Vulnerability For Bipolar Disorder Research Articles

Poor subjective sleep quality and trait impulsivity in patients with bipolar disorder.

Sleep disturbance and impulsivity are key components of mood vulnerability in bipolar disorder (BD), but few studies have assessed the association between these two symptoms among patients with BD. Forty-seven euthymic patients with bipolar I disorder (BDI) or bipolar II disorder (BDII) and 58 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Trait impulsivity was measured using the Barratt Impulsiveness Scale Version 11 (BIS-11), which yielded 3 second-order factors: attention, motor, and non-planning. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI). General linear models (GLMs) were used to assess the associations between subjective poor sleep and trait impulsivity with multiple testing corrections. Patients with BD scored higher in BIS-11 and PSQI than healthy controls. PSQI total scores positively correlated with BIS-11 total scores, while sleep disturbance and daytime dysfunction were associated with attentional impulsiveness after controlling for covariates. Participants with higher PSQI total scores (>10) had higher scores in BIS-11 total, attention, and non-planning than those with low PSQI scores (≤5). These findings support the hypothesis that poor sleep quality might lead to impulsivity and add to the growing evidence that improving sleep quality may be a therapeutic target for patients with BD.

Neurocognitive Deficits in Recently Diagnosed Young Remitted Bipolar I Disorder and At-Risk Subjects: Potential Endophenotypes?

Neurocognitive deficits have been reported consistently in euthymic bipolar disorder (BD) across studies. Endophenotype potential of such deficits have been reported in a few studies. However, data from the Indian subcontinent is sparse, and no studies had a sample (patients and high-risk group) aged 20-25 years, which is the actual risk period for developing BD. We studied cognitive deficits, as a potential endophenotype for BD, in recently diagnosed BD (FEM-first episode mania) in remission, young unaffected first-degree relatives (HR) of patients with BD, and healthy controls (HC). Cross-sectional study design using convenient sampling was employed. We recruited FEM (n = 25), HR (n = 25), and age-matched HC (n = 25) between 18 and 30 years. All HR subjects were <25 years of age, which is the period of vulnerability for BD. All the groups were screened using MINI Version 6. Neurocognitive assessments were done using the NIMHANS neuropsychology battery. The cognitive domains assessed were processing speed, attention, working memory, executive functions, and visual and verbal memory. The three groups were comparable in age and sex (all P > 0.06). The mean (SD) age of the FEM subjects was 23.7 (3.47) years, and the mean duration of illness was 5.92 (2.94) months. Compared to the HC group, the FEM group performed poorly on multiple cognitive domains (all P < 0.05). Performance of the HR group was comparable to the FEM group, but they showed significantly poorer performance compared to HC on the verbal fluency test-controlled oral word association (COWA, F = 12.36, P = 0.001), and the visual learning and memory test-complex figure test-immediate recall (CFT-IR, F = 8.10 and p = 0.001). Cognition is impaired very early in the course of BD. Visual memory and executive function (verbal fluency) have endophenotypic potential. These findings are particularly important given that the HR group were still within the vulnerable period to develop BD. These findings imply a tremendous potential for early diagnosis and prevention by early interventions in BD.

Antidepressants that increase mitochondrial energetics may elevate risk of treatment-emergent mania

Preclinical evidence suggests that antidepressants (ADs) may differentially influence mitochondrial energetics. This study was conducted to investigate the relationship between mitochondrial function and illness vulnerability in bipolar disorder (BD), specifically risk of treatment-emergent mania (TEM). Participants with BD already clinically phenotyped as TEM+ (n = 176) or TEM− (n = 516) were further classified whether the TEM associated AD, based on preclinical studies, increased (Mito+, n = 600) or decreased (Mito−, n = 289) mitochondrial electron transport chain (ETC) activity. Comparison of TEM+ rates between Mito+ and Mito− ADs was performed using generalized estimating equations to account for participants exposed to multiple ADs while adjusting for sex, age at time of enrollment into the biobank and BD type (BD-I/schizoaffective vs. BD-II). A total of 692 subjects (62.7% female, 91.4% White, mean age 43.0 ± 14.0 years) including 176 cases (25.3%) of TEM+ and 516 cases (74.7%) of TEM- with previous exposure to Mito+ and/or Mito- antidepressants were identified. Adjusting for age, sex and BD subtype, TEM+ was more frequent with antidepressants that increased (24.7%), versus decreased (13.5%) mitochondrial energetics (OR = 2.21; p = 0.000009). Our preliminary retrospective data suggests there may be merit in reconceptualizing AD classification, not solely based on monoaminergic conventional drug mechanism of action, but additionally based on mitochondrial energetics. Future prospective clinical studies on specific antidepressants and mitochondrial activity are encouraged. Recognizing pharmacogenomic investigation of drug response may extend or overlap to genomics of disease risk, future studies should investigate potential interactions between mitochondrial mechanisms of disease risk and drug response.

