High Genetic Risk For Bipolar Disorder Research Articles

State- and trait-related dysfunctions in bipolar disorder across different mood states: a graph theory study.

The interplay between state- and trait-related disruptions in structural networks remains unclear in bipolar disorder (BD), but graph theory can offer insights into global and local network changes. We sought to use diffusion-tensor imaging (DTI) and graph theory approaches to analyze structural topological properties across distinct mood states and identify high-risk individuals by examining state- and trait-related impairments in BD. We studied changes in white matter network among patients with BD and healthy controls, exploring relationships with clinical variables. Secondary analysis involved comparing patients with BD with unaffected people at high genetic risk for BD. We included 152 patients with BD, including 52 with depressive BD (DBD), 64 with euthymic BD (EBD) and 36 with manic BD (MBD); we also included 75 healthy controls. Secondary analyses involved 27 unaffected people at high genetic risk for BD. Patients with DBD and MBD exhibited significantly lower global efficiencies than those with EBD and healthy controls, with patients with DBD showing the lowest global efficiencies. In addition, patients with DBD displayed impaired local efficiency and normalized clustering coefficient (γ). At a global level, γ correlated negatively with depression and anxiety. Compared with healthy controls, and across mood states, patients with BD showed abnormal shortest path lengths in the frontolimbic circuit, a trend mirrored among those at high genetic risk for BD. Considerations include medication effects, absence of recorded BD episode counts and the cross-sectional nature of the study. Mood-specific whole-brain network metrics could serve as potential biomarkers in BD for transitions between mood states. Moreover, these findings contribute to evidence of trait-related frontolimbic circuit irregularities, shedding light on underlying pathophysiological mechanisms in BD.

Structural dysconnectivity of key cognitive and emotional hubs in young people at high genetic risk for bipolar disorder

Emerging evidence suggests that psychiatric disorders are associated with disturbances in structural brain networks. Little is known, however, about brain networks in those at high risk (HR) of bipolar disorder (BD), with such disturbances carrying substantial predictive and etiological value. Whole-brain tractography was performed on diffusion-weighted images acquired from 84 unaffected HR individuals with at least one first-degree relative with BD, 38 young patients with BD and 96 matched controls (CNs) with no family history of mental illness. We studied structural connectivity differences between these groups, with a focus on highly connected hubs and networks involving emotional centres. HR participants showed lower structural connectivity in two lateralised sub-networks centred on bilateral inferior frontal gyri and left insular cortex, as well as increased connectivity in a right lateralised limbic sub-network compared with CN subjects. BD was associated with weaker connectivity in a small right-sided sub-network involving connections between fronto-temporal and temporal areas. Although these sub-networks preferentially involved structural hubs, the integrity of the highly connected structural backbone was preserved in both groups. Weaker structural brain networks involving key emotional centres occur in young people at genetic risk of BD and those with established BD. In contrast to other psychiatric disorders such as schizophrenia, the structural core of the brain remains intact, despite the local involvement of network hubs. These results add to our understanding of the neurobiological correlates of BD and provide predictions for outcomes in young people at high genetic risk for BD.

Facial emotion recognition in euthymic patients with bipolar disorder and their unaffected first-degree relatives

BackgroundFacial emotion recognition (FER) is an important task associated with social cognition because facial expression is a significant source of non-verbal information that guides interpersonal relationships. Increasing evidence suggests that bipolar disorder (BD) patients present deficits in FER and these deficits may be present in individuals at high genetic risk for BD. The aim of this study was to evaluate the occurrence of FER deficits in euthymic BD patients, their first-degree relatives, and healthy controls (HC) and to consider if these deficits might be regarded as an endophenotype candidate for BD. MethodsWe studied 23 patients with DSM-IV BD type I, 22 first-degree relatives of these patients, and 27 HC. We used the Penn Emotion Recognition Tests to evaluate tasks of FER, emotion discrimination, and emotional acuity. Patients were recruited from outpatient facilities at the Institute of Psychiatry of the University of Sao Paulo Medical School, or from the community through media advertisements, had to be euthymic, with age above 18years old and a diagnosis of DSM-IV BD type I. ResultsEuthymic BD patients presented significantly fewer correct responses for fear, and significantly increased time to response to recognize happy faces when compared with HC, but not when compared with first-degree relatives. First-degree relatives did not significantly differ from HC on any of the emotion recognition tasks. ConclusionOur results suggest that deficits in FER are present in euthymic patients, but not in subjects at high genetic risk for BD. Thus, we have not found evidence to consider FER as an endophenotype candidate for BD.

Serum BDNF levels in unaffected first-degree relatives of patients with bipolar disorder.

