A Critical Appraisal of Neuroimaging Studies of Bipolar Disorder: Toward a New Conceptualization of Underlying Neural Circuitry and a Road Map for Future Research

Abstract

Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual-level data. Such studies will help identify clinically-relevant biomarkers to guide diagnosis and treatment decision-making for individuals with bipolar disorder.

Bipolar disorder in children and adolescents: from the beginning to the consequences

“…There is general acceptance that BD symptomatology often has an onset in the mid to late teenage years [11,99,100] and that BD can be present in children and younger adolescents, but with a much less certain prognosis [10,11,101,102]. This disorder is a lifelong disease associated with frequent recurrences that requires long-term management using pharmaceuticals [2,78]. …”

“…In the neurological context, white matter abnormalities detected by Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) have been consistently reported both in BD patients [5, 78,79] and in their non-BD relatives in adulthood [5, [80][81][82]. Children and adolescents with BD also have been found to display decreased fractional anisotropy (FA), a measure of fibers coherence and organization, but findings differ across studies [5, [83][84][85].…”

784. Structural Dysconnectivity of Key Cognitive and Emotional Hubs in Young People at High Genetic Risk for Bipolar Disorder

“…Studies have inferred reduced WM integrity in BD from alterations to diffusion tensor imaging-derived indices, such as fractional anisotropy. [11][12][13][14] Although findings are somewhat inconsistent, there is a trend towards diffusion tensor imaging-derived alterations in BD patients compared with controls (CNs) in circuits linking prefrontal, striatal and limbic regions. 14 Such findings suggest a link between the emotional and cognitive phenotype of BD and dysfunction in the networks supporting these functions.…”

Is There Validity to the Bipolar Prodrome?

“…For example, neuroimaging has been used to identify biological targets such as aberrant brain structure and function supporting emotion processing, emotion regulation, and reward processing in individuals with and at familial risk for developing bipolar disorder. 17 This work is aimed both to bridge a clinical assessment of mood symptoms with biologically mediated brain abnormalities and to advance our understanding of the Is There Validity to the Bipolar Prodrome?…”