Machine learning algorithms revealed distorted retinal vascular branching in individuals with bipolar disorder

BackgroundConverging evidence designate vascular vulnerability in bipolar disorder. The predisposition progresses into distortion in time, thus detection of the vascular susceptibility may help reducing morbidity and mortality. It was aimed to assess retinal fundus vasculature in cardiovascular risk-free patients with bipolar disorder. MethodsTotal of 68 individuals (38 patients with bipolar disorder, 30 healthy controls) were enrolled. In order to avoid from degenerative processes, participants were between 18 and 45 years of age, vascular risk factors were eliminated. Microscopic retinal fundus images were processed with machine learning algorithms (multilayer perceptron and support vector machine) and artificial neural network approaches. ResultsIn comparison to the healthy control group, the bipolar disorder group had lower number of breaking points (P < 0.001), lower number of curved vessel segments (P < 0.001). Total length of smooth vessels was longer (P = 0.040), and total length of curved vessel segments was significantly shorter (P < 0.001) than the control group. Vascular endothelial growth factor levels and gender were the confounders. There were significant correlations between vascular measures and serum lipid levels. LimitationsSample size was small and patients were on various medications. ConclusionsThese results indicate distortion in retinal vascular branching in bipolar disorder. Disrupted branching may reflect disturbed prosperity of retinal vascular plexus in patients with bipolar disorder. Alterations in the retinal vessels might be indicators of disruption in cerebral vascular system efficiency and thus neurovascular unit dysfunction in bipolar disorder.

Resting-state functional connectivity graph-properties correlate with bipolar disorder-risk in young medication-free depressed subjects: Bipolar-risk Resting State Functional Connectivity in Major Depression

BackgroundMajor Depressive Disorder (MDD) is frequently associated with risk factors for the development of Bipolar Disorder (BD). Using graph theory, we investigated brain network properties associated with BD risk factors in young MDD subjects. MethodsResting-state fMRI was acquired from a large cohort (N= 104) of medication-free currently depressed participants (25 BD depression (BDD), 79 MDD). Lifetime mania symptom count (LMSC), current Young Mania Rating Scale (YMRS) score, and family history of mood disorders (FHMD) were examined as BD risk factors. Functional connectivity matrices from 280 regions of interests (ROIs) were first entered into the Network Based Statistic (NBS) toolbox to identify connections that varied with each risk factor. Next, within the correlated network for each risk factor, global and nodal graph properties for the top five linked nodes were calculated. Last, using identified graph properties, machine learning classification (MLC) between BDD, MDD with BD risk factors (MDD+), and without BD risk factors (MDD-) was conducted. ResultsLMSC positively correlated with left lateral orbitofrontal cortex (LOFC) Communication Efficiency and with left middle temporal Eigenvector Centrality. Current YMRS score positively correlated with right amygdala Communication Efficiency and Closeness Centrality. FHMD positively correlated with right insula Eigenvector Centrality. Acceptable MLC accuracy was seen between BDD and MDD- using middle temporal Eigenvector Centrality, whereas moderate accuracy was seen between MDD+ and MDD- using OFC Communication Efficiency. LimitationAlthough participants were medication-free, they were not medication-naïve. ConclusionFunctional connectome graph properties may serve as BD vulnerability biomarkers in young individuals with MDD.

Comparison of Effect of Bipolar I Disorder on Neurocognitive Functions between Full Biological Siblings of Patients from Simplex and Multiplex Families

Background: Cognitive deficits seem to be more prevalent in relatives of patients with bipolar disorder type I compared to relatives of BD type II patients. Assessment of cognitive performance in siblings of bipolar disorder from simplex (only one known case of bipolar disorder in first degree relatives) and multiplex (more than one known case of bipolar disorder in first degree relatives) families may provide some light to investigate the biological vulnerability in bipolar disorder. There is limited data pertaining to studies on siblings of patients with bipolar disorder and especially on comparison of effect of Bipolar I Disorder on neurocognitive functions between full biological siblings of patients from simplex and multiplex Families. Materials and Methods: This is a prospective, teaching hospital based, single point non-invasive study of 29 unaffected full biological siblings of patients diagnosed (as per DSM-IV-TR) as bipolar disorder I (BD-I) from Simplex and Multiplex families. Results: The siblings belonging to the multiplex group performed poorly on most domains of the Wisconsin Card Sorting Test (WCST). Comparison of the performance of the siblings belonging to the multiplex sub-group to those of simplex sub-group on the various domains of the Continuous Performance Test (CPT) and Spatial Working Memory Test (SWMT) did not show statistically significant difference. Conclusions: The performance in WCST is significantly affected in siblings from multiplex families than in simplex ones.

