Euthymic State Research Articles

The relationship between insight and coping attitudes in bipolar disorder patients

ABSTRACT Bipolar disorder is thought to determine the insights and coping attitudes that affect a patient’s compliance with treatment, which can positively affect the prognosis of the disease. This study aimed to investigate the relationship between insight and coping attitudes in bipolar disorder patients. This descriptive study was carried out with 127 volunteer patients who were diagnosed with bipolar disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and who were in a euthymic state. The Personal Information Form, Beck Cognitive Insight Scale (BCIS) and Scale of Coping Attitudes (COPE) were used as data collection tools. We found positive correlations between the total COPE score, the total BCIS score and the self-reflectivity subscale score of the BCIS. A positive and significant correlation was also determined between the BCIS subscales and total scores and coping attitudes toward adaptation with the COPE subscales (p < 0.05). A positive and significant relationship was found between the insight scores and total coping scores of the patients and their coping attitudes toward adaptation. We found that when patients’ levels of insight increased, their coping attitudes toward adaptation were used more frequently. This study revealed that individuals with high self-reflectivity can cope more effectively with the situations they face.

Changes in the medial prefrontal cortex metabolites after 6 months of medication therapy for patients with bipolar disorder: A 1H-MRS study.

The study aimed to assess brain metabolite differences in the medial prefrontal cortex (mPFC) between acute and euthymic episodes of bipolar disorder (BD) with both mania and depression over a 6-month medication treatment period. We utilized 1H-MRS technology to assess the metabolite levels in 53 individuals with BD (32 in depressive phase, 21 in manic phase) and 34 healthy controls (HCs) at baseline. After 6 months of medication treatment, 40 subjects underwent a follow-up scan in euthymic state. Metabolite levels, including N-acetyl aspartate (NAA), glutamate (Glu), and Glutamine (Gln), were measured in the mPFC. Patients experiencing depressive and manic episodes exhibited a notable reduction in NAA/Cr + PCr ratios at baseline compared to healthy controls (p = 0.004; p = 0.006) in baseline, compared with HCs. Over the 6-month follow-up period, the manic group displayed a significant decrease in Gln/Cr + PCr compared to the initial acute phase (p = 0.03). No significant alterations were found in depressed group between baseline and follow-up. This study suggests that NAA/Cr + PCr ratios and Gln/Cr + PCr ratios in the mPFC may be associated with manic and depressive episodes, implicating that Gln and NAA might be useful biomarkers for distinguishing mood phases in BD and elucidating its mechanisms.

Daily Self-Monitoring and Feedback of Circadian Rhythm Measures in Major Depression and Bipolar Disorder Using Wearable Devices and Smartphones-The Circadian Rhythm for Mood (CRM®) Trial Protocol: A Randomized Sham Controlled Double-Blind Trial.

The circadian rhythm for mood (CRM) is a digital therapeutic, which aims to prevent mood episode and improve clinical course in patients with major mood disorders. Developed on the circadian rhythm hypothesis of mood disorder, CRM predicts the impending risk of mood episode with its built-in algorithm, utilizing wearable devices data and daily self-reports, and provides personalized feedback. In a pilot study of the CRM, the users experienced less frequent and shorter duration of mood episodes than the non-users. To investigate the efficacy of the upgraded CRM, a double-blind, randomized, sham-controlled, parallel-group trial is designed. Patients aged between 19 and 70, diagnosed with bipolar I disorder, bipolar II disorder, or major depressive disorder, in a euthymic state for more than two months, can participate. During this 12-month trial, participants are assessed for episode recurrence every three months, and the efficacy of the CRM as a potential digital therapeutic is evaluated. Trial registration: ClinicalTrials.gov Identifier: NCT05400785.

Prescribed psychostimulants and other pro-cognitive medications in bipolar disorder: A systematic review and meta-analysis of recurrence of manic symptoms.

