Neuroprogression in bipolar disorder

Physician Scientist Training Program, Neuroscience Graduate Program Department, University of Cincinnati College of Medicine, Cincinnati, OH 45219-0516, USA.
Bipolar Disorders (Impact Factor: 4.97). 06/2012; 14(4):356-74. DOI: 10.1111/j.1399-5618.2012.01024.x
Source: PubMed


Recent theories regarding the neuropathology of bipolar disorder suggest that both neurodevelopmental and neurodegenerative processes may play a role. While magnetic resonance imaging has provided significant insight into the structural, functional, and connectivity abnormalities associated with bipolar disorder, research assessing longitudinal changes has been more limited. However, such research is essential to elucidate the pathophysiology of the disorder. The aim of our review is to examine the extant literature for developmental and progressive structural and functional changes in individuals with and at risk for bipolar disorder.
We conducted a literature review using MEDLINE and the following search terms: bipolar disorder, risk, child, adolescent, bipolar offspring, MRI, fMRI, DTI, PET, SPECT, cross-sectional, longitudinal, progressive, and developmental. Further relevant articles were identified by cross-referencing with identified manuscripts.
There is some evidence for developmental and progressive neurophysiological alterations in bipolar disorder, but the interpretation of correlations between neuroimaging findings and measures of illness exposure or age in cross-sectional studies must be performed with care. Prospective longitudinal studies placed in the context of normative developmental and atrophic changes in neural structures and pathways thought to be involved in bipolar disorder are needed to improve our understanding of the neurodevelopmental underpinnings and progressive changes associated with bipolar disorder.

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    • "The cyclic nature of manic and depressive symptoms has been appointed as the major cause of disability in BD patients [4]. BD is characterized by a temporal progression of symptoms , that is, increase in the frequency and severity of mood episodes and less response to treatment [5] [6] [7] [8]. Several studies have also reported cognitive impairment along with structural (decrease of hippocampal and amygdala volumes and total gray matter) and neurophysiological changes [5– 9]. "
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    ABSTRACT: Bipolar disorder (BD) is a severe, chronic, and recurrent psychiatric illness. It has been associated with high prevalence of medical comorbidities and cognitive impairment. Its neurobiology is not completely understood, but recent evidence has shown a wide range of immune changes. Cytokines are proteins involved in the regulation and the orchestration of the immune response. We performed a review on the involvement of cytokines in BD. We also discuss the cytokines involvement in the neuroprogression of BD. It has been demonstrated that increased expression of cytokines in the central nervous system in postmortem studies is in line with the elevated circulating levels of proinflammatory cytokines in BD patients. The proinflammatory profile and the immune imbalance in BD might be regarded as potential targets to the development of new therapeutic strategies.
    Neural Plasticity 09/2014; 2014:360481. DOI:10.1155/2014/360481 · 3.58 Impact Factor
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    • "Bipolar disorder (BD) is one of the major psychiatric illnesses which can be appeared across all age groups including children and adults. BD which may lead to emotional and cognitive function impairments [1] is always characterized by alternating mood state between mania or hypomania, and depression. As compared with adult BD, pediatric BD (PBD) often shows more atypical symptoms and comorbidities [2]. "
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    ABSTRACT: Background Pediatric bipolar disorder (PBD) has attracted increasing attentions due to its high prevalence and great influence on social functions of children and adolescents. However, the pathophysiology underlying PBD remains unclear. In the present study, the resting-state functional magnetic resonance imaging (fMRI) was used to detect abnormalities of baseline brain functions in depressed PBD youth.Methods Seventeen youth with PBD-depression aged 10 - 18 years old and 18 age- and sex-matched normal controls were recruited in this study. The fMRI data under resting state were obtained on a Siemens 3.0 Tesla scanner and were analyzed using the regional homogeneity (ReHo) method. Correlations between the ReHo values of each survived area and the severity of depression symptoms in patients were further analyzed.ResultsAs compared with the control group, PBD-depression patients showed decreased ReHo in the medial frontal gyrus, bilateral middle frontal gyrus and middle temporal gyrus, and the right putamen. Significant negative correlations of the mood and feelings questionnaire scores with mean ReHo values in the medial frontal gyrus and the right middle frontal gyrus in PBD-depression patients were observed.Conclusion Our results suggest that extensive regions with altered baseline brain activities are existed in PBD-depression and these brain regions mainly locate in the fronto-limbic circuit and associated striatal structures. Moreover, the present findings also add to our understanding that there could be unique neuropathophysiological mechanisms underlying PBD-depression.
    BMC Psychiatry 08/2014; 14(1):222. DOI:10.1186/s12888-014-0222-y · 2.21 Impact Factor
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    • "Altered activity of and changed connectivity between 232 brain regions like the orbitofrontal cortex, rostral cin- 233 gulate cortex, amygdala and striatum that are involved 234 in motivation (Diekhof et al., 2008; Ernst et al., 2004) 235 have been reported in patients with bipolar disorder 236 (for reviews see Blond et al., 2012; Strakowski et 237 al., 2012b) and might constitute the neuronal "
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    ABSTRACT: Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60-80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.
    04/2013; 32(1). DOI:10.3233/RNN-139007
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