Chapter 16 - Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework
Introduction
Anxiety is a sustained state of elevated apprehension, arousal, and vigilance that occurs in the absence of clear and immediate danger (Davis et al., 2010; Grupe and Nitschke, 2013; LeDoux, 2015; Shackman and Fox, 2016). Anxiety lies on a continuum and, when expressed in extreme ways or in inappropriate contexts, can become debilitating (Conway et al., n.d.; Craske et al., 2017; Salomon et al., 2015; Shackman et al., 2016b). Anxiety disorders are the most prevalent family of mental illnesses (Global Burden of Disease Collaborators, 2016; U.S. Burden of Disease Collaborators, 2018; Wang et al., 2017). They typically emerge early in life, enabling greater cumulative damage, and can contribute to the development of depression, substance abuse, and other adverse outcomes (Bitsko et al., 2018; Fox and Kalin, 2014; Kessler et al., 2007, Kessler et al., 2012; Lee et al., 2014; McGorry et al., 2011; Pratt et al., 2016; Shackman et al., 2016b, Torvik et al., n.d.). Existing treatments are underutilized, inconsistently effective, and, in the case of pharmaceuticals, associated with significant adverse effects (Craske et al., 2017; Gordon and Redish, 2016; Griebel and Holmes, 2013). In short, anxiety disorders impose a staggering burden on public health and the global economy, underscoring the urgency of developing a more complete understanding of the underlying mechanisms (DiLuca and Olesen, 2014; Global Burden of Disease Collaborators, 2016; Roehrig, 2016; U.S. Burden of Disease Collaborators, 2018).
We begin by describing new insights into the nature and the biological bases of dispositional negativity, a central dimension of mammalian temperament that confers elevated risk for the development of anxiety disorders and other stress-sensitive psychiatric diseases. Like anxiety disorders, dispositional negativity is a complex, multidimensional phenotype that encompasses variation in behavior, peripheral physiology, feelings, and cognition (Cavanagh and Shackman, 2015; Grupe and Nitschke, 2013; LeDoux, 2015; Shackman et al., 2016a, Shackman et al., 2016b). A key challenge is to identify the mechanisms underlying these features and discover how they contribute to the etiology of psychiatric disease in adults and youth. Here, we focus on recent advances in our understanding of threat-relateda attentional biases and deficits in executive control. These intermediate cognitive phenotypes are key features of dispositional negativity and there is compelling evidence that each can contribute to the development and course of anxiety disorders. While important strides have been made at delineating the neural underpinnings of attentional biases to threat, much less scientific attention has been devoted to executive deficits. In the final section, we highlight emerging evidence that these intermediate phenotypes can interact when threat-related cues are present but unrelated to on-going goals. While these new observations provide important insights, they also raise a number of interesting questions. We conclude by outlining some of the most important avenues for future research and some strategies for addressing them.