Clinicians are often hesitant to prescribe psychostimulants in bipolar disorder (BD) due to concerns of inducing (hypo)mania, despite limited published evidence on associations between prescribed psychostimulant use and recurrence of mood episodes in BD. The current systematic review and meta-analysis evaluated the emergence of (hypo)manic symptoms in patients with BD receiving prescribed psychostimulants or other pro-cognitive medications in euthymic or depressive states. A systematic search was performed of MEDLINE, Embase, and PsychINFO from inception to April 5, 2023 and search of Clinicaltrials.gov and Clinicaltrialsregister.eu for unpublished data. References of included studies were hand-searched. Randomized trials and prospective longitudinal studies that evaluated psychostimulants and non-stimulant medications recommended for the treatment of ADHD by the Canadian ADHD practice guidelines were included. The review was reported in line with PRISMA guidelines and was preregistered on PROSPERO (CRD42022358588). After screening 414 unique records, we included 27 studies, of which five reported data that was quantitatively synthesized (n = 1653). The use of psychostimulants in BD was not associated with increased scores on the Young Mania Rating Scale in patients who were in a euthymic or depressed state (SMD IV -0.17; 95% CI, -0.40 to 0.06) compared to placebo. There was a high degree of study-level heterogeneity (I2 = 80%). A qualitative synthesis of studies revealed a limited risk of medication-induced manic symptoms. Our review provides preliminary evidence to suggest psychostimulants and non-stimulant ADHD medications have a limited risk of precipitating (hypo)mania symptoms. More extensive studies evaluating the safety and efficacy of these medications are warranted.

Sleep Disturbance in Bipolar Disorder. Treatment Implications

IntroductionRelationship between sleep and bipolar disorder involves the following aspects: decreased need for sleep is a fundamental marker of the manic state, sleep deprivation is one cause of mania and may in fact be a fundamental etiological agent in mania, total sleep time is a predictor of future manic episodes, and total sleep time may be a marker of response as well as a target of treatment in mania.ObjectivesThis e-poster aimed to summarize evidence regarding the sleep disturbance in Bipolar Disorder.MethodsBibliopgraphical review was performed using PubMed platform. All relevant articles were found using the keywords: sleep disturbance, bipolar disorder, mania.ResultsSleep disturbances are frequent in BD patients in different phases of illness, including the euthymic state and remission. These sleep aberrations are represented not only by insomnia but also by sleep–wake rhythm disorders, especially delayed sleep–wake phase disorders. During the manic state, most patients experience a reduced need for sleep and longer sleep onset latency. Likewise, in the depressive state, insomnia and hypersomnia are commonly observed. Meta-analyses of trials conducted on remitted BD patients demonstrated prolonged total sleep time, increased awakenings after sleep onset, greater variability of sleep–wake variables, and reduced sleep efficiency.ConclusionsOverall, all kinds of sleep disorders and parasomnias are very common especially in youth patients with BD. Thus, compared to the general population, youth with BD exhibit lower sleep efficiency, longer slow wave sleep, and reduced REM sleep, features that could affect the genesis and prognosis of the disorder. Sleep disturbances may also be used as predictors of the onset of BD in a subset of high-risk young subjects.Disclosure of InterestNone Declared

Can mindful eating be a psycho-marker of obesity in bipolar disorder?

