Euthymic Bipolar Disorder Patients Research Articles

Peripheral inflammation is associated with impaired sadness recognition in euthymic bipolar patients

BackgroundInflammation impairs cognitive function in healthy individuals and people with psychiatric disorders, such as bipolar disorder (BD). This effect may also impact emotion recognition, a fundamental element of social cognition. Our study aimed to investigate the relationships between pro-inflammatory cytokines and emotion recognition in euthymic BD patients and healthy controls (HCs). MethodsWe recruited forty-four euthymic BD patients and forty healthy controls (HCs) and measured their inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and TNF-α. We applied validated cognitive tasks, the Wisconsin Card-Sorting Test (WCST) and Continuous Performance Test (CPT), and a social cognitive task for emotion recognition, Diagnostic Analyses of Nonverbal Accuracy, Taiwanese Version (DANVA-2-TW). We analyzed the relationships between cytokines and cognition and then explored possible predictive factors of sadness recognition accuracy. ResultsRegarding pro-inflammatory cytokines, TNF-α was elevated in euthymic BD patients relative to HCs. In euthymic BD patients only, higher TNF-α levels were associated with lower accuracy of sadness recognition. Regression analysis revealed that TNF-α was an independent predictive factor of sadness recognition in patients with euthymic BD when neurocognition was controlled for.Conclusions: We demonstrated that enhanced inflammation, indicated by increased TNF-α, was an independent predictive factor of impaired sadness recognition in BD patients but not in HCs. Our findings suggested a direct influence of TNF-α on sadness recognition and indicated vulnerability to depression in euthymic BD patients with chronic inflammation.

Similar imaging changes and their relations to genetic profiles in bipolar disorder across different clinical stages

Bipolar disorder (BD) across different clinical stages may present shared and distinct changes in brain activity. We aimed to reveal the neuroimaging homogeneity and heterogeneity of BD and its relationship with clinical variables and genetic variations. In present study, we conducted fractional amplitude of low-frequency fluctuations (fALFF), functional connectivity (FC) and genetic neuroimaging association analyses with 32 depressed, 26 manic, 35 euthymic BD patients and 87 healthy controls (HCs). Significant differences were found in the bilateral pre/subgenual anterior cingulate cortex (ACC) across the four groups, and all bipolar patients exhibited decreased fALFF values in the ACC when compared to HCs. Furthermore, positive associations were significantly observed between fALFF values in the pre/subgenual ACC and participants' cognitive functioning. No significant changes were found in ACC-based FC. We identified fALFF-alteration-related genes in BD, with enrichment in biological progress including synaptic and ion transmission. Taken together, abnormal activity in ACC is a characteristic change associated with BD, regardless of specific mood stages, serving as a potential neuroimaging feature in BD patients. Our genetic neuroimaging association analysis highlights possible heterogeneity in biological processes that could be responsible for different clinical stages in BD.

Abelson Helper Integration Site 1 haplotypes and peripheral blood expression associates with lithium response and immunomodulation in bipolar patients

RationaleIn bipolar disorder (BD), immunological factors play a role in the pathogenesis and treatment of the illness. Studies showed the potential link between Abelson Helper Integration Site 1 (AHI1) protein, behavioural changes and innate immunity regulation. An immunomodulatory effect was suggested for lithium, a mood stabilizer used in BD treatment.ObjectivesWe hypothesized that AHI1 may be an important mediator of lithium treatment response. Our study aimed to investigate whether the AHI1 haplotypes and expression associates with lithium treatment response in BD patients. We also examined whether AHI1 expression and lithium treatment correlate with innate inflammatory response genes.ResultsWe genotyped seven AHI1 single nucleotide polymorphisms in 97 euthymic BD patients and found that TG haplotype (rs7739635, rs9494332) was significantly associated with lithium response. We also showed significantly increased AHI1 expression in the blood of lithium responders compared to non-responders and BD patients compared to healthy controls (HC). We analyzed the expression of genes involved in the innate immune response and inflammatory response regulation (TLR4, CASP4, CASP5, NLRP3, IL1A, IL1B, IL6, IL10, IL18) in 21 lithium-treated BD patients, 20 BD patients treated with other mood stabilizer and 19 HC. We found significantly altered expression between BD patients and HC, but not between BD patients treated with different mood stabilizers.ConclusionsOur study suggests the involvement of AHI1 in the lithium mode of action. Moreover, mood-stabilizing treatment associated with the innate immunity-related gene expression in BD patients and only the lithium-treated BD patients showed significantly elevated expression of anti-inflammatory IL10, suggesting lithium’s immunomodulatory potential.

