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The Role of Resilience and the Interplay between Genetics and Environment in Bipolar Disorder

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Bipolar disorder is a complex psychiatric disorder that affects between 1% and 3% of the population worldwide and is characterized by episodes of mania/hypomania and depression. Both genetic and environmental factors play relevant roles in its pathophysiology and treatment. However, the complex biological ...

Bipolar disorder is a complex psychiatric disorder that affects between 1% and 3% of the population worldwide and is characterized by episodes of mania/hypomania and depression. Both genetic and environmental factors play relevant roles in its pathophysiology and treatment. However, the complex biological mechanisms underlying this disorder are still unclear, and little is known about the interaction between genetic and environmental risk factors that alter clinical outcomes. In this context, while some people may present only one risk component (either genetic predisposition or exposure to an environmental trigger) and not develop the illness, others may have no identifiable risk factor and develop the disorder anyway. In addition, such heterogeneity is also seen among patients, in which only a subset of them may develop a progressive course related to distinct neurobiological underpinnings and worse clinical outcomes, such as reduced responsiveness to treatment, recurrent mood episodes, and impaired cognition and functioning. Understanding why different subjects show such varying degrees of risk may provide valuable information to the field, ultimately informing mechanisms related to heterogeneous clinical presentations in patients, as well.

What is the explanation for these differences? Resilience may be one of the answers. In Psychology, resilience is defined as the process of adapting well in the face of adversity, trauma, threats or significant sources of stress. At the cellular level, resilience is the ability of cells to adapt to different insults or stressful conditions, activating molecular pathways to restore the cellular balance. Impaired resilience may be one possible explanation for an increased vulnerability for some individuals to develop bipolar disorder, and for those who show worse prognoses. Which factors are likely to be crucial for resilience? How could these factors influence the risk of developing bipolar disorder and impact on its progression? Considering the biological and psychological points of view, how can we measure and improve them? How are different types of resilience parameters linked to bipolar disorder?

Several molecular pathways related to bipolar disorder pathophysiology have already been identified and may help with understanding the progressive biological and clinical changes associated with this illness. Understanding the relationship across complex hierarchies of such biological processes (from the genome and transcriptional regulation, protein, and cellular changes), environmental influence and finally the ultimate clinical phenotype, will be a crucial focus of research in this field and will help to clarify the pathophysiology of the disorder and provide novel insights into personalized medicine.

This Research Topic welcomes scientific contributions, including Original Research, Reviews, meta-analyses, Case Report, and theoretical reflections and Perspectives that focus on understanding how resilience interacts with genetic and environmental factors to impact on biological changes in the body and clinical outcomes in bipolar disorder.

We welcome clinical and pre-clinical studies (including basic research in humans and/or animals) focused on identifying resilience factors at different levels, from cellular to psychological resilience (biological, social, and environmental factors), elucidating how such factors interact with known risk factors in bipolar disorder and lead to biological changes (alterations in peripheral and central biomarkers, imaging, genetics, epigenetics, molecular pathways) and clinical outcomes (functional/cognitive impairments, illness progression, response to treatment).


Keywords: Bipolar Disorder, Resilience, Genetic Risk Factor, Epigenetics, Environmental Risk Factor


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