obesity is a very important problem in individuals with bipolar disorder. The study was aimed to determine the prevalence of obesity in individuals with bipolar disorder and to evaluate the effects of factors affecting eating behavior such as mindful eating, impulsivity and eating disorders on the development of obesity in these individuals. this study is a cross-sectional study. A total of 109 individuals (52 female; 57 male) with bipolar disorder who were in a euthymic state at the time of the interview and underwent outpatient follow-up, treatment and monitorization, and 109 age- and sex-matched healthy individuals as the control group were included in the study. The Mindful Eating Questionnaire-30 (MEQ-30), Three-Factor Eating Questionnaire (TFEQ-21), Barratt Impulsiveness Scale 11-Short Form (BIS-11-SF), and Eating Attitude Test-26 (EAT-26) were used, and anthropometric measurements (height, bodyweight, etc.) were taken. the obesity rate was 50.4 % among the cases and 24.8 % in the control group. Moreover, disinhibition (3.4 ± 0.93), emotional eating (3.5 ± 1.13), and mindfulness (2.6 ± 0.54) scores of individuals with BD were significantly lower than for healthy individuals (3.7 ± 0.82, 4.0 ± 0.93, 2.8 ± 0.55, respectively). The risk of obesity was 5.19 times higher in cases compared to the age- and gender-matched controls (OR = 5.19, 95 % CI (2.01-13.37), p = 0.001). The risk of obesity was 2.76 times higher in those with low mindful eating level (OR = 2.76, 95 % CI (1.07-5.47), p = 0.014) and 4.29 times higher in those using antipsyhotics/mood stabilizers (OR = 4.29, 95 % CI (1.12-12.24), p < 0.001). A comprehensive education program on mindful eating and healthy eating would be helpful in elucidating the mechanisms of the possible relationships between bipolar disorder-specific risk factors and mindful eating.

Reporting Psychiatric Disease Characteristics in Post-Mortem- and Biological Research.

Inflammation is a prominent hypothesis in the neurobiology of depression. In our transcriptomic profiling study of microglia in chronic major depressive disorder (MDD), we revealed a distinct disease-associated microglia (DAM) transcriptomic profile exclusively found in cortical gray matter, that we have designated DepDAM. These DepDAM revealed an immune-suppressed state, with a possible upstream mechanism for microglial suppression, by upregulation of CD200 and CD47 ("don't eat me signals") located on synapses. We extensively report on disease characteristics, such as cause of death, reason for euthanasia, and psychiatric state when deceased. When excluding MDD donors in a euthymic state, the trend of lower CD45 membrane expression on white matter microglia became significant, and the difference in gray matter microglia became larger. For Western blot analysis of CD47 and CD200, both means of the definitely depressed donor groups (MDD-D) increased. This underscores the utmost importance of reporting on patient and episode characteristics, such as severity, episode traits, (type of) suicidality, mode of decease, and state of illness at death in post-mortem- and biological psychiatric research. For psychiatric post-mortem research, we suggest using well-characterized donors (eg, after "psychological autopsy") selected by an experienced clinician.

Major depressive disorder and bistability in an HPA-CNS toggle switch.

Major depressive disorder (MDD) is the most common psychiatric disorder. It has a complex and heterogeneous etiology. Most treatments take weeks to show effects and work well only for a fraction of the patients. Thus, new concepts are needed to understand MDD and its dynamics. One of the strong correlates of MDD is increased activity and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which produces the stress hormone cortisol. Existing mathematical models of the HPA axis describe its operation on the scale of hours, and thus are unable to explore the dynamic on the scale of weeks that characterizes many aspects of MDD. Here, we propose a mathematical model of MDD on the scale of weeks, a timescale provided by the growth of the HPA hormone glands under control of HPA hormones. We add to this the mutual inhibition of the HPA axis and the hippocampus and other regions of the central nervous system (CNS) that forms a toggle switch. The model shows bistability between euthymic and depressed states, with a slow timescale of weeks in its dynamics. It explains why prolonged but not acute stress can trigger a self-sustaining depressive episode that persists even after the stress is removed. The model explains the weeks timescale for drugs to take effect, as well as the dysregulation of the HPA axis in MDD, based on gland mass changes. This understanding of MDD dynamics may help to guide strategies for treatment.

Elevated Brain-Derived Neurotrophic Factor Levels During Depressive Mixed States.

