Mood States In Bipolar Disorder Research Articles

Association of circulating monocyte number and monocyte–lymphocyte ratio with cardiovascular disease in patients with bipolar disorder

BackgroundCardiovascular disease (CVD) is the leading cause of excessive and premature mortality in patients with bipolar disorder (BD). Despite immune cells participating considerably in the pathogenesis of CVD, limited data are available regarding leukocyte phenotypes in patients with BD and CVD. This study aimed to evaluate associations between circulating leukocyte subset and CVD among patients with BD.MethodsA total of 109 patients with BD-I and cardiologist-confirmed CVD diagnosis (i.e., case) were matched with 109 BD-I patients without CVD (i.e., control) according to the age (± 2 years), sex, and date of most recent psychiatric admission because of acute mood episode (± 2 years). Leukocyte subset data were retrieved from complete blood count tests performed on the next morning after the most recent acute psychiatric admission.ResultsDuring the most recent acute psychiatric hospitalization, circulating monocyte counts in the case group were significantly higher than those in the age- and sex-matched controls (p = 0.020). In addition, monocyte–lymphocyte ratios (MLRs) in the case group were significantly higher than those in the control group (p = 0.032). Multiple logistic regression showed that together with serum levels of uric acid and manic symptoms, circulating monocyte counts (95% CI, OR: 1.01–1.05) and MLRs (95% CI, OR: 1.01–1.09) were significantly associated with CVD in patients with BD, respectively.ConclusionsMonocyte activation in an acute manic episode may play a critical role in the pathogenesis of CVD among patients with BD. Future research is required to investigate markers of monocyte activation and indices of cardiovascular structure and function across the different mood states of BD.

Functional connectivity of the amygdala subnuclei in various mood states of bipolar disorder.

Amygdala functional dysconnectivity lies at the heart of the pathophysiology of bipolar disorder (BD). Recent preclinical studies suggest that the amygdala is a heterogeneous group of nuclei, whose specific connectivity could drive positive or negative emotional valence. We investigated functional connectivity (FC) changes within these circuits emerging from each amygdala's subdivision in 127 patients with BD in different mood states and 131 healthy controls (HC), who underwent resting-state functional MRI. FC was evaluated between lateral and medial nuclei of amygdalae, and key subcortical regions of the emotion processing network: anterior and posterior parts of the hippocampus, and core and shell parts of the nucleus accumbens. FC was compared across groups, and subgroups of patients depending on their mood states, using linear mixed models. We also tested correlations between FC and depression (MADRS) and mania (YMRS) scores. We found no difference between the whole sample of BD patients vs. HC but a significant correlation between MADRS and right lateral amygdala /right anterior hippocampus, right lateral amygdala/right posterior hippocampus and right lateral amygdala/left anterior hippocampus FC (r = -0.44, r = -0.32, r = -0.27, respectively, all pFDR<0.05). Subgroup analysis revealed decreased right lateral amygdala/right anterior hippocampus and right lateral amygdala/right posterior hippocampus FC in depressed vs. non-depressed patients and increased left medial amygdala/shell part of the left nucleus accumbens FC in manic vs non-manic patients. These results demonstrate that acute mood states in BD concur with FC changes in individual nuclei of the amygdala implicated in distinct emotional valence processing. Overall, our data highlight the importance to consider the amygdala subnuclei separately when studying its FC patterns including patients in distinct homogeneous mood states.

