Altered amygdala-prefrontal response to facial emotion in offspring of parents with bipolar disorder

Abstract

This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls.

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].…”

“…Altered connectivity between the ventrolateral PFC and the amygdala, with individuals atrisk for BD showing more functional connectivity between these regions during emotion processing tasks [23,26] and less functional connectivity during affective cognitive tasks [25], partially overlaps with findings of abnormally heightened functional connectivity between the amygdala and ventrolateral PFC during rest or emotional processing in BD patients [21]. 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].…”

“…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.…”

“…Manelis and colleagues [26] performed a fMRI study with an implicit facial emotion processing paradigm, 'the dynamic faces task' [33]. The authors compared the functional connectivity between offspring of parents with BD, offspring of non-bipolar parents and controls, employing psychophysiological interaction (PPI) analysis.…”