Neurotrophin-like brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines may modulate the pathophysiology of mood disorders. Although several studies show alterations in these biomarkers during the depressive, manic, and euthymic states of mood disorders, evidence is lacking for those in a mixed state. Therefore, this study aimed to investigate the relationship between the depressive mixed state (DMX) and peripheral neurobiological factors. We enrolled 136 patients with major depressive episodes. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J). The severity of DMX was assessed using the self-administered 12-item questionnaire (DMX-12). Categorical screening as DMX-positive (n=54) was determined by a cutoff score of 13 or more in the specific eight symptoms from the DMX-12; the remaining were DMX-negative (n=82). Serum BDNF, tumor necrosis factor-α, highsensitivity C-reactive protein, and interleukin-6 levels were measured. When comparing biomarkers between the DMX-positive and DMX-negative groups, higher serum BDNF concentration in the DMX-positive group than in the DMX-negative group was the only significant finding (p=0.009). A positive correlation existed between the total score of the eight specific symptoms of DMX-12 and the BDNF concentration (r=0.190, p=0.027). After adjustment for confounders, logistic regression analysis revealed that BDNF (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.00-1.14, p=0.045), bipolar diagnosis (OR=3.43, 95% CI=1.36-8.66, p=0.009), and total QIDS-SR-J score (OR=1.29, 95% CI=1.15-1.43, p<0.001) were significantly associated with DMX positivity. BDNF was positively associated with DMX severity, suggesting that higher BDNF concentrations may be involved in the pathophysiology of DMX.

Electrodermal activity in bipolar disorder: Differences between mood episodes and clinical remission using a wearable device in a real-world clinical setting

BackgroundBipolar disorder (BD) lacks objective measures for illness activity and treatment response. Electrodermal activity (EDA) is a quantitative measure of autonomic function, which is altered in manic and depressive episodes. We aimed to explore differences in EDA (1) inter-individually: between patients with BD on acute mood episodes, euthymic states and healthy controls (HC), and (2) intra-individually: longitudinally within patients during acute mood episodes of BD and after clinical remission. MethodsA longitudinal observational study. EDA was recorded using a research-grade wearable in patients with BD during acute manic and depressive episodes and at clinical remission. Euthymic BD patients and HC were recorded during a single session. We compared EDA parameters derived from the tonic (mean EDA, mEDA) and phasic components (EDA peaks per minute, pmEDA, and EDA peaks mean amplitude, pmaEDA). Inter- and intra-individual comparisons were computed respectively with ANOVA and paired t-tests. Results49 patients with BD (15 manic, 9 depressed, and 25 euthymic), and 19 HC were included. Patients with bipolar depression showed significantly reduced mEDA (p = 0.003) and pmEDA (p = 0.001), which increased to levels similar to euthymia or HC after clinical remission (mEDA, p = 0.011; pmEDA, p < 0.001; pmaEDA, p < 0.001). Manic patients showed no differences compared to euthymic patients and HCs, but a significant reduction of tonic and phasic EDA parameters after clinical remission (mEDA, p = 0.035; pmEDA, p = 0.004). LimitationsLimited sample size, high inter-individual variability of EDA parameters, limited comparability to previous studies and non-adjustment for medication. ConclusionEDA ecological monitoring might provide several opportunities for early detection of depressive symptoms, and might aid at assessing early response to treatments in mania and bipolar depression.

Is brain perfusion correlated to switching mood states and cognitive impairment in bipolar disorder type I? A longitudinal study using perfusion imaging approach.

