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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.

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.

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. [ABSTRACT FROM AUTHOR]

This study evaluated how continuities and discontinuities in the intergenerational transmission of maltreatment affect offspring psychopathology. Data from a multigenerational prospective, longitudinal study were used to compare the severity of offspring psychopathology in families with no history of maltreatment (controls) and those in which parents, offspring, or both experienced childhood maltreatment (cycle breakers, initiators, and maintainers, respectively). Participants included 454 parents (M age = 47.1, SD age = 3.4) and their 697 offspring (M age = 22.3, SD age = 6.3). Offspring of cycle breakers reported less psychopathology than offspring of cycle maintainers and did not report more psychopathology than offspring of controls. Offspring of cycle initiators and maintainers reported comparable levels of psychopathology. Results suggest that breaking the cycle of maltreatment buffers offspring from risk for psychopathology associated with parental maltreatment, with no enduring or additive effects of maltreatment across generations. Our findings highlight the need for maltreatment prevention programs and further research to identify conditions and characteristics that reduce the probability of intergenerational transmission. [ABSTRACT FROM AUTHOR]

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.

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 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 rigorously 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 non-fungible. 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 mechanistic research.

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.

Background: Approximately a quarter of the global population experiences chest pain during their lifetime worldwide. Although largely non-life-threatening, many patients experience mental, physical, social, and financial consequences., Aim: This study aimed to describe and determine the epidemiology and consequences of patients presenting with atypical chest pain (ACP).  Method: Data were obtained from 102 participants, from a desired sample size of 166. The target population was patients who presented with ACP at the Accident and Emergency Department of a Teaching Hospital in Trinidad during a two-year period, from January 2021 to December 2022. The data collection instrument used was a 34-item online questionnaire. Data were analyzed using both descriptive and inferential statistical methods., Results: Participants were predominantly women (63.7%; n = 65), between 31 and 50 years of age (74.5%; n = 76), in full-time employment (n = 58; 56.9%), who lived with at least one person (90.2%; n = 92) at the time of the episode. Overall, 61.8% (n = 63) reported having a stressful life. Hypertension (30.4%; n = 31) and diabetes (18.6%; n = 19) were the leading comorbidities. Participants experienced mild to severe anxiety (53.9%; n = 55), moderate to severe depression (25.5%; n = 26), moderate stress (65.7%; n = 67), and loneliness (25.5%; n = 26). A stressful life was associated with, and was a predictor of, both anxiety and loneliness. No sociodemographic variables were associated with depression or stress. The most common self-reported consequences were "fear as a result of the pain" (68.6%; n = 69), "interruptions to daily life" (60.8%; n = 61), "reduction in time spent on hobbies" (62.7%; n = 63), and costly diagnostic/investigative tests (62.7%; n = 64). The majority of patients (52.9%; n = 53) reported reduced quality of life. The most common treatment prescribed was paracetamol (53.9%; n = 55) and exercise (23.5%; n = 24)., Conclusion: The study participants were mainly women, 31-50 years old, who had experienced anxiety, stress, or depression. They mainly experienced fear and self-reported a reduced quality of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Bahall et al.)