Reward Processing in Healthy Offspring of Parents With Bipolar Disorder

Abstract

IMPORTANCE Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder.OBJECTIVE To determine whether anomalous neural processing of reward characterizes children at familial risk for BD in the absence of a personal history of a psychopathologic disorder. DESIGN, SETTING, AND PARTICIPANTSThis study compared neural activity and behaviors of children at high and low risk for mania while they anticipate and respond to reward and loss. The study was performed from September 15, 2009, through February 17, 2012, in a university functional magnetic resonance imaging facility and included 8-to 15-year-old children without disorders born to a parent with BD (n = 20 high-risk children) and demographically matched healthy comparison children (n = 25 low-risk children). MAIN OUTCOMES AND MEASURESNeural activity, as measured with functional magnetic resonance imaging, during anticipation and receipt of reward and loss during a monetary incentive delay task.RESULTS While anticipating losses, high-risk children had less activation in the pregenual cingulate than did their low-risk counterparts (t 19 = −2.44, P = .02). When receiving rewards, high-risk children had greater activation in the left lateral orbitofrontal cortex than did low-risk children (t 43 = −3.04, P = .004). High-risk children also had weaker functional connectivity between the pregenual cingulate and the right ventrolateral prefrontal cortex while anticipating rewards than did low-risk children (t 19 = −4.38, P < .001) but had a stronger connectivity between these regions while anticipating losses (t 24 = 2.76, P = .01). Finally, in high-but not low-risk children, novelty seeking was associated with increased striatal and amygdalar activation in the anticipation of losses, and impulsivity was associated with increased striatal and insula activation in the receipt of rewards.CONCLUSIONS AND RELEVANCE Aberrant prefrontal activations and connectivities during reward processing suggest mechanisms that underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania. Longitudinal studies are needed to examine whether these patterns of neural activation predict the onset of mania and other mood disorders in high-risk children.

Altered functioning of reward circuitry in youth offspring of parents with bipolar disorder

“…BOLD images were registered to the high-resolution structural images using FLIRT; the high-resolution images were registered to the MNI152_T1_2mm template, as in previous neuroimaging studies of youth with age ranges comparable to that in the present study (Burgund et al 2002;Kang et al 2003;Singh et al 2013, 2014;Bebko et al 2014;Olsavsky et al 2014), using FNIRT, and the two resulting transformations were concatenated and applied to the original BOLD image to transform it to MNI space. The registration quality was checked for each subject.…”

“…Only one previous study compared neural underpinnings of reward processing in BO vs. HC (Singh et al 2014). This study showed elevated vlPFC activity and altered vlPFC-ACC functional connectivity during reward processing in healthy BO vs. HC (Singh et al 2014).…”

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

“…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.…”

“…The authors reported a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral PFC to the inferior frontal gyrus that is unique to the at-risk cohort, suggesting distinct brain network mechanisms for the integration of cognitive control and emotion perception in these clinical population. The first study [28] that compared functional connectivity data between healthy offspring of parents with BD and controls using a reward processing task ('the monetary incentive delay task') employed psychophysiological interaction (PPI) analysis. The seed region was the pregenual cingulate and the target regions the bilateral amygdalae, insula, nucleus accumbens and ventrolateral PFC.…”