Striatal Functional Alterations Link to Distinct Symptomatology Across Mood States in Bipolar Disorder

BackgroundAs a central hub in cognitive and emotional brain circuits, the striatum is considered likely to be integrally involved in the psychopathology of bipolar disorder (BD). However, it remains unclear how alterations in striatal function contribute to distinct symptomatology of BD during different mood states. MethodsBehavioral assessment (i.e., emotional symptoms and cognitive performance) and neuroimaging data were collected from 125 participants comprising 31 (hypo)manic, 31 depressive, and 31 euthymic patients with BD, and 32 healthy control participants. We compared the functional connectivity (FC) of striatal subregions across BD mood states with healthy control participants and then used a multivariate data-driven approach to explore dimensional associations between striatal connectivity and behavioral performance. Finally, we compared the FC and behavioral composite scores, which reflect the individual weighted representation of the associations, among different mood states. ResultsPatients in all mood states exhibited increased FC between the bilateral ventral rostral putamen and ventrolateral thalamus. Bipolar (hypo)mania uniquely exhibited increased ventral rostral putamen connectivity and superior ventral striatum connectivity. One latent component was identified, whereby increased FCs of striatal subregions were associated with distinct psychopathological symptomatology (more manic symptoms, elevated positive mood, less depressive symptoms, and worse cognitive performance). Patients with bipolar (hypo)mania had the highest FC and behavioral composite scores while bipolar patients with depression had the lowest scores. ConclusionsOur data demonstrated both trait features of BD and state features specific to bipolar (hypo)mania. The findings underscored the fundamental role of the striatum in the pathophysiological processes underlying specific symptomatology across all mood states.

Drug Repurposing and Personalized Treatment Strategies for Bipolar Disorder Using Transcriptomic.

The present study combined transcriptomic data and computational techniques based on gene expression signatures to identify novel bioactive compounds or FDA-approved drugs for the management of Bipolar Disorder (BD). Five transcriptomic datasets, comprising a total of 165 blood samples from BD case-control, were selected from the Gene Expression Omnibus repository (GEO). The number of subjects varied from 6 to 60, with a mean age ranging from 35 to 48, with a gender variation between them. Most of the patients were on pharmacological treatment. Master Regulator Analysis (MRA) and Gene Set Enrichment Analysis (GSEA) were performed to identify statistically significant genes between BD and HC and their association with the mood states of BD. Additionally, existing molecules with the potential to reverse the transcriptomic profiles of disease-altered regulons in BD were identified using the LINCS and cMap databases. MRA identified 59 potential MRs candidates modulating the regulatory units enriched with genes altered in BD, while the GSEA identified 134 enriched genes, and a total of 982 regulons had their activation state determined. Both analyses showed genes exclusively associated with mania, depression, or euthymia, and some genes were common between the three mood states. We identified bioactive compounds and licensed drug candidates, including antihypertensives and antineoplastics, as promising candidates for treating BD. Nevertheless, experimental validation is essential to authenticate these findings in subsequent studies. Although preliminary, our data provides some insights regarding the biological patterns of BD into distinct mood states and potential therapeutic targets. The combined transcriptomic and bioinformatics strategy offers a route to advance drug discovery and personalized medicine by tapping into gene expression information.

Brain functional changes across mood states in bipolar disorder: from a large-scale network perspective.

Exploring the neural basis related to different mood states is a critical issue for understanding the pathophysiology underlying mood switching in bipolar disorder (BD), but research has been scarce and inconsistent. Resting-state functional magnetic resonance imaging data were acquired from 162 patients with BD: 33 (hypo)manic, 64 euthymic, and 65 depressive, and 80 healthy controls (HCs). The differences of large-scale brain network functional connectivity (FC) between the four groups were compared and correlated with clinical characteristics. To validate the generalizability of our findings, we recruited a small longitudinal independent sample of BD patients (n = 11). In addition, we examined topological nodal properties across four groups as exploratory analysis. A specific strengthened pattern of network FC, predominantly involving the default mode network (DMN), was observed in (hypo)manic patients when compared with HCs and bipolar patients in other mood states. Longitudinal observation revealed an increase in several network FCs in patients during (hypo)manic episode. Both samples evidenced an increase in the FC between the DMN and ventral attention network, and between the DMN and limbic network (LN) related to (hypo)mania. The altered network connections were correlated with mania severity and positive affect. Bipolar depressive patients exhibited decreased FC within the LN compared with HCs. The exploratory analysis also revealed an increase in degree in (hypo)manic patients. Our findings identify a distributed pattern of large-scale network disturbances in the unique context of (hypo)mania and thus provide new evidence for our understanding of the neural mechanism of BD.