Type I Bipolar disorder (BD-I) is a neuropsychiatric disorder characterized by manic or mixed-featured episodes, impaired cognitive functioning, and persistent work and social functioning impairment. This study aimed to investigate within-subject; (i) differences in brain perfusion using Single-photon emission computed tomography (SPECT) between manic and euthymic states in BD-I patients; (ii) explore potential associations between altered brain perfusion and cognitive status; and (iii) examine the relationship between cerebral perfusion and mania symptom ratings. Seventeen adult patients diagnosed with BD-I in a manic episode were recruited, and clinical assessments, cognitive tests, and brain perfusion studies were conducted at baseline (mania state) and a follow-up visit 6 months later. The results showed cognitive impairment during the manic episode, which persisted during the euthymic state at follow-up. However, no significant changes in brain perfusion were observed between the manic and euthymic states. During mania, trends toward decreased perfusion in the left cerebellum and right superior parietal lobule were noted. Additionally, trends indicated a higher perfusion imbalance in the left superior and middle frontal gyrus during mania and the right superior and middle frontal gyrus during euthymia. No significant correlations existed between brain perfusion, mania symptom ratings, and cognitive performance, indicating that symptomatology might represent more than neural hemodynamics. These findings suggest that cognitive impairment may persist in BD-I patients and highlight the need for therapeutic interventions targeting cognitive deficits. More extensive studies with extended follow-up periods are warranted further to investigate brain perfusion and cognitive functioning in BD-I patients.

Reduced heart rate variability during mania in a repeated naturalistic observational study.

Bipolar disorder (BD) is a chronic recurrent mood disorder associated with autonomic nervous system (ANS) dysfunction, indexed by heart rate variability (HRV). Changes in HRV between mood states are sparsely studied longitudinally. We aimed to compare HRV of hospitalized manic individuals with their own euthymic selves in a naturalistic observational study. 34 individuals were included, of which 16 were lost to follow-up. Ultimately 15 patients provided reliable heart rate data in both a manic and euthymic state, using photoplethysmography (PPG) sensor wristbands overnight. We calculated HRV measures Root Mean Square of Successive Differences (RMSSD), High-frequency (HF: 0.15-0.40 Hz), Low-frequency (LF: 0.40-0.15 Hz), Very low-frequency (VLF: 0.0033-0.04 Hz), Total power and Sample Entropy in 5-min night-time resting samples. We compared HRV measures by mood state within individuals using paired t-tests and linear regression to control for age and sex. HRV was lower in the manic state when compared to the euthymic state for all HRV metrics (p ≤ 0.02), with large to medium effect sizes (g = 1.24 to 0.65). HRV changes were not significantly affected by age or sex. This longitudinal study provides evidence of lower HRV in manic states compared to euthymia, indicating an association between ANS dysregulation and changes in bipolar mood state. This corroborates previous cross-sectional studies, although the association may be less clear or reversed in hypomanic states. Further investigation in larger longitudinal samples is warranted.

The purpose of early maladaptive schemas (EMS) in the relationship dysfunction among people with bipolar disorder in the euthymic phase