The Mixed Tendency in Bipolar Disorder: An Operational Proposal for the Integration of Mixed Episodes in Predominant Polarity

Predominant Polarity (PP) is an established specifier of Bipolar Disorder (BD), holding significant clinical implications. Nevertheless, there exists no consensus on how to incorporate mixed states into PP, leaving patients prone to mixed recurrences that are unclassified. In a comprehensive study involving 701 euthymic BD patients, we sought to redefine PP by introducing a novel metric, the “mixed tendency”, and establish a practical threshold to identify patients with a “mixed phenotype”. Furthermore, we investigated potential associations between the mixed phenotype and specific PP categories. Our findings revealed that the mixed tendency correlated significantly with early BD type I, lifetime suicide attempts, self-aggressive behaviour, and lifetime number of affective episodes (>5). Using a ROC curve analysis, we determined an optimal cut-off point for the mixed tendency at 0.228, suggesting that patients with ~25% of lifetime mixed episodes relative to total affective episodes should be identified as having a mixed phenotype. Notably, the mixed phenotype was positively associated with undetermined PP and negatively with manic and depressive PP. This study introduces a promising approach to incorporating mixed episodes into the PP definition, potentially enabling tailored interventions for patients with a substantial history of mixed episodes. However, further research in large, longitudinal cohorts is essential to validate these findings.

Impaired olfactory function in bipolar disorder patients during acute episodes regardless of psychotic symptoms.

The aim of this study was to analyze whether the presence of psychotic symptoms affects olfactory function in patients with bipolar disorder (BD). We also compared olfactory function between the period of episode and remission in patients with BD. BD patients in the acute phase were tracked to the remission stage. The psychiatric symptoms and social function of the enrolled subjects were assessed using the Hamilton Rating Scale for Depression (HAMD), the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Anxiety (HAMA), the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment Function (GAF). Olfactory sensitivity (OS) and olfactory identification (OI) was assessed using the Sniffin' Sticks test. Differences in OS and OI among the episodic group, the euthymic group, and the healthy control (HC) group were compared. According to whether BD is accompanied by psychotic symptoms, the OS and OI in the BD with psychotic symptoms group (P-BD), the BD without psychotic symptoms group (NP-BD), and the HC group were compared. The P-BD and NP-BD groups exhibited impaired OI compared with the HC group, but there was no significant difference in OI between the P-BD and NP-BD groups, or in OS among all three groups. All patients with episodic BD had significantly lower OS and OI compared with the HC group. OI in euthymic BD patients was still impaired; however, OS recovered, showing no significant difference compared with that in the HC group. The results indicate that patients with episodic BD have impaired OS and OI, regardless of psychotic symptoms. OI may be a characteristic marker of BD, and OS may be a state marker that can be used to distinguish between episodic and euthymic BD.

Language Network Connectivity of Euthymic Bipolar Patients Is Altered at Rest and during a Verbal Fluency Task.

Abnormalities of the Language Network (LN) have been found in different psychiatric conditions (e.g., schizophrenia and bipolar disorder), supporting the hypothesis that language plays a central role in a high-level integration/connectivity of second-level cognitive processes and the underlying cortical regions. This view implies a continuum of shared neural alterations along the psychotic disorder spectrum. In particular, bipolar disorder (BD) patients were recently documented to have an altered LN asymmetry during resting state. The extent to which the LN architecture is altered and stable also during a language task has yet to be investigated. To address this question, we analyzed fMRI data recorded during an open-eyes resting state session and a silent verbal fluency task in 16 euthymic BD patients and 16 matched healthy controls (HC). Functional connectivity in the LN of both groups was computed using spatial independent component analysis, and group comparisons were carried out to assess the network organization during both rest and active linguistic task conditions. The LN of BD patients involved left and right brain areas during both resting state and linguistic task. Compared to the left-lateralized network found in HC, the BD group was characterized by two anterior clusters (in left frontal and right temporo-insular regions) and the disengagement of the posterior language areas, especially during the verbal fluency task. Our findings support the hypothesis that reduced language lateralization may represent a biological marker across different psychotic disorders and that the altered language network connectivity found at rest in bipolar patients is stable and pervasive as it is also impaired during a verbal fluency task.