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

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

Smaller left anterior cingulate cortex in non-bipolar relatives of patients with bipolar disorder.

Objective:Bipolar disorder (BD) is highly heritable. The present study aimed at identifying brain morphometric features that could represent markers of BD vulnerability in non-bipolar relatives of bipolar patients.Methods:In the present study, structural magnetic resonance imaging brain scans were acquired from a total of 93 subjects, including 31 patients with BD, 31 non-bipolar relatives of BD patients, and 31 healthy controls. Volumetric measurements of the anterior cingulate cortex (ACC), lateral ventricles, amygdala, and hippocampus were completed using the automated software FreeSurfer.Results:Analysis of covariance (with age, gender, and intracranial volume as covariates) indicated smaller left ACC volumes in unaffected relatives as compared to healthy controls and BD patients (p = 0.004 and p = 0.037, respectively). No additional statistically significant differences were detected for other brain structures.Conclusion:Our findings suggest smaller left ACC volume as a viable biomarker candidate for BD.

Familial risk for psychiatric disorders in military veterans who have post-traumatic stress disorder with psychosis: a retrospective electronic record review.

Post-traumatic stress disorder (PTSD) is a leading cause of morbidity among military veterans, with up to one-in-five individuals with PTSD also having psychotic symptoms. The current study was designed to determine the association between a known family history of psychiatric illness and risk of developing psychosis in patients with PTSD. Retrospective medical record review was performed on a cohort study of 414 consecutive individuals admitted to the Veteran Administration in 2014 with a diagnosis of military-related PTSD, but without a prior diagnosis of a psychotic disorder. PTSD with psychotic features was defined as the presence of hallucinations, paranoia, other delusions, thought insertion, withdrawal, broadcasting, and/or dissociative episodes. Overall, 22.9% of individuals with PTSD had psychotic symptoms. Having a first-degree relative with bipolar affective and with anxiety disorders was associated with an increased risk of PTSD with psychosis (odds ratio=2.01, 95% confidence interval: 1.01-4.45 and odds ratio=2.72, 95% confidence interval: 1.16-6.41, respectively). A family history of schizophrenia or depression was not associated with risk of developing psychotic features in patients with PTSD. In veterans with military-related PTSD, a familial vulnerability for bipolar disorder and anxiety disorders was associated with an increased risk of developing PTSD with psychotic features. These are preliminary data, given the limitations of a retrospective record review design. These results await replication in future prospective direct family interview studies.

Markers of neuroinflammation and neuronal injury in bipolar disorder: Relation to prospective clinical outcomes

Neuroimmune mechanisms have been linked to the pathophysiology of bipolar disorder based on studies of biomarkers in plasma, cerebrospinal fluid (CSF), and postmortem brain tissue. There are, however, no longitudinal studies investigating if CSF markers of neuroinflammation and neuronal injury predict clinical outcomes in patients with bipolar disorder. We have in previous studies found higher CSF concentrations of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1/CCL-2), chitinase-3-like protein 1 (CHI3L1/YKL-40), and neurofilament light chain (NF-L) in euthymic patients with bipolar disorder compared with controls. Here, we investigated the relationship of these CSF markers of neuroinflammation and neuronal injury with clinical outcomes in a prospective study.77 patients with CSF analyzed at baseline were followed for 6–7years. Associations of baseline biomarkers with clinical outcomes (manic/hypomanic and depressive episodes, suicide attempts, psychotic symptoms, inpatient care, GAF score change) were investigated.Baseline MCP-1 concentrations were positively associated with manic/hypomanic episodes and inpatient care during follow-up. YKL-40 concentrations were negatively associated with manic/hypomanic episodes and with occurrence of psychotic symptoms. The prospective negative association between YKL-40 and manic/hypomanic episodes survived multiple testing correction. Concentrations of IL-8 and NF-L were not associated with clinical outcomes.High concentrations of these selected CSF markers of neuroinflammation and neuronal injury at baseline were not consistently associated with poor clinical outcomes in this prospective study. The assessed proteins may be involved in adaptive immune processes or reflect a state of vulnerability for bipolar disorder rather than being of predictive value for disease progression.

