Decreased dynamic variability of the cerebellum in the euthymic patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a complex mental illness characterized by different mood states, including depression, mania/hypomania, and euthymia. This study aimed to comprehensively evaluate dynamic changes in intrinsic brain activity by using dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic degree centrality (dDC) in patients with BD euthymia or depression and healthy individuals. METHODS: The resting-state functional magnetic resonance imaging data were analyzed from 37 euthymic and 28 depressed patients with BD, as well as 85 healthy individuals. Using the sliding-window method, the dfALFF and dDC were calculated for each participant. These values were compared between the 3 groups using one-way analysis of variance (ANOVA). Additional analyses were conducted using different window lengths, step width, and window type to ensure the reliability of the results. RESULTS: The euthymic group showed significantly lower dfALFF and dDC values of the left and right cerebellum posterior lobe compared with the depressed and control groups (cluster level PFWE < 0.05), while the latter two groups were comparable. Brain regions showing significant group differences in the dfALFF analysis overlapped with those with significant differences in the dDC analysis. These results were consistent across different window lengths, step width, and window type. CONCLUSIONS: These findings suggested that patients with euthymic BD exhibit less flexibility of temporal functional activities in the cerebellum posterior lobes compared to either depressed patients or healthy individuals. These results could contribute to the development of neuropathological models of BD, ultimately leading to improved diagnosis and treatment of this complex illness.

Factors associated with the discrepancy between objective and subjective cognitive impairment in bipolar disorder.

OBJECTIVE: The aim of this study is to evaluate the discrepancy between objective cognitive measures and cognitive subjective complaints in a sample of euthymic patients with bipolar disorder (BD). METHODS: One hundred and sixteen participants (83 euthymic patients with BD and 33 healthy controls) were enrolled for this study. Patients were assessed with a comprehensive neuropsychological battery and they also reported their subjective cognitive complaints with the Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA). The discrepancy between objective and subjective data was calculated using a novel methodology proposed in a previous study (Miskowiak, 2016). Statistical analyses included Pearson correlations and multiple linear regression. RESULTS: Higher number of previous depressive episodes was identified as one variable associated with the global sensitivity composite score (Beta = 0.25; t = 2.1; p = 0.04) and with the verbal learning and memory sensitivity score (Beta = 0.26; t = 2.16; p = 0.03). That is, patients with more previous depressive episodes tend to over-report cognitive complaints. In contrast, higher number of previous hospitalizations was associated with stoicism in the global total score (Beta = -0.27; t = -2.24: p = 0.029) and in the domain of attention/processing speed (Beta = -0.34; t = -2.52; p = 0.016), indicating patients with more hospitalizations tend to report less cognitive complaints. DISCUSSION: Our study identified some factors that might help to explain the discrepancy between objective and subjective cognitive measures in BD, including number of previous depressive episodes and number of previous hospitalizations. This highlights the need of the combined use of both types of cognitive measures to make an accurate assessment of cognitive dysfunctions and their effective treatment.

Impact of hypomanic personality traits on brain functional connectivity during a dynamic theory-of-mind task.

Hypomanic personality traits are present in the general population and represent a risk factor for developing bipolar disorder. This personality style, notably its social component, is linked to difficulties in theory of mind (i.e., ability to infer mental states). Exploring the neural correlates of mental states' inference in individuals with these personality traits can provide meaningful insights into the development of bipolar disorder. The aim of the present study was therefore to investigate the potential impact of hypomanic traits on brain activation and task-based connectivity strength during a dynamic theory of mind task in a nonclinical population. A total of 52 nonclinical participants were recruited, and hypomanic traits were assessed with the Hypomanic Personality Scale. The severity of hypomanic traits was positively associated with right middle and inferior frontal gyri activations (in high vs. low inference in nonemotional condition and emotion vs. no emotion in high inference, respectively). It was also associated with stronger connectivity between the salience network (i.e., bilateral putamen and pallidum) and bilateral superior temporal gyri (high inference in nonemotional condition), and between cerebellar and temporal areas (high inference in emotional condition). These changes may either reflect adaptations or differential processing, and further studies are therefore mandatory.

Comparison of olfactory function, cognitive function and serum tumor necrosis factor-α between bipolar and schizophrenic patients in the remission stage.

