Relatives Of Bipolar Disorder Patients Research Articles

Facial emotion recognition and its association with quality of life and socio-occupational functioning in patients with bipolar disorder and their first-degree relatives

Facial emotion recognition deficits (FERD) are common even in the remitted phase of bipolar disorder (BD). Research regarding FERD in first-degree relatives is inconclusive. This study aimed to assess the facial emotion recognition in remitted patients of bipolar disorder and first-degree relatives(FDR) in comparison with healthy controls. Correlation between FERD and quality of life and socio-occupational functioning was also assessed. It was an observational, cross-sectional study done at a tertiary hospital in India. Study population (n=75) included remitted patients of bipolar disorder (n=27), first-degree relatives of BD patients (FDR) (n=20) and healthy controls (HC) (n=28). Facial emotion recognition, social and occupational functioning, and quality of life (QoL) was measured using Tool for Recognition of Emotions in Neuropsychiatric Disorders, Social & Occupational Functioning Assessment Scale and World Health Organization Quality of Life-Bref, respectively, in all the participants. The BD group did significantly worse in facial emotion recognition in comparison to FDR and HC groups (p<0.001). Emotion recognition of fear, anger, surprise, and happy were most affected. FDR did not vary significantly from HC in facial emotion recognition. Lower scores on facial emotion recognition were associated with lower QoL in the social domain(p=0.006) and poorer socio- occupational functioning scores (p=0.01), but it was not significant within the BD group. FERD is seen in remitted patients of bipolar disorder but not in the first -degree relatives. FERD affects social quality of life and functioning. Poorer social functioning in remitted patients of bipolar disorder might be multifactorial and cannot be attributed solely to FERD.

Genetic Predisposition and Disease Expression of Bipolar Disorder Reflected in Shape Changes of the Anterior Limbic Network

Bipolar disorder (BD) is a genetically and phenotypically complex psychiatric disease. Although previous studies have suggested that the relatives of BD patients have an increased risk of experiencing affective disturbances, most relatives who have similar genotypes may not manifest the disorder. We aim to identify the neuroimaging alterations—specifically, the cortical folding structures of the anterior limbic network (ALN)—in BD patients and their siblings, compared to healthy controls. The shared alterations in patients and their siblings may indicate the hereditary predisposition of BD, and the altered cortical structures unique to BD patients may be a probe of BD expression. High-resolution, T1-weighted magnetic resonance images for 17 euthymic patients with BD, 17 unaffected siblings of BD patients, and 22 healthy controls were acquired. We categorized the cortical regions within the ALN into sulcal and gyral areas, based on the shape index, followed by the measurement of the folding degree, using the curvedness. Our results revealed that the changes in cortical folding in the orbitofrontal and temporal regions were associated with a hereditary predisposition to BD. Cortical folding structures in multiple regions of the ALN, particularly in the striatal–thalamic circuit and anterior cingulate cortex, could be used to differentiate BD patients from healthy controls and unaffected siblings. We concluded that the cortical folding structures of ALN can provide potential biomarkers for clinical diagnosis of BD and differentiation from the unaffected siblings.

Nonlinear dynamics of mood regulation in unaffected first-degree relatives of bipolar disorder patients

BackgroundMood regulation is a complex and poorly understood process. In this study, we aimed to analyze the underlying dynamics of mood regulation in unaffected first degree relatives of patients diagnosed with bipolar disorder using time-series analysis. MethodsWe recruited 30 unaffected first-degree relatives of bipolar disorder patients. Participants rated their mood, anxiety and energy levels using a paper-based visual analog scale; they recorded their sleep and life events as well. Participants provided information on these variables over a three month period, twice per day. We compared their data using Box-Jenkins time series analysis with data from 30 healthy controls (HC) and 30 euthymic bipolar patients (BD) to obtain information on the autocorrelation and cross-correlation of the series, and calculated entropy for mood, anxiety and energy series. ResultsWe analyzed 14,980 data points: 5200 in the healthy control group; 4970 in the bipolar group and 4810 in the unaffected relatives group. There were no significant differences between groups in terms of age, sex or education levels. Using Kolmogorov-Smirnov test, we found that individual measures were normally distributed in the whole sample (D = 0.23, p > 0.1). Autocorrelation functions for mood in all groups are governed by the ARIMA (1,1,0) model, which means that current values in the series are related to one previous point only. In terms of entropy for the mood series, unaffected relatives and bipolar patients showed lower values [mean (SD) : 1.028 ± 0.679; 1.042 ± 0.680], respectively, compared to healthy controls [(1.476 ± 0.33); F (2,74) = 4.39, p < 0.01]. The same case was seen in the energy series, with lower values in the unaffected relatives and bipolar patient groups [mean (SD) : 1.644 ± 0.566; 1.511 ± 0.879], respectively, compared to healthy controls [2.230 ± 0.531; F(2, 75) = 7.89, p < 0.001]. LimitationsLow resolution for the visual analog scale. ConclusionsUsing nonlinear analyses, we found that the underlying structure of mood regulation in unaffected relatives is undistinguishable from the one found in bipolar patients. Compared to healthy controls, both bipolar patients and their unaffected relatives showed lower entropy levels, which is in keeping with a more rigid system, not as flexible to cope with the demands of a changing environment.