Dynamic functional hippocampal markers of residual depressive symptoms in euthymic bipolar disorder.

Bipolar disorder (BD) is a severe, chronic, affective disorder characterized by recurrent switching between mood states, psychomotor and cognitive symptoms, which can linger in euthymic states as residual symptoms. Hippocampal alterations may play a key role in the neural processing of BD symptoms. However, its dynamic functional connectivity (dFC) remains unclear. Therefore, the present study explores hippocampal dFC in relation to BD symptoms. We assessed hippocampus-based dFC coactivation patterns (CAPs) on resting-state fMRI data of 25 euthymic BD patients and 25 age- and sex-matched healthy controls (HC). Bilateral hippocampal dFC with somatomotor networks (SMN) was reduced in BD, compared to HC, while at the same time dFC between the left hippocampus and midcingulo-insular salience system (SN) was higher in BD. Correlational analysis between CAPs and clinical scores revealed that dFC between the bilateral hippocampus and the default-like network (DMN) correlated with depression scores in BD. Furthermore, pathological hyperconnectivity between the default mode network (DMN) and SMN and the frontoparietal network (FPN) was modulated by the same depression scores in BD. Overall, we observed alterations of large-scale functional brain networks associated with decreased flexibility in cognitive control, salience detection, and emotion processing in BD. Additionally, the present study provides new insights on the neural architecture underlying a self-centered perspective on the environment in BD patients. dFC markers may improve detection, treatment, and follow-up of BD patients and of disabling residual depressive symptoms in particular.

Comparison of Behavioral Addictions Between Euthymic Bipolar Disorder Patients and Healthy Volunteers

Comparison of Behavioral Addictions Between Euthymic Bipolar Disorder Patients and Healthy Volunteers

Aggression and its association with childhood trauma in euthymic bipolar disorder patients

IntroductionAggression and negative behaviours are used to be present in individuals with bipolar disorder, who are sensitive to life events. Thus, many studies investigated the emergence of impulsivity and aggression in the developmental process and revealed its relationship with childhood adversities.ObjectivesThe aim of this study was to determine the relationship between childhood trauma and aggressive behaviour in euthymic patients with bipolar disorder.MethodsIt was a cross-sectional descriptive and analytical study involving patients diagnosed with bipolar disorder and followed in the psychiatric department at the University Hospital ofSfax (Tunisia).All subjects completed the Childhood trauma questionnaire (CTQ) and the Buss–Perry Aggression Scale (BPAS). Euthymiawas defined as a score on the Montgomery-Åsberg Depression Rating Scale (MADRS) not higher than 14 and by a score on theYoung Mania Rating Scale (YMRS)not higher than seven.ResultsWe included 35 patients. Their mean age was 46.69 ± 12.01 years with a sex ratio (M/F) =0.45. Most of them lived in urban areas (91.42%) and had a moderate socioeconomic level(88.57%).The most frequent trauma type was physical neglect with 74.28%, followed by emotional abuse (42.85%), emotional neglect (42.85%), physical abuse (37.14%) and sexual abuse (31.42%).The mean score of CTQ was 58.57 ±9.51. Theaverage total score of BPAS was 82.26 ±14.57.The mean scores of subscales of BPAS were 25.49±4.59 for physical aggression, 13.74±3.51for verbal aggression, 19.14±6.22 for anger and 23.89±5.57 for hostility.A statistically significant and positive correlation was determined between CTQ and BPAS (p=0.011). The score of BPAS was significantly correlated with physical abuse (p=0.003) and physical neglect (p=0.014).Conclusions The relationship between CTQ and BGHA scores suggests the possibility that childhood trauma may be one determinant of aggression in patients with bipolar disorder. Considering the childhood trauma history in the evaluation of these patients may prevent their aggression and thus their psychosocial functioning.Disclosure of InterestNone Declared

Altered intrinsic brain activity and cognitive impairment in euthymic, unmedicated individuals with bipolar disorder.