OBJECTIVES: Olfactory function, serum tumor necrosis factor-α (TNF-α) and cognitive function were compared between bipolar disorder (BD) and schizophrenia (SP) patients in the remission stage combined with correlation analysis, with the aim of identifying new indicators for the auxiliary diagnosis of these psychiatric illnesses. METHODS: A total of 46 euthymic BD patients, 42 clinically stable SP patients and 42 healthy controls (HC) were included in this study. Olfactory sensitivity (OS) and olfactory identification (OI) were assessed using Sniffin' Sticks test, and serum TNF-α levels were measured by ELISA. Clinical symptoms were evaluated with the Hamilton Rating Scale for Depression, Young Mania Rating Scale, Hamilton anxiety scale, and the Positive and Negative Syndrome Scale (PANSS). Social function was evaluated with the Global Assessment Function (GAF) scale. Cognitive function was evaluated using the Trail Making Test-A (TMT-A) and Digit Cancellation Test (DCT). RESULTS: OI and cognitive function scores and serum TNF-α levels were significantly lower in the BD and SP patients compared with the HC participants. There was no significant difference between the BD and SP groups, and there were no significant differences in OS among the three groups. OI score was positively correlated with years of education in both the BD and SP groups. OI score in the SP group was negatively correlated with age and PANSS score, and positively correlated with GAF score. In the BD group, OS was positively correlated with DCT II and DCT III. In the SP group, OS and OI scores were positively correlated with DCT III, and negatively correlated with TMT-A time. Furthermore, there was a positive correlation between TNF-α and DCT II in the BD group. There was no significant linear correlation between olfactory function and TNF-α in the BD or SP group. CONCLUSION: OI may be a trait marker for BD and SP. Some cognitive functions may be correlated not only with TNF-α in BD patients in remission, but also with olfactory function in BD and SP patients in remission.

Predicting functional impairment in euthymic patients with mood disorder: A 5-year follow-up.

Major Depressive Disorder and Bipolar Disorder are psychiatric disorders associated with psychosocial impairment. Despite clinical improvement, functional complaints usually remain, mainly impairing occupational and cognitive performance. The aim of this study was to use machine learning techniques to predict functional impairment in patients with mood disorders. For that, analyzes were performed using a population-based cohort study. Participants diagnosed with a mood disorder at baseline and reassessed were considered (n = 282). Random forest (RF) with previous recursive feature selection and LASSO algorithms were applied to a training set with imputed data by bagged trees resulting in two main models. Following recursive feature selection, 25 variables were retained. The RF model had the best performance compared to LASSO. The most important variables in predicting functional impairment were sexual abuse, severity of depressive, anxiety, and somatic symptoms, physical neglect, emotional abuse, and physical abuse. The model demonstrated acceptable performance to predict functional impairment. However, our sample is composed of young participants and the model may not generalize to older individuals with mood disorders. More studies are needed in this direction. The presented calculator has clinical, sociodemographic, and environmental data, demonstrating that it is possible to use such information to predict functional performance.

Altered white matter integrity in euthymic children with bipolar disorder: A tract-based spatial statistical analysis of diffusion tensor imaging.

Pediatric Bipolar Disorder (BD) is a serious mental illness that affects children and adolescents, characterized by episodes of mania, depression, and mixed episodes. Recent studies have suggested that abnormalities in the white matter (WM) may be a contributing factor. The neuropathogenesis of BD in children is not well-described, and research in this area is limited. Euthymic phase is a period in which clinical symptoms are present but not severe enough to significantly impact mood and daily behavior. In order to better understand the WM changes associated with BD in children, this study utilized Diffusion Tensor Imaging (DTI), to investigate alterations in WM microstructure. 20 confirmed euthymic BD children (aged 7-16) and 20 typically developing children were included in the study. DTI scans were obtained using a 3 T Magnetom Skyra and were analyzed using tract-based spatial statistics (TBSS) to examine changes in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Results showed that compared to the healthy control group, the euthymic BD group exhibited increased FA, AD, RD, and MD values in several brain regions, including the thalamus, precentral corticospinal tract, and superior longitudinal fasciculus. Conversely, decreased values were observed in the body of the corpus callosum and inferior fronto-occipital fasciculus. These findings suggest that alterations in WM microstructure are a hallmark of pediatric bipolar disorder. These findings provide important insights into the brain changes associated with pediatric bipolar disorder and open the door for new avenues of research.

