Genetic neuroimaging of bipolar disorder: a systematic 2017–2020 update

Janiri, Delfina; Kotzalidis, Georgios D.; Luzio, Michelangelo Di; Giuseppin, Giulia; Simonetti, Alessio; Janiri, Luigi; Sani, Gabriele

doi:10.1097/ypg.0000000000000274

Cited by 6 publications

(3 citation statements)

References 147 publications

(150 reference statements)

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“…Moreover, higher polygenic liability for bipolar disorder and schizophrenia, as indexed by polygenic risk scores, have been associated with thinner ventromedial prefrontal cortex [ 50 ]. With respect to specific genetic variants, a recent systematic review of genetic neuroimaging findings from cross-sectional studies concluded that the most consistent finding is the influence of the CACNA1C rs1006737 polymorphism on cortical thickness [ 51 ], albeit that most studies remain to be replicated.…”

Section: Factors Contributing To Brain Changesmentioning

confidence: 99%

Mania-related effects on structural brain changes in bipolar disorder – a narrative review of the evidence

et al. 2023

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Cross-sectional neuroimaging studies show that bipolar disorder is associated with structural brain abnormalities, predominantly observed in prefrontal and temporal cortex, cingulate gyrus, and subcortical regions. However, longitudinal studies are needed to elucidate whether these abnormalities presage disease onset or are consequences of disease processes, and to identify potential contributing factors. Here, we narratively review and summarize longitudinal structural magnetic resonance imaging studies that relate imaging outcomes to manic episodes. First, we conclude that longitudinal brain imaging studies suggest an association of bipolar disorder with aberrant brain changes, including both deviant decreases and increases in morphometric measures. Second, we conclude that manic episodes have been related to accelerated cortical volume and thickness decreases, with the most consistent findings occurring in prefrontal brain areas. Importantly, evidence also suggests that in contrast to healthy controls, who in general show age-related cortical decline, brain metrics remain stable or increase during euthymic periods in bipolar disorder patients, potentially reflecting structural recovering mechanisms. The findings stress the importance of preventing manic episodes. We further propose a model of prefrontal cortical trajectories in relation to the occurrence of manic episodes. Finally, we discuss potential mechanisms at play, remaining limitations, and future directions.

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Section: Factors Contributing To Brain Changesmentioning

confidence: 99%

Mania-related effects on structural brain changes in bipolar disorder – a narrative review of the evidence

et al. 2023

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“…One study of healthy adolescents found that, compared to G allele carriers, A allele homozygotes exhibited increased amygdala activation when viewing negative stimuli and decreased amygdala activation when instructed to downregulate their emotional response to negative stimuli (Sumner et al 2015 ). In addition to regional task-related brain activation, rs1006737 has been associated with aberrant functional connectivity in both adults with and without BD (Janiri et al 2021 ; Ou et al 2015 ). Task-based functional connectivity studies of healthy adults have found that rs1006737 A allele carriers showed altered fronto-limbic connectivity, including amygdala, prefrontal cortex, hippocampus, medial temporal lobe, and anterior cingulate cortex (ACC) (Cosgrove et al 2017 ; Erk et al 2010 ; Paulus et al 2014 ; Wang et al 2011 ).…”

Section: Introductionmentioning

confidence: 99%

The association of genetic variation in CACNA1C with resting-state functional connectivity in youth bipolar disorder

Jiang

Sultan

Dimick

et al. 2023

Int J Bipolar Disord

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Background CACNA1C rs1006737 A allele, identified as a genetic risk variant for bipolar disorder (BD), is associated with anomalous functional connectivity in adults with and without BD. Studies have yet to investigate the association of CACNA1C rs1006737 with resting-state functional connectivity (rsFC) in youth BD. Methods Participants included 139 youth with BD-I, -II, or -not otherwise specified, ages 13–20 years, including 27 BD A-carriers, 41 BD non-carriers, 32 healthy controls (HC) A-carriers, and 39 HC non-carriers. Anterior cingulate cortex (ACC), amygdala, and orbitofrontal cortex (OFC) were examined as regions-of-interest in seed-to-voxel analyses. General linear models included main effects of diagnosis and rs1006737, and an interaction term, controlling for age, sex, and race. Results We observed a main effect of BD diagnosis on rsFC between the right amygdala and the right occipital pole (p = 0.02), and a main effect of rs1006737 genotypes on rsFC between the right OFC and bilateral occipital cortex (p < 0.001). Two significant BD diagnosis-by-CACNA1C rs1006737 interactions were also identified. The A allele was associated with positive rsFC between the right ACC and right amygdala in BD but negative rsFC in HC (p = 0.01), and negative rsFC between the left OFC and left putamen in BD but positive rsFC in HC (p = 0.01). Conclusion This study found that the rs1006737 A allele, identified as a genetic risk variant for BD in adults, was differentially associated with rsFC in youth with BD in regions relevant to emotion, executive function, and reward. Future task-based approaches are warranted to better understand brain connectivity in relation to CACNA1C in BD.

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“…The advantage of linking risk genes for psychiatric disorders to ICV in the general population is that, if a relationship is present, this may represent the effect of the risk genes on ICV without confounds of (premorbid) disease or potential gene-by-environment interactions. To date, no large studies in the general population have been conducted in which the effect of the polygenic risk scores for schizophrenia and/or bipolar disorder on ICV has been reported [18,19]. Due to the large genetic overlap between schizophrenia and bipolar disorder [2][3][4], a cross-disorder approach may provide crucial information to the shared and/or unique genetic contribution of polygenic risk for schizophrenia and bipolar disorder to ICV.…”

Section: Introductionmentioning

confidence: 99%

Schizophrenia and Bipolar Polygenic Risk Scores in Relation to Intracranial Volume

Zwarte

Brouwer

Kahn

et al. 2022

Genes

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Schizophrenia and bipolar disorder are neurodevelopmental disorders with overlapping symptoms and a shared genetic background. Deviations in intracranial volume (ICV)—a marker for neurodevelopment—differ between schizophrenia and bipolar disorder. Here, we investigated whether genetic risk for schizophrenia and bipolar disorder is related to ICV in the general population by using the UK Biobank data (n = 20,196). Polygenic risk scores for schizophrenia (SZ-PRS) and bipolar disorder (BD-PRS) were computed for 12 genome wide association study P-value thresholds (PT) for each individual and correlations with ICV were investigated. Partial correlations were performed at each PT to investigate whether disease specific genetic risk variants for schizophrenia and bipolar disorder show different relationships with ICV. ICV showed a negative correlation with SZ-PRS at PT ³ 0.005 (r < -0.02, P < 0.005). ICV was not associated with BD-PRS; however, a positive correlation between BD-PRS and ICV at PT = 0.2 and PT = 0.4 (r = +0.02, P < 0.005) appeared when the genetic overlap between schizophrenia and bipolar disorder was accounted for. Despite small effect sizes, a higher load of schizophrenia risk genes is associated with a smaller ICV in the general population, while risk genes specific for bipolar disorder are correlated with a larger ICV. These findings suggest that schizophrenia and bipolar disorder risk genes, when accounting for the genetic overlap between both disorders, have opposite effects on early brain development.

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Genetic neuroimaging of bipolar disorder: a systematic 2017–2020 update

Cited by 6 publications

References 147 publications

Mania-related effects on structural brain changes in bipolar disorder – a narrative review of the evidence

Mania-related effects on structural brain changes in bipolar disorder – a narrative review of the evidence

The association of genetic variation in CACNA1C with resting-state functional connectivity in youth bipolar disorder

Schizophrenia and Bipolar Polygenic Risk Scores in Relation to Intracranial Volume

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