Cognitive impairment in euthymic bipolar disorder (BD) contributes to poor functional outcomes. Resting-state magnetic resonance imaging (MRI)may help us understand the neurobiology of cognitive impairment in BD. Here, forty unmedicated euthymic BD patients and thirty-nine healthy controls were recruited, undergoing MRI scans and neuropsychological measures. The amplitude of low-frequency fluctuation (ALFF) and ALFF-based functional connectivity (FC) analysis was employed to explore the potential alterations of neural activity. Voxel-wised correlation was calculated between clinical and cognitive variables and abnormal brain activity. Compared with healthy controls, euthymic BD patients showed worse cognitive performance in Trail Making Test, Digit Span Test, and Stroop Color-Word Test (SCWT). The euthymic BD group had significantly lower ALFF in the left medial frontal gyrus, right middle frontal gyrus, right postcentral gyrus, and left superior frontal gyrus. Furthermore, we found decreased ALFF values in the right middle frontal gyrus that was negatively correlated with cognitive inhibition, (r=-0.43, P=0.015). ALFF-based FC analysis showed that BD group showed significantly decreased FC between the right middle frontal gyrus (seed) and left middle temporal gyrus and left medial frontal gyrus, (Two-tailed, PFWE < 0.05, TFCE corrected). The findings demonstrated that individuals with BD during the euthymic phase exhibited decreased ALFF and hypoconnectivity of key brain areas within the frontoparietal network. These altered spontaneous brain activity in euthymic BD patients may be involved in the pathophysiology mechanism of cognitive deficits.

Correlates of neurological soft signs in bipolar disorder.

Recent research has focused on neurological soft signs (NSS) in bipolar disorder (BD), but there is still scarce evidence on their correlates with other relevant variables. The aim of this study was to explore the association between NSS and clinical demographic, neurocognitive, and functional variables. Eighty-eight euthymic BD patients were included in whom NSS were assessed using the Neurological Evaluation Scale. All subjects performed an extensive neurocognitive battery selected to assess premorbid IQ, attention, language, verbal memory, and executive functions. Psychosocial outcomes were assessed by means of the Functioning Assessment Short Test. Among the demographical variables, NSS tended to be negatively associated with years of education and increased with age. Likewise, NSS were higher in BD type I than in BD type II, but independent of age at illness onset and number of previous affective episodes. There was a negative correlation between NSS and premorbid IQ, as well as with performance in attention, language, and executive functions. Results tended to be unchanged when controlled for potential confounders. Although NSS were associated with poor psychosocial functioning in the bivariate analysis, when added to a multiple regression model including neurocognition, these neurological features did not significantly contribute to the variance of the functional outcome. Our findings contribute to a better characterization of NSS in BD; their potential clinical and theoretical implications are discussed in the manuscript.

Predominant polarity as a neurobiological specifier in bipolar disorder: Evidence from a multimodal neuroimaging study

BackgroundWhile predominant (PP) and onset polarity (OP) have considerable clinical and treatment implications in bipolar disorder (BD), the neurobiological underpinnings of PP and OP from a radiological perspective remain largely unknown. The main objective of this study is to investigate the neuroanatomical profile of polarity subphenotypes (PP and OP) in euthymic BD patients, using a standardized multimodal neuroimaging protocol to evaluate regional gray matter (GM) volumes, cortical thickness, as well as white matter (WM) integrity of major projection, commissural and association tracts. MethodsForty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this computational neuroimaging study to comprehensively characterize gray and white matter alterations. Univariate analyses of covariance (ANCOVAs) were conducted with Bonferroni corrections for each MRI modality and Cohen's d effect sizes were calculated for group comparisons. ResultsPhenotype-associated cortical thickness abnormalities and volumetric alterations were identified, but no WM changes ascertained. Specifically, we found a main effect of OP on GM volume of left middle frontal gyrus and of OP and PP (either or both) on cortical thickness of various regions previously implicated in BD, i.e. inferior frontal gyrus-pars opercularis (left) and pars orbitalis (bilateral), left lateral orbitofrontal gyrus, bilateral medial segment of the superior frontal gyrus, left planum polare, right anterior cingulate gyrus, left anterior and posterior insula, bilateral frontal operculum (both OP and PP); left anterior and posterior orbitofrontal gyrus, left transverse temporal gyrus, right posterior insula (only OP); and right medial frontal cortex (only PP). Based on the magnitude of differences on pairwise comparisons, we found a large effect of OP on cortical thickness in a single region (left anterior orbitofrontal gyrus) (OP-M > OP-D), while PP subgroups showed large or medium effect size differences in cortical thickness (PP-M > PP-D) in a wider array of regions (right medial frontal cortex, left frontal operculum, left inferior frontal gyrus-pars opercularis, bilateral medial segment of the superior frontal gyrus). For most regions, PP-D patients showed the greatest decreases in cortical thickness compared to HC while PP-M showed the smallest, with PP-U showing an “unspecified” pattern mostly lying in-between PP-D and PP-M. ConclusionsOur multimodal imaging findings suggest specific polarity BD subgroups with compromised cortical thickness; we recorded a greater impact of PP on brain structure compared to OP, which provides additional evidence that PP can be considered as a neurobiological specifier in BD.