ObjectivesAlthough free from characterized manic and depressive episodes, the euthymic period in bipolar disorder (BD) remains characterized by a whole host of difficulties, particularly relational. These difficulties are factors of vulnerabilities and relapses. People's perception of their own relationships has an impact on their symptomatology, their responses to treatment and on relapse rates. Young's early maladaptive schemas (EMS) approach proves to be relevant for understanding the construction of these perceptions and working on them. Nevertheless, to this date, few studies have investigated which EMS are related to relationship dysfunction in this particular population. Determining the link between EMS and relationship difficulties would be relevant to understand psychosocial impairment of people with BD in euthymic states. The present study aims to investigate the associations between the different domains of EMS and relationship dysfunction among patients with bipolar disorder in the euthymic phase. MethodsData are extracted from the FACE-BD cohort, within the BD Expert Center in Versailles. Inclusion criteria were to be aged between 18 and 65 and to be an outpatient with a diagnosis of bipolar disorder (DSM-IV-TR). Patients had to be euthymic at the time of inclusion, according to DSM-IV-TR criteria with a cut-off score of 14 on the Montgomery-Asberg Depression Rating Scale and the Young Mania Rating Scale. Non-inclusion criteria were meeting at the time of the study the criteria for characteristic depressive episode, hypomania or mania according to the DSM-IV-TR. Sociodemographic data, clinical features associated with relationship dysfunction were assessed. EMS and EMS domains were assessed with the YSQ-R short form (Young Schema Questionnaire 3 Short Form) and current relationship dysfunction were assessed with the FAST (Functioning assessment short test subscale). Successive simple linear regression analyses were performed to investigate the association between the severity scores of each EMS and the intensity of relationship dysfunction. Furthermore, successive simple linear regression analyses investigated the association between EMS domain scores and intensity of relationship dysfunction. Multiple linear regression analyses were performed to test the association between EMS scores, then EMS domains, and the intensity of relationship dysfunction after adjusting for age as well as the intensity of residual depressive and manic symptoms. ResultsRelationship dysfunction is partly associated with EMS activation in particular in the separation and rejection domain (P<0.0001), the other-directedness domain (P=0.031) and the over-vigilance and inhibition domain (P=0.005). Having residual depressive symptoms is also among the factors contributing to the relationship dysfunctions of people with bipolar disorder in the euthymic phase. DiscussionThis is the first study demonstrating that the activation of several domains of EMS is a risk factor of relationships difficulties for people in euthymic phase of bipolar disorder. It is necessary to identify which EMS are specifically activated and their domains of belonging in order to prevent and reduce them. EMS are a lever for functional remission. It is therefore relevant to refer people reporting relationship problems to schema therapy consistent with a personalized care. Finally, future studies should focus on the mechanisms underlying the complex relationship between EMS domains and relationship dysfunction in people with bipolar disorder in the euthymic phase. It may also be relevant for future research to control for different types of relationship dysfunction. EMS may be differentially associated with several types of interpersonal problems. The relations between different adaptation styles and EMS should be further investigated to offer more personalized care, with the aim to improve functional remission.

MAY PPAR GAMMA BE SIGNIFICANT IN BIPOLAR DISORDER ONLY IN THE PRESENCE OF METABOLIC SYNDROME?

Peroxisome proliferator-activated receptor γ (PPARγ) has a key role in regulating both neurogenesis and various metabolic processes, including adipogenesis and glucose homeostasis. In this study, it was aimed to compare the serum PPARγ levels and metabolic syndrome (MetS) parametres of patients with Bipolar Disorder (BD) diagnosed manic-depressive-euthymic episodes with those of healthy subjects. We included 121 male patients with BD type I, 44 in mania, 35 in depression and 42 in euthymic state, and 41 healthy controls. Serum PPARγ levels, inflammation indicators (CRP, neutrophil, leukocyte, and albumin) and Mets parametres were measured. There were no statistically significant differences between the groups in terms of PPARγ values. PPARγ serum level is highest in the control group and then euthymic, manic and depressive episodes continue to decrease, respectively. However, there was a significant difference between the depressive group with MetS and without MetS in terms of serum PPARγ levels. A statistically significant correlation was found between PPARγ and the other serum markers such as low-density lipoprotein (p=0.022), HbA1c (p=0.002), neutrophils levels (0.001), white blood cell (p=0.025), and clinical features such as age at first treatment (p=0.024), age at first episode (p=0.039), and smoking (0.013). We suggest that PPARγ may be a key factor in the BD depressive group with MetS. Not finding any relationship between the PPARγ levels and the episode of BD may be related with the absence of MetS in the individuals. MetS parametres must also be considered if PPARγ is to be evaluated in the future investigations.

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.

Variations in olfactory function among bipolar disorder patients with different episodes and subtypes.

