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Neuroticism/negative emotionality (N/NE)-the tendency to experience anxiety, fear, and other negative emotions-is a fundamental dimension of temperament with profound consequences for health, wealth, and well-being. Elevated N/NE is associated with a panoply of adverse outcomes, from reduced socioeconomic attainment to psychiatric illness. Animal research suggests that N/NE reflects heightened reactivity to uncertain threat in the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce), but the relevance of these discoveries to humans has remained unclear. Here we used a novel combination of psychometric, psychophysiological, and neuroimaging approaches to test this hypothesis in an ethnoracially diverse, sex-balanced sample of 220 emerging adults selectively recruited to encompass a broad spectrum of N/NE. Cross-validated robust-regression analyses demonstrated that N/NE is preferentially associated with heightened BST activation during the uncertain anticipation of a genuinely distressing threat (aversive multimodal stimulation), whereas N/NE was unrelated to BST activation during certain-threat anticipation, Ce activation during either type of threat anticipation, or BST/Ce reactivity to threat-related faces. It is often assumed that different threat paradigms are interchangeable assays of individual differences in brain function, yet this has rarely been tested. Our results revealed negligible associations between BST/Ce reactivity to the anticipation of threat and the presentation of threat-related faces, indicating that the two tasks are nonfungible. These observations provide a framework for conceptualizing emotional traits and disorders; for guiding the design and interpretation of biobank and other neuroimaging studies of psychiatric risk, disease, and treatment; and for refining mechanistic research.
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Tonsila do Cerebelo , Emoções , Imageamento por Ressonância Magnética , Neuroticismo , Núcleos Septais , Núcleos Septais/fisiologia , Núcleos Septais/diagnóstico por imagem , Humanos , Masculino , Feminino , Tonsila do Cerebelo/fisiologia , Tonsila do Cerebelo/diagnóstico por imagem , Adulto Jovem , Neuroticismo/fisiologia , Adulto , Emoções/fisiologia , Incerteza , Medo/fisiologia , Medo/psicologia , AdolescenteRESUMO
Temporal dynamics play a central role in models of emotion: "fear" is widely conceptualized as a phasic response to certain-and-imminent danger, whereas "anxiety" is a sustained response to uncertain-or-distal harm. Yet the underlying human neurobiology remains contentious. Leveraging an ethnoracially diverse sample, translationally relevant paradigm, and theory-driven modeling approach, we demonstrate that certain and uncertain threat recruit a shared threat-anticipation circuit. This cortico-subcortical circuit exhibits persistently elevated activation when anticipating uncertain-threat encounters and a transient burst of activation in the moments before certain encounters. For many scientists and clinicians, feelings are the defining feature of human fear and anxiety. Here we used an independently validated brain signature to covertly decode the momentary dynamics of anticipatory distress for the first time. Results mirrored the dynamics of neural activation. These observations provide fresh insights into the neurobiology of threat-elicited emotions and set the stage for more ambitious clinical and mechanistic research.
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Social anxiety-which typically emerges in adolescence-lies on a continuum and, when extreme, can be devastating. Socially anxious individuals are prone to heightened fear, anxiety, and the avoidance of contexts associated with potential social scrutiny. Yet most neuroimaging research has focused on acute social threat. Much less attention has been devoted to understanding the neural systems recruited during the uncertain anticipation of potential encounters with social threat. Here we used a novel fMRI paradigm to probe the neural circuitry engaged during the anticipation and acute presentation of threatening faces and voices in a racially diverse sample of 66 adolescents selectively recruited to encompass a range of social anxiety and enriched for clinically significant levels of distress and impairment. Results demonstrated that adolescents with more severe social anxiety symptoms experience heightened distress when anticipating encounters with social threat, and reduced discrimination of uncertain social threat and safety in the bed nucleus of the stria terminalis (BST), a key division of the central extended amygdala (EAc). Although the EAc-including the BST and central nucleus of the amygdala-was robustly engaged by the acute presentation of threatening faces and voices, the degree of EAc engagement was unrelated to the severity of social anxiety. Together, these observations provide a neurobiologically grounded framework for conceptualizing adolescent social anxiety and set the stage for the kinds of prospective-longitudinal and mechanistic research that will be necessary to determine causation and, ultimately, to develop improved interventions for this often-debilitating illness.