Intersections of phenomenology, voice beliefs and distress in bipolar disorder: a comparison with schizophrenia.

Auditory verbal hallucinations (AVH), or voice-hearing, can be a prominent symptom during fluctuating mood states in bipolar disorder (BD). The current study aimed to: (i) compare AVH-related distress in BD relative to schizophrenia (SCZ), (ii) examine correlations between phenomenology and voice beliefs across each group, and (iii) explore how voice beliefs may uniquely contribute to distress in BD and SCZ. Participants were recruited from two international sites in Australia (BD=31; SCZ=50) and the UK (BD=17). Basic demographic-clinical information was collected, and mood symptoms were assessed. To document AVH characteristics, a 4-factor model of the Psychotic Symptoms Rating Scale and the Beliefs about Voices Questionnaire-Revised were used. Statistical analyses consisted of group-wise comparisons, Pearson's correlations and multiple hierarchical regressions. It was found that AVH-related distress was not significantly higher in BD than SCZ, but those with BD made significantly more internal attributions for their voices. In the BD group, AVH-related distress was significantly positively correlated with malevolence, omnipotence and resistance, However, only resistance, alongside mania and depressive symptoms, significantly contributed to AVH-related distress in BD. Our findings have several clinical implications, including identification of voice resistance as a potential therapeutic target to prioritise in BD. Factoring in the influence of mood symptoms on AVH-related distress as well as adopting more acceptance-oriented therapies may also be of benefit.

Dynamic time warp analysis of individual symptom trajectories in individuals with bipolar disorder.

Manic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic Time Warp (DTW) is an algorithm that may capture symptom interactions from panel data with sparse observations over time. The Young Mania Rating Scale and Quick Inventory of Depressive Symptomatology were repeatedly assessed in 141 individuals with BD, with on average 5.5 assessments per subject every 3-6 months. Dynamic Time Warp calculated the distance between each of the 27 × 27 pairs of standardized symptom scores. The changing profile of standardized symptom scores of BD participants was analyzed in individual subjects, yielding symptom dimensions in aggregated group-level analyses. Using an asymmetric time-window, symptom changes that preceded other symptom changes (i.e., Granger causality) yielded a directed network. The mean age of the BD participants was 40.1 (SD 13.5) years old, and 60% were female participants. Idiographic symptom networks were highly variable between subjects. Yet, nomothetic analyses showed five symptom dimensions: core (hypo)mania (6 items), dysphoric mania (5 items), lethargy (7 items), somatic/suicidality (6 items), and sleep (3 items). Symptoms of the "Lethargy" dimension showed the highest out-strength, and its changes preceded those of "somatic/suicidality," while changes in "core (hypo)mania" preceded those of "dysphoric mania." Dynamic Time Warp may help to capture meaningful BD symptom interactions from panel data with sparse observations. It may increase insight into the temporal dynamics of symptoms, as those with high out-strength (rather than high in-strength) could be promising targets for intervention.

A comparative meta-analysis of peripheral 8-hydroxy-2′-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) levels across mood episodes in bipolar disorder

ObjectiveOxidative DNA damage has been associated with the pathophysiology of bipolar disorder (BD) as one of the common pathways between increased medical comorbidity and premature aging in BD. Previous evidence shows increased levels of oxidatively induced DNA damage markers, 8-hydroxy-2′-deoxyguanosine (8-OHdG) or its tautomer 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), in patients with BD in comparison to healthy individuals. With the current research, we aim to analyze data on peripheral (blood or urine) 8-OHdG/8-oxo-dG levels across mood states of BD using a meta-analytical approach. MethodA literature search was conducted using the databases PubMed, Scopus, and Web of Science to identify eligible studies (January 1989 to July 2022). Relevant studies were systematically reviewed; a random-effects meta-analysis and a meta-regression analysis were conducted. ResultsThe current meta-analysis included 12 studies consisting of 808 BD patients (390 in euthymia, 156 in mania, 137 in depression, 16 in mixed episode, 109 not specified) and 563 healthy controls. BD patients that were currently depressed had significantly higher levels of 8-OHdG/8-oxo-dG than healthy controls, while euthymic or manic patients did not differ from healthy controls. A meta-regression analysis showed sex distribution (being female) and older age to be significantly related to increased 8-OHdG/8-oxo-dG levels. ConclusionOur findings suggest that 8-OHdG/8-oxo-dG may be a state-related marker of depression in BD and may be affected by older age and female gender.