50 Years After Schizophrenia and Cyclothymia, Results and Problems / A 50 años de Esquizofrenia y Ciclotimia, resultados y problemas.

Análisis del libro: Esquizofrenia y Ciclotimia, resultados y problemas, Comp. Gerd Huber, Ed. Morata, Madrid, 1972.

Euthymic and depressed bipolar patients are characterized by different RNA editing patterns in blood.

Bipolar disorder (BD) is a worldwide leading cause of disability. Inflammation roles in this disease is well established. ADAR1-mediated RNA editing is one of the key mechanisms regulating the inflammatory response. We have identified a panel of RNA editing-based blood biomarkers which allowed to discriminate unipolar from BD depression with high accuracy. We confirmed here the diagnostic value of this panel in a new cohort of BD patients recruited in Brazil. We also identified new combinations which allow a clear discrimination of BD from healthy controls and among BD subgroups, confirming that RNA editing is a key mechanism in BD.

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

BACKGROUND: 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. SUBJECTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Effect of affective temperament on illness characteristics of subjects with bipolar disorder and major depressive disorder.

BACKGROUND: Affective temperaments represent the stable, biologically determined substrates of mood disorders. The relationship between affective temperaments and bipolar disorder (BD) or major depressive disorder (MDD) has been described. However, the strength of such relationship should be tested while considering other factors influencing the diagnosis of BD/MDD. Literature also lacks a comprehensive description of the interplay between affective temperament and characteristics of mood disorders. The aim of the present study is to address these issues. METHODS: This is a multicentric observational study including 7 Italian university sites. Five-hundred-fifty-five euthymic subjects with BD/MDD were enrolled and further divided in those with hyperthymic (Hyper, N = 143), cyclothymic (Cyclo, N = 133), irritable (Irr, N = 49), dysthymic (Dysth, N = 155), and anxious (Anx N = 76) temperaments. Linear, binary, ordinal and logistic regressions were performed to assess the association between affective temperaments and i) diagnosis of BD/MDD; ii) characteristics of illness severity and course. RESULTS: Hyper, Cyclo and Irr were more likely to be associated with BD, together with earlier age of onset and presence of a first-degree relative with BD. Anx and Dysth were more associated with MDD. Differences in association between affective temperaments and characteristics of BD/MDD were observed for hospital admissions, phase-related psychotic symptoms, length and type of depression, comorbidity and pharmacological intake. LIMITATIONS: Small sample size, cross-sectional design, recall biases. CONCLUSION: Specific affective temperaments were associated to certain characteristics of illness severity and course of BD or MDD. Evaluation of affective temperaments might help a deeper understanding of mood disorders.

The role of affective temperaments in bipolar disorder: The solid role of the cyclothymic, the contentious role of the hyperthymic, and the neglected role of the irritable temperaments.

BACKGROUND: The aim of the present study is to evaluate the role of individual affective temperaments as clinical predictors of bipolarity in the clinical setting. METHODS: The affective temperaments of 1723 consecutive adult outpatients presenting for various symptoms to a university-based mental health clinical setting were assessed. Patients were administered the Hypomania Checklist-32 and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego - Auto-questionnaire (TEMPS-A) and were diagnosed by psychiatrists according to the DSM-5 criteria. TEMPS-A scores were studied as both continuous and normalized categorical z-scores from a previously established nationwide study on the general population of Lebanon. Simple and multiple binary logistic regressions were done on patients who have any of the DSM-5 defined bipolar types, as a combined group or separately, versus patients without any bipolar diagnosis. RESULTS: At the multivariable level and taking into account all temperaments, the irritable temperament is a consistent predictor of bipolar I and bipolar II disorders. Cyclothymic temperament also played a strong role in bipolarity but more decisively so in bipolar II and substance-induced bipolarity. The hyperthymic temperament had no role in bipolar I or bipolar II disorder.

Affective Temperaments Misdiagnosed as Adult Attention Deficit Disorder: Prevalence and Treatment Effects.