All stressed out? Introducing a German version of the perceived stress scale: Validation, psychometric properties and sample differences in healthy and clinical populations

Heightened impulsivity has been suggested as a possible risk factor for bipolar disorder (BD). However, studies on high-risk populations are scarce and have mainly focused on individuals with a genetic risk. The present study investigated two high-risk samples for BD with regard to several aspects of the impulsivity construct.Unaffected relatives of BD patients (genetically defined high-risk group, N=29) and participants scoring high on the Hypomanic Personality Scale (psychometrically defined high-risk sample, N=25) were being compared to respective control groups (N=27 and N=25) using a multi-method approach. Participants were accessed on the Barratt Impulsiveness Scale-11 (BIS-11, trait impulsivity), the Stop Signal Task (response inhibition), and the Cambridge Gambling Task (impulsive behavior in decision-making processes).Both high-risk groups reported heightened impulsivity on the BIS-11, as well as impulsive decision-making, whereas no significant group differences in response inhibition were observed.Limitations were the lack in specificity of the results for BD and the cross-sectional study design, which does not allow conclusions about the influence of impulsivity on the development of or resilience for BD in risk groups.Our findings support the assumption that increased trait impulsivity and impulsive decision-making are a vulnerability marker for and an endophenotype of BD.

320. Studying Mood in Those who Do Not Get Sick: Nonlinear Dynamics of Mood Regulation in First-Degree Healthy Relatives of Bipolar Disorder Patients

320. Studying Mood in Those who Do Not Get Sick: Nonlinear Dynamics of Mood Regulation in First-Degree Healthy Relatives of Bipolar Disorder Patients

Prospective longitudinal study of subcortical brain volumes in individuals at high familial risk of mood disorders with or without subsequent onset of depression

Subcortical volumetric brain abnormalities have been observed in mood disorders. However, it is unknown whether these reflect adverse effects predisposing to mood disorders or emerge at illness onset. Magnetic resonance imaging was conducted at baseline and after two years in 111 initially unaffected young adults at increased risk of mood disorders because of a close family history of bipolar disorder and 93 healthy controls (HC). During the follow-up, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the others remaining well (HR-well). Volumes of the lateral ventricles, caudate, putamen, pallidum, thalamus, hippocampus and amygdala were extracted for each hemisphere. Using linear mixed-effects models, differences and longitudinal changes in subcortical volumes were investigated between groups (HC, HR-MDD, HR-well). There were no significant differences for any subcortical volume between groups controlling for multiple testing. Additionally, no significant differences emerged between groups over time. Our results indicate that volumetric subcortical brain abnormalities of these regions using the current method appear not to form familial trait markers for vulnerability to mood disorders in close relatives of bipolar disorder patients over the two-year time period studied. Moreover, they do not appear to reduce in response to illness onset at least for the time period studied.

P1.a.029 Early-life trauma as susceptibility to develop depression in hepatitis C virus patients following long-term treatment with interferon-alpha