Mobile-based, emotion-sensitive video diaries and ambulatory third-party assessments as indicators of mood states in bipolar disorder

article: Mobile-based, emotion-sensitive video diaries and ambulatory third-party assessments as indicators of mood states in bipolar disorder - Minerva Psychiatry 2022 December;63(4):407-18 - Minerva Medica - Journals

Complexity and variability analyses of motor activity distinguish mood states in bipolar disorder.

Changes in motor activity are core symptoms of mood episodes in bipolar disorder. The manic state is characterized by increased variance, augmented complexity and irregular circadian rhythmicity when compared to healthy controls. No previous studies have compared mania to euthymia intra-individually in motor activity. The aim of this study was to characterize differences in motor activity when comparing manic patients to their euthymic selves. Motor activity was collected from 16 bipolar inpatients in mania and remission. 24-h recordings and 2-h time series in the morning and evening were analyzed for mean activity, variability and complexity. Lastly, the recordings were analyzed with the similarity graph algorithm and graph theory concepts such as edges, bridges, connected components and cliques. The similarity graph measures fluctuations in activity reasonably comparable to both variability and complexity measures. However, direct comparisons are difficult as most graph measures reveal variability in constricted time windows. Compared to sample entropy, the similarity graph is less sensitive to outliers. The little-understood estimate Bridges is possibly revealing underlying dynamics in the time series. When compared to euthymia, over the duration of approximately one circadian cycle, the manic state presented reduced variability, displayed by decreased standard deviation (p = 0.013) and augmented complexity shown by increased sample entropy (p = 0.025). During mania there were also fewer edges (p = 0.039) and more bridges (p = 0.026). Similar significant changes in variability and complexity were observed in the 2-h morning and evening sequences, mainly in the estimates of the similarity graph algorithm. Finally, augmented complexity was present in morning samples during mania, displayed by increased sample entropy (p = 0.015). In conclusion, the motor activity of mania is characterized by altered complexity and variability when compared within-subject to euthymia.

The Role of Kynurenines in Cognitive Dysfunction in Bipolar Disorder

Introduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway metabolites are key inflammatory mediators, studies investigating the association between KYN metabolism and cognition in BD are scarce. We aimed to explore the relationship between KYN metabolism and cognitive functioning across different mood states in BD. Methods: Sixty-seven patients with BD (35 depressed and 32 [hypo] manic) and 29 healthy controls were included. Cognitive functioning was assessed at 3 time intervals (baseline, 4, and 8 months) assessing processing speed, sustained attention, verbal memory, working memory, and response inhibition. Plasma samples for quantification of 3-hydroxykynurenine, quinolinic acid, and kynurenic acid (KYNA) were concurrently provided. Linear mixed models were used for statistical analysis. Results: The manic group showed deficits in all assessed cognitive domains with the exception of verbal memory at all test moments. The bipolar depression group showed deficits in the processing speed at all test moments. Throughout the whole follow-up period, KYNA was significantly lower in both patient groups than in controls. Only in the bipolar depression group, low KYNA was associated with worse global cognitive functioning (B = 0.114, p = 0.02) and slower processing speed in particular (B = 0.139, p = 0.03). Conclusion: Only in the bipolar depression group, lower KYNA was associated with worse cognitive functioning. Future large-scale longitudinal studies are warranted to confirm the role of KYN metabolites in cognitive impairment in patients with BD and the possible therapeutic implications of this relationship.

