Processing In Bipolar Disorder Research Articles

Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder

BackgroundElucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD. MethodsPositron emission tomography (PET) with [18F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25). ResultsConsistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r≥0.904, p≤0.005) and attention (r≥0.809, p≤0.028). LimitationsThe modest sample size is the primary limitation. ConclusionsDeficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights.

Concentration of HSPA1A and transthyretin proteins in the blood serum of patients with bipolar disorder

IntroductionInsufficient knowledge about the pathophysiological processes in bipolar disorder (BD) leads to difficulties in differentiating this disorder from other affective disorders. Quantitative analysis of serum protein profiles in BD expands our understanding of the pathophysiology of the disease and may aid in subsequent diagnosis. As a result of a previously conducted comparative mass spectrometric study of serum proteins in patients with depression, bipolar disorder and healthy donors, increased expression of Heat Shock 70kDa Protein1A (HSPA1A) and transthyretin was identified.ObjectivesDetermination of HSPA1A and transthyretin concentrations in the blood serum of patients with mental disorders.MethodsBlood serum of 28 patients with bipolar disorder aged 49 years [33;52], 30 patients with recurrent depressive disorder aged 40 years [31; 51] and 130 patients with schizophrenia aged 38 years [31;49], as well as 20 mentally and somatically healthy individuals aged 35 years [31;40] was studied. The amount of Heat shock protein 1A (HSPA1A) and Transthyretin (thyroxine and retinol transport protein) was determined using a Enzyme-linked Immunosorbent Assay Kit from Homo sapiens (Cloud-Clone Corp). Statistical data processing was carried out in the Statistica 12.0 program.ResultsA statistically significant (p = 0.016) increase in the level of HSPA1A was found in patients with BD (0.84 [0.59; 1.09] ng/ml), compared with healthy individuals (0.61 [0.51; 0.77] ng/ml). HSPA1A plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins. It is known that this protein is involved in the embryonic development of the central nervous system, as well as in neuroprotection by preventing the death of neurons due to its anti-apoptotic properties. A statistically significant (p = 0.047) increase in the level of transthyretin was found in patients with BD 21.8 рg/ml, compared with healthy individuals 19.4 pg/ml. Transthyretin plays an important role in ensuring the normal state of the central nervous system and is involved in cognitive processes.ConclusionsThus, the HSPA1A and transthyretin are probably involved in the pathogenesis of BD and can be proposed as be proposed as an additional paraclinical criterion for differential diagnosis.Support by RSF №23-75-00023.Disclosure of InterestNone Declared

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.

Neurodegenerative Processes in Bipolar Disorder

Neurodegenerative Processes in Bipolar Disorder

Ferritin as a potential disease marker in patients with bipolar disorder

BackgroundLow-grade inflammation and oxidative stress have been implicated as potential pathophysiological processes in bipolar disorder, but the underlying mechanism is unknown. Ferritin is a marker of iron stores and involved in redox processes and inflammation but its role in bipolar disorder is unclear. MethodsWe investigated the possible association of increased plasma ferritin levels and bipolar disorder. We pooled two studies using similar longitudinal repeated measures designs and included 330 blood- and urinary samples from 95 patients with bipolar disorder across all affective states and 84 samples from 84 healthy control individuals. Plasma ferritin was measured along with multiple blood inflammatory markers and urinary markers of oxidatively generated damage to DNA and RNA. ResultsPlasma ferritin levels, adjusting for multiple demographical- and lifestyle variables, did not differ between patients with bipolar disorder compared with healthy control individuals (b = 1.09, 95 % CI: 0.86 to 1.39, p = 0.49). Within patients with bipolar disorder ferritin levels were higher in a depressed state compared with euthymia (b = 1.12, 95 % CI: 1.01 to 1.24, p < 0.04), and ferritin levels were positively associated with Interleukin-18 blood levels and urinary levels of 8-oxodG. LimitationsPatients with bipolar disorder received medication which could potentially influence iron metabolism. ConclusionElevated ferritin levels in depressed patients with bipolar disorder may point to a role for iron metabolism in bipolar disorder pathophysiology, and potentially as a biomarker, linking low-grade inflammation with redox biology and the well-known increased risk of medical comorbidity and reduced life expectancy.

