Differential patterns of activity and functional connectivity in emotion processing neural circuitry to angry and happy faces in adolescents with and without suicide attempt

Background - Neural substrates of emotion dysregulation in adolescent suicide attempters remain unexamined. Method - We used functional magnetic resonance imaging to measure neural activity to neutral, mild or intense (i.e. 0%, 50% or 100% intensity) emotion face morphs in two separate emotion-processing runs (angry and happy) in three adolescent groups: (1) history of suicide attempt and depression (ATT, n = 14); (2) history of depression alone (NAT, n = 15); and (3) healthy controls (HC, n = 15). Post-hoc analyses were conducted on interactions from 3 group × 3 condition (intensities) whole-brain analyses (p < 0.05, corrected) for each emotion run. Results - To 50% intensity angry faces, ATT showed significantly greater activity than NAT in anterior cingulate gyral–dorsolateral prefrontal cortical attentional control circuitry, primary sensory and temporal cortices; and significantly greater activity than HC in the primary sensory cortex, while NAT had significantly lower activity than HC in the anterior cingulate gyrus and ventromedial prefrontal cortex. To neutral faces during the angry emotion-processing run, ATT had significantly lower activity than NAT in the fusiform gyrus. ATT also showed significantly lower activity than HC to 100% intensity happy faces in the primary sensory cortex, and to neutral faces in the happy run in the anterior cingulate and left medial frontal gyri (all p < 0.006,corrected). Psychophysiological interaction analyses revealed significantly reduced anterior cingulate gyral–insula functional connectivity to 50% intensity angry faces in ATT v. NAT or HC. Conclusions - Elevated activity in attention control circuitry, and reduced anterior cingulate gyral–insula functional connectivity, to 50% intensity angry faces in ATT than other groups suggest that ATT may show inefficient recruitment of attentional control neural circuitry when regulating attention to mild intensity angry faces, which may represent a potential biological marker for suicide risk

Is there a neuroanatomical basis of the vulnerability to suicidal behavior?: a coordinate-based meta-analysis of structural and functional MRI studies

Objective: We conducted meta-analyses of functional and structural neuroimaging studies comparing adolescent and adult individuals with a history of suicidal behavior and a psychiatric disorder to psychiatric controls in order to objectify changes in brain structure and function in association with a vulnerability to suicidal behavior. Methods: Magnetic resonance imaging studies published up to July 2013 investigating structural or functional brain correlates of suicidal behavior were identified through computerized and manual literature searches. Activation foci from 12 studies encompassing 475 individuals, i.e., 213 suicide attempters and 262 psychiatric controls were subjected to meta-analytical study using anatomic or activation likelihood estimation (ALE). Result: Activation likelihood estimation revealed structural deficits and functional changes in association with a history of suicidal behavior. Structural findings included reduced volumes of the rectal gyrus, superior temporal gyrus and caudate nucleus. Functional differences between study groups included an increased reactivity of the anterior and posterior cingulate cortices. Discussion: A history of suicidal behavior appears to be associated with (probably interrelated) structural deficits and functional overactivation in brain areas, which contribute to a decision-making network. The findings suggest that a vulnerability to suicidal behavior can be defined in terms of a reduced motivational control over the intentional behavioral reaction to salient negative stimuli

Imaging suicidal thoughts and behaviors: a comprehensive review of 2 decades of neuroimaging studies

Funder: American Foundation for Suicide Prevention (AFSP); doi: https://doi.org/10.13039/100001455Funder: Brain and Behavior Research Foundation (Brain & Behavior Research Foundation); doi: https://doi.org/10.13039/100000874Funder: MQ Brighter Futures Award MQBFC/2, International Bipolar Foundation, For the Love of Travis Foundation, Women's Health Research at Yale, John and Hope Furth EndowmentFunder: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)Funder: Brain and Behavior Research Foundation (Brain & Behavior Research Foundation)Funder: Robert E. Leet and Clara Guthrie Patterson Trust (Robert E. Leet & Clara Guthrie Patterson Trust); doi: https://doi.org/10.13039/100000938Funder: U.S. Department of Veterans Affairs (Department of Veterans Affairs); doi: https://doi.org/10.13039/100000738Abstract: 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

Functional brain imaging studies of youth depression: A systematic review

AbstractBackgroundThere is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD.MethodsA literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13–18 and 19–25years of age, respectively.ResultsTwenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in “extended medial network” regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition.ConclusionsYouth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression

Neuroimaging alterations of the suicidal brain and its relevance to practice: an updated review of MRI studies

Suicide is a leading cause of death in the United States. Historically, scientific inquiry has focused on psychological theory. However, more recent studies have started to shed light on complex biosignatures using MRI techniques, including task-based and resting-state functional MRI, brain morphometry, and diffusion tensor imaging. Here, we review recent research across these modalities, with a focus on participants with depression and Suicidal Thoughts and Behavior (STB). A PubMed search identified 149 articles specific to our population of study, and this was further refined to rule out more diffuse pathologies such as psychotic disorders and organic brain injury and illness. This left 69 articles which are reviewed in the current study. The collated articles reviewed point to a complex impairment showing atypical functional activation in areas associated with perception of reward, social/affective stimuli, top-down control, and reward-based learning. This is broadly supported by the atypical morphometric and diffusion-weighted alterations and, most significantly, in the network-based resting-state functional connectivity data that extrapolates network functions from well validated psychological paradigms using functional MRI analysis. We see an emerging picture of cognitive dysfunction evident in task-based and resting state fMRI and network neuroscience studies, likely preceded by structural changes best demonstrated in morphometric and diffusion-weighted studies. We propose a clinically-oriented chronology of the diathesis-stress model of suicide and link other areas of research that may be useful to the practicing clinician, while helping to advance the translational study of the neurobiology of suicide

Neurocircuitry Of Suicidal Behavior In Adolescents And Young Adults With Bipolar And Major Depressive Disorder

Suicide is one of the leading causes of death in the adolescent and young adult population. Furthermore, it is estimated that for every completed suicide there are many more attempters. The majority of suicide attempters have a mood disorder and neuroimaging research on the neural circuitry of suicidal behavior has primarily focused on these individuals. However, few studies have been designed to compare suicidal behavior across diagnoses. We used diffusion tensor imaging (DTI) to investigate white matter (WM) integrity in Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in adolescents and young adults with a history of suicide attempt. Participants included 21 BD attempters, 18 MDD attempters, 25 BD non-attempters, 17 MDD non-attempters and 43 healthy control (HC) subjects. Analyses were performed to identify similarities and differences in fractional anisotropy (FA) between attempters as compared to non-attempters and HCs. Correlations between FA values and several clinical variables were explored including childhood maltreatment, a risk factor for mood disorders and suicidal behavior. Across all attempters, there was decreased FA in WM in regions of the left and right dorsomedial prefrontal cortex (dmPFC), bilateral ventral anterior commissure/uncinate fasciculus (AC/UF), right anterior cingulate cortex (ACC), and a region within the right putamen. BD attempters showed distinct decreases in WM FA, compared to BD non-attempters, in bilateral uncinate fasciculus (UF), and the right orbitofrontal cortex (OFC). MDD attempters showed decreases in FA in WM within the dorsolateral prefrontal cortex (dlPFC). Across all BD and MDD subjects, suicidal ideation was negatively correlated with FA values in the left dmPFC, right dmPFC bilateral AC/UF, and right ACC. In addition, across all attempters, physical abuse was positively correlated with values in the left dlPFC These results provide evidence for commonalites in suicide attempters across BD and MDD as well as differences within diagnoses. Commonalities within this age group may provide evidence for shared mechanisms of development of suicidal behavior. Further investigation of the differences may be useful for diagnosis-specific suicide prevention and treatment studies