ABSTRACT: Adult attention-deficit disorder (ADD) is a common diagnosis, and amphetamine medications are increasingly used. Recent reports suggest high prevalence of affective temperaments, such as cyclothymia, in adult ADD. This study reexamines prevalence rates as reflecting misdiagnosis and reports for the first time on the effects of amphetamine medications on mood/anxiety and cognition in relation to affective temperaments. Among outpatients treated at the Tufts Medical Center Mood Disorders Program (2008-2017), 87 cases treated with amphetamines were identified, versus 163 non-amphetamine-treated control subjects. Using the Temperament Scale of Memphis, Pisa, Paris and San Diego-Autoquestionnaire, 62% had an affective temperament, most commonly cyclothymia (42%). In amphetamine-treated cases, mood/anxiety symptoms worsened notably in 27% ( vs. 4% in the control group, risk ratio [RR] 6.2, confidence interval [CI], 2.8-13.8), whereas 24% had moderate improvement in cognition ( vs. 6% in the control group; RR, 3.93; CI, 1.9-8.0). Affective temperaments, especially cyclothymia, are present in persons about one-half of persons diagnosed with adult ADD and/or treated with amphetamines.

A multicomponent positive psychology intervention for euthymic patients with bipolar disorder to improve mental well-being and personal recovery: A pragmatic randomized controlled trial.

OBJECTIVE: Mental well-being and personal recovery are important treatment targets for patients with bipolar disorder (BD). The goal of this study was to evaluate the effectiveness of an 8-week group multicomponent positive psychology intervention (PPI) for euthymic patients with BD as an adjunct to treatment as usual (TAU) compared to TAU alone. METHODS: Patients with BD were randomized to receive TAU (n = 43) or the PPI in addition to TAU (n = 54). The primary outcome was well being measured with the Mental Health Continuum-Short Form. Personal recovery was measured with the Questionnaire about the Process of Recovery. Data were collected at baseline, mid-treatment, post-treatment and 6- and 12-month follow-up. Life chart interviews were conducted at 12 months to retrospectively assess recurrence of depression and mania. RESULTS: Significant group-by-time interaction effects for well-being and personal recovery were found favouring the PPI. At post-treatment, between-group differences were significant for well-being (d = 0.77) and personal recovery (d = 0.76). Between-group effects for well-being were still significant at 6-month follow-up (d = 0.72). Effects on well-being and personal recovery within the intervention group were sustained until 12-month follow-up. Survival analyses showed no significant differences in time to recurrence. CONCLUSIONS: The multicomponent PPI evaluated in this study is effective in improving mental well-being and personal recovery in euthymic patients with BD and would therefore be a valuable addition to the current treatment of euthymic BD patients. The fact that the study was carried out in a pragmatic RCT demonstrates that this intervention can be applied in a real-world clinical setting.

Childhood trauma and cognitive functioning in mood disorders: A systematic review.

BACKGROUND: Cognitive impairment is a core feature of mood disorders and has been identified as an important treatment target. A better understanding of the factors contributing to cognitive impairment in mood disorders would be beneficial in developing interventions to address cognitive impairment. One key factor is childhood trauma. The aim of this review was to systematically synthesise and review research examining associations between reported childhood trauma and cognitive functioning in mood disorders. METHODS: Studies in adult samples examining the relationship between objective cognitive function and reported childhood trauma in major depressive disorder and/or bipolar disorder (in-episode or euthymia) were identified. Searches were conducted on PubMed, Embase and PsycINFO until January 2022. A narrative review technique was used due to the heterogeneity of group comparisons, cognitive tests and data analysis across studies. RESULTS: Seventeen studies met the criteria for inclusion (mood disorders N = 1723, healthy controls N = 797). Evidence for childhood trauma being related to poorer cognitive functioning was consistent across global cognitive functioning and executive function domains for euthymic patients and psychomotor speed for in-episode patients. There was mixed evidence for verbal learning and memory and executive function for in-episode patients. Identification of patterns within other domains was difficult due to limited number of studies. CONCLUSION: Findings from this review suggest childhood trauma is associated with poorer cognitive functioning in people with mood disorders. Targeted interventions to improve cognition may be warranted for this group.

Temporal self and reflected appraisals in euthymic and depressed individuals.