Reductions in regional theta power and fronto-parietal theta-gamma phase-amplitude coupling during gaze processing in bipolar disorder

Impaired social cognition is common in bipolar disorder (BD) and predicts poor functional outcomes. A critical determinant of social cognition is the ability to discriminate others’ gaze direction, and its alteration may contribute to functional impairment in BD. However, the neural mechanisms underlying gaze processing in BD are unclear. Because neural oscillations are crucial neurobiological mechanisms supporting cognition, we aimed to understand their role in gaze processing in BD. Using electroencephalography (EEG) data recorded during a gaze discrimination task for 38 BD and 34 controls (HC), we examined: theta and gamma power over bilateral posterior and midline anterior locations associated with early face processing and higher-level cognitive processing, and theta-gamma phase-amplitude coupling (PAC) between locations. Compared to HC, BD showed reduced midline-anterior and left-posterior theta power, and diminished bottom-up/top-down theta-gamma PAC between anterior/posterior sites. Reduced theta power and theta-gamma PAC related to slower response times. These findings suggest that altered theta oscillations and anterior-posterior cross-frequency coupling between areas associated with higher-level cognition and early face processing may underlie impaired gaze processing in BD. This is a crucial step towards translational research that may inform novel social cognitive interventions (e.g., neuromodulation to target specific oscillatory dynamics) to improve functioning in BD.

The Atypical Emotional Processing in Bipolar Disorder and Relevant Interventions

Individuals with bipolar disorder (BD) demonstrate impaired functioning including cognitive deficits, neurological damage, and psychosocial dysfunction. Atypical emotional processing, the lack of normal functioning in identifying human emotions, is one of the most significant impairments observed in individuals with BD. Such abnormal emotional processing has different causes. Deficits in emotion perception and recognition can contribute to the impaired social functioning in separation or in combination, which can further impede social functioning. Both facial emotion recognition deficits (FERD) and alexithymia are proven to be powerful predictors of BD development. Relevant interventions including Mindfulness-Based Cognitive Therapy for Children (MBCT-C), Dialectical Behavior Therapy (DBT), and Positive emotion regulation (PRE) intervention are verified to be effective in treatment for BD patients with deficits in emotional processing. By examining recent literature, this review encapsulates the relationships between atypical emotion recognition and perception and impaired social functioning, the relationship between deficits in emotional processing and BD symptoms, and efficacy of the interventions focusing on mindfulness, presenting a more comprehensive understanding in this area. It can provide some guidance to the prevention and intervention studies and practices for at-risk adolescents.

Impaired Self-Referential Cognitive Processing in Bipolar Disorder: A Functional Connectivity Analysis

Patients with bipolar disorder have deficits in self-referenced information. The brain functional connectivity during social cognitive processing in bipolar disorder is unclear. Electroencephalogram (EEG) was recorded in 23 patients with bipolar disorder and 19 healthy comparison subjects. We analyzed the time-frequency distribution of EEG power for each electrode associated with self, other, and font reflection conditions and used the phase lag index to characterize the functional connectivity between electrode pairs for 4 frequency bands. Then, the network properties were assessed by graph theoretic analysis. The results showed that bipolar disorder induced a weaker response power and phase lag index values over the whole brain in both self and other reflection conditions. Moreover, the characteristic path length was increased in patients during self-reflection processing, whereas the global efficiency and the node degree were decreased. In addition, when discriminating patients from normal controls, we found that the classification accuracy was high. These results suggest that patients have impeded integration of attention, memory, and other resources of the whole brain, resulting in a deficit of efficiency and ability in self-referential processing.

Combined influence of medication and symptom severity on visual processing in bipolar disorder

Previous studies have reported visual impairments in patients with bipolar disorder (BPD), but unclear were whether clinical variables would be associated with those disturbances. Here, we investigate the relationship between visual functioning, in terms of color discrimination, and the impact of BPD duration, mood state, and the patients' medication. Forty-five participants (25–45 years old) were recruited for this study. Color discrimination was performed using the Cambridge Colour Test. Serial multiple mediations were run to investigate the assumption of association between color discrimination and the clinical variables. Our findings showed that, compared with healthy controls, BPD patients' performance was worse for the Protan, Deutan, and Tritan vectors, revealing deterioration of color discrimination. In addition, the mediation analyses revealed a strong direct (p < .001) and moderate-to-high indirect effects (p < .01) of medication and symptom severity on color discrimination. Overall, both longer the duration of the disease and greater the symptom severity of BPD patients resulted in worse performance. It highlights the importance of examining the wider clinical context of an affective disorder to understand how it affects visual processing in this population.

Facial processing in bipolar disorder is mediated by clinical and biological aspects.

