Aerobic capacity and mitochondrial function in bipolar disorder: a longitudinal study during acute phases and after clinical remission.

Background: Aerobic capacity has shown to predict physical and mental health-related quality of life in bipolar disorder (BD). However, the correlation between exercise respiratory capacity and mitochondrial function remains understudied. We aimed to assess longitudinally intra-individual differences in these factors during mood episodes and remission in BD. Methods: This study included eight BD patients admitted to an acute psychiatric unit. Incremental cardiopulmonary exercise test (CPET) was conducted during acute episodes (T0), followed by constant work rate cycle ergometry (CWRCE) to evaluate endurance time, oxygen uptake at peak exercise (VO2peak) and at the anaerobic threshold. The second test was repeated during remission (T1). Mitochondrial respiration rates were assessed at T0 and T1 in peripheral blood mononuclear cells. Results: Endurance time, VO2peak, and anaerobic threshold oxygen consumption showed no significant variations between T0 and T1. Basal oxygen consumption at T1 tended to inversely correlate with maximal mitochondrial respiratory capacity (r=-0.690, p=0.058), and VO2peak during exercise at T1 inversely correlated with basal and minimum mitochondrial respiration (r=-0.810, p=0.015; r=-0.786, p=0.021, respectively). Conclusions: Our preliminary data showed that lower basal oxygen consumption may be linked to greater mitochondrial respiratory capacity, and maximum oxygen uptake during the exercise task was associated with lower basal mitochondrial respiration, suggesting that lower oxygen requirements could be associated with greater mitochondrial capacity. These findings should be replicated in larger samples stratified for manic and depressive states.

Associations of altered leukocyte DDR1 promoter methylation and childhood trauma with bipolar disorder and suicidal behavior in euthymic patients.

Altered DNA methylation (DNAm) patterns of discoidin domain receptor 1 (DDR1) have been found in the blood and brain of patients with schizophrenia (SCZ) and the brain of patients with bipolar disorder (BD). Childhood trauma (CT) is associated with changes in DNAm that in turn are related to suicidal behavior (SB) in patients with several psychiatric disorders. Here, using MassARRAY® technology, we studied 128 patients diagnosed with BD in remission and 141 healthy controls (HCs) to compare leukocyte DDR1 promoter DNAm patterns between patients and HCs and between patients with and without SB. Additionally, we investigated whether CT was associated with DDR1 DNAm and mediated SB. We found hypermethylation at DDR1 cg19215110 and cg23953820 sites and hypomethylation at cg14279856 and cg03270204 sites in patients with BD compared to HCs. Logistic regression models showed that hypermethylation of DDR1 cg23953820 but not cg19215110 and CT were risk factors for BD, while cg14279856 and cg03270204 hypomethylation were protective factors. In patients, CT was a risk factor for SB, but DDR1 DNAm, although associated with CT, did not mediate the association of CT with SB. This is the first study demonstrating altered leukocyte DDR1 promoter DNAm in euthymic patients with BD. We conclude that altered DDR1 DNAm may be related to immune and inflammatory mechanisms and could be a potential blood biomarker for the diagnosis and stratification of psychiatric patients.

Cognitive reserve moderates the relationship between childhood maltreatment, objective and subjective cognition, and psychosocial functioning in individuals with first-episode psychosis.