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To effectively address the staggering burden of mental illness, clinical psychological science will need to face some uncomfortable truths about current training practices. In a commentary authored by 23 current or recent trainees, Palitsky and colleagues highlight a number of urgent challenges facing today's clinical interns. They provide a thoughtful framework for reform, with specific recommendations and guiding questions for a broad spectrum of stakeholders. Key suggestions are applicable to the entire sequence of clinical training. While there is cause for cautious optimism, overcoming these systemic barriers will require a coordinated, all-hands approach and a more collaborative approach to policy-making.
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Neuroticism/Negative Emotionality (N/NE)-the tendency to experience anxiety, fear, and other negative emotions-is a fundamental dimension of temperament with profound consequences for health, wealth, and wellbeing. Elevated N/NE is associated with a panoply of adverse outcomes, from reduced socioeconomic attainment and divorce to mental illness and premature death. Work in animals suggests that N/NE reflects heightened reactivity to uncertain threat in the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce), but the relevance of these discoveries to the human brain and temperament have remained unclear. Here we used a combination of psychometric, psychophysiological, and neuroimaging approaches to rigorously test this hypothesis in an ethnoracially diverse sample of 220 emerging adults selectively recruited to encompass a broad spectrum of N/NE. Cross-validated robust-regression analyses demonstrated that N/NE is selectively associated with heightened BST activation during the uncertain anticipation of a genuinely distressing threat. In contrast, N/NE was unrelated to BST activation during certain-threat anticipation, Ce activation during either type of threat anticipation, or BST/Ce reactivity to 'threat-related' faces. Implicit in much of the neuroimaging literature is the assumption that different threat paradigms are statistically interchangeable probes of individual differences in neural function, yet our results revealed negligible evidence of convergence between popular threat-anticipation and emotional-face tasks. These observations provide a framework for conceptualizing emotional traits and disorders; for guiding the design and interpretation of biobank and other neuroimaging studies of psychiatric risk, disease, and treatment; and for informing the next generation of mechanistic research.
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Tobacco smoking imposes a staggering burden on public health, underscoring the urgency of developing a deeper understanding of the processes that maintain addiction. Clinical and experience-sampling data highlight the importance of anxious withdrawal symptoms, but the underlying neurobiology has remained elusive. Mechanistic work in animals implicates the central extended amygdala (EAc)-including the central nucleus of the amygdala and the neighboring bed nucleus of the stria terminalis-but the translational relevance of these discoveries remains unexplored. Here we leveraged a randomized trial design, well-established threat-anticipation paradigm, and multidimensional battery of assessments to understand the consequences of 24-hour nicotine abstinence. The threat-anticipation paradigm had the expected consequences, amplifying subjective distress and arousal, and recruiting the canonical threat-anticipation network. Abstinence increased smoking urges and withdrawal symptoms, and potentiated threat-evoked distress, but had negligible consequences for EAc threat reactivity, raising questions about the translational relevance of prominent animal and human models of addiction. These observations provide a framework for conceptualizing nicotine abstinence and withdrawal, with implications for basic, translational, and clinical science.
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Núcleos Septais , Síndrome de Abstinência a Substâncias , Humanos , Tonsila do Cerebelo/fisiologia , Ansiedade , Medo/fisiologia , Nicotina/efeitos adversos , Núcleos Septais/fisiologiaRESUMO
Pathological fear and anxiety are a leading cause of human misery and morbidity, afflicting millions of individuals worldwide. Yet existing treatments are inconsistently effective or associated with significant adverse effects, underscoring the urgency of developing a more complete understanding of the neural systems governing fear and anxiety in humans. This emphasis reflects the fact that fear and anxiety disorders are defined and diagnosed based on subjective symptoms, and human studies are essential for understanding the neural mechanisms that underlie the experience of fear and anxiety. Human studies are also crucial for identifying the features of animal models that are conserved and, hence, most relevant to human disease and treatment development ('forward translation'). Finally, human studies afford opportunities for developing objective biomarkers of disease or disease risk, accelerating the development of new diagnostic and treatment strategies, and generating novel hypotheses that can be mechanistically assessed in animal models ('reverse translation'). The present Special Issue-The Neurobiology of Human Fear and Anxiety-provides a concise survey of recent progress in this burgeoning area of research. Here we provide an Introduction to the Special Issue, highlighting some of the most significant and exciting advances.
