Rethinking "aggression" and impulsivity in bipolar disorder: Risk, clinical and brain circuitry features.

BACKGROUND: Elevated aggression and impulsivity are implicated in Bipolar Disorder (BD); however, relationships between these behavioral constructs have not been clarified, which can lead to misconceptions with negative consequences including stigma and adverse outcomes including suicide. The study aimed to clarify brain-based distinctions between the two constructs and their associations to risk factors, symptoms and suicide thoughts and behaviors. METHODS: Self-rated Brown-Goodwin Aggression (BGA) and Barratt Impulsiveness Scale (BIS) scores were compared between adults with BD (n = 38, 74% female) and healthy controls (HC, n = 29, 64% female). Relationships were examined between BGA and BIS with childhood trauma questionnaire (CTQ), mood, comorbidities, and magnetic resonance imaging gray matter volume (GMV) assessments. RESULTS: In BD, BGA and BIS total scores were both elevated and associated with childhood maltreatment (CM), particularly emotional CM, depression, substance use disorders (SUDs) and suicide attempts (SAs). BGA scores were increased by items corresponding to dysregulation of emotional and social behavior and associated with elevated mood states and suicide ideation and GMV decreases in bilateral orbitofrontal cortex and left posterior insula brain regions, previously associated with these behaviors and clinical features. BIS motor impulsiveness scores were associated with GMV decreases in anterior cingulate cortex implicated in mood and behavioral dyscontrol. LIMITATIONS: modest sample size, self-reports CONCLUSIONS: The findings suggest separable brain-based domains of dysfunction in BD of motor impulsiveness versus emotionally dysregulated feelings that are primarily self-directed. Both domains are associated with suicide behavior and modifiable risk factors of CM, depression and SUDs that could be targeted for prevention.

Graph theory analysis of whole brain functional connectivity to assess disturbances associated with suicide attempts in bipolar disorder.

Brain targets to lower the high risk of suicide in Bipolar Disorder (BD) are needed. Neuroimaging studies employing analyses dependent on regional assumptions could miss hubs of dysfunction critical to the pathophysiology of suicide behaviors and their prevention. This study applied intrinsic connectivity distribution (ICD), a whole brain graph-theoretical approach, to identify hubs of functional connectivity (FC) disturbances associated with suicide attempts in BD. ICD, from functional magnetic resonance imaging data acquired while performing a task involving implicit emotion regulation processes important in BD and suicide behaviors, was compared across 40 adults with BD with prior suicide attempts (SAs), 49 with BD with no prior attempts (NSAs) and 51 healthy volunteers (HVs). Areas of significant group differences were used as seeds to identify regional FC differences and explore associations with suicide risk-related measures. ICD was significantly lower in SAs than in NSAs and HVs in bilateral ventromedial prefrontal cortex (vmPFC) and right anterior insula (RaIns). Seed connectivity revealed altered FC from vmPFC to bilateral anteromedial orbitofrontal cortex, left ventrolateral PFC (vlPFC) and cerebellum, and from RaIns to right vlPFC and temporopolar cortices. VmPFC and RaIns ICD were negatively associated with suicidal ideation severity, and vmPFC ICD with hopelessness and attempt lethality severity. The findings suggest that SAs with BD have vmPFC and RaIns hubs of dysfunction associated with altered FC to other ventral frontal, temporopolar and cerebellar cortices, and with suicidal ideation, hopelessness, and attempt lethality. These hubs may be targets for novel therapeutics to reduce suicide risk in BD.