The effects of reward and frustration in patients with bipolar disorder: Evidence from a computerized task with non-contingent feedback

Background: Bipolar disorder (BD) is characterized by mood changes that implies alterations in reward sensitivity and frustration tolerance. This study examined the effects of monetary reward and frustration on attentional performance and on affective experience across mood states in BD. Methods: An Affective Posner Task in which the nature of contingencies are divided in the three successive blocks (baseline condition, monetary reward and non-contingent feedback) was applied to BD individuals in their different episodes: mania (n = 30), depression (n = 30), and euthymia (n = 30) as well as to a group of healthy controls (n = 30). Results: Monetary reward improved performance (in terms of faster response times) in the euthymic group and the control group, whereas it impaired performance in the manic group and has not significant effect in the depressed group. In addition, an increased interference of frustration on response accuracy was exhibited in the three groups of BD patients (including euthymia) compared with healthy controls. Limitations: Participants' affective experience was self-informed by a Likert scale, so the reliability of this measure can be undermined in symptomatic patients in terms of stability and objectivity. Although it was statistically controlled, at the time of testing, all BD patients were medicated. Conclusions: A dissociated effect of reward and frustration was found between symptomatic and euthymic states in BD: whereas the benefit from monetary reward is affected only during symptomatic episodes (i.e., a state), the notably increased interference of frustration is exhibited also during euthymia (i.e., a trait).

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

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

Altered dynamic functional connectivity across mood states in bipolar disorder

BackgroundThis study aims to identify how the large-scale brain dynamic functional connectivity (dFC) differs between mood states in bipolar disorder (BD). The authors analyzed dFC in subjects with BD in depressed and euthymic states using resting-state functional magnetic resonance imaging (rsfMRI) data, and compared these states to healthy controls (HCs). Method20 subjects with BD in a depressive episode, 23 euthymic BD subjects, and 31 matched HCs underwent rsfMRI scans. Using an existing parcellation of the whole brain, we measured dFC between brain regions and identified the different patterns of brain network connections between groups. ResultsIn the analysis of whole brain dFC, the connectivity between the left Superior Temporal Gyrus (STG) in the somatomotor network (SMN), the right Middle Temporal Gyrus (MTG) in the default mode network (DMN) and the bilateral Postcentral Gyrus (PoG) in the DMN of depressed BD was greater than that of euthymic BD, while there was no significant difference between euthymic BD and HCs in these brain regions. Euthymic BD patients had abnormalities in the frontal-striatal-thalamic (FST) circuit compared to HCs. ConclusionsDifferences in dFC within and between DMN and SMN can be used to distinguish depressed and euthymic states in bipolar patients. The hyperconnectivity within and between DMN and SMN may be a state feature of depressed BD. The abnormal connectivity of the FST circuit can help identify euthymic BD from HCs.

Traits related to bipolar disorder are associated with an increased post-illumination pupil response

Mood states in bipolar disorder appear to be closely linked to changes in sleep and circadian function. It has been suggested that hypersensitivity of the circadian system to light may be a trait vulnerability for bipolar disorder. Healthy persons with emotional-behavioural traits associated with bipolar disorder also appear to exhibit problems with circadian rhythms, which may be associated with individual differences in light sensitivity. This study investigated the melanopsin-driven post-illumination pupil response (PIPR) in relation to emotional-behavioural traits associated with bipolar disorder (measured with the General Behavior Inventory) in a non-clinical group (n = 61). An increased PIPR was associated with increased bipolar disorder-related traits. Specifically, the hypomania scale of the General Behavior Inventory was associated with an increased post-blue PIPR. Further, both the full hypomania and shortened ‘7 Up’ scales were significantly predicted by PIPR, after age, sex and depressive traits were controlled. These findings suggest that increased sensitivity to light may be a risk factor for mood problems in the general population, and support the idea that hypersensitivity to light is a trait vulnerability for, rather than symptom of, bipolar disorder.