The purpose of this study is to examine the prevalence of affective temperaments between clinically unaffected relatives of bipolar patients and secondarily to investigate the impact of these “subaffective” forms on their quality of life (QoL).The study was performed in seven sites across Argentina. We administered the scales TEMPS-A and Quality of Life Index to a sample of 114 non-ill first degree relatives of bipolar disorder patients (“cases”) and 115 comparison subjects without family history of affective illness (“controls”). We used The Mood Disorder Questionnaire to rule out clinical bipolarity.Mean scores on all TEMPS-A subscales were significantly higher in cases, except for hyperthymia. The prevalence of affective temperaments, according to Argentinean cut-off points, was also higher, with statistical significance for cyclothymic and anxious temperaments. Regarding QoL, we found no significant differences between both groups, except for interpersonal functioning, which was better in controls. A detailed subanalysis showed significant effects of QoL domains for all temperaments, except for the hyperthymic.We used self-report measures. A larger sample size would have provided us greater statistical power for certain analyses.Our findings support the concept of a spectrum of subthreshold affective traits or temperaments – especially for the cyclothymic and anxious – in bipolar pedigrees. We further demonstrated that, except for the hyperthymic, quality of life was affected by these temperaments in “clinically well” relatives. Overall, our data are compatible with the “endophenotype” and “subaffective” theses for affective temperaments.

Gray matter abnormalities as brain structural vulnerability factors for bipolar disorder: A review of neuroimaging studies of individuals at high genetic risk for bipolar disorder

Cortical and subcortical gray matter abnormalities have been reported in individuals at high genetic risk for bipolar disorder, but the findings are inconsistent. The aim of this study was to review the available literature to identify common findings that could represent brain structural vulnerability factors for bipolar disorder and to discuss challenges for the advancement of the field. A systematic search was conducted using the PubMed database to identify all original articles investigating cortical or subcortical gray matter abnormalities in first-degree relatives of bipolar disorder patients. Very few findings were replicated, with the exception of larger insular cortex volumes in adult first-degree relatives and larger right inferior frontal gyrus in offspring of probands with bipolar disorder, both when compared with healthy controls. Isolated findings included decreased gray matter density in the left thalamus, decreased gray matter volumes in the left hippocampus and parahippocampal gyrus, and thicker right hippocampus in unaffected first-degree relatives. Genetic liability for bipolar disorder was associated with gray matter volumes in regions of the anterior cingulate cortex, ventral striatum, medial frontal gyrus, right precentral gyrus, right insular cortex, and medial orbital gyrus. Some studies found no evidence for gray matter abnormalities in first-degree relatives of bipolar disorder patients. Possible reasons for the discrepancies of findings across studies include small samples sizes, small effect size of susceptibility genes, the phenotypic heterogeneity of bipolar disorder, and the possible confounding effect of other Axis I psychopathologies among the relatives of patients. Future multisite, prospective, large studies with more homogeneous samples would be a key strategy to advance the field. The ultimate benefit would be an understanding of how to use brain imaging tools to identify individuals at increased risk for bipolar disorder and develop preventive strategies for that population.

Cognitive endophenotypes in a family with bipolar disorder with a risk locus on chromosome 4

We studied cognitive function in high-risk relatives belonging to a single extended family showing linkage of bipolar disorder to a locus on chromosome 4. High-risk relatives were defined as those that carried the risk haplotype of polymorphic markers, identified in a previous linkage study. This family provided a rare opportunity to characterize a neuropsychological endophenotype in a homogeneous sample of relatives with a common genetic risk factor. Fifteen family members carrying the risk haplotype (eight diagnosed with bipolar disorder or depression and seven with no psychiatric diagnosis), unrelated patients with bipolar disorder (n = 36) and major depressive disorder (n = 40), and healthy control subjects (n = 33) were administered the California Verbal Learning Test, Verbal Fluency Test, Hayling Sentence Completion Test, and Brixton Spatial Anticipation Test to assess verbal memory, verbal fluency, and executive function. Compared with healthy controls, family members carrying the risk haplotype were impaired in indices of memory and executive function. There were no significant differences between unaffected and affected haplotype-carrying family members in any cognitive measure. Pronounced deficits in the encoding stage of verbal memory and category verbal fluency were evident in individuals with the risk haplotype. Verbal learning and semantic verbal fluency impairments may represent a cognitive endophenotype for both bipolar disorder and major depression in relatives of bipolar disorder patients, as impairment was also present in high-risk relatives who had not developed any affective disorder symptoms. These findings suggest that impairment in semantic organization may be linked to the genetic aetiology of bipolar disorder.

Is impulsivity a common trait in bipolar and unipolar disorders?

