Research from JAMA Psychiatry — A Functional Magnetic Resonance Imaging Study of Bipolar Disorder — State- and Trait-Related Dysfunction in Ventral Prefrontal Cortices

Identifying brain alterations that contribute to suicidal thoughts and behaviors (STBs) are important to develop more targeted and effective strategies to prevent suicide. In the last decade, and especially in the last 5 years, there has been exponential growth in the number of neuroimaging studies reporting structural and functional brain circuitry correlates of STBs. Within this narrative review, we conducted a comprehensive review of neuroimaging studies of STBs published to date and summarize the progress achieved on elucidating neurobiological substrates of STBs, with a focus on converging findings across studies. We review neuroimaging evidence across differing mental disorders for structural, functional, and molecular alterations in association with STBs, which converges particularly in regions of brain systems that subserve emotion and impulse regulation including the ventral prefrontal cortex (VPFC) and dorsal PFC (DPFC), insula and their mesial temporal, striatal and posterior connection sites, as well as in the connections between these brain areas. The reviewed literature suggests that impairments in medial and lateral VPFC regions and their connections may be important in the excessive negative and blunted positive internal states that can stimulate suicidal ideation, and that impairments in a DPFC and inferior frontal gyrus (IFG) system may be important in suicide attempt behaviors. A combination of VPFC and DPFC system disturbances may lead to very high risk circumstances in which suicidal ideation is converted to lethal actions via decreased top-down inhibition of behavior and/or maladaptive, inflexible decision-making and planning. The dorsal anterior cingulate cortex and insula may play important roles in switching between these VPFC and DPFC systems, which may contribute to the transition from suicide thoughts to behaviors. Future neuroimaging research of larger sample sizes, including global efforts, longitudinal designs, and careful consideration of developmental stages, and sex and gender, will facilitate more effectively targeted preventions and interventions to reduce loss of life to suicide.

THE NEUROBIOLOGY of adolescent and adult bipolar disorder (BD) has received little study, although the identification of brain abnormalities associated with early onset and age-related disease progression could help to inform prevention and treatment strategies. Medial temporal lobe abnormalities have been implicated in the pathophysiology of BD by studies of localized lesions, seizure disorders, and neuropsychological test performance. Lesions in this brain region, especially those that produce seizure foci, are associated with episodic symptoms that range from inappropriate elation, grandiosity, distractibility, and hypersexuality to depression, excessive guilt, circumstantiality, and paranoia.^1-4 Preclinical observation of the vulnerability of medial temporal structures to sensitization spawned a valuable heuristic model to conceptualize the increased rate of BD cycling as a consequence of the increasing accumulation of multiple, untreated affective episodes.⁵ The reduction of sensitization by anticonvulsants led to their successful implementation in the treatment of BD.^5,6 In adult BD, the impaired recognition of facial affects and the inappropriate emotional biasing of cognitive functions have implicated disturbances in amygdala functioning.^7-10 Verbal learning deficits during times of mania and euthymia in adults with BD,^11-13 discordant monozygotic twins, and nontwin siblings^14,15 implicate a trait deficit in hippocampal functioning.