Disrupted network switching in euthymic bipolar disorder: Working memory and self-referential paradigms

BackgroundPatients with bipolar disorder (BD) frequently suffer from neurocognitive deficits that can persist during periods of clinical stability. Specifically, impairments in executive functioning such as working memory and in self-processing have been identified as the main components of the neurocognitive profile observed in euthymic BD patients. The study of the neurobiological correlates of these state-independent alterations may be a prerequisite to develop reliable biomarkers in BD. MethodsA sample of 27 euthymic BD patients and 25 healthy participants (HC) completed working memory and self-referential functional Magnetic Resonance Imaging (fMRI) tasks. Activation maps obtained for each group and contrast images (i.e., 2-back > 1-back/self > control) were used for comparisons between patients and HC. ResultsEuthymic BD patients, in comparison to HC, showed a higher ventromedial prefrontal cortex activation during working memory, a result driven by the lack of deactivation in BD patients. In addition, euthymic BD patients displayed a greater dorsomedial and dorsolateral prefrontal cortex activation during self-reference processing. LimitationsPharmacotherapy was described but not included as a confounder in our models. Sample size was modest. ConclusionOur findings revealed a lack of deactivation in the anterior default mode network (aDMN) during a working memory task, a finding consistent with prior research in BD patients, but also a higher activation in frontal regions within the central executive network (CEN) during self-processing. These results suggest that an imbalance of neural network dynamics underlying external/internal oriented cognition (the CEN and the aDMN, respectively) may be one of the first reliable biomarkers in euthymic bipolar patients.

Deep neural network to differentiate brain activity between patients with euthymic bipolar disorders and healthy controls during verbal fluency performance: A multichannel near-infrared spectroscopy study

In this study, we aimed to differentiate between euthymic bipolar disorder (BD) patients and healthy controls (HC) based on frontal activity measured by fNIRS that were converted to spectrograms with Convolutional Neural Networks (CNN). And also, we investigated brain regions that cause this distinction. In total, 29 BD patients and 28 HCs were recruited. Their brain cortical activities were measured using fNIRS while performing letter versions of VFT. Each one of the 24 fNIRS channels was converted to a 2D spectrogram on which a CNN architecture was designed and utilized for classification. We found that our CNN algorithm using fNIRS activity during a VFT is able to differentiate subjects with BD from healthy controls with 90% accuracy, 80% sensitivity, and 100% specificity. Moreover, validation performance reached an AUC of 94%. From our individual channel analyses, we observed channels corresponding to the left inferior frontal gyrus (left-IFC), medial frontal cortex (MFC), right dorsolateral prefrontal cortex (DLPFC), Broca area, and right premotor have considerable activity variation to distinguish patients from HC. fNIRS activity during VFT can be used as a potential marker to classify euthymic BD patients from HCs. Activity particularly in the MFC, left-IFC, Broca's area, and DLPFC have a considerable variation to distinguish patients from healthy controls.