OBJECTIVE: This study aimed to assess the relationship between childhood maltreatment (CM), objective and subjective cognition, and psychosocial functioning in adults with first-episode psychosis (FEP) by examining the moderating role of cognitive reserve (CR). A secondary objective was to explore whether unique CM subtypes (physical and/or emotional abuse, sexual abuse, physical and/or emotional neglect) were driving this relationship. METHOD: Sixty-six individuals with FEP (Mage = 27.3, SD = 7.2 years, 47% male) completed a comprehensive neuropsychological test battery, the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA), the Functioning Assessment Short Test (FAST), the Childhood Trauma Questionnaire (CTQ), and the Cognitive Reserve Assessment Scale in Health (CRASH). Linear regression analyses were conducted to evaluate the interaction effect of CR between CM and cognitive and psychosocial variables, controlling for age, sex, and social desirability (CTQ-denial-minimization). RESULTS: In adults with FEP overall CM interacted with CR to predict COBRA-subjective cognitive complaints, but not neurocognitive or psychosocial functioning. Sexual abuse and physical neglect interacted with CR to predict verbal memory. Most of the CM subtypes interacted with CR to predict FAST-leisure time, whereas only emotional neglect interacted with CR to predict FAST-interpersonal relationships. Overall, greater CR was related to better functioning. CONCLUSIONS: The current results indicate that associations between specific CM subtypes, subjective and objective cognition, and psychosocial domains are moderated through CR with greater functioning. Early interventions focused on CR seeking to improve cognitive and psychosocial outcomes, with emphasis on improving subjective cognitive functions would be beneficial for individuals with FEP and CM. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Processing speed mediates the relationship between DDR1 and psychosocial functioning in euthymic patients with bipolar disorder presenting psychotic symptoms.

The DDR1 locus is associated with the diagnosis of schizophrenia and with processing speed in patients with schizophrenia and first-episode psychosis. Here, we investigated whether DDR1 variants are associated with bipolar disorder (BD) features. First, we performed a case‒control association study comparing DDR1 variants between patients with BD and healthy controls. Second, we performed linear regression analyses to assess the associations of DDR1 variants with neurocognitive domains and psychosocial functioning. Third, we conducted a mediation analysis to explore whether neurocognitive impairment mediated the association between DDR1 variants and psychosocial functioning in patients with BD. Finally, we studied the association between DDR1 variants and white matter microstructure. We did not find any statistically significant associations in the case‒control association study; however, we found that the combined genotypes rs1264323AA-rs2267641AC/CC were associated with worse neurocognitive performance in patients with BD with psychotic symptoms. In addition, the combined genotypes rs1264323AA-rs2267641AC/CC were associated with worse psychosocial functioning through processing speed. We did not find correlations between white matter microstructure abnormalities and the neurocognitive domains associated with the combined genotypes rs1264323AA-rs2267641AC/CC. Overall, the results suggest that DDR1 may be a marker of worse neurocognitive performance and psychosocial functioning in patients with BD, specifically those with psychotic symptoms.

Patterns of pharmacotherapy for bipolar disorder: A GBC survey.

OBJECTIVES: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well-characterized individuals with BD in North America, Europe, and Australia. METHODS: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta-analyses with generalized linear mixed methods were conducted to identify prescription patterns. RESULTS: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD-I (60%; vs. BD-II = 33%). Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First-generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD-II (47%) compared to BD-I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. CONCLUSIONS: Mood-stabilizing anticonvulsants, second-generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first-generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence-based guidelines to help improve treatment practices in BD.

Difficulties during delivery, brain ventricle enlargement and cognitive impairment in first episode psychosis.

BACKGROUND: Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances. METHODS: We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis-Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups. RESULTS: FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio. CONCLUSIONS: Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

Reduced mitochondrial respiratory capacity in patients with acute episodes of bipolar disorder: Could bipolar disorder be a state-dependent mitochondrial disease?