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Ansiedade , Medo , Animais , Humanos , Transtornos de Ansiedade , Encéfalo , Modelos AnimaisRESUMO
Our capacity to measure diverse aspects of human biology has developed rapidly in the past decades, but the rate at which these techniques have generated insights into the biological correlates of psychopathology has lagged far behind. The slow progress is partly due to the poor sensitivity, specificity and replicability of many findings in the literature, which have in turn been attributed to small effect sizes, small sample sizes and inadequate statistical power. A commonly proposed solution is to focus on large, consortia-sized samples. Yet it is abundantly clear that increasing sample sizes will have a limited impact unless a more fundamental issue is addressed: the precision with which target behavioral phenotypes are measured. Here, we discuss challenges, outline several ways forward and provide worked examples to demonstrate key problems and potential solutions. A precision phenotyping approach can enhance the discovery and replicability of associations between biology and psychopathology.
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Fear and anxiety play a central role in mammalian life, and there is considerable interest in clarifying their nature, identifying their biological underpinnings, and determining their consequences for health and disease. Here we provide a roundtable discussion on the nature and biological bases of fear- and anxiety-related states, traits, and disorders. The discussants include scientists familiar with a wide variety of populations and a broad spectrum of techniques. The goal of the roundtable was to take stock of the state of the science and provide a roadmap to the next generation of fear and anxiety research. Much of the discussion centered on the key challenges facing the field, the most fruitful avenues for future research, and emerging opportunities for accelerating discovery, with implications for scientists, funders, and other stakeholders. Understanding fear and anxiety is a matter of practical importance. Anxiety disorders are a leading burden on public health and existing treatments are far from curative, underscoring the urgency of developing a deeper understanding of the factors governing threat-related emotions.
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Ansiedade , Medo , Animais , Humanos , Ansiedade/psicologia , Medo/psicologia , Transtornos de Ansiedade/psicologia , Emoções , Neurobiologia , MamíferosRESUMO
Among individuals with psychotic disorders, paranoid ideation is common and associated with increased impairment, decreased quality of life, and a more pessimistic prognosis. Although accumulating research indicates negative affect is a key precipitant of paranoid ideation, the possible protective role of positive affect has not been examined. Further, despite the interpersonal nature of paranoid ideation, there are limited and inconsistent findings regarding how social context, perceptions, and motivation influence paranoid ideation in real-world contexts. In this pilot study, we used smartphone ecological momentary assessment to understand the relevance of hour-by-hour fluctuations in mood and social experience for paranoid ideation in adults with psychotic disorders. Multilevel modeling results indicated that greater negative affect is associated with higher concurrent levels of paranoid ideation and that it is marginally related to elevated levels of future paranoid ideation. In contrast, positive affect was unrelated to momentary experiences of paranoid ideation. More severe momentary paranoid ideation was also associated with an elevated desire to withdraw from social encounters, irrespective of when with familiar or unfamiliar others. These observations underscore the role of negative affect in promoting paranoid ideation and highlight the contribution of paranoid ideation to the motivation to socially withdraw in psychotic disorders.