A prospective study of bipolar disorder vulnerability in relation to behavioural activation, behavioural inhibition and dysregulation of the Behavioural Activation System

BackgroundThe weak regulation, or “dysregulation”, of the Behavioural Activation System (BAS) is implicated in the development and recurrence of bipolar disorder. However, there has been a lack of prospective studies investigating the predictive role of BAS dysregulation in relation to bipolar-vulnerability. Furthermore, no studies have tested the prospective predictive utility of the DYS self-report measure of BAS dysregulation in an analogue sample. The goal of the current study was to redress this gap. MethodsParticipants (n=127) completed baseline self-report measures of mood symptoms (Internal States Scale [ISS]), the Hypomanic Personality Scale (HPS), behavioural activation, inhibition and dysregulation of BAS (BIS/BAS and DYS), and at six months, the Mood Disorders Questionnaire (MDQ). ResultsLinear regression analysis indicated a significant main effect of BAS Dysregulation, and a significant interaction between BIS and BAS Fun Seeking, on prospective MDQ scores whilst controlling for baseline mood symptoms and HPS scores. The interaction effect indicated that the relationship between high BAS Fun Seeking and follow-up MDQ scores was strongest when BIS scores were high, whilst the lowest MDQ scores were observed for a combination of low BAS Fun Seeking and high BIS. However, DYS scores were the stronger predictor of MDQ scores compared to the BAS Fun Seeking and BIS interaction. ConclusionsBipolar-vulnerability is prospectively associated with heightened BAS Dysregulation, as measured by the DYS subscale, similar to prior findings in clinical samples. Further research investigating the longer-term associations between BAS Dysregulation with the development of clinically significant bipolar mood symptoms is required.

Creativity, Bipolar Disorder Vulnerability and Psychological Well-Being: A Preliminary Study

The aim of this research was to investigate the relationships between creativity, subclinical bipolar disorder symptomatology, and psychological well-being. The study method was of descriptive, correlational type. Significant tests were performed using multivariate regression analysis. Students of the 4th grade of 6 different Italian colleges (N = 329) completed voluntarily the test of divergent feelings (TDF) included in the creative assessment packet (CAP), the Temperament Evaluation of Memphis, Paris, Pisa and San Diego—Autoquestionnaire (TEMPS-A), and the psychological well-being scale (PWB). Significant positive correlations between creativity and bipolar disorder vulnerability, especially hyperthymia, were found. Creativity was, instead, poorly associated to psychological well-being subscales, except autonomy and personal growth. In addition, although multivariate regression showed that creativity was not a significant predictor of almost all the psychological well-being subscales, it did show a significant association with personal growth. On the contrary, bipolar disorder vulnerability, in particular hyperthymia, was found to significantly predict all psychological well-being scales, except personal growth. These results improve knowledge on the mutual association of creativity, psychological well-being, and bipolar vulnerability, giving a theoretical framework in which situate these constructs.

Towards person-centered neuroimaging markers for resilience and vulnerability in Bipolar Disorder

Improved clinical care for Bipolar Disorder (BD) relies on the identification of diagnostic markers that can reliably detect disease-related signals in clinically heterogeneous populations. At the very least, diagnostic markers should be able to differentiate patients with BD from healthy individuals and from individuals at familial risk for BD who either remain well or develop other psychopathology, most commonly Major Depressive Disorder (MDD). These issues are particularly pertinent to the development of translational applications of neuroimaging as they represent challenges for which clinical observation alone is insufficient. We therefore applied pattern classification to task-based functional magnetic resonance imaging (fMRI) data of the n-back working memory task, to test their predictive value in differentiating patients with BD (n=30) from healthy individuals (n=30) and from patients’ relatives who were either diagnosed with MDD (n=30) or were free of any personal lifetime history of psychopathology (n=30). Diagnostic stability in these groups was confirmed with 4-year prospective follow-up. Task-based activation patterns from the fMRI data were analyzed with Gaussian Process Classifiers (GPC), a machine learning approach to detecting multivariate patterns in neuroimaging datasets. Consistent significant classification results were only obtained using data from the 3-back versus 0-back contrast. Using contrast, patients with BD were correctly classified compared to unrelated healthy individuals with an accuracy of 83.5%, sensitivity of 84.6% and specificity of 92.3%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their relatives with MDD, were respectively 73.1%, 53.9% and 94.5%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their healthy relatives were respectively 81.8%, 72.7% and 90.9%. We show that significant individual classification can be achieved using whole brain pattern analysis of task-based working memory fMRI data. The high accuracy and specificity achieved by all three classifiers suggest that multivariate pattern recognition analyses can aid clinicians in the clinical care of BD in situations of true clinical uncertainty regarding the diagnosis and prognosis.

