What causes bipolar in the brain
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Causes of Bipolar Disorder in the Brain
Genetic Factors and Bipolar Disorder
Genetic Susceptibility and Polymorphisms
Bipolar disorder (BD) has a strong genetic component, with numerous studies identifying various genetic factors that contribute to its development. Genome-wide association studies (GWAS) have highlighted polymorphisms in genes such as CACNA1C, which is involved in calcium channel functioning, as significant contributors to BD5 10. Additionally, polymorphisms in the brain-derived neurotrophic factor (BDNF) gene have been linked to increased susceptibility to BD, suggesting that genetic variations play a crucial role in the disorder's pathogenesis7.
Neuroanatomical Risk Factors
Neuroimaging studies have identified structural brain abnormalities in individuals with BD, which may serve as biological risk factors. Abnormalities in the volume of the striatum, white matter, thalamus, and anterior cingulate have been observed in both affected individuals and their unaffected relatives, indicating a potential genetic predisposition4. These structural changes are thought to contribute to the neurocognitive and affective symptoms of BD2.
Neuroinflammation and Bipolar Disorder
Inflammatory Markers
Neuroinflammation has been extensively studied as a potential etiopathophysiological cause of BD. Postmortem studies have shown evidence of inflammation in the brains of individuals with BD, including changes in microglia, astrocytes, and cytokine levels3. However, the findings are inconsistent, with some studies reporting no significant effects, highlighting the need for further research to clarify the role of neuroinflammation in BD3.
Chronic Stress and Inflammation
Chronic stress and inflammation are also implicated in the development of BD. Stress can trigger mania and sleep disturbances, which in turn cause low-grade inflammation. This inflammation can desynchronize the internal clock, leading to mood instability. Contemporary Western lifestyles, characterized by high stress, poor diet, and limited physical activity, exacerbate these inflammatory processes, suggesting that lifestyle changes could be a crucial component of BD treatment8.
Neurotransmitter and Neurotrophic Pathways
Neurotransmitter Dysregulation
BD is associated with dysregulation in various neurotransmitter systems, including serotonin, dopamine, and glutamate pathways. These neurotransmitter imbalances are thought to contribute to the mood swings and cognitive deficits observed in BD1. Defects in neurotransmitter signaling pathways, such as those involving calcium channels and neurotrophic factors, further complicate the disorder's pathophysiology1 5.
Neurotrophic Factors
The role of neurotrophic factors, particularly BDNF, is significant in BD. BDNF is involved in neuroplasticity and brain development, and its dysregulation has been linked to mood disorders. Studies have shown that specific polymorphisms in the BDNF gene are associated with BD, suggesting that alterations in neurotrophic signaling pathways may contribute to the disorder7.
Structural and Functional Brain Changes
Structural Abnormalities
MRI studies have revealed various structural abnormalities in the brains of individuals with BD, including changes in the volume of the ventricles, caudate, putamen, amygdala, hippocampus, and subgenual prefrontal cortex4. These abnormalities are thought to be both neurodevelopmental and neurodegenerative in origin, contributing to the cognitive and affective symptoms of BD2 4.
Functional Brain Changes
Functional changes in critical neural networks, driven by genetic variations, are also implicated in BD. These changes affect attention, learning, memory, and executive function, contributing to the neurocognitive dysfunction observed in individuals with BD2. The interplay between genetic factors and brain function underscores the complexity of BD's neurobiological basis6.
Conclusion
Bipolar disorder is a multifaceted condition with a complex interplay of genetic, neuroinflammatory, neurotransmitter, and structural brain factors. Genetic polymorphisms, particularly in calcium channel and neurotrophic factor genes, play a significant role in predisposing individuals to BD. Neuroinflammation and chronic stress further exacerbate the condition, while structural and functional brain changes contribute to its clinical manifestations. Understanding these diverse factors is crucial for developing more effective treatments and interventions for BD.
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Most relevant research papers on this topic
Biological hypotheses and biomarkers of bipolar disorder
Bipolar disorder is a complex, multifactorial disorder influenced by genetics, neurotransmitter systems, neuroinflammation, autoimmunity, cytokines, stress axis activity, chronobiology, oxidative stress, and mitochondrial dysfunctions.
Rigorous Journal
Highly CitedNeuropsychological dysfunction in bipolar affective disorder: a critical opinion.
Genetically driven functional changes in critical neural networks underpin both the neurocognitive and affective symptoms of bipolar disorder.
Highly CitedPostmortem evidence of brain inflammatory markers in bipolar disorder: a systematic review
Postmortem brain samples show evidence of inflammation in bipolar disorder, but the exact presence of neuroinflammation remains unclear due to heterogeneity in studies and multiple factors.
Systematic Review
Very Rigorous JournalHighly CitedNeuroanatomical abnormalities as risk factors for bipolar disorder.
Neuroanatomical abnormalities in the subgenual prefrontal cortex, striatum, white matter, and possibly the hippocampus and amygdala may be potential risk factors for bipolar disorder.
Systematic ReviewHighly CitedNEUROBIOLOGICAL BASIS OF BIPOLAR DISORDER
Bipolar disorder may be linked to various genetic factors, and understanding neuronal phenotypes at the microscopic level may help develop effective treatments.
Whole Brain Expression of Bipolar Disorder Associated Genes: Structural and Genetic Analyses
Bipolar disorder-associated genes show distinct expression patterns in the brain, but their expression profiles do not explain most structural abnormalities, but may help identify new candidate genes.
Meta-AnalysisRigorous JournalThe brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study.
A DNA variant in the brain-derived neurotrophic factor gene may increase susceptibility to bipolar disorder, but the causative site is likely nearby and in linkage disequilibrium with the 3-G haplotype identified in this study.
Observational StudyHighly CitedBipolar disorder: An evolutionary psychoneuroimmunological approach
Bipolar disorder is linked to chronic stress and inflammation, driven by contemporary Western lifestyles, and reducing these factors through lifestyle changes is crucial for effective treatment.
The genetics of bipolar disorder: genome ‘hot regions,’ genes, new potential candidates and future directions
Bipolar disorder is linked to a number of genes, but further research is needed to confirm these findings and disentangle conflicting findings.
Literature ReviewRigorous JournalHighly CitedThe Emerging Neurobiology of Bipolar Disorder
Recent advances in neuroscience, genomics, and digital approaches are revolutionizing our understanding of bipolar disorder, with potential treatments focusing on risk genes and persistent mood instability.
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