Objective:Unaffected relatives of bipolar disorder (BD) patients have been investigated for the identification of endophenotypes in an attempt to further elucidate the pathophysiology of the disease. Brain-derived neurotrophic factor (BDNF) is considered to be implicated in the pathophysiology of BD, but its role as an endophenotype has been poorly studied. We investigated abnormal serum BDNF levels in BD patients, in their unaffected relatives, and in healthy controls.Methods:BDNF levels were obtained from 25 DSM-IV bipolar I disorder patients, 23 unaffected relatives, and 27 healthy controls. All BD patients were in remission. The unaffected subjects were first-degree relatives of the proband who had no lifetime DSM-IV diagnosis of axis I disorder. BDNF serum levels were determined by sandwich ELISA using monoclonal BDNF-specific antibodies.Results:There were no statistical differences in BDNF levels among BD patients, relatives, and healthy controls.Conclusion:Serum BDNF levels may not indicate high genetic risk for BD, possibly acting as state markers rather than trait markers of the disease.

What clinical features precede the onset of bipolar disorder?

Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12–30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD (‘AR’), b) participants from families without mental illness (‘controls’), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.

Impulsivity in children and adolescents with mood disorders and unaffected offspring of bipolar parents

ObjectiveIncreased impulsivity seems to be present across all phases of bipolar disorder (BD). Impulsivity may therefore represent an endophenotype for BD, if it is also found among normal individuals at high genetic risk for mood disorders. In this study, we assessed impulsivity across four different groups of children and adolescents: patients with BD, major depressive disorder (MDD) patients, unaffected offspring of bipolar parents (UO), and healthy controls (HC). Subjects and Methods52 patients with BD, 31 with MDD, 20 UO, and 45 HC completed the Barratt Impulsiveness Scale (BIS-11), an instrument designed to measure trait impulsivity. ResultsUO displayed significantly higher total BIS-11 impulsivity scores than HC (p=0.02) but lower scores than BD patients (F=27.12, p<0.01). Multiple comparison analysis revealed higher BIS-11 total scores among BD patients when compared to HC (p<0.01) and UO (p<0.01). MDD patients had higher BIS-11 scores when compared to HC (p<0.01). Differences between MDD patients and UO, as well as between MDD and BD patients, were not statistically significant. ConclusionOur findings suggest that trait impulsivity is increased among children and adolescents with mood disorders, as well as in unaffected individuals at high genetic risk for BD.

Comparison of Cognitive Vulnerability Indicators in Bipolar disorder (BD) and Schizophrenia (SZ)

Event Abstract Back to Event Comparison of Cognitive Vulnerability Indicators in Bipolar disorder (BD) and Schizophrenia (SZ) Anastasia-Tessa Christodoulou1* 1 Institute of Psychiatry, United Kingdom Background:Investigation of cognitive deficits in healthy individuals (No Axis I or II disorders) at high genetic risk for BD and SZ. Materials and Methods: 17 and 15 (BD-R and SZ-R) and 23 controls. They underwent assessment of Full Scale IQ (Wechsler Adult Intelligence Scale Revised, WAIS-R), verbal memory and learning (California Verbal Learning test, CVLT), working memory (N-back), inhibition and initiation (Hayling Sentence Completion Task, HSCT), verbal fluency (Controlled Oral Word Association, COWA) and tasks requiring switching between stimulus independent and orientated conditions. The Structured Clinical Interview for DSM-IV (SCID) confirmed the lack of Axis I and II disorders. Level of symptomatology was assessed with the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). Results: No difference was found in the IQ. Loss of inhibition was found for both SZ-R and BD-R (HSCT) who also underperformed compared to controls in short and long delay recall in the verbal learning and memory (CVLT). SZ-R made more intrusions and perseverations (CVLT). Both produced fewer words compared to controls whereas the SZ-R made more errors (COWA). The SZ-R had fewer correct responses (n-back) and failed to inhibit relatively fast erroneous responses, leading to errors but not reaction times (switching). Conclusions: Genetic predisposition to SZ may be mediated by dysfunction in the anterior and Ventral Prefrontal Cortex (VPFC) (BA45/47), Dorsal Prefrontal Cortex (DPFC) and posterior (BA9, 44, 46) areas of the inferior frontal gyrus, the right rostrolateral PFC (BA 10), right DPFC and bilateral superior parietal cortex and temporal networks. In BD-R impairment was limited in the VPFC (BA45/47) whereas the DPFC (BA9, 46) and related functions were preserved. SZ and BD share inhibition deficits associated with the VPFC whereas impairments in the frontotemporal networks and the DPFC may be associated with genetic predisposition to SZ. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Christodoulou A (2009). Comparison of Cognitive Vulnerability Indicators in Bipolar disorder (BD) and Schizophrenia (SZ). Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.114 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Jun 2009; Published Online: 08 Jun 2009. * Correspondence: Anastasia-Tessa Christodoulou, Institute of Psychiatry, London, United Kingdom, tessa_christodoulou@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anastasia-Tessa Christodoulou Google Anastasia-Tessa Christodoulou Google Scholar Anastasia-Tessa Christodoulou PubMed Anastasia-Tessa Christodoulou Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.