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

Abstract

Background Offspring of parents with BD (BO) are at higher risk of bipolar disorder (BD) than offspring of parents with non-BD psychopathology (NBO), although both groups are at higher risk than offspring of psychiatrically healthy parents (HC) for other affective and psychiatric disorders. Abnormal functioning in reward circuitry has been demonstrated previously in individuals with BD. We aimed to determine whether activation and functional connectivity in this circuitry during risky decision-making differentiated BO, NBO and HC. Methods BO (n=29;mean age=13.8 years;14 female), NBO (n=28;mean age=13.9 years;12 female) and HC (n=23;mean age=13.7 years;11 female) were scanned while performing a number guessing reward task. 11 BO and 12 NBO had current non-BD psychopathology; 5 BO and 4 NBO were taking psychotropic medications. Results A 3(Group) x 2(Conditions:Win-Control/Loss-Control) ANOVA revealed a main effect of Group on right frontal pole activation: BO showed significantly greater activation than HC. There was a significant main effect of Group on functional connectivity between bilateral ventral striatum (VS) and right ventrolateral prefrontal cortex (Z>3.09, cluster-p<0.05): BO showed significantly greater negative functional connectivity than other participants. These between-group differences remained after removing youth with psychiatric disorders and psychotropic medications from analyses. Conclusions This is the first study to demonstrate that reward circuitry activation and functional connectivity distinguish BO from NBO and HC. The fact that the pattern of findings remained when comparing healthy BO vs. healthy NBO vs. HC suggests that these neuroimaging measures may represent trait-level neurobiological markers conferring either risk for, or protection against, BD in youth.

Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder

“…Two recent fMRI studies have also observed functional abnormalities during reward tasks in OBP. In one report, elevated negative bilateral VS-right VLPFC connectivity to win and loss trials (vs. control trials) distinguished OBP from both offspring of healthy parents and offspring of parents with non-BD disorders (Manelis et al, 2016). Another study observed elevated left VLPFC activation and reduced pregenual ACC-VLPFC connectivity during reward processing in healthy OBP relative to healthy control youths (Singh et al, 2014).…”

“…Neuroimaging studies have identified functional abnormalities within neural circuitry supporting information processing domains known to be disturbed in BD, such as reward processing (Phillips and Swartz, 2014). As parental history of BD is one of the most robust risk factors for developing BD (Birmaher et al, 2009), recent neuroimaging studies have focused on examining reward-related neural circuitry in offspring of bipolar parents (OBP), and have yielded valuable insights into neural processes that may predispose to BD (Manelis et al, 2016, Singh et al, 2014). Yet, while OBP are at elevated risk for BD, many do not develop the disorder.…”

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.…”

“…Manelis and colleagues [27] compared the functional connectivity between offspring of parents with BD, offspring of non-bipolar parents and controls, employing psychophysiological interaction (PPI) analysis to data of an fMRI study with a reward processing paradigm, 'the card number-guessing game' [35]. The seed region was bilateral ventral striatum and the target regions comprised bilateral anterior cingulate cortex, medial PFC, orbitofrontal cortex, ventrolateral PFC and insula.…”