Most studies on olfactory function in individuals with bipolar disorder (BD) have not distinguished between the different subtypes or between the acute phase (mania or depression) and euthymic state. In this study, we compared olfactory function among BD patients with different subtypes and episodes to explore the potential use of olfactory function as a biomarker for the early identification of BD. The study sample consisted of 117 BD patients who were hospitalized between April 2019 and June 2019, and 47 healthy volunteers as controls. The BD patients were divided into a bipolar I disorder (BD I) (n = 86) and bipolar II disorder (BD II) group (n = 31) according to the different subtypes, and divided into depressive BD (n = 36), manic BD (n = 44), or euthymic BD (n = 37) groups according to the types of episodes they experienced. We assessed olfactory sensitivity (OS) and olfactory identification (OI) via the Sniffin' Sticks test and used the Hamilton Depression Rating Scale (HAMD) and Young Manic Rating Scale (YMRS) to evaluate BD characteristics among all subjects. Compared with controls, the participants with BD showed decreased OS and OI. We found statistically significant differences in OS and OI between the BD I group and controls, as well as differences in OS between the BD I and BD II group. Least-significant difference multiple comparisons revealed statistically significant differences in OS between the depressive BD group, manic BD group and controls and also between the manic BD and euthymic BD group. OI was positively correlated with the YMRS score in the BD I group and OS was negatively correlated with the HAMD score in the BD II group. This may be the first study to compare olfactory function in patients with BD I vs. BD II via pairwise comparisons. Our findings suggest that OS may have potential as a biomarker for distinguishing the different subtypes of BD and as a state-related biomarker for differentiating the acute phase from the euthymic state of BD. However, further prospective research is warranted.

Daring to Feel: Emotion-Focused Psychotherapy Increases Amygdala Activation and Connectivity in Euthymic Bipolar Disorder—A Randomized Controlled Trial

BackgroundIn bipolar disorder (BD), the alternation of extreme mood states indicates deficits in emotion processing, accompanied by aberrant neural function of the emotion network. The present study investigated the effects of an emotion-centered psychotherapeutic intervention on amygdala responsivity and connectivity during emotional face processing in BD. MethodsIn a randomized controlled trial within the multicentric BipoLife project, euthymic patients with BD received one of two interventions over 6 months: an unstructured, emotion-focused intervention (FEST), where patients were guided to adequately perceive and label their emotions (n = 28), or a specific, structured, cognitive behavioral intervention (SEKT) (n = 31). Before and after interventions, functional magnetic resonance imaging was conducted while patients completed an emotional face-matching paradigm (final functional magnetic resonance imaging sample of patients completing both measurements: SEKT, n = 17; FEST, n = 17). Healthy control subjects (n = 32) were scanned twice after the same interval without receiving any intervention. Given the focus of FEST on emotion processing, we expected FEST to strengthen amygdala activation and connectivity. ResultsClinically, both interventions stabilized patients’ euthymic states in terms of affective symptoms. At the neural level, FEST versus SEKT increased amygdala activation and amygdala-insula connectivity at postintervention relative to preintervention time point. In FEST, the increase in amygdala activation was associated with fewer depressive symptoms (r = 0.72) 6 months after intervention. ConclusionsEnhanced activation and functional connectivity of the amygdala after FEST versus SEKT may represent a neural marker of improved emotion processing, supporting the FEST intervention as an effective tool in relapse prevention in patients with BD.

The anatomical networks based on probabilistic structurally connectivity in bipolar disorder across mania, depression, and euthymic states

BackgroundsThere have pieces of evidence of the distinct aberrant functional network topology profile in bipolar disorder (BD) across mania, depression, and euthymic episodes. However, the underlying anatomical network topology pattern in BD across different episodes is unclear. MethodsWe calculated the whole-brain probabilistic structurally connectivity across 143 subjects (72 with BD [34 depression; 13 mania; 25 euthymic] and 53 healthy controls), and used graph theory to examine the trait- and state-related topology alterations of the structural connectome in BD. The correlation analysis was further conducted to explore the relationship between detected network measures and clinical symptoms. ResultsThere no omnibus alteration of any global network metrics were observed across all diagnostic groups. In the regional network metrics level, bipolar depression showed increased clustering coefficient in the right lingual gyrus compared with all other groups, and the increased clustering coefficient in the right lingual gyrus positively correlated with depression, anxiety, and illness burden symptoms but negatively correlated with mania symptoms; manic and euthymic patients showed decreased clustering coefficient in the left inferior occipital gyrus compared with HCs. LimitationsThe moderate sample size of all patient groups (especially for subjects with mania) might have contributed to the negative findings of the trait feature in this study. ConclusionsWe demonstrated the altered regional connectivity pattern in the occipital lobe of the bipolar depression and mania episode, especially the lingual gyrus. The association of the clustering coefficient in the lingual gyrus with clinical symptoms helps monitor the state of BD.