Section snippets
The nature of dispositional negativity
Dispositional negativity or “negative emotionality”—the propensity to experience and express more frequent, intense, or persistent fear, anxiety, and other negative emotions—is a fundamental dimension of childhood temperament and adult personality (Shackman et al., 2016b, Shackman et al., 2018a). We conceptualize dispositional negativity as an extended family of closely related phenotypes that first emerge early in development, persist into adulthood, and reflect a combination of heritable and
The nature, consequences, and neurobiology of attentional biases to threat
Alterations in vigilance, risk assessment, and other aspects of attention are hallmarks of dispositional negativity and anxiety (Blanchard et al., 2001; Grupe and Nitschke, 2013; Shackman et al., 2016a). Attention is a fundamental property of perception and cognition. Attentional mechanisms prioritize the most relevant sources of information while inhibiting or ignoring potential distractions and competing courses of action (Desimone and Duncan, 1995). Once a target is selected, attention
The nature of executive function and cognitive control
Lapses in concentration and problems with cognitive function are clinically significant features of anxiety disorders and other psychiatric illnesses (American Psychiatric Association, 2013). Yet the contributions of executive function and cognitive control—the basic building blocks of intelligence and complex everyday cognition—to pathological anxiety have received considerably less empirical attention than attentional biases to threat. Executive function refers to the processes involved in
Emerging evidence for the interplay of attentional biases and executive control
While most research has focused on attentional biases to threat or deficits in executive control in isolation, an emerging body of data and theory suggests that these processes are intimately related and can reciprocally interact (Bishop, 2008, Bishop, 2009; Bishop and Forster, 2013; Derakshan et al., 2009a; Eysenck and Derakshan, 2011; Eysenck et al., 2007; Iordan et al., 2013; Mogg and Bradley, 2016, Mogg and Bradley, 2018; Mogg et al., 2017; Tottenham and Gabard-Durnam, 2017). From a
Future challenges
The data that we have reviewed provide new insights into the neurocognitive mechanisms that support individual differences in dispositional negativity and that link this disposition to the development of anxiety disorders and other psychiatric diseases. Yet, it is clear that our understanding remains far from complete. Throughout the review, we highlighted a number of specific conceptual and methodological challenges for future research in this area. Here, we outline some broader questions for
Conclusions
The work that we have reviewed highlights the importance of amygdala, frontoparietal, and cingular-opercular circuits to individual differences in dispositional negativity and two prominent intermediate phenotypes: threat-related attentional biases and deficits in executive control. Collectively, these observations provide an integrative translational framework for understanding the development and maintenance of anxiety and mood disorders in adults and youth and set the stage for developing
Acknowledgments
Authors acknowledge assistance from M. Barstead, K. DeYoung, L. Friedman, M. Gamer, S. Haas, C. Kaplan, K. Rubin, J. Smith, R. Tillman and financial support from the California National Primate Center; National Institute of Health (DA040717, MH107444); University of California, Davis; and University of Maryland, College Park. Authors declare no conflicts of interest.
References (539)
- et al.
A causal model of post-traumatic stress disorder: disentangling predisposed from acquired neural abnormalities
Trends Cogn. Sci.
(2013) Human lesion studies in the 21st century
Neuron
(2016)- et al.
The neural correlates of impaired inhibitory control in anxiety
Neuropsychologia
(2011) - et al.
Eye tracking of attention in the affective disorders: a meta-analytic review and synthesis
Clin. Psychol. Rev.
(2012) - et al.
Expectancy biases in fear and anxiety and their link to biases in attention
Clin. Psychol. Rev.
(2015) - et al.
Executive function and PTSD: disengaging from trauma
Neuropharmacology
(2012) - et al.
Impaired threat prioritisation after selective bilateral amygdala lesions
Cortex
(2015) - et al.
Application of a cognitive neuroscience perspective of cognitive control to late-life anxiety
J. Anxiety Disord.
(2013) - et al.
Attentional control deficits in trait anxiety: why you see them and why you don’t
Biol. Psychol.
(2013) - et al.
Neural substrates of childhood anxiety disorders: a review of neuroimaging findings
Child Adolesc. Psychiatr. Clin. N. Am.
(2012)
Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic
Neurosci. Biobehav. Rev.
Attentional mechanisms of social perception are biased in social phobia
J. Anxiety Disord.
Exposure to subliminal arousing stimuli induces robust activation in the amygdala, hippocampus, anterior cingulate, insular cortex and primary visual cortex: a systematic meta-analysis of fMRI studies
NeuroImage
A social relations examination of neuroticism and emotional support
J. Res. Pers.
Risk factors for relapse and recurrence of depression in adults and how they operate: a four-phase systematic review and meta-synthesis
Clin. Psychol. Rev.
A neurobehavioral mechanism linking behaviorally inhibited temperament and later adolescent social anxiety
J. Am. Acad. Child Adolesc. Psychiatry
Frontal midline theta reflects anxiety and cognitive control: meta-analytic evidence
J. Physiol. Paris
Mechanisms of attentional biases towards threat in anxiety disorders: an integrative review
Clin. Psychol. Rev.