Sleep disturbances in the context of neurohormonal dysregulation in patients with bipolar disorder

BackgroundSleep dysfunction is a core symptom in bipolar disorder (BD), especially during major mood episodes. This study investigated the possible link between subjective and objective sleep disturbances in inter-episode BD, changes in melatonin and cortisol levels, and circadian melatonin alignment. The study included 21 euthymic BD patients and 24 healthy controls. Participants had to wear an actigraphy device, keep a weekly sleep diary and take salivary samples: five samples on the last evening to determine the dim light melatonin onset (DLMO) and one the following morning to measure rising cortisol. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and Regensburg Insomnia Scale (RIS), and circadian alignment by the phase angle difference (PAD).ResultsIn comparison to healthy controls, BD patients had: (1) higher PSQI (5.52 ± 3.14 vs. 3.63 ± 2.18; p = 0.022) (significant after controlling for age and gender), and higher RIS scores (8.91 ± 5.43 vs. 5.83 ± 3.76; p = 0.031); (2) subjective a longer mean TST (p = 0.024) and TIB (p = 0.002) (both significant after controlling for age and gender), longer WASO (p = 0.019), and worse SE (p = 0.036) (significant after controlling for gender); (3) actigraphically validated earlier sleep onset (p = 0.002), less variation in sleep onset time (p = 0.005) and no longer TST (p = 0.176); (4) no differing melatonin levels (4.06 ± 2.77 vs. 3.35 ± 2.23 p = 0.352), an 1.65 h earlier DLMO (20.17 ± 1.63 vs. 21.82 ± 1.50; p = 0. 001) (significant after controlling for gender), and a phase advance of melatonin (6.35 ± 1.40 vs. 7.48 ± 1.53; p = 0.017) (significant after controlling for gender); and (5) no differing cortisol awakening response (16.97 ± 10.22 vs 17.06 ± 5.37 p = 0.969).ConclusionsPatients with BD, even in euthymic phase, have a significantly worse perception of their sleep. Advanced sleep phases in BD might be worth further investigation and could help to explain the therapeutic effects of mood stabilizers such as lithium and valproate.

Temperament and character dimensions as psychological markers of mood disorders in Polish adolescents and young adults-A prospective study.

An increasing incidence of mood disorders in adolescents and young adults is being observed. The assessment of personality traits seems to be an interesting tool in identifying early markers of major depression (MD) or bipolar disorder (BD) as well as predictors of the course of the disease. The aim of this study was to compare the personality profiles in young patients with MD and BD in acute and remitted mood states. Seventy-nine adolescents and young adults with mood disorder diagnoses (MD or BD) were included in the study. The participants were assessed based on structured diagnostic interviews and completed the Temperament and Character Inventory (TCI). The clinical evaluation was conducted during the acute episodes and after reaching the stabilized mood in the course of follow-up visits in a 2-year study observation. At baseline, MD patients had higher scores on the harm avoidance (HA) with more pronounced anticipatory worry and fatigability subscale than BD patients. Conversely, BD patients reached higher scores in the total self-directedness (SD) character dimension and its sub-dimensions. MD patients with acute depressive symptoms had higher scores in the HA dimension and its subscale: anticipatory worry, shyness, and fatigability compared with their euthymic states. No significant differences in TCI dimensions between baseline and euthymia in the BD subgroup were found, and no differences between euthymic MD and BD patients. Higher ST and SD sub-dimensions may constitute a personality profile specific to BD, while high HA seems to be related to major depression in both acute and remitted states in young patients.

Characterisation of Deficits and Sex Differences in Verbal and Visual Memory/Learning in Bipolar Disorder.

Cognitive impairment is consistently reported in bipolar disorder (BD), but few studies have characterised which memory component processes are affected. Further, it is unknown whether the component processes underlying memory impairment are moderated by sex. The present study examined diagnosis and sex differences in both verbal and visual memory/learning domains in patients with BD and psychiatrically healthy controls. Verbal and visual memory/learning were measured using the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R). 114 patients with BD (n = 50 males, n = 64 females), were compared to 105 psychiatrically healthy controls (n = 42 males, n = 63 females). Patients with BD had worse performance in verbal and visual immediate and total recall, verbal and visual delayed free recall, and verbal recognition discrimination scores, but there were no group differences in learning slopes and cumulative learning index scores. There were trends for BD females to outperform BD males in visual memory/learning free recall and cumulative learning, but these results did not survive multiple testing correction. These findings did not change in a secondary sensitivity analysis comparing only strictly euthymic BD patients to controls (n = 64). The present study found trait-like verbal and visual memory/learning impairment in BD that was attributable to deficient encoding and/or consolidation processes rather than deficits in learning. We did not find marked sex differences in either visual or verbal memory/learning measures, although some trend level effects were apparent and deserve exploration in future studies.