BACKGROUND: Bipolar disorder (BD) is a chronic and recurrent disease characterized by acute mood episodes and periods of euthymia. The available literature postulates that a biphasic dysregulation of mitochondrial bioenergetics might underpin the neurobiology of BD. However, most studies focused on inter-subject differences rather than intra-subject variations between different mood states. To test this hypothesis, in this preliminary proof-of-concept study, we measured in vivo mitochondrial respiration in patients with BD during a mood episode and investigated differences compared to healthy controls (HC) and to the same patients upon clinical remission. METHODS: This longitudinal study recruited 20 patients with BD admitted to our acute psychiatric ward with a manic (n = 15) or depressive (n = 5) episode, and 10 matched HC. We assessed manic and depressive symptoms using standardized psychometric scales. Different mitochondrial oxygen consumption rates (OCRs: Routine, Leak, electron transport chain [ETC], Rox) were assessed during the acute episode (T0) and after clinical remission (T1) using high-resolution respirometry at 37°C by polarographic oxygen sensors in a two-chamber Oxygraph-2k system in one million of peripheral blood mononuclear cells (PMBC). Specific OCRs were expressed as mean ± SD in picomoles of oxygen per million cells. Significant results were adjusted for age, sex, and body mass index. RESULTS: The longitudinal analysis showed a significant increase in the maximal oxygen consumption capacity (ETC) in clinical remission (25.7 ± 16.7) compared to the acute episodes (19.1 ± 11.8, p = 0.025), and was observed separately for patients admitted with a manic episode (29.2 ± 18.9 in T1, 22.3 ± 11.9 in T0, p = 0.076), and at a trend-level for patients admitted with a depressive episode (15.4 ± 3.9 in T1 compared to 9.4 ± 3.2 in T0, p = 0.107). Compared to HC, significant differences were observed in ETC in patients with a bipolar mood episode (H = 11.7; p = 0.003). Individuals with bipolar depression showed lower ETC than those with a manic episode (t = -3.7, p = 0.001). Also, significant differences were observed in ETC rates between HC and bipolar depression (Z = 1.000, p = 0.005). CONCLUSIONS: Bioenergetic and mitochondrial dysregulation could be present in both manic and depressive phases in BD and, importantly, they may restore after clinical remission. These preliminary results suggest that mitochondrial respiratory capacity could be a biomarker of illness activity and clinical response in BD. Further studies with larger samples and similar approaches are needed to confirm these results and identify potential biomarkers in different phases of the disease.

Improved estimation of the risk of manic relapse by combining clinical and brain scan data.

INTRODUCTION: Estimating the risk of manic relapse could help the psychiatrist individually adjust the treatment to the risk. Some authors have attempted to estimate this risk from baseline clinical data. Still, no studies have assessed whether the estimation could improve by adding structural magnetic resonance imaging (MRI) data. We aimed to evaluate it. MATERIAL AND METHODS: We followed a cohort of 78 patients with a manic episode without mixed symptoms (bipolar type I or schizoaffective disorder) at 2-4-6-9-12-15-18 months and up to 10 years. Within a cross-validation scheme, we created and evaluated a Cox lasso model to estimate the risk of manic relapse using both clinical and MRI data. RESULTS: The model successfully estimated the risk of manic relapse (Cox regression of the time to relapse as a function of the estimated risk: hazard ratio (HR)=2.35, p=0.027; area under the curve (AUC)=0.65, expected calibration error (ECE)<0.2). The most relevant variables included in the model were the diagnosis of schizoaffective disorder, poor impulse control, unusual thought content, and cerebellum volume decrease. The estimations were poorer when we used clinical or MRI data separately. CONCLUSION: Combining clinical and MRI data may improve the risk of manic relapse estimation after a manic episode. We provide a website that estimates the risk according to the model to facilitate replication by independent groups before translation to clinical settings.

Corrigendum: Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: differences between males and females.

[This corrects the article DOI: 10.3389/fpsyt.2022.982583.].

Widespread intra-axonal signal fraction abnormalities in bipolar disorder from multicompartment diffusion MRI: Sensitivity to diagnosis, association with clinical features and pharmacologic treatment.

Despite diffusion tensor imaging (DTI) evidence for widespread fractional anisotropy (FA) reductions in the brain white matter of patients with bipolar disorder, questions remain regarding the specificity and sensitivity of FA abnormalities as opposed to other diffusion metrics in the disorder. We conducted a whole-brain voxel-based multicompartment diffusion MRI study on 316 participants (i.e., 158 patients and 158 matched healthy controls) employing four diffusion metrics: the mean diffusivity (MD) and FA estimated from DTI, and the intra-axonal signal fraction (IASF) and microscopic axonal parallel diffusivity (Dpar) derived from the spherical mean technique. Our findings provide novel evidence about widespread abnormalities in other diffusion metrics in BD. An extensive overlap between the FA and IASF results suggests that the lower FA in patients may be caused by a reduced intra-axonal volume fraction or a higher macromolecular content in the intra-axonal water. We also found a diffuse alteration in MD involving white and grey matter tissue and more localised changes in Dpar. A Machine Learning analysis revealed that FA, followed by IASF, were the most helpful metric for the automatic diagnosis of BD patients, reaching an accuracy of 72%. Number of mood episodes, age of onset/duration of illness, psychotic symptoms, and current treatment with lithium, antipsychotics, antidepressants, and antiepileptics were all significantly associated with microstructure abnormalities. Lithium treatment was associated with less microstructure abnormality.

A systematic review of manic/hypomanic and depressive switches in patients with bipolar disorder in naturalistic settings: The role of antidepressant and antipsychotic drugs.

The present systematic review was aimed at critically summarizing the evidence about treatment-emergent manic/hypomanic and depressive switches during the course of bipolar disorder (BD). A systematic search of the MEDLINE, EMBASE, CINAHL, Web of Science, and PsycInfo electronic databases was conducted until March 24th, 2021, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Observational studies clearly reporting data regarding the prevalence of treatment-emergent mood switches in patients with BD were considered for inclusion. Thirty-two original studies met the inclusion criteria. In the majority of cases, manic switches were analyzed; only 3 papers investigated depressive switches in type I BD. Treatment-emergent mania/hypomania in BD subjects ranged from 17.3% to 48.8% and was more frequent with antidepressant monotherapy compared to combination treatment with mood stabilizers, especially lithium, or second-generation antipsychotics. A higher likelihood of mood switch has been reported with tricyclics and a lower rate with bupropion. Depressive switches were detected in 5-16% of type I BD subjects and were associated with first-generation antipsychotic use, the concomitant use of first- and second-generation antipsychotics, and benzodiazepines. The included studies presented considerable methodological heterogeneity, small sample sizes and comparability flaws. In conclusion, many studies, although heterogeneous and partly discordant, have been conducted on manic/hypomanic switches, whereas depressive switches during treatment with antipsychotics are poorly investigated. In BD subjects, both antidepressant and antipsychotic medications seems to play a role in the occurrence of mood switches, although the effects of different pharmacological compounds have yet to be fully investigated.

Obstetric complications and clinical presentation in first episode of psychosis.

OBJECTIVE: Psychotic disorders exhibit a complex aetiology that combines genetic and environmental factors. Among the latter, obstetric complications (OCs) have been widely studied as risk factors, but it is not yet well understood how OCs relate to the heterogeneous presentations of psychotic disorders. We assessed the clinical phenotypes of individuals with a first episode of psychosis (FEP) in relation to the presence of OCs. METHODS: Two-hundred seventy-seven patients with an FEP were assessed for OCs using the Lewis-Murray scale, with data stratified into three subscales depending on the timing and the characteristics of the obstetric event, namely: complications of pregnancy, abnormal foetal growth and development and difficulties in delivery. We also considered other two groups: any complications during the pregnancy period and all OCs taken altogether. Patients were clinically evaluated with the Positive and Negative Syndrome Scale for schizophrenia. RESULTS: Total OCs and difficulties in delivery were related to more severe psychopathology, and this remained significant after co-varying for age, sex, traumatic experiences, antipsychotic dosage and cannabis use. CONCLUSIONS: Our results highlight the relevance of OCs for the clinical presentation of psychosis. Describing the timing of the OCs is essential in understanding the heterogeneity of the clinical presentation.

Failure of deactivation in bipolar disorder during performance of an fMRI adapted version of the Stroop task.

INTRODUCTION: Few studies have examined the functional brain correlates of the performance of the Stroop task in bipolar disorder (BD). It is also not known whether it is associated with failure of de-activation in the default mode network, as has been found in studies using other tasks. METHODS: Twenty-four BD patients and 48 age, sex and educationally estimated intellectual quotient (IQ) matched healthy subjects (HS) underwent a functional MRI during performance of the counting Stroop task. Task-related activations (incongruent versus congruent condition) and de-activations (incongruent versus fixation) were examined using whole-brain, voxel-based methodology. RESULTS: Both the BD patients and the HS showed activation in a cluster encompassing the left dorsolateral and ventrolateral prefrontal cortex and the rostral anterior cingulate cortex and supplementary motor area, with no differences between them. The BD patients, however, showed significant failure of de-activation in the medial frontal cortex and the posterior cingulate cortex/precuneus. CONCLUSIONS: The failure to find activation differences between BD patients and controls suggests that the 'regulative' component of cognitive control remains intact in the disorder, at least outside episodes of illness. The failure of de-activation found adds to evidence documenting trait-like default mode network dysfunction in the disorder.

Obstetric complications and genetic risk for schizophrenia: Differential role of antenatal and perinatal events in first episode psychosis.

BACKGROUND: Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors. STUDY DESIGN: 405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis-Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS-SZ) and interactions between these. RESULTS: Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case-control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS-SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe. CONCLUSIONS: We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk.

Exploring Digital Biomarkers of Illness Activity in Mood Episodes: Hypotheses Generating and Model Development Study.

BACKGROUND: Depressive and manic episodes within bipolar disorder (BD) and major depressive disorder (MDD) involve altered mood, sleep, and activity, alongside physiological alterations wearables can capture. OBJECTIVE: Firstly, we explored whether physiological wearable data could predict (aim 1) the severity of an acute affective episode at the intra-individual level and (aim 2) the polarity of an acute affective episode and euthymia among different individuals. Secondarily, we explored which physiological data were related to prior predictions, generalization across patients, and associations between affective symptoms and physiological data. METHODS: We conducted a prospective exploratory observational study including patients with BD and MDD on acute affective episodes (manic, depressed, and mixed) whose physiological data were recorded using a research-grade wearable (Empatica E4) across 3 consecutive time points (acute, response, and remission of episode). Euthymic patients and healthy controls were recorded during a single session (approximately 48 h). Manic and depressive symptoms were assessed using standardized psychometric scales. Physiological wearable data included the following channels: acceleration (ACC), skin temperature, blood volume pulse, heart rate (HR), and electrodermal activity (EDA). Invalid physiological data were removed using a rule-based filter, and channels were time aligned at 1-second time units and segmented at window lengths of 32 seconds, as best-performing parameters. We developed deep learning predictive models, assessed the channels' individual contribution using permutation feature importance analysis, and computed physiological data to psychometric scales' items normalized mutual information (NMI). We present a novel, fully automated method for the preprocessing and analysis of physiological data from a research-grade wearable device, including a viable supervised learning pipeline for time-series analyses. RESULTS: Overall, 35 sessions (1512 hours) from 12 patients (manic, depressed, mixed, and euthymic) and 7 healthy controls (mean age 39.7, SD 12.6 years; 6/19, 32% female) were analyzed. The severity of mood episodes was predicted with moderate (62%-85%) accuracies (aim 1), and their polarity with moderate (70%) accuracy (aim 2). The most relevant features for the former tasks were ACC, EDA, and HR. There was a fair agreement in feature importance across classification tasks (Kendall W=0.383). Generalization of the former models on unseen patients was of overall low accuracy, except for the intra-individual models. ACC was associated with "increased motor activity" (NMI>0.55), "insomnia" (NMI=0.6), and "motor inhibition" (NMI=0.75). EDA was associated with "aggressive behavior" (NMI=1.0) and "psychic anxiety" (NMI=0.52). CONCLUSIONS: Physiological data from wearables show potential to identify mood episodes and specific symptoms of mania and depression quantitatively, both in BD and MDD. Motor activity and stress-related physiological data (EDA and HR) stand out as potential digital biomarkers for predicting mania and depression, respectively. These findings represent a promising pathway toward personalized psychiatry, in which physiological wearable data could allow the early identification and intervention of mood episodes.

Identifying pathways between psychiatric symptoms and psychosocial functioning in the general population.