BACKGROUND: Temporal self-appraisal (TSA) theory, reflected appraisal theory, and their clinical applications have previously been explored as independent constructs. This study investigates how TSA corresponds to temporal reflected appraisal (TRA), and how the relationship between them differs in the presence of depression. METHODS: 273 adults (57 % female), recruited using Amazon Mechanical Turk, filled out a series of measures of mood and self-appraisal assessments (TSA and TRA versions of the Me/Not Me task). Repeated measures MANOVAs were used to assess between group differences. RESULTS: The TSA trajectory of depressed individuals replicated the 'V' shape found in previous research, whereas the TRA of depressed individuals did not decline from past to present. There was little difference between TSA and TRA "past" and "future" appraisals, though there was a significant difference in appraisal of the "present." Individuals with depression believe that others perceive them as doing much better currently than the way they view themselves. By contrast, euthymic individuals had no significant differences between the TSA and TRA appraisals of their present selves, indicating they think their self-perception matches how others view them. LIMITATIONS: We assessed depression using online self-reports. Cross-sectional data limits causality determination but suffices for studying mood-related self-perceptions over time. CONCLUSIONS: Temporal self-appraisal and temporal reflected appraisal have varying relationships among euthymic and depressed individuals. This more precise characterization of depressed individuals' identity can further aid clinicians in understanding the nature of identity development and treating identity disruption among depressed individuals.

Pharmacological Strategies for Bipolar Disorders in Acute Phases and Chronic Management with a Special Focus on Lithium, Valproic Acid, and Atypical Antipsychotics.

Bipolar disorders (BDs) are a heterogeneous group of severe affective disorders generally described by the alternation of (hypo)manic, depressive, and mixed phases, with euthymic intervals of variable duration. BDs are burdened with high psychiatric and physical comorbidity, increased suicide risk and reduced life expectancy. In addition, BDs can progress into complicated forms (e.g., mixed states, rapid/irregular cycling), which are more difficult to treat and often require personalized pharmacological combinations. Mood stabilizers, particularly Lithium and Valproic acid (VPA), still represent the cornerstones of both acute and chronic pharmacotherapies of BDs. Lithium is the gold standard in BD-I and BDII with typical features, while VPA seems more effective for atypical forms (e.g., mixed-prevalence and rapid-cycling). However, despite appropriate mood stabilization, many patients show residual symptoms, and more than a half recur within 1-2 years, highlighting the need of additional strategies. Among these, the association of atypical antipsychotics (AAPs) with mood stabilizers is recurrent in the treatment of acute phases, but it is also being growingly explored in the maintenance pharmacotherapy. These combinations are clinically more aggressive and often needed in the acute phases, whereas simplifying pharmacotherapies to mood stabilizers only is preferable in the long-term, whenever possible. When mood stabilizers are not enough for maintenance treatment, Quetiapine and, less consistently, Aripiprazole have been proposed as the most advisable adjunctive strategies, for their safety and tolerability profiles. However, in view of the increased risk of serious adverse effects, a careful patient-centered balance between costs and benefits is mandatory.

Neurological and cerebellar soft signs in bipolar disorder: The role of staging, type and history of psychotic symptoms.

AIM: Bipolar disorder (BD) patients show neurological abnormalities in form of neurological and cerebellar soft signs (NSS and CSS). NSS represents heterogeneous group of symptoms representing i.a. deficits of motor coordination, sequencing of complex motor acts and sensory integration. CSS were introduced as group of the neurological deficits of posture, gait, kinetic functions, eye movements and speech, associated more specifically to cerebellar abnormalities than NSS. Studies show significant effect size variability of those symptoms in BD group suggesting the existence of differing subpopulations. The aim of our study was to evaluate the effect of BD type, stage and the history of psychotic symptoms (HoPS) on the severity of CSS and NSS as none of the previous studies had verified the role of those categories. METHODS: This study involved 181 participants: 116 euthymic BD patients (66 BD I, 50 BD II) and 65 healthy controls (HC). CSS was assessed with the International Cooperative Ataxia Rating Scale and NSS with Neurological Evaluation Scale. Patients were divided into early and late stage of the disorder according to Kapczinski's criteria. Rater was blind to patients' stage, type and HoPS. RESULTS: Staging was related to vast majority of CSS and NSS scores. HoPS was related to oculomotor deficits. The effect of BD type was the least significant. Late stage BD showed more severe CSS and NSS than HC in every measure. There were no differences between early stage BD and HC, apart of posture and gait disturbances. Except of sensory integration scores, late stage BD showed higher CSS and NSS rates than early stage patients. CONCLUSION: In this hitherto the largest study of neurological abnormalities in BD we have shown significant role of staging in CSS and NSS severity. Progression criteria based on inter-episode psychosocial functioning may stand as unrecognised factor responsible for variability observed in previous studies evaluating neurological abnormalities in BD. Our study suggests that in clinical practice NSS and CSS may be potentially used as easy-to-assess biological marker of BD staging. Observed severity of neurological impairments of BD patients may more likely correspond to the disease progression than to BD type and HoPS.

Performance of a measure to assess distress in bipolar disorder.

INTRODUCTION: Bipolar disorder is a condition that causes distress even for euthymic patients, having an impact on functional capabilities and quality of life. Personal and social variables are potential sources of distress. Yet, there is a lack of measures to identify specific distress in bipolar disorder. This study describes the development and evaluation of a brief measure for assessing distress in patients with bipolar disorder. We also identify associations with related constructs such as functioning, stigma, and personal beliefs regarding mental illness. MATERIAL AND METHODS: We used a sample of 101 euthymic bipolar outpatients. Psychological assessment consisted of the Young Mania Rating Scale (YMRS) and the Hamilton Depression Scale (HAM-D) to establish euthymia. Distress was assessed with Distress on Bipolar Patients-Short (DISBIP-S); associated variables were assessed with the Functioning Assessment Short Scale (FAST), the Internalized Stigma of Mental Illness (ISMI), and the Personal Beliefs about Illness Questionnaire (PBIQ). RESULTS: The DISBIP-S has strong internal consistency (Cronbach's alpha=0.90), and medium-high correlation coefficients with the time since last relapse (r=-0.401), predominant polarity (r=0.309), HDRS (r=-0.644), FAST (r=0.453), ISMI (r=0.789), and PBIQ (r=-0.796). Taken together, the scores on the ISMI, and PBIQ and the time since last relapse together explain 69.2% of the variability in distress. CONCLUSIONS: The DISBIP-S can be used as a first step to develop interventions aimed at dealing with problematic personal beliefs and interpersonal sources of distress. Reducing distress experienced by bipolar disorder patients could help improve their quality of life and daily functioning.

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

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

Cardioprotective potential of lithium and role of fractalkine in euthymic patients with bipolar disorder.

OBJECTIVE: Over a half century, lithium has been used as the first-line medication to treat bipolar disorder. Emerging clinical and laboratory studies suggest that lithium may exhibit cardioprotective effects in addition to neuroprotective actions. Fractalkine (CX3CL1) is a unique chemokine associated with the pathogenesis of mood disorders and cardiovascular diseases. Herein we aimed to ascertain whether lithium treatment is associated with favorable cardiac structure and function in relation to the reduced CX3CL1 among patients with bipolar disorder. METHODS: We recruited 100 euthymic patients with bipolar I disorder aged over 20 years to undergo echocardiographic study and measurement of plasma CX3CL1. Associations between lithium treatment, cardiac structure and function and peripheral CX3CL1 were analyzed according to the cardiovascular risk. The high cardiovascular risk was defined as (1) age ⩾ 45 years in men or ⩾ 55 years in women or (2) presence of concurrent cardiometabolic diseases. RESULTS: In the high cardiovascular risk group (n = 61), patients who received lithium as the maintenance treatment had significantly lower mean values of left ventricular internal diameters at end-diastole (Cohen's d = 0.65, p = 0.001) and end-systole (Cohen's d = 0.60, p = 0.004), higher mean values of mitral valve E/A ratio (Cohen's d = 0.51, p = 0.019) and superior performance of global longitudinal strain (Cohen's d = 0.51, p = 0.037) than those without lithium treatment. In addition, mean plasma levels of CX3CL1 in the high cardiovascular risk group were significantly lower among patients with lithium therapy compared with those without lithium treatment (p = 0.029). Multiple regression models showed that the association between lithium treatment and mitral value E/A ratio was contributed by CX3CL1. CONCLUSION: Data from this largest sample size study of the association between lithium treatment and echocardiographic measures suggest that lithium may protect cardiac structure and function in patients with bipolar disorder. Reduction of CX3CL1 may mediate the cardioprotective effects of lithium.