Mitochondrial DNA Copy Number Raises the Potential of Left Frontopolar Hemodynamic Response as a Diagnostic Marker for Distinguishing Bipolar Disorder From Major Depressive Disorder.

Background: Given a lack of markers, diagnoses of bipolar disorder (BD) and major depressive disorder (MDD) rely on clinical assessment of symptoms. However, the depressive mood states of BD and depressive symptoms of MDD are often difficult to distinguish, which leads to misdiagnoses, which in turn leads to inadequate treatment. Previous studies have shown that the hemodynamic responses of the left frontopolar cortex measured by near-infrared spectroscopy (NIRS) differ between BD and MDD; these hemodynamic responses are associated with altered mitochondrial metabolism; and mitochondrial DNA copy number (mtDNAcn), an index of mitochondrial dysfunction, tends to decrease in BD and increase in MDD patients. In this study, we confirmed that mtDNAcn trends in opposite directions in BD and MDD. We then determined whether mtDNAcn could enhance the utility of NIRS as a diagnostic marker to distinguish between BD and MDD. Methods: We determined mtDNAcn in peripheral blood samples from 58 healthy controls, 79 patients with BD, and 44 patients with MDD. Regional hemodynamic responses during a verbal fluency task (VFT) in 24 BD patients and 44 MDD patients, matched by age and depression severity, were monitored using NIRS. Results: Measurements of mtDNAcn were lower in BD patients and higher in MDD patients than in controls. The left frontopolar region exhibited the most significant differences in mean VFT-related oxy-Hb changes between the BD and MDD groups. Multivariate logistic regression analysis with variables including age, sex, hemodynamic response of the left frontopolar region, and mtDNAcn showed high accuracy for distinguishing BD from MDD (area under the curve = 0.917; 95% confidence interval = 0.849–0.985). For the BD group, we observed a positive correlation between hemodynamic responses in the left frontopolar region and mtDNAcn, while for the MDD group, we observed a negative correlation. Conclusions: Our findings suggest that the association between hemodynamic response and mitochondrial dysfunction in BD or MDD plays an important role in differentiating the pathophysiological mechanisms of BD from those of MDD.

Mood as a lock gate canalizing multiple creativity: A heuristic single-case study

BackgroundThe concept of creativity encompasses the ability to produce innovatively original solutions that exceed the status quo. Eminent creatives are frequently afflicted with bipolar disorders, and persons presenting certain forms of bipolar disorder might have enhanced creativity. The link between creativity and bipolar disorder has intrigued researchers but no definite liaison has been established between creativity and mood alterations. MethodsWe address this issue on this perspective by analysing various expression forms of creativity, as well as creative achievement according to the clinically diagnosed mood states at an eminent person, treated for bipolar disorder. Beside full agreement of the patient, an ethical committee approval has been granted for processing and publishing the case. ResultsHypomania boosts visual artistic creativity and scientific work while mild to moderate depression facilitates literary performance. Severe depression and depressive mixed states do not promote either aspect of creativity, and euthymia, with blunted mood swings by medication, is also detrimental to creativity. ConclusionsIt appears that positive but also negative mood have curvilinear effects on creativity. We argue that there are different correlates of a creative process in one person, where mood functions as a lock gate to canalize various creativity forms, resulting in multiple creativity as a function of distinct mood states in bipolar disorder. LimitationsThe lack of performing the studies of personality is a limitation of the paper.