Impulsivity is increased in bipolar and unipolar disorders during episodes and is associated with substance abuse disorders and suicide risk. Impulsivity between episodes predisposes to relapses and poor therapeutic compliance. However, there is little information about impulsivity during euthymia in mood disorders. We sought to investigate trait impulsivity in euthymic bipolar and unipolar disorder patients, comparing them to healthy individuals and unaffected relatives of bipolar disorder patients. Impulsivity was evaluated by the Barratt Impulsiveness Scale (BIS-11A) in 54 bipolar disorder patients, 25 unipolar disorder patients, 136 healthy volunteers, and 14 unaffected relatives. The BIS-11A mean scores for all four groups were compared through the Games-Howell test for all possible pairwise combinations. Additionally, we compared impulsivity in bipolar and unipolar disorder patients with and without a history of suicide attempt and substance abuse disorder. Bipolar and unipolar disorder patients scored significantly higher than the healthy controls and unaffected relatives on all measures of the BIS-11A except for attentional impulsivity. On the attentional impulsivity measures there were no differences among the unaffected relatives and the bipolar and unipolar disorder groups, but all three of these groups scored higher than the healthy participant group. There was no difference in impulsivity between bipolar and unipolar disorder subjects with and without suicide attempt. However, impulsivity was higher among bipolar and unipolar disorder subjects with past substance use disorder compared to patients without such a history. Questionnaire-measured impulsivity appears to be relatively independent of mood state in bipolar and unipolar disorder patients; it remains elevated in euthymia and is higher in individuals with past substance abuse. Elevated attentional and lower non-planning impulsivity in unaffected relatives of bipolar disorder patients distinguished them from healthy participants, suggesting that increased attentional impulsivity may predispose to development of affective disorders, while reduced attentional impulsivity may be protective.

The Neural Basis of Familial Risk and Temperamental Variation in Individuals at High Risk of Bipolar Disorder

Bipolar disorder is a highly heritable psychiatric disorder characterized by episodic elevation or depression of mood. Bipolar disorder is associated with structural and functional brain abnormalities but it is unclear whether these are present in relatives of affected individuals and if they are associated with subclinical symptoms or traits associated with the disorder. Functional magnetic resonance imaging scans were conducted on 93 unrelated relatives of bipolar disorder patients and 70 healthy comparison subjects performing the Hayling sentence completion paradigm. Examination of comparison subjects versus high-risk individuals was followed by assessments of associations with depression scores and measures of cyclothymic temperament. Examination of comparison subjects versus high-risk subjects revealed increased activation in the high-risk group in the left amygdala. No interaction effects were observed between the groups for scores of depression or cyclothymia and activation in any region. Significant associations were found across the groups with depression ratings and activation in the ventral striatum and with cyclothymia and activation in ventral prefrontal regions, however no interaction effects were observed between the groups. Differences in activation in the left amygdala in those at familial risk may represent a heritable endophenotype of bipolar disorder. Activation in striatal and ventral prefrontal regions may, in contrast, represent a distinct biological basis of subclinical features of the illness regardless of the presence of familial risk.

Dissociable functional connectivity changes during the Stroop task relating to risk, resilience and disease expression in bipolar disorder

Reduced cognitive control is considered a core feature of bipolar disorder (BD). Abnormalities in ventrolateral prefrontal cortex (VLPFC) and other functionally linked regions that underpin cognitive control during the Stroop Colour Word Task (SCWT) have been reported in patients with BD and their relatives. In this functional magnetic resonance study we used psychophysiological interaction analysis to examine functional connectivity during the SCWT in 39 euthymic BD patients, 39 of their first-degree relatives (25 with no Axis I disorders and 14 with major depressive disorder) and 48 healthy controls. The aim of this study was to identify potential diagnosis-specific functional connectivity changes differentiating patients with BD from their relatives with MDD, as well as functional connectivity correlates of resilience in relatives of BD patients who remain well. Psychophysiological interactions in healthy controls revealed a negative functional connectivity between the VLPFC and the ventral anterior cingulate cortex and insula and a positive connectivity between the VLPFC and the caudate and parietal cortices. Abnormalities in fronto-insular connectivity emerged as a key correlate of predisposition and disease expression for BD. Reduced fronto-cingulate connectivity was also observed in association with predisposition to BD irrespective of clinical outcome. BD patients and their MDD relatives showed additional abnormalities in frontal-basal ganglia connectivity while increased coupling between the ventral and dorsal lateral PFC was observed in relatives without any Axis I disorder. These findings suggest that during the SCWT the VLPFC and subcortical regions are involved in a dynamic interplay. Breakdown in these interactions is associated with risk and disease expression for mood disorders while increased functional coupling between dorsal and ventral prefrontal regions may reflect adaptive functional changes associated with resilience.