Altered task-modulated functional connectivity during emotional face processing in euthymic bipolar patients: A whole-brain psychophysiological interaction study

BackgroundPatients with bipolar disorder (BD) show deficits of facial emotion processing even in the euthymic phase. However, the large-scale functional brain network mechanism underlying the emotional deficit of BD remains unclear. Specifically, it is of importance to understand how the task-modulated functional connectivity (FC) was alternated over distributed brain networks in BD. MethodsIn this study, we analyzed functional MRI data of a face-matching task from 29 euthymic BD patients and 29 healthy controls (HC), and performed whole-brain psychophysiological interaction (PPI) analysis to obtain task-modulated FC. Abnormal FC patterns were identified through support vector machine-based classification. The topological organization of task-modulated FC networks was estimated by the graph theoretical analysis and compared between BD and HC. ResultsBD exhibited widely distributed aberrant task-modulated FC patterns not only in core neurocognitive intrinsic brain networks (the fronto-parietal, cingulo-opercular, and default mode networks), but also in the cerebellum and primary processing networks (sensorimotor and visual). Furthermore, the local efficiency of the frontal-parietal network was significantly increased in BD. LimitationsThe modest sample size. Only face pictures with negative emotion were used. Only unidirectional task-modulated FC was investigated. ConclusionsBD patients showed a widely distributed aberrant task-modulated FC pattern. Particularly, the fronto-parietal network, as one of the core neurocognitive intrinsic brain networks, was the primary network that demonstrated changes of both FC strength and local efficiency in BD. These findings on the task-modulated FC between these intrinsic brain networks might be considered an endophenotype of the BD condition persistent in the euthymic state.

The Relationship between Cognition and Asymmetric Dimethyl Arginine, Symmetric Dimethyl Arginine, Nitric Oxide Levels and Total Antioxidant Capacity in Euthymic Bipolar Disorder Patients

The Relationship between Cognition and Asymmetric Dimethyl Arginine, Symmetric Dimethyl Arginine, Nitric Oxide Levels and Total Antioxidant Capacity in Euthymic Bipolar Disorder Patients

Default-mode and fronto-parietal network connectivity during rest distinguishes asymptomatic patients with bipolar disorder and major depressive disorder

Bipolar disorder (BD) is commonly misdiagnosed as major depressive disorder (MDD). This is understandable, as depression often precedes mania and is otherwise indistinguishable in both. It is therefore imperative to identify neural mechanisms that can differentiate the two disorders. Interrogating resting brain neural activity may reveal core distinguishing abnormalities. We adopted an a priori approach, examining three key networks documented in previous mood disorder literature subserving executive function, salience and rumination that may differentiate euthymic BD and MDD patients. Thirty-eight patients with BD, 39 patients with MDD matched for depression severity, and 39 age-gender matched healthy controls, completed resting-state fMRI scans. Seed-based and data-driven Independent Component analyses (ICA) were implemented to examine group differences in resting-state connectivity (pFDR < 0.05). Seed analysis masks were target regions identified from the fronto-parietal (FPN), salience (SN) and default-mode (DMN) networks. Seed-based analyses identified significantly greater connectivity between the subgenual cingulate cortex (DMN) and right dorsolateral prefrontal cortex (FPN) in BD relative to MDD and controls. The ICA analyses also found greater connectivity between the DMN and inferior frontal gyrus, an FPN region in BD relative to MDD. There were also significant group differences across the three networks in both clinical groups relative to controls. Altered DMN–FPN functional connectivity is thought to underlie deficits in the processing, management and regulation of affective stimuli. Our results suggest that connectivity between these networks could potentially distinguish the two disorders and could be a possible trait mechanism in BD persisting even in the absence of symptoms.