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Personality neuroscience is the study of persistent psychological individual differences, typically in the general population, using neuroscientific methods. It has the potential to shed light on the neurobiological mechanisms underlying individual differences and their manifestation in ongoing behavior and experience. The field was inaugurated many decades ago, yet has only really gained momentum in the last two, as suitable technologies have become widely available. Personality neuroscience employs a broad range of methods, including molecular genetics, pharmacological assays or manipulations, electroencephalography, and various neuroimaging modalities, such as magnetic resonance imaging and positron emission tomography. Although exciting progress is being made in this young field, much remains unknown. In this brief review, we discuss discoveries that have been made, methodological challenges and advances, and important questions that remain to be answered. We also discuss best practices for personality neuroscience research and promising future directions for the field.
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The objective of this study was to understand the associations of sleep and cardiorespiratory fitness with hippocampal volume and global cognition among older adults (n = 30, age = 65.8 years, female = 73.3%). Wrist actigraphy provided objective measures of nighttime sleep including sleep duration, average wake bout length (WBL; sleep disturbance), and wake-to-sleep transition probability (WTSP; sleep consolidation). Cardiorespiratory fitness was quantified via cycle exercise using a modified heart rate recovery approach. Magnetic resonance imaging was used to determine hippocampal volume and the Mini-Mental State Examination was used to assess global cognition. Fitness moderated associations of sleep with hippocampal volume and cognitive performance, whereby the association of WBL-an index of poor sleep-with hippocampal atrophy was stronger among less-fit individuals, and the association of sleep duration with cognitive performance was stronger among more-fit individuals. Across the fitness levels, a longer WBL was associated with lower cognitive performance, and a higher WTSP-an index of more consolidated sleep-was associated with greater hippocampal volume. Sleep and fitness were unrelated to the volume of an amygdala control region, suggesting a degree of neuroanatomical specificity. In conclusion, higher cardiorespiratory fitness may attenuate sleep disturbance-related hippocampal atrophy and magnify the cognitive benefits of good sleep. Prospective studies are needed to confirm these findings.
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Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT1 can be used later in life.
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Ansiedade , Temperamento , Ansiedade/psicologia , Transtornos de Ansiedade , Encéfalo/fisiologia , Pré-Escolar , Humanos , Estudos Retrospectivos , Temperamento/fisiologiaRESUMO
Negative affect is a fundamental dimension of human emotion. When extreme, it contributes to a variety of adverse outcomes, from physical and mental illness to divorce and premature death. Mechanistic work in animals and neuroimaging research in humans and monkeys have begun to reveal the broad contours of the neural circuits governing negative affect, but the relevance of these discoveries to everyday distress remains incompletely understood. Here, we used a combination of approaches-including neuroimaging assays of threat anticipation and emotional-face perception and more than 10,000 momentary assessments of emotional experience-to demonstrate that individuals who showed greater activation in a cingulo-opercular circuit during an anxiety-eliciting laboratory paradigm experienced lower levels of stressor-dependent distress in their daily lives (ns = 202-208 university students). Extended amygdala activation was not significantly related to momentary negative affect. These observations provide a framework for understanding the neurobiology of negative affect in the laboratory and in the real world.
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Tonsila do Cerebelo , Ansiedade , Tonsila do Cerebelo/diagnóstico por imagem , Animais , Ansiedade/psicologia , Emoções/fisiologia , Humanos , Imageamento por Ressonância Magnética , NeuroimagemRESUMO
The central goal of clinical psychology is to reduce the suffering caused by mental health conditions. Anxiety, mood, psychosis, substance use, personality, and other mental disorders impose an immense burden on global public health and the economy. Tackling this burden will require the development and dissemination of intervention strategies that are more effective, sustainable, and equitable. Clinical psychology is uniquely poised to serve as a transdisciplinary hub for this work. But rising to this challengerequires an honest reckoning with the strengths and weaknesses of current training practices. Building on new data, we identify the most important challenges to training the next generation of clinical scientists. We provide specific recommendations for the full spectrum of stakeholders-from funders, accreditors, and universities to program directors, faculty, and students-with an emphasis on sustainable solutions that promote scientific rigor and discovery and enhance the mental health of clinical scientists and the public alike.
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Transtornos Psicóticos , Saúde Global , Humanos , Saúde MentalRESUMO
Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach.