Early signs of anomalous neural functional connectivity in healthy offspring of parents with bipolar disorder

Abstract

Objectives Bipolar disorder (BD) has been associated with dysfunctional brain connectivity and with family chaos. It is not known whether aberrant connectivity occurs before illness onset, representing vulnerability for developing BD amidst family chaos. We used resting state functional magnetic resonance imaging (fMRI) to examine neural network dysfunction in healthy offspring living with parents with BD and healthy comparison youth. Methods Using two complementary methodologies [data-driven independent component analyses (ICA) and hypothesis-driven region-of-interest (ROI)-based intrinsic connectivity], we examined resting state fMRI data in 8–17-year-old healthy offspring of a parent with BD (n = 24, high risk) and age-matched healthy youth without any personal or family psychopathology (n = 25, low risk). Results ICA revealed that relative to low-risk youth, high-risk youth showed increased connectivity in the ventrolateral prefrontal cortex (VLPFC) subregion of the left executive control network (ECN), which includes frontoparietal regions important for emotion regulation. ROI-based analyses revealed that high-risk versus low-risk youth had decreased connectivities between left amygdala and pregenual cingulate, between subgenual cingulate and supplementary motor cortex, and between left VLPFC and left caudate. High-risk youth showed stronger connections in the VLPFC with age and higher functioning, which may be neuroprotective, and weaker connections between the left VLPFC and caudate with more family chaos, suggesting an environmental influence on frontostriatal connectivity. Conclusions Healthy offspring of parents with BD show atypical patterns of prefrontal and subcortical intrinsic connectivity that may be early markers of resilience from or vulnerability for developing BD. Longitudinal studies are needed to determine whether these patterns predict outcomes.

Neural connectivity in youth at-risk for bipolar disorder: a review of functional magnetic resonance imaging studies

“…Abnormally high connectivity between the amygdala and ventrolateral PFC may represent a lack of flexibility to incorporate feedback from other neocortical areas, such as the dorsolateral PFC and ACC, that may predispose youths to the development of mood dysregulation and eventually BD [37]. This is also compatible with findings in BD at-risk subjects of more negative right amygdala -ACC functional connectivity during emotional processing tasks [26], decreased connectivity between the left amygdala and pregenual cingulate [29] in resting state and prefrontal dysconnectivity patterns during emotional cognition tasks [25,31] and resting state [29,32].…”

“…No additional article was found in the manual search. Most of the studies were conducted in adolescents [23][24][25][26][27][28][29][30] with only two studies conducted in young adults [31,32]. The samples of subjects at-risk for BD were comprised of healthy offspring of bipolar patients [25,28,29], healthy and symptomatic offspring of bipolar patients [24,26,27,30], symptomatic offspring of bipolar patients [23] and healthy and symptomatic offspring or siblings of bipolar patients [31,32].…”

“…The samples of subjects at-risk for BD were comprised of healthy offspring of bipolar patients [25,28,29], healthy and symptomatic offspring of bipolar patients [24,26,27,30], symptomatic offspring of bipolar patients [23] and healthy and symptomatic offspring or siblings of bipolar patients [31,32]. Some studies were conducted by the same research groups, with partially overlapping samples [23,26,27,30] The studies focused in 4 functional imaging domains: 2 studies employed an emotion processing task [23,26]; 2 studies employed a cognitive-affective task [25,31]; 3 studies employed a reward processing task [27,28,30] and 3 were resting state fMRI studies [24,29,32]. Table 1 resume the main methodological characteristics and results of the selected studies.…”

“…Singh and colleagues [29] compared resting state fMRI data between the offspring of parents with BD, offspring of non-bipolar parents and controls, using two connectivity analysis methods: data-driven independent component analysis (ICA) and hypothesis-driven region-of-interest (ROI) based intrinsic connectivity. In the ROI analysis, the authors have selected neural circuits that underlie emotional and inhibitory control: the left and right amygdala, the left and right ventrolateral PFC, and the subgenual anterior cingulate.…”

Treatment of Psychiatric Symptoms Among Offspring of Parents With Bipolar Disorder

“…Recent research demonstrates that among families affected by Bipolar Disorder, these nature and nurture factors interact and may impact the neurodevelopment of Bipolar Disorder. For example, families with Bipolar Disorder tend to have low cohesion, organization and expressiveness, but high conflict; and chaos in the family may be associated with prefrontal-subcortical disconnectivity [25]. Interventions aimed at improving communication and reducing family stress are beneficial to these high-risk youth [26] and may improve prefrontal regulation of subcortically driven mood dysregulation [27].…”