Background Pathophysiological models of bipolar disorder postulate that mood dysregulation arises from fronto-limbic dysfunction, marked by reduced prefrontal cortex (PFC) inhibitory control. This may occur both due to disruptions within PFC networks and abnormal inhibition over subcortical structures involved in emotional processing. However, no study has examined global PFC dysconnectivity in bipolar disorder and tested if regions with within-PFC dysconnectivity also exhibit fronto-limbic connectivity deficits. Further, no study has investigated whether such connectivity disruptions differ for bipolar patients with psychosis history, who may exhibit a more severe clinical course. Methods We collected resting-state fMRI at 3T in 68 remitted bipolar I patients (34 with psychosis history) and 51 demographically-matched healthy participants. We employed a recently developed Global Brain Connectivity method, restricted to PFC (rGBC). We also independently tested connectivity between anatomically-defined amygdala and PFC. Results Bipolar patients exhibited reduced medial PFC (mPFC) rGBC, increased amygdala-MPFC connectivity, and reduced connectivity between amygdala and dorso-lateral PFC. All effects were driven by psychosis history. Moreover, the magnitude of observed effects was significantly associated with lifetime psychotic symptom severity. Conclusions This convergence between rGBC, seed-based amygdala findings and symptom severity analyses highlights that mPFC, a core emotion regulation region, exhibits both within-PFC dysconnectivity and connectivity abnormalities with limbic structures in bipolar illness. Furthermore, lateral PFC dysconnectivity in patients with psychosis history converges with published work in schizophrenia, indicating possible shared risk factors. Observed dysconnectivity in remitted patients suggests a bipolar trait characteristic and may constitute a risk factor for phasic features of the disorder.

Objective Impulsivity, conceptualized as impairment in planning and poor attentional and inhibitory control, is a key feature of bipolar disorder. Familial risk for bipolar disorder is known to affect inhibitory control but its impact on the attentional and planning dimensions of impulsivity is still unclear. Methods We administered the Barratt Impulsiveness Scale, version 11 (BIS-11) to 54 euthymic individuals with DSM–IV bipolar I disorder, 57 of their clinically unaffected siblings, and 49 healthy comparison subjects. Groups were compared on the attentional (rapid shifts in attention/impatience with complexity), motor (acting impetuously), and non-planning (absence of weighing upon long-term consequences of actions) subscales of the BIS-11, and on total BIS-11 score. To investigate functional implications of trait impulsivity, total BIS-11 score was examined in relation to current psychosocial functioning and criminal history. Results Individuals with bipolar I disorder had elevated scores compared to healthy comparison subjects on BIS-11 total score and all three subscales (p < 0.0001). Unaffected siblings had elevated BIS-11 total score (p = 0.0037), motor (p = 0.0027), and non-planning (p = 0.0379) subscales in comparison to unrelated healthy controls. Total BIS-11 score was negatively associated with global assessment of functioning (GAF) score (β = −0.32, p < 0.0001). Conclusions Our results suggest that impulsivity is sensitive to familial liability for the illness, making it a potential endophenotype for bipolar disorder.

Objective Despite evidence that individuals with bipolar disorder have neurocognitive impairment that persists during euthymia, the impact of changes in affective symptoms on cognitive function has not been well established. Here, we sought to determine whether specific neurocognitive functions are sensitive to mood changes in individuals with bipolar disorder assessed three months apart without changes in treatment regimen. Methods A total of 29 individuals with DSM-IV bipolar disorder and 30 healthy controls participated in the study. All participants received a comprehensive neuropsychological assessment and ratings of depressive [Hamilton Depression Rating Scale (HAMD)] and manic [Young Mania Rating Scale (YMRS)] symptoms at baseline and follow-up. Changes in symptoms over time were calculated and were examined in relation to changes in neurocognitive performance. Results At baseline, clinically stable but symptomatic patients were impaired on measures of speed of processing and attention. Over the three-month follow-up period, HAMD scores changed by 6 points on average [range: −10 to +18] and YMRS scores changed by 5.31 points on average [range −11 to +15]. Changes in depressive symptoms were correlated with poorer verbal fluency, while no relationship between manic symptoms and neuropsychological performance was detected. Conclusions Individuals with bipolar disorder showed consistent impairment on speed of processing and attention over time, despite significant changes in mood.

Risk-taking behavior and impulsivity are core features of bipolar disorder. Whether they are part of the inherited aspect of the illness is not clear. We aimed to evaluate risk-taking behavior as a potential endophenotype for bipolar disorders, and its relationship with impulsivity and illness features. The Balloon Analogue Risk Task (BART) and Barratt Impulsiveness Scale-11 (BIS-11) were used to assess risk-taking behavior and impulsivity respectively in 30 euthymic bipolar I patients (BD), their 25 asymptomatic first-degree relatives (BD-R), and 30 healthy controls (HC). The primary BART outcome measure was the behavioral adjustment score (number of pumps after trials where the balloon did not pop minus the number of pumps after trials where the balloon popped). BD (p < .001) and BD-R (p = .001) had similar and significantly lower adjustment scores than HC. Only BD scored significantly higher on BIS-11 total (p = .01) and motor (p = .04) subscales than HC. Neither the BART, nor impulsivity scores associated with illness features. A limitation of this study is medicated patients and a heterogeneous BD-R were included. Riskiness may be a candidate endophenotype for bipolar disorder as it appears independently from illness features, presents similarly in BD and BD-R groups and differs from impulsivity.