Personality in the age of industry: structure, heritability, and correlates of personality in middle childhood from the perspective of parents, teachers, and children
J. Res. Pers.
Predictors of amygdala activation during the processing of emotional stimuli: a meta-analysis of 385 PET and fMRI studies
Brain Res. Rev.
Social anxiety: from the inside and outside
Personal. Individ. Differ.
Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness
bioRxiv
Association between attention bias to threat and anxiety symptoms in children and adolescents
Depress. Anxiety
Metabolic rate in the right amygdala predicts negative affect in depressed patients
Neuroreport
Stratifying depression by neuroticism: revisiting a diagnostic tradition using GWAS data
bioRxiv
Human vulnerability to stress depends on amygdala's predisposition and hippocampal plasticity
Proc. Natl. Acad. Sci. U. S. A.
A mechanism for impaired fear recognition after amygdala damage
Nature
A central extended amygdala circuit that modulates anxiety
J. Neurosci.
Differentially methylated plasticity genes in the amygdala of young primates are linked to anxious temperament, an at risk phenotype for anxiety and depressive disorders
J. Neurosci.
A multi-dimensional characterization of anxiety in monozygotic twin pairs reveals susceptibility loci in humans
Transl. Psychiatry
Linking big five personality traits to sexuality and sexual health: a meta-analytic review
Psychol. Bull.
Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
Emotion in the wilds of nature: the coherence and contagion of fear during threatening group-based outdoors experiences
Emotion
The human BNST: functional role in anxiety and addiction
Neuropsychopharmacology
Predicting actual behavior from the explicit and implicit self-concept of personality
J. Pers. Soc. Psychol.
Executive function: the search for an integrated account
Curr. Dir. Psychol. Sci.
Threat-related attentional bias in anxious and nonanxious individuals: a meta-analytic study
Psychol. Bull.
The nature, diagnosis, and treatment of neuroticism: back to the future
Clin. Psychol. Sci.
The unified protocol for transdiagnostic treatment of emotional disorders compared with diagnosis-specific protocols for anxiety disorders: a randomized clinical trial
JAMA Psychiat.
Alcohol effects on performance monitoring and adjustment: affect modulation and impairment of evaluative cognitive control
J. Abnorm. Psychol.
Trait anxiety modulates the neural efficiency of inhibitory control
J. Cogn. Neurosci.
Anxiety: an evolutionary approach
Can. J. Psychiatry
Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans
Science
Panic search: fear produces efficient visual search for nonthreatening objects
Psychol. Sci.
The amygdala: functional organization and involvement in neurologic disorders
Neurology
Development of a single-session, transdiagnostic preventive intervention for young adults at risk for emotional disorders
Behav. Modif.
Beyond brain mapping: using neural measures to predict real-world outcomes
Curr. Dir. Psychol. Sci.
Combined neurostimulation and neuroimaging in cognitive neuroscience: past, present, and future
Ann. N. Y. Acad. Sci.
The Mechanism of the Brain: And the Function of the Frontal Lobes
Evolutionarily conserved dysfunction of prefrontal-amygdalar connectivity in early-life anxiety
Mol. Psychiatry
Cited by (56)
Transdiagnostic symptom of depression and anxiety associated with reduced gray matter volume in prefrontal cortex
2024, Psychiatry Research - NeuroimagingIntroduction to the special issue on the Neurobiology of Human Fear and Anxiety
2023, Neuroscience and Biobehavioral ReviewsUnderstanding anxiety symptoms as aberrant defensive responding along the threat imminence continuum
2023, Neuroscience and Biobehavioral ReviewsThe nature and neurobiology of fear and anxiety: State of the science and opportunities for accelerating discovery
2023, Neuroscience and Biobehavioral ReviewsAttentional biases in human anxiety
2022, Neuroscience and Biobehavioral Reviews