Can Risk-Taking Be an Endophenotype for Bipolar Disorder? A Study on Patients with Bipolar Disorder Type I and Their First-Degree Relatives

Hıdıroğlu, Ceren; Esen, Özlem Demirci; Tunca, Zeliha; Yalçìn, Şehnaz Neslihan Gűrz; Lombardo, Lauren; Glahn, David C.; Özerdem, Ayşegül

doi:10.1017/s1355617713000015

Cited by 40 publications

(27 citation statements)

References 40 publications

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“…However, specificity of impulsivity to BD is questionable as it shows shared genetic liability with SCH and major depressive disorder [30] and requires further studies. Risk-taking behavior may also be a potential endophenotype and predictor of BD [32, 33]. …”

Section: Resultsmentioning

confidence: 99%

Neurobiology of Risk for Bipolar Disorder

Özerdem

Ceylan

Can

2016

Curr Treat Options Psych

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Opinion statementBipolar disorder (BD) is a chronic mental illness which follows a relapsing and remitting course and requires lifetime treatment. The lack of biological markers for BD is a major difficulty in clinical practice. Exploring multiple endophenotypes to fit in multivariate genetic models for BD is an important element in the process of finding tools to facilitate early diagnosis, early intervention, prevention of new episodes, and follow-up of treatment response in BD. Reviewing of studies on neuroimaging, neurocognition, and biochemical parameters in populations with high genetic risk for the illness can yield an integrative perspective on the neurobiology of risk for BD. The most up-to-date data reveals consistent deficits in executive function, response inhibition, verbal memory/learning, verbal fluency, and processing speed in risk groups for BD. Functional magnetic resonance imaging (fMRI) studies report alterations in the activity of the inferior frontal gyrus, medial prefrontal cortex, and limbic areas, particularly in the amygdala in unaffected first-degree relatives (FDR) of BD compared to healthy controls. Risk groups for BD also present altered immune and neurochemical modulation. Despite inconsistencies, accumulating data reveals cognitive and imaging markers for risk and to a less extent resilience of BD. Findings on neural modulation markers are preliminary and require further studies. Although the knowledge on the neurobiology of risk for BD has been inadequate to provide benefits for clinical practice, further studies on structural and functional changes in the brain, neurocognitive functioning, and neurochemical modulation have a potential to reveal biomarkers for risk and resilience for BD. Multimodal, multicenter, population-based studies with large sample size allowing for homogeneous subgroup analyses will immensely contribute to the elucidation of biological markers for risk for BD in an integrative model.

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Section: Resultsmentioning

confidence: 99%

Neurobiology of Risk for Bipolar Disorder

Özerdem

Ceylan

Can

2016

Curr Treat Options Psych

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“…However, the results do not show the underlying causes that link them. Within BD, relatively few relatives meet full diagnostic criteria for the disorder, but many experience high levels of impulsivity when compared to healthy controls ( Hıdıroğlu et al, 2013 ). One possibility is that lack of inhibitory control in relatives is a marker of familial contexts which are prone to maltreatment behaviors.…”

Section: Discussionmentioning

confidence: 99%

Integrative Understanding of Familial Impulsivity, Early Adversity and Suicide Risk

et al. 2017

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Introduction: Impulsivity is a core characteristic of bipolar disorder and it was observed as elevated in individuals with the disorder and in their relatives. Both impulsivity and history of maltreatment are risk factors for suicide attempts, however, these two key variables may not be independent, given the fact that parental impulsivity and associated social context could increase the risk of child maltreatment. In this study it was examined the association between the impulsivity of relatives and child maltreatment taking into consideration the conjoint and unique effects of these two variables on the risk of suicide attempts among the patients.Materials and Methods: Participants of the study consisted of 117 patients diagnosed with bipolar disorder and 25 first-degree relatives. Linear regression model was conducted to describe associations between facets of impulsivity of relatives and levels of child maltreatment reported by patients. The independent associations of suicide attempt history with the dimensions of impulsivity of the patient and maltreatment were tested by multinomial logistic regression.Results: Impulsivity of relatives and, more specifically, inhibitory control can predict the maltreatment of the patient. Inhibitory control and emotional abuse were related, conjointly, to a greater likelihood of having a history of more than one suicide attempt.Discussion: Considering that the impulsivity of relatives predicts child maltreatment, it is possible that a genetically shared impulsivity is an underlying feature associated with the history of multiple suicide attempts. These findings highlight the importance of considering child maltreatment, impulsivity and suicide attempt history in integrative models.

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“…Dysmodulation of reward and emotion processing and emotion regulation, including failure to down-regulate emotional reactivity to positive stimuli, may represent a specific endophenotype of BD given evidence of co-segregation of these traits in families at risk for BD. Behavioural studies have found that BD patients and URs compared to healthy controls showed a reduced ability to modulate risk taking in the face of certain types of stressors (Hidiroglu et al 2013 ) and increased trait impulsivity and impulsive decision-making (Wessa et al 2015 ).…”

Section: Cognitive Emotional and Reward Processing Endophenotypesmentioning

confidence: 99%

Evaluating endophenotypes for bipolar disorder

Guglielmo

Hasler

2021

Int J Bipolar Disord

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Background Phenotypic heterogeneity is a major impediment to the elucidation of the neurobiology and genetics of bipolar disorder. Endophenotype could help in reducing heterogeneity by defining biological traits that are more direct expressions of gene effects. The aim of this review is to examine the recent literature on clinical, epidemiological, neurobiological, and genetic findings and to select and evaluate candidate endophenotypes for bipolar disorder. Evaluating putative endophenotype could be helpful in better understanding the neurobiology of bipolar disorder by improving the definition of bipolar-related phenotypes in genetic studies. In this manner, research on endophenotypes could be useful to improve psychopathological diagnostics in the long-run by dissecting psychiatric macro phenotypes into biologically valid components. Main body The associations among the psychopathological and biological endophenotypes are discussed with respect to specificity, temporal stability, heritability, familiarity, and clinical and biological plausibility. Numerous findings regarding brain function, brain structure, neuropsychology and altered neurochemical pathways in patients with bipolar disorder and their relatives deserve further investigation. Overall, major findings suggest a developmental origin of this disorder as all the candidate endophenotypes that we have been able to select are present both in the early stages of the disorder as well as in subjects at risk. Conclusions Among the stronger candidate endophenotypes, we suggest circadian rhythm instability, dysmodulation of emotion and reward, altered neuroimmune state, attention and executive dysfunctions, anterior cingulate cortex thickness and early white matter abnormalities. In particular, early white matter abnormalities could be the result of a vulnerable brain on which new stressors are added in young adulthood which favours the onset of the disorder. Possible pathways that lead to a vulnerable brain are discussed starting from the data about molecular and imaging endophenotypes of bipolar disorder.

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Can Risk-Taking Be an Endophenotype for Bipolar Disorder? A Study on Patients with Bipolar Disorder Type I and Their First-Degree Relatives

Cited by 40 publications

References 40 publications

Neurobiology of Risk for Bipolar Disorder

Neurobiology of Risk for Bipolar Disorder

Integrative Understanding of Familial Impulsivity, Early Adversity and Suicide Risk

Evaluating endophenotypes for bipolar disorder

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