Associations between circadian rhythm instability, appraisal style and mood in bipolar disorder

BackgroundInternal appraisal styles, in addition to circadian and social rhythm instability, have been implicated in the development of mood experiences in bipolar disorder (BD), yet potential interactions between these variables remain under researched. MethodsThis study used online questionnaires to examine relationships between social and circadian rhythm instability, appraisal style and mood within populations at varying vulnerability for BD. ResultsParticipants with BD (n=51), and those at behavioural high-risk (BHR; n=77), exhibited poor sleep quality and a stronger tendency to form internal appraisals of both positive and negative experiences compared to non-clinical controls (n=498) and participants with fibromyalgia (n=80). Participants with BD also exhibited a stronger tendency to adopt an internal, negative appraisal style compared to individuals at BHR. Sleep disturbance and internal appraisal styles were significantly associated with low mood in BD. LimitationsSleep quality and social rhythm stability were assessed using self-report measures only, which may differ from objective measures. Causal relationships between constructs could not be examined due to the cross-sectional design. ConclusionsThe findings suggest the importance of attending to internal appraisal styles and sleep quality when working therapeutically with individuals diagnosed with BD. Potential differences in the effect of appraisal style at the state and trait level warrant further exploration.

Extreme Appraisals of Internal States and Duration of Remission in Remitted Bipolar Patients.

To identify dysfunctional attitudes seen in bipolar disorder (BPD) is important for the cognitive theories of BPD and corresponding psychosocial interventions. Cognitions are seen as vulnerability factors in the development and maintenance of BPD. The present study aims to contribute to the cognitive literature on BPD by examining depressive and hypomanic attitudes and their contribution to the prediction of BPD diagnosis as well as by exploring the relationship between dysfunctional cognitions and clinical features (types of episodes experienced, duration of illness, and duration of remission). One hundred and eighteen remitted bipolar patients and 103 healthy controls completed the Mood Disorder Questionnaire (MDQ), Turkish Brief-Hypomanic Interpretations and Positive Predictions Inventory (HAPPI), and Dysfunctional Attitudes Scale. The bipolar group had significantly higher depressive and hypomanic attitudes than the control group. No significant differences were found regarding the types of episodes experienced and duration of illness. However, both types of attitudes decreased as the duration of remission increased. They were also found to contribute to the prediction of bipolar diagnosis together with the screening of the MDQ. The results pointed out that dysfunctional cognitions may be utilized as possible indicators for the risk of relapse in clinical groups and vulnerability for BPD among other populations.

Impaired regulation of emotion: neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives.

Deficient emotion regulation has been proposed as a crucial pathological mechanism in bipolar disorder (BD). We therefore investigated emotion regulation impairments in BD, the related neural underpinnings and their etiological relevance for the disorder. Twenty-two euthymic patients with bipolar-I disorder and 17 unaffected first-degree relatives of BD-I patients, as well as two groups of healthy gender-, age- and education-matched controls (N=22/17, respectively) were included. Participants underwent functional magnetic resonance imaging while applying two different emotion regulation techniques, reappraisal and distraction, when presented with emotional images. BD patients and relatives showed impaired downregulation of amygdala activity during reappraisal, but not during distraction, when compared with controls. This deficit was correlated with the habitual use of reappraisal. The negative connectivity of amygdala and orbitofrontal cortex (OFC) observed during reappraisal in controls was reversed in BD patients and relatives. There were no significant differences between BD patients and relatives. As being observed in BD patients and unaffected relatives, deficits in emotion regulation through reappraisal may represent heritable neurobiological abnormalities underlying BD. The neural mechanisms include impaired control of amygdala reactivity to emotional stimuli and dysfunctional connectivity of the amygdala to regulatory control regions in the OFC. These are, thus, important aspects of the neurobiological basis of increased vulnerability for BD.

Common and rare variant analysis in early-onset bipolar disorder vulnerability.