Childhood Trauma And Emotion Processing Neurocircuitry

Childhood trauma is one of the strongest risk factors for a range of common and debilitating neuropsychiatric disorders, including anxiety, depression, and posttraumatic stress disorder (PTSD). These emotion-related disorders have their roots in childhood and adolescence, underscoring a critical need to understand their biological bases in early life. In this dissertation, we evaluate how childhood trauma impacts emotion processing neurocircuitry in a sample of high-risk urban youth, ages 7-15. In four inter-related studies, we test neural function and functional connectivity of core emotion processing regions, including the amygdala, insula, and pregenual/subgenual anterior cingulate cortex (pgACC/sgACC). To examine the relevance of observed neurological changes, we evaluate behavioral performance on emotion processing neuropsychological tasks, as well as specific dimensions of subjective affective experience. Results indicate that, relative to matched comparison youth, trauma-exposed youth have (1) increased neural response to salient emotional cues in amygdala and insula, (2) reduced functional connectivity between amygdala and pgACC/sgACC, a pathway critical for emotion regulation, and (3) altered within- and between-network connectivity of the salience network, involved in detecting and orienting attention to salient emotional stimuli. These neurological changes are accompanied by behavioral alterations: trauma-exposed youth have a lower ability to ignore distracting emotional information, and to automatically regulate emotion. Additionally, observed neurobehavioral changes relate to a specific dimension of affective experience – reward sensitivity (RS), rather than negative affect. Moreover, trauma-exposed youth with the greatest neurobehavioral impairment report lower RS, suggesting reduced positive environmental engagement. These results suggest that RS may be a marker of stress susceptibility, a notion supported by emerging basic and clinical research. Based on our neurobehavioral findings, we discuss potential implications for intervention, and relay an emerging framework that dissociates neurological effects of different trauma types (i.e., threat/victimization vs. deprivation/neglect). In closing, we discuss future directions, including longitudinal research and evaluating the modulation of learned fear – a neurobehavioral mechanism that depends on emotion processing neurocircuitry, but has yet to be tested in trauma-exposed youth

Brain Structure and Function in Emotion Processing, Emotion Regulation, and Reward Processing Neural Circuitries in Offspring at Risk for Bipolar Disorder

Bipolar Disorder (BD) is a serious psychiatric illness with demonstrated structural and functional abnormalities in emotion processing, emotion regulation, and reward processing neural circuitries. BD is also a highly heritable disorder, placing first-degree relatives of patients with BD at great risk for developing the disorder, themselves. There are many similarities, however, between BD and other psychiatric illnesses, such as Major Depressive Disorder, Attention Deficit/Hyperactive Disorder, and Anxiety Disorders, which often makes it difficult to diagnose BD. By detecting abnormalities in neural measures and symptomatology that uniquely distinguish youth at risk for BD, we have the potential to identify objective biological markers of BD risk that may aid in the development of improved diagnostic and therapeutic strategies for BD. In this dissertation, we use elastic net regression analyses to examine structural, functional, and symptomatic measures in offspring of bipolar parents (OBP) compared with offspring of comparison parents with non-BD psychiatric disorders (OCP) and offspring of healthy parents (OHP). In chapter 3, we present findings demonstrating greater rostral anterior cingulate cortex (ACC) activity when regulating attention away from positive (i.e. happy) emotions, as well as greater bilateral amygdala-left caudal ACC functional connectivity (FC) when regulating attention away from all (i.e. fearful, happy, and neutral) emotions in OBP compared with OCP. In chapter 4, we demonstrate lower right ventral striatum-left caudal ACC FC when processing loss and greater right pars orbitalis-orbitofrontal cortex FC when processing reward in OBP compared with both OCP and OHP. In chapter 5, we demonstrate inverse relationships between right cingulum-cingulate gyrus length and bilateral caudal ACC activity, as well as between forceps minor radial diffusivity and bilateral rostral ACC activity, when processing positive emotions in OBP compared with OCP. Throughout these analyses, significant relationships were observed between the ACC and affective lability severity. Together, these studies identify the ACC as a key neural region that may help distinguish youth at risk for BD from youth at risk for other psychiatric disorders. These findings provide specific neural and symptomatic targets which may improve the diagnosis and treatment of BD, leading to overall better outcomes for youth at risk for BD

Brain function and clinical characterization in the Boston adolescent neuroimaging of depression and anxiety study

We present a Human Connectome Project study tailored toward adolescent anxiety and depression. This study is one of the first studies of the Connectomes Related to Human Diseases initiative and is collecting structural, functional, and diffusion-weighted brain imaging data from up to 225 adolescents (ages 14–17 years), 150 of whom are expected to have a current diagnosis of an anxiety and/or depressive disorder. Comprehensive clinical and neuropsychological evaluations and long-itudinal clinical data are also being collected. This article provides an overview of task functional magnetic resonance imaging (fMRI) protocols and preliminary findings (N = 140), as well as clinical and neuropsychological characterization of adolescents. Data collection is ongoing for an additional 85 adolescents, most of whom are expected to have a diagnosis of an anxiety and/or depressive disorder. Data from the first 140 adolescents are projected for public release through the National Institutes of Health Data Archive (NDA) with the timing of this manuscript. All other data will be made publicly-available through the NDA at regularly scheduled intervals. This article is intended to serve as an introduction to this project as well as a reference for those seeking to clinical, neurocognitive, and task fMRI data from this public resource