The process of detecting faces can be considered one of the initial steps in face recognition, which is essential for human interaction. We sought to investigate whether a face perception task reliably detects subtle perceptual disturbances between patients with bipolar disorder (BD) and healthy controls. In this multisite study, we examined differences between BD patients and matched healthy controls. Participants were instructed to detect the orientation (either left or right) of a face when it was presented as a face/non-face pair on a computer screen using Bayesian entropy estimation. Data analyses compared performance between the groups. Overall, BD patients exhibited more perceptual disturbances compared with controls. BD patients who took olanzapine had better performance and faster reaction times (RTs) than patients who took lithium or were medication-naive. BD patients who took lithium had better performance and faster RTs than medication-naive patients. The medication-naive BD group exhibited greater disturbances than all other groups. These findings highlight the reliability of the face perception task used herein and may be important for public health initiatives and follow-up studies that seek to understand the diverse effects of other variables that can affect sensory processing in this population.

Gray matter volume covariance networks are associated with altered emotional processing in bipolar disorder: a source-based morphometry study

Widespread regional gray matter volume (GMV) alterations have been reported in bipolar disorder (BD). Structural networks, which are thought to better reflect the complex multivariate organization of the brain, and their clinical and psychological function have not been investigated yet in BD. 24 patients with BD type-I (BD-I), and 30 with BD type-II (BD-II), and 45 controls underwent MRI scan. Voxel-based morphometry and source-based morphometry (SBM) were performed to extract structural covariation patterns of GMV. SBM components associated with morphometric differences were compared among diagnoses. Executive function and emotional processing correlated with morphometric characteristics. Compared to controls, BD-I showed reduced GMV in the temporo-insular-parieto-occipital cortex and in the culmen. An SBM component spanning the prefrontal-temporal-occipital network exhibited significantly lower GMV in BD-I compared to controls, but not between the other groups. The structural network covariance in BD-I was associated with the number of previous manic episodes and with worse executive performance. Compared to BD-II, BD-I showed a loss of GMV in the temporal-occipital regions, and this was correlated with impaired emotional processing. Altered prefrontal-temporal-occipital network structure could reflect a neural signature associated with visuospatial processing and problem-solving impairments as well as emotional processing and illness severity in BD-I.

Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder.

The etiopathology of bipolar disorder is largely unknown. We collected cerebrospinal fluid (CSF) samples from two independent case-control cohorts (total n = 351) to identify proteins associated with bipolar disorder. A panel of 92 proteins targeted towards central nervous system processes identified two proteins that replicated across the cohorts: the CSF concentrations of testican-1 were lower, and the CSF concentrations of C-type lectin domain family 1 member B (CLEC1B) were higher, in cases than controls. In a restricted subgroup analysis, we compared only bipolar type 1 with controls and identified two additional proteins that replicated in both cohorts: draxin and tumor necrosis factor receptor superfamily member 21 (TNFRSF21), both lower in cases than controls. This analysis additionally revealed several proteins significantly associated with bipolar type 1 in one cohort, falling just short of replicated statistical significance in the other (tenascin-R, disintegrin and metalloproteinase domain-containing protein 23, cell adhesion molecule 3, RGM domain family member B, plexin-B1, and brorin). Next, we conducted genome-wide association analyses of the case-control-associated proteins. In these analyses, we found associations with the voltage-gated calcium channel subunit CACNG4, and the lipid-droplet-associated gene PLIN5 with CSF concentrations of TNFRSF21 and CLEC1B, respectively. The reported proteins are involved in neuronal cell-cell and cell-matrix interactions, particularly in the developing brain, and in pathways of importance for lithium's mechanism of action. In summary, we report four novel CSF protein associations with bipolar disorder that replicated in two independent case-control cohorts, shedding new light on the central nervous system processes implicated in bipolar disorder.

Relation between smoking and visual processing in bipolar disorder

Background: Although some studies have shown impairments in patients with bipolar disorder (BPD) and in smokers, it is unclear how these two factors work together. Our premise was that chronic smoking affects color discrimination and this is more pronounced in BPD. Objective: Our main purpose was to investigate the influence of smoking and BPD on color discrimination. Methods: Twenty-three smokers and 23 BPD smokers patients, aged 25–45 years old, participated in this study. Color vision testing was performed using the Trivector subtest of the Cambridge Colour Test. Participants’ task was to indicate the pseudoisochromatic stimulus in four directions (up, down, right, and left). Results: It was shown that the smokers had better color vision than BPD smokers for the Protan (p < .001), Deutan (p < .001), and Tritan (p < .001) (red, green, and blue, respectively) axes. Thus, the BPD smokers’ group had greater difficulty distinguishing the chromaticity variations (i.e., presented diffuse color vision impairments and not specific to any axis). Conclusions: The present study highlights a possible relationship between smoking and BPD in color discrimination. This highlights the importance of understanding the diffuse effects of this relationship.