Bipolar disorder is one of the most common and devastating psychiatric disorders whose mechanisms remain largely unknown. Despite a strong genetic contribution demonstrated by twin and adoption studies, a polygenic background influences this multifactorial and heterogeneous psychiatric disorder. To identify susceptibility genes on a severe and more familial sub-form of the disease, we conducted a genome-wide association study focused on 211 patients of French origin with an early age at onset and 1,719 controls, and then replicated our data on a German sample of 159 patients with early-onset bipolar disorder and 998 controls. Replication study and subsequent meta-analysis revealed two genes encoding proteins involved in phosphoinositide signalling pathway (PLEKHA5 and PLCXD3). We performed additional replication studies in two datasets from the WTCCC (764 patients and 2,938 controls) and the GAIN-TGen cohorts (1,524 patients and 1,436 controls) and found nominal P-values both in the PLCXD3 and PLEKHA5 loci with the WTCCC sample. In addition, we identified in the French cohort one affected individual with a deletion at the PLCXD3 locus and another one carrying a missense variation in PLCXD3 (p.R93H), both supporting a role of the phosphatidylinositol pathway in early-onset bipolar disorder vulnerability. Although the current nominally significant findings should be interpreted with caution and need replication in independent cohorts, this study supports the strategy to combine genetic approaches to determine the molecular mechanisms underlying bipolar disorder.

Eveningness and Seasonality are Associated with the Bipolar Disorder Vulnerability Trait

Trait theories of vulnerability to bipolar disorder (BD) are increasingly common in the literature, yet poorly understood. The aim of the current study was to complement existing knowledge of trait theories by investigating two biological rhythm features often associated with BD – eveningness and seasonality – in a sample assessed as vulnerable to the disorder. Two hundred and thirteen participants completed an online survey consisting of the General Behavior Inventory, Seasonal Pattern Assessment Questionnaire, and Morningness-Eveningness Questionnaire. Hierarchical regressions controlling for sex and age showed that greater levels of seasonality and a tendency towards an eveningness chronotype were weak, but significant predictors of the BD vulnerability trait. When the traits of vulnerability to depression and mania were investigated separately, seasonality and eveningness were significant predictors of the former, but only seasonality was a significant predictor of the latter. The Autumn/Winter pattern of seasonality was a weak predictor of trait vulnerability to mania but not depression. The current findings advance understanding of the BD vulnerability trait, and may have consequences for the behavioural management of those who are considered to be ‘at risk’ of the disorder.

Attentional biases toward emotional images in the different episodes of bipolar disorder: An eye-tracking study

Attentional biases toward emotional information may represent vulnerability and maintenance factors in bipolar disorder (BD). The present experimental study examined the processing of emotional information in BD patients using the eye-tracking technology. Bipolar patients in their different states (euthymia, mania, depression) simultaneously viewed four pictures with different emotional valence (happy, neutral, sad, threatening) for 20s while their eye movements were monitored. A group of healthy individuals served as the control. The data revealed the following: (i) a decrease in attention to happy images in BD patients in their depressive episodes compared to healthy individuals, and (ii) an increase in attention to threatening images in BD patients (regardless of their episode) relative to the healthy controls. These biases appeared in the late stages of information processing and were sustained over the 20s interval. Thus, the present findings reveal that attentional biases toward emotional information can be a key feature of BD, in that: (i) an anhedonic lack of sensitivity to positive stimuli during the bipolar depressive episode may be considered a maintaining factor of this clinical state, and (ii) the trait-bias toward threat, even in asymptomatic patients, may reflect a marker of vulnerability in BD.

Reduced Amplitude of the 24 Hour Activity Rhythm

In this study, we sought to advance understanding of trait vulnerability to bipolar disorder (BD) by testing whether instability of the 24-hr activity rhythm was a biomarker of the trait. Locomotor activity was measured over 7 days using actigraphy in participants allocated to groups of high ( n = 36) and low ( n = 36) trait vulnerability for BD. As predicted, the high-vulnerability group recorded a significantly lower 24-hr activity rhythm amplitude than the low-vulnerability group, indicating a less stable activity pattern. Consistent with the notion of accumulating risk, results showed the lowest activity rhythm amplitudes in participants in the high-vulnerability group with a history of depression. Secondary investigations showed that mania proneness explained more variance than depression proneness, pointing to specificity of the findings for BD. The data reinforce claims that instability of daily rhythms is a biomarker of trait vulnerability to BD.