Executive and verbal working memory dysfunction in first-degree relatives of patients with bipolar disorder

The authors aimed to investigate cognitive performance of first-degree relatives of probands with bipolar disorder (BD). They hypothesized that the relatives of BD patients would have impaired performance on cognitive tests of frontal-executive functions. A neuropsychological battery was administered to 34 first-degree relatives of BD probands and 25 control subjects. Relatives showed significant impairment in verbal working memory and executive function. Verbal memory and psychomotor performances of relatives were not different from control subjects. One particular component of executive function, cognitive flexibility, was associated with family history of mood episodes with psychotic features. Verbal working memory and executive function deficits may be useful endophenotypic markers of genetic vulnerability to BD.

Neurocognition in first‐degree healthy relatives (siblings) of bipolar affective disorder patients

Cognitive deficits have been presupposed to be endophenotypic markers in bipolar disorder, but few studies have ascertained the cognitive deficits in healthy relatives of bipolar disorder patients. The aim of the present study was to assess the cognitive functions of first-degree relatives of patients with bipolar disorder and compare them with healthy controls. Ten first-degree apparently healthy relatives of patients with bipolar disorder were compared with 10 age- and education-matched control subjects on computer-based cognitive tests. As compared to the control group, the relatives group performed significantly poorly on tests for executive function and vigilance, while on the test for working memory the performance was not significantly different on most of the parameters. Executive functioning and vigilance could be potential markers of the endophenotype in bipolar patients.

Bipolar disorders and affective temperaments: A national family study testing the “endophenotype” and “subaffective” theses using the TEMPS-A Buenos Aires

Background The purpose of this study is to examine the prevalence of affective temperaments between clinically unaffected relatives of bipolar patients and secondarily to investigate the impact of these “subaffective” forms on their quality of life (QoL). Methods The study was performed in seven sites across Argentina. We administered the scales TEMPS-A and Quality of Life Index to a sample of 114 non-ill first degree relatives of bipolar disorder patients (“cases”) and 115 comparison subjects without family history of affective illness (“controls”). We used The Mood Disorder Questionnaire to rule out clinical bipolarity. Results Mean scores on all TEMPS-A subscales were significantly higher in cases, except for hyperthymia. The prevalence of affective temperaments, according to Argentinean cut-off points, was also higher, with statistical significance for cyclothymic and anxious temperaments. Regarding QoL, we found no significant differences between both groups, except for interpersonal functioning, which was better in controls. A detailed subanalysis showed significant effects of QoL domains for all temperaments, except for the hyperthymic. Limitations We used self-report measures. A larger sample size would have provided us greater statistical power for certain analyses. Conclusions Our findings support the concept of a spectrum of subthreshold affective traits or temperaments – especially for the cyclothymic and anxious – in bipolar pedigrees. We further demonstrated that, except for the hyperthymic, quality of life was affected by these temperaments in “clinically well” relatives. Overall, our data are compatible with the “endophenotype” and “subaffective” theses for affective temperaments.

Reduced Glucocorticoid Receptor α Expression in Mood Disorder Patients and First-Degree Relatives

Individuals with mood disorders exhibit altered function of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. The glucocorticoid receptor (GR) plays an important role in the negative feedback regulation of the HPA axis. There are two protein isoforms of GR, GRalpha and GRbeta, which have distinct biological activity. It has not been examined whether GRalpha messenger RNA (mRNA) and GRbeta mRNA expressions are altered in peripheral blood cells of mood disorder patients. Using quantitative reverse transcription polymerase chain reaction (RT-PCR), GRalpha mRNA and GRbeta mRNA were measured in peripheral blood cells of major depressive disorder patients (depressive n = 18; remissive n = 38), bipolar disorder patients (depressive n = 13; remissive n = 35), normal control subjects (n = 31), and first-degree relatives of major depressive (n = 17) and bipolar (n = 15) disorder patients. Reduced expression of GRalpha mRNA was shown in both bipolar and major depressive disorder patients in a current depressive state as well as in remission. First-degree relatives of bipolar disorder patients also showed GRalpha mRNA reduction. Altered GRbeta mRNA expression was not found in mood disorder patients. Our results suggest that reduced GRalpha mRNA expression might be trait-dependent and associated with the pathophysiology of mood disorders.