Neural Functional Connectivity During Emotional Processing in Bipolar Disorder: Relations With Coping Drinking Motives and Alcohol Use

Neural Functional Connectivity During Emotional Processing in Bipolar Disorder: Relations With Coping Drinking Motives and Alcohol Use

Disturbances of Dynamic Function in Patients With Bipolar Disorder I and Its Relationship With Executive-Function Deficit.

Abnormity in brain regional function and inter-regional cooperation have been linked with the dysfunction during cognitive and emotional processing in bipolar disorder (BD) patients. Recent evidences have suggested that brain function is not static but temporal dynamic. In present study, we aimed to characterize the temporal dynamics of regional function and inter-regional cooperation in BD and its relationship with executive dysfunction, an important deficit in BD. Resting-state functional MRI was performed in patients with bipolar I disorder (BDI) (n = 18) and healthy controls (HCs, n = 19). We first assessed local-function temporal variety with dynamic amplitude of low-frequency fluctuation (dALFF). Region with significant inter-groups difference in dALFF was chosen as a seed to calculate inter-regions connective temporal variety with dynamic functional connectivity (dFC). The executive function was measured by Verbal Fluency Test (VFT). The relationship between executive function and brain dynamics were examined. Compared with HC, the BDI group showed decreased dALFF (less temporal variability) in the posterior cingulate cortex (PCC) and decreased dFC between PCC and medial prefrontal cortex (mPFC). The PCC-mPFC dFC was positively associated with VFT in BDI patients, but not in HC. These findings implicated the reduced temporal variability in local region and inter-regions cooperation in BDI, which may be a neural substrate of executive-function deficit in BDI.

Electrophysiological correlates of emotional scene processing in bipolar disorder

Emotional dysfunction is a core feature of bipolar I disorder (BD). Behavioral data suggest that emotional processing may differ based on history of psychosis, but physiological studies frequently disregard this differentiating feature. Face processing studies indicate that emotion-related components of event-related potentials (ERPs) are abnormal in BD, but fMRI data using emotional scenes are mixed. The current study used ERPs to examine emotional scene perception in BD with and without a history of psychosis (BDP, BDNP). 386 participants from the PARDIP consortium (HC = 181, BDP = 130, BDNP = 75) viewed neutral, pleasant, and unpleasant scenes from the International Affective Picture System (IAPS) during continuous EEG recording. The early posterior negativity (EPN) and late positive potential (LPP) were examined for group and stimulus effects. Analyses were conducted for groups on and off medications to examine associations between medication status, psychosis, and ERP response. Group differences were found between HC and BD in emotional modulation of the EPN and between HC and BDP in the LPP to pleasant images. There was a significant interaction between psychosis history and anticonvulsant status in the EPN, but no other medication associations were found. The relationship between neural/self-reported emotional responses and clinical symptoms were examined with canonical correlations, but no significant associations were found. Results from this large well characterized sample indicate mild deviations in neural reactivity related to medication, mood, and psychosis history. However, processing of emotional scenes appears mostly intact in individuals with BD regardless of symptom severity.

Neural responses to monetary incentives in bipolar disorder.

Although behavioral sensitivity to reward predicts the onset and course of mania in bipolar disorder, the evidence for neural abnormalities in reward processing in bipolar disorder is mixed. To probe neural responsiveness to anticipated and received rewards in the context of bipolar disorder, we scanned individuals with remitted bipolar I disorder (n = 24) and well-matched controls (n = 24; matched for age and gender) using Functional Magnetic Resonance Imaging (FMRI) during a Monetary Incentive Delay (MID) task. Relative to controls, the bipolar group showed reduced NAcc activity during anticipation of gains. Across groups, this blunting correlated with individual differences in impulsive responses to positive emotions (Positive Urgency), which statistically accounted for the association of blunted NAcc activity with bipolar diagnosis. These results suggest that blunted NAcc responses during gain anticipation in the context of bipolar disorder may reflect individual differences in Positive Urgency. These findings may help resolve discrepancies in the literature on neural responses to reward in bipolar disorder, and clarify the relationship between brain activity and the propensity to experience manic episodes.