Buffering against maladaptive perfectionism in bipolar disorder: The role of self-compassion

BackgroundMaladaptive perfectionism is a transdiagnostic risk and maintaining factor for a range of mental health conditions, including bipolar disorder (BD). Self-compassion represents a potential protective factor against maladaptive perfectionism, however no studies to date have examined the relationship of these constructs in BD. The aim of the present study was to examine associations between maladaptive perfectionism, self-compassion and symptoms among individuals with BD. MethodsBaseline data were collected from 302 participants with a DSM-IV diagnosis of BD participating in an international randomised controlled trial. Participants completed measures of maladaptive perfectionism, self-compassion, symptom severity and emotion regulation difficulties. Clinician-administered measures of depression and mania severity were additionally collected. Correlation and mediation analyses were conducted. ResultsMaladaptive perfectionism was positively associated with depression, anxiety and emotion regulation difficulties. Lower levels of self-compassion correlated with greater self-reported depression, anxiety and emotion regulation difficulties. Self-compassion partially mediated relationships between maladaptive perfectionism, depression, anxiety and emotion regulation difficulties. LimitationsThe cross-sectional design limits conclusions about causal relationships between study variables. Results may not be generalizable to other BD populations. The role of maladaptive perfectionism and self-compassion in elevated mood states of BD remains unclear. ConclusionSelf-compassion represents one mechanism through which maladaptive perfectionism influences symptoms of depression, anxiety and emotion regulation difficulties in BD. Self-compassion represents a modifiable treatment target; individuals with BD exhibiting maladaptive perfectionistic tendencies may benefit from interventions fostering self-compassion.

Differential mitochondrial DNA copy number in three mood states of bipolar disorder

BackgroundAccumulating evidences indicated that mitochondrial abnormalities were associated with bipolar disorder. As a sensitive index of mitochondrial function and biogenesis, Mitochondrial DNA copy number (mtDNAcn) may be involved in the pathophysiology of bipolar disorder.MethodsLeukocyte relative mtDNAcn was measured by quantitative polymerase chain reaction in subjects with BD (n = 131) in manic, depressive, and euthymic symptoms. Thirty-four healthy individuals were used as comparison control. BD clinical symptomatology was evaluated by Young Mania Rating Scale (YMRS), Hamilton Depression Scale (HAM-D), Clinical Global Impression-Bipolar Disorder-Severity of Illness Scale (CGI-BD-S), and the Positive and Negative Syndrome Scale (PANSS).ResultsCompared to healthy controls, BD patients with manic and depressive symptoms presented significantly decreased mtDNAcn levels (p-value = 0.009 and 0.041, respectively). No significant differences were detected in mtDNAcn between euthymic patients and healthy controls. The mtDNAcn was negatively correlated with the number of relapses in manic patients (β = − 0.341, p = 0.044).ConclusionsOur study described the first evidence of (1) a significant decline of mtDNAcn in manic BD patients, (2) a similar decreased level of mtDNAcn between manic and depressed BD patients, (3) a negative correlation of mtDNAcn with number of relapses in patients suffering from manic states. Alterations of mtDNAcn in manic and depressed patients, which may reflect disturbances of energy metabolism, supported the role of mitochondrial abnormalities in the pathophysiology of BD.

Impaired sensory processing measured by functional MRI in Bipolar disorder manic and depressed mood states.

Bipolar disorder is characterized by recurring episodes of depression and mania. Defining differences in brain function during these states is an important goal of bipolar disorder research. However, few imaging studies have directly compared brain activity between bipolar mood states. Herein, we compare functional magnetic resonance imaging (fMRI) responses during a flashing checkerboard stimulus between bipolar participants across mood states (euthymia, depression, and mania) in order to identify functional differences between these states. 40 participants with bipolar I disorder and 33 healthy controls underwent fMRI during the presentation of the stimulus. A total of 23 euthymic-state, 16 manic-state, 15 depressed-state, and 32 healthy control imaging sessions were analyzed in order to compare functional activation during the stimulus between mood states and with healthy controls. A reduced response was identified in the visual cortex in both the depressed and manic groups compared to euthymic and healthy participants. Functional differences between bipolar mood states were also observed in the cerebellum, thalamus, striatum, and hippocampus. Functional differences between mood states occurred in several brain regions involved in visual and other sensory processing. These differences suggest that altered visual processing may be a feature of mood states in bipolar disorder. The key limitations of this study are modest mood-state group size and the limited temporal resolution of fMRI which prevents the segregation of primary visual activity from regulatory feedback mechanisms.