematic peer functioning. Greater manic symptoms were associated with poorer performance on negative emotional stimuli but not positive. Conclusions In addition to impairments in facial emotion processing, youth with PBD also show impairments in the ability to correctly identify emotion from body postures. In this group, greater manic symptomatology appears to impair processing for negative facial expressions and body postures, but not positive ones. Interestingly, facial emotion processing impairments appear to be a better indicator of real-world psychosocial difficulties among PBD patients compared to body postures. Psychosocial treatments for youth with PBD should focus on improving the ability to accurately identify and respond to various facial and body postural cues, as well as symptom management and emotion regulation strategies.

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.

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.

Clinical differences between patients with pediatric bipolar disorder with and without a parental history of bipolar disorder

Pediatric Bipolar Disorder (PBD) is a highly heritable condition responsible for 18% of all pediatric mental health hospitalizations. Despite the heritability of this disorder, few studies have assessed potential differences in the clinical manifestation of PBD among patients with a clear parental history of BD. Additionally, while recent studies suggest that attentional deficits are a potential endophenotypic marker of PBD, it is unclear whether heritability is a relevant contributor to these symptoms. In order to address this gap, the present study assessed 61 youth with PBD (6–17 years old), corresponding to 27 offspring of BD patients, and 31 PBD patients without a parental history of the disorder. All standardized assessments, including the K-SADS-PL-W were performed by trained child and adolescent psychiatrists. We performed a logistic multivariate model using the variables of ADHD, rapid cycling, and lifetime psychosis. Rates of ADHD comorbidity were significantly higher among PBD patients who had a parent with BD. Furthermore, PBD patients who had a parent with BD showed a trend toward significance of earlier symptom onset. PBD offspring did not show increased rates of suicide attempts, rapid cycling, or psychosis. Given these findings, it appears that PBD patients who have a parent with BD may represent a distinct endophenotype of the disorder. Future longitudinal and larger studies are required to confirm our findings.

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.

Correlates of childhood trauma in children and adolescents with bipolar disorder spectrum: A preliminary study

ObjectiveHistories of childhood trauma (CT) are risk factors for affect dysregulation and poor clinical outcomes in women with bipolar disorder (BD). While much is known about the link between BD and CT in adult patients, there is limited data on this research topic in pediatric BD (PBD). The present study aims to investigate the impact of CT on irritability, aggressive and suicidal behaviors in PBD patients across gender types. MethodsFrom 2013 to 2015, 59 PBD patients Aged 6–17 (30 female) were administered the Childhood Trauma Questionnaire (CTQ) along with scales assessing irritability (Affective Reactivity Index), aggression (Modified Overt Aggression Scale) and suicidal thoughts and behaviors (Columbia-Suicide Severity Rating Scale). We examined the severity of these behaviors across types of CT and gender using univariate regression analyses. Findings were adjusted for age, number of traumas, and CTQ denial score. ResultsIn PBD patients, analyses showed that the effect of physical abuse depended on gender, whereby females were more likely than males to engage in suicidal thoughts and behaviors (p < 0.05). Male gender and CT were strong determinants of irritability (p < 0.05). Violence against property and people was found to be reduced in females, and increased in males with a history of emotional and sexual abuse, respectively (p < 0.05). ConclusionThese preliminary findings highlight the significant impact of CT in PBD and suggest that gender may predict the risk for dysfunctional behaviors in PBD patients with CT. Future large scale, longitudinal, investigations focusing on fear processing and extinction may provide a deeper understanding of these gender differences, and their role in the course of BD.