Relationship between Childhood Adversities, Emotion Dysregulation and Cognitive Processes in Bipolar Disorder and Recurrent Depressive Disorder

Cognitive development is susceptible to environmental distress, leading to cognitive distortions. Cognitive distortions may affect clinical course of psychiatric disorders. We aimed to assess whether childhood maltreatment and emotion dysregulation impair automatic thoughts (ATs) and meta-cognitions (MCs) in Bipolar Disorder (BD) and Major Depressive Disorder - Recurrent (MDB-RE) in this study. 85 patients with BD, 81 MDD-RE in remission and 86 healthy participants were enrolled. Automatic Thoughts Scale (ATS), Metacognition Questionnaire (MCQ-30), Childhood Trauma Questionnaire (CTQ- 28), Difficulties in Emotion Regulation Strategies Scale (DERS) were the measures used. ATs were determined by CTQ physical abuse (β=0.34, p<0.01), DERS goals (β=-0.37, p<0.01), impulse (β=0.53, p<0.01) and non-accept (β=0.23, p<0.05) subscales in BD (F=21.08, p<0.01) and CTQ emotional neglect (β=0.22, p<0.05), DERS strategies (β=0.39, p<0.05) in MDD-RE (F=9.97, p<0.05). MCs were predicted by sexual abuse (β=0.46, p<0.01) in BD (F=4.88, p<0.01), and emotional abuse (B=-0.30, p<0.05) in MDD-RE (F= 7.02, p<0.01). These results suggest that emotion dysregulation and childhood adversities are associated with cognitive processes such as MCs and ATs in MDD-RE and BD. Cognitive processes can cause various clinical manifestations and emotion dysregulation and childhood traumas should be considered as psychopathological components that can affect the course of mood disorders via various components. Further follow-up studies and larger samples are needed to better understand the effects of these components.

Medicine and meaning—How experienced therapists describe the role of medication in recovery processes in bipolar disorder

AbstractIntroductionPharmacological interventions are viewed as central to clinical work with people diagnosed with bipolar disorder. But what is the meaning of medicine? How do clinicians view the role of medication in recovery processes in bipolar disorder? The aim of this study was to explore the perspectives of experienced therapists regarding the role of medicine in the treatment of people with bipolar disorder.MethodsIn a Norwegian specialist mental health care setting, we conducted 12 semi‐structured individual interviews with experienced therapists and analysed the resulting transcripts using a team‐based thematic analysis method.FindingsWe identified four themes: (a) the bedrock of therapy; (b) an imperfect answer and a dangerous tool; (c) the hallmark of insight; and (d) negotiating medicine, negotiating meaning.ConclusionWe relate our findings to the shortcomings of the dominant medical model and argue that a recovery perspective can be a helpful tool for counsellors and psychotherapists in understanding the meaning of medicine for people with bipolar disorder.

Characterizing decision-making and reward processing in bipolar disorder: A cluster analysis

The presence of abnormalities in emotional decision-making and reward processing among bipolar patients (BP) has been well rehearsed. These disturbances are not limited to acute phases and are common even during remission. In recent years, the existence of discrete cognitive profiles in this psychiatric population has been replicated. However, emotional decision making and reward processing domains have barely been studied. Therefore, our aim was to explore the existence of different profiles on the aforementioned cognitive dimensions in BP. The sample consisted of 126 euthymic BP. Main sociodemographic, clinical, functioning, and neurocognitive variables were gathered. A hierarchical-clustering technique was used to identify discrete neurocognitive profiles based on the performance in the Iowa Gambling Task. Afterward, the resulting clusters were compared using ANOVA or Chi-squared Test, as appropriate. Evidence for the existence of three different profiles was provided. Cluster 1 was mainly characterized by poor decision ability. Cluster 2 presented the lowest sensitivity to punishment. Finally, cluster 3 presented the best decision-making ability and the highest levels of punishment sensitivity. Comparison between the three clusters indicated that cluster 2 was the most functionally impaired group. The poorest outcomes in attention, executive function domains, and social cognition were also observed within the same group. In conclusion, similarly to that observed in “cold cognitive” domains, our results suggest the existence of three discrete cognitive profiles concerning emotional decision making and reward processing. Amongst all the indexes explored, low punishment sensitivity emerge as a potential correlate of poorer cognitive and functional outcomes in bipolar disorder.