The present study aims to identify pathways between psychiatric network symptoms and psychosocial functioning and their associated variables among functioning clusters in the general population. A cross-sectional web-based survey was administered in a total of 3,023 individuals in Brazil. The functioning clusters were derived by a previous study identifying three different groups based on the online Functioning Assessment Short Test. Networking analysis was fitted with all items of the Patient-Reported Outcomes Measurement Information System for depression and for anxiety (PROMIS) using the mixed graphical model. A decision tree model was used to identify the demographic and clinical characteristics of good and low functioning. A total of 926 (30.63%) subjects showed good functioning, 1,436 (47.50%) participants intermediate functioning, and 661 (21.86%) individuals low functioning. Anxiety and uneasy symptoms were the most important nodes for good and intermediate clusters but anxiety, feeling of failure, and depression were the most relevant symptoms for low functioning. The decision tree model was applied to identify variables capable to discriminate individuals with good and low functioning. The algorithm achieved balanced accuracy 0.75, sensitivity 0.87, specificity 0.63, positive predictive value 0.63 negative predictive value 0.87 (p<0.001), and an area under the curve of 0.83 (95%CI:0.79-0.86, p<0.01). Our results show that individuals who present psychological distress are more likely to experience poor functional status, suggesting that this subgroup should receive a more comprehensive psychiatric assessment and mental health care.

Chronotype is associated with affective temperaments, clinical severity and worse treatment outcomes in bipolar disorders: results from a two-center, cross-sectional study.

OBJECTIVE: The present study was aimed at investigating the clinical correlates of evening chronotype in a population of subjects suffering from bipolar disorders (BD). METHODS: We assessed chronotype using the Morningness-Eveningness Questionnaire. We administered the brief Temperament Evaluation of Memphis, Pisa, and San Diego, the Barratt Impulsiveness Scale, and the Alda Scale to evaluate affective temperaments, impulsiveness, and response to mood stabilisers. We performed bivariate analyses and ran a logistic regression model to analyse clinical variables associated with evening chronotype. RESULTS: In our sample (n = 178), subjects with an evening chronotype (n = 56, 31.5%) more often suffered from BD type I and reported higher prevalence of seasonality, antidepressant-induced mood switches, psychotic, aggressive, mixed, and anxiety features, and substance use disorders. The number of lifetime suicide attempts and mood episodes was higher in this subgroup. Depressive, cyclothymic, irritable, and anxious temperament scores were higher among evening-chronotype subjects, who also displayed greater levels of impulsiveness and worse treatment response. At the logistic regression, evening chronotype was associated with depressive and irritable temperaments. CONCLUSIONS: Subjects with evening chronotype display higher clinical severity and worse BD course. Clinicians should evaluate the presence of evening chronotype in BD subjects, especially in those with irritable or depressive temperament.Key pointsEvening chronotype is a frequent clinical feature in subjects suffering from bipolar disorders (BD);Affective temperaments, particularly depressive and irritable, are associated with evening chronotype in BD;Evening chronotype underpins higher severity of the clinical picture in BD, as well as a worse response to mood stabiliser treatment;Circadian preferences should be systematically assessed in subjects suffering from BD, with particular attention to evening preference.

The relationship between cognition and functioning in Bipolar Disorder: An investigation using functional imaging during working memory performance.

The psychosocial functioning of individuals suffering from bipolar disorder (BD) has a significant impact on prognosis and quality of life. The aim of this study was to assess brain functional correlates of psychosocial functioning in BD individuals during the performance of a working memory task. Sixty-two subjects (31 euthymic BD individuals and 31 matched healthy controls) underwent structural and functional magnetic resonance imaging scanning while performing the 1- and 2-back versions of the n-back task (1-back and 2-back). The Functional Assessment Short Test (FAST) and its subdomains were used to assess functioning. Whole brain analysis revealed only overall activation differences between BD patients and healthy controls, but the patients showed failure of de-activation in the medial frontal cortex. Six clusters of significant inverse correlation with the FAST scores were found in the dorsolateral prefrontal cortex, the superior parietal cortex, and temporo-occipital regions bilaterally, and in the left inferior frontal cortex. Cognitive and occupational functioning were the subdomains most significantly associated with brain activation in these clusters. The results suggest that poor psychosocial functioning in BD individuals is associated with hypoactivation in a range of cortical regions, including the fronto-parietal working memory network and inferior temporo-occipital regions.