Abstract
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.
Highlights
Suicides in the United States are increasing at an alarming rate
To map functional disturbances associated with suicide attempts in Bipolar Disorder (BD) and explore their associations with subjective suicide riskrelated domains
Demographic and clinical measures Groups differed significantly in age (F(2, 137) = 5.42, p = 0.005); the healthy volunteers (HVs) group was significantly older than the suicide attempts (SAs) group (t(89) = 3.4, Bonferroni corrected pcorr < 0.004)
Summary
Suicides in the United States are increasing at an alarming rate. Bipolar disorder (BD) is the disorder that carries the highest suicide risk. Neuroimaging studies have begun to probe the brain circuitry underlying suicide thoughts and behaviors (STBs), and the most convergent findings have been in the ventromedial prefrontal cortex (vmPFC), a region that subserves emotion regulation [4]. Lower function in the vmPFC has previously been shown to be associated with emotion regulation difficulties [5] and STBs in BD [2, 6]. A subset implemented functional connectivity (FC) approaches [6, 10,11,12] and these predominantly relied on a priori assumptions about involved brain regions [6, 10, 12]. Most studies that investigated suicide risk for their associations with brain function have focused on constructs of behavioral dyscontrol, such as impulsivity [13]. While impulsivity can lower the threshold to suicide behaviors, its study may not reflect subjective experiences such as hopelessness and ideation that drive suicide behavior
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