Relations of gray matter volume to dimensional measures of cognition and affect in mood disorders.

Understanding the relationship between brain measurements and behavioral performance is an important step in developing approaches for early identification of any psychiatric difficulties and interventions to modify these challenges. Conventional methods to identify associations between regional brain volume and behavioral measures are not optimized, either in scale, scope, or specificity. To find meaningful associations between brain and behavior with greater sensitivity and precision, we applied data-driven factor analytic models to identify and extract individual differences in latent cognitive functions embedded across several computerized cognitive tasks. Furthermore, we simultaneously utilized a keyword-based neuroimaging meta-analytic tool (i.e., NeuroSynth), restricted atlas-parcel matching, and factor-analytic models to narrow down the scope of search and to further aggregate gray matter volume (GMV) data into empirical clusters. We recruited an early adult community cross-sectional sample (Total n=177, age 18-30) that consisted of individuals with no history of any mood disorder (healthy controls, n=44), those with remitted major depressive disorder (rMDD, n=104), and those with a diagnosis of bipolar disorder currently in euthymic state (eBP, n=29). Study participants underwent structural magnetic resonance imaging (MRI) scans and separately completed behavioral testing using computerized measures. Factor-analyzing five computerized tasks used to assess aspects of cognitive and affective processing resulted in seven latent dimensions: (a) Emotional Memory, (b) Interference Resolution, (c) Reward Sensitivity, (d) Complex Inhibitory Control, (e) Facial Emotion Sensitivity, (f) Sustained attention, and (g)Simple Impulsivity/Response Style. These seven dimensions were then labeled with specific keywords which were used to create neuroanatomical maps using NeuroSynth. These masks were further subdivided into GMV clusters. Using regression, we identified GMV clusters that were predictive of individual differences across each of the aforementioned seven cognitive dimensions. We demonstrate that a dimensional approach consistent with core principles of RDoC can be utilized to identify structural variability predictive of critical dimensions of human behavior.

A longitudinal study of the association between pro-inflammatory cytokines and mood symptoms in bipolar disorder.

Because of a relative dearth of longitudinal studies, the directionality of the relationship between mood and inflammation among patients with bipolar disorder (BD) is still unclear. We aimed to investigate the longitudinal associations of pro-inflammatory markers with mood symptom severity in BD. Hundred and thirty-two adult patients with BD were enrolled. At the baseline and 1-year follow-up visit, all participants received mood assessment with Montgomery Åsberg depression rating scale (MADRS) and Young mania rating scale, and underwent blood draws to quantify metabolic profile and serum levels of the pro-inflammatory markers, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), monocyte chemoattractant protein-1, and C-reactive protein. A four-factor model of MADRS, consisting of sadness, negative thoughts, detachment, and neurovegetative symptoms, were applied. At baseline, 65 patients with BD were in depressed state, and 67 patients with BD were in euthymic state. Among patients in depressed state, baseline MADRS total score positively correlated with sTNF-αR1 level at follow-up. While baseline sTNF-αR1 level positively predicted sadness symptom in euthymic patients with BD who later developed depression (n=22), sadness in patients with bipolar depression predicted later increase in serum sTNF-αR1 level even after remission (n=17). Moreover, lithium had a stronger effect of lowering peripheral sTNF-αR1 level as compared with other mood stabilizers. Our results indicate the bidirectional inflammation-depression relationship in BD.