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.
"Therefore, studies with large samples are more likely to detect subtle but relevant structural abnormalities. New studies should also investigate white matter abnormalities in relatives of BD patients , since initial evidence for this has been found in this population (Arat et al., 2015) and it has been postulated that changes in white matter might be a vulnerability trait factor for BD rather than changes in GM (Schneider et al., 2012). On the other hand, our study has considerable strengths. "
[Show abstract][Hide abstract] ABSTRACT: Bipolar disorder (BD) is highly heritable. First-degree relatives of BD patient have an increased risk to develop the disease. We investigated abnormalities in gray matter (GM) volumes in healthy first-degree relatives of BD patients to identify possible brain structural endophenotypes for the disorder. 3D T1-weighted magnetic resonance images were obtained from 25 DSM-IV BD type I patients, 23 unaffected relatives, and 27 healthy controls (HC). A voxel-based morphometry protocol was used to compare differences in GM volumes between groups. BD patients presented reduced GM volumes bilaterally in the thalamus compared with HC. Relatives presented no global or regional GM differences compared with HC. Our negative results do not support the role of GM volume abnormalities as endophenotypes for BD. Thalamic volume abnormalities may be associated the pathophysiology of the disease.
"Additionally, a notable challenge for the investigation of brain–behaviour relationships in neuropsychiatric disorders is the effect of age, which is known to have a significant influence on both brain morphology and cognition (Caserta et al., 2009). This is of particular relevance in the study of bipolar disorder, given emerging work suggesting that some aspects of the disorder are related to alterations of neurodevelopmental processes, whereas other consequences of the disorder such as cognitive impairment may be due to progressive brain changes that become more apparent with increasing age (Fries et al., 2012; Schneider et al., 2012; Budni et al., 2013; Gama et al., 2013). Some investigators postulate that toxicity accumulates over the course of the illness, resulting in accelerated neurodegeneration, which could explain observations of increasing clinical severity with disease progression (Budni et al., 2013). "
"The cyclic nature of manic and depressive symptoms has been appointed as the major cause of disability in BD patients . 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    . 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]. "
[Show abstract][Hide abstract] 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.
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