Alexander Joseph Shackman

• Ph.D.
• Professor at University of Maryland, College Park

Background: Anxiety, depression, and related internalizing illnesses are a leading burden on global public health, and often emerge during times of stress. Yet the underlying neurobiology has remained enigmatic, hindering treatment development. Methods: Here we used a combination of tools--including a well-established threat-anticipation fMRI parad...

Are scientific papers providing all essential details necessary to ensure the replicability of study protocols? Are authors effectively conveying study design, data analysis, and the process of drawing inferences from their results? These represent only a fraction of the pressing questions that cognitive psychology and neuropsychology face in addre...

Graduate students are a vital component of the academic enterprise. They produce research, teach, mentor, and provide healthcare and other critical services. Evidence suggests that a large proportion of graduate students experience high levels of depression and anxiety, attracting the attention of policy makers. Yet past work has relied on cross-se...

Background and Hypothesis Among individuals living with psychotic disorders, social impairment is common, debilitating, and challenging to treat. While the roots of this impairment are undoubtedly complex, converging lines of evidence suggest that social motivation and pleasure (MAP) deficits play a central role. Yet most neuroimaging studies have...

Anxiety disorders are a leading source of human misery, morbidity, and premature mortality. Existing treatments are far from curative for many, underscoring the need to clarify the underlying neural mechanisms. Although many brain regions contribute, the amygdala has received the most intense scientific attention. Over the past several decades, thi...

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...

Understanding the neurobiological mechanisms involved in psychopathology has been hindered by the limitations of categorical nosologies. The Hierarchical Taxonomy of Psychopathology (HiTOP) is an alternative dimensional system for characterizing psychopathology, derived from quantitative studies of covariation among diagnoses and symptoms. HiTOP pr...

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 r...

Among individuals living with psychotic disorders, social impairment is common, debilitating, and challenging to treat. While the roots of this impairment are undoubtedly complex, converging lines of evidence suggest that social motivation and pleasure (MAP) deficits play a key role. Yet most neuroimaging studies have focused on monetary rewards, p...

Graduate students are a vital component of the academic enterprise. They produce research, teach, mentor, and provide healthcare and other critical services. Evidence suggests that a large proportion of graduate students experience high levels of depression and anxiety, attracting the attention of policy makers1-8. Yet past work has relied on cross...

Graduate students are a vital component of the academic enterprise. They produce research, teach, mentor, and provide healthcare and other critical services. Evidence suggests that a large proportion of graduate students experience high levels of depression and anxiety, attracting the attention of policy makers. Yet past work has relied on cross-se...

BACKGROUND Stress is widely acknowledged as a risk factor for various negative health outcomes. Therefore, assessing everyday stress through longitudinal research has gained interest, with a focus on capturing stress and its components using intra-individual approaches and ecological momentary assessment (EMA). OBJECTIVE Building on the proposal o...

In psychotic disorders, motivation and pleasure (MAP) deficits are associated with decreased affiliation and heightened functional impairment. We leveraged a transdiagnostic sample enriched for psychosis and a multimethod approach to test the hypothesis that MAP deficits undermine the stress-buffering benefits of affiliation. Participants completed...

Social anxiety, which typically emerges in adolescence, lies on a continuum and, when extreme, can be devastating, with clear functional impairment evident even at subdiagnostic levels. Socially anxious individuals are prone to heightened fear, anxiety, and avoidance of social interactions and contexts associated with the potential for social scrut...

Elevated levels of Neuroticism/Negative Emotionality (N/NE) and, less consistently, lower levels of Extraversion/Positive Emotionality (E/PE) confer risk for pathological depression and anxiety. To date, most prospective-longitudinal research has narrowly focused on traditional diagnostic categories, creating uncertainty about the precise nature of...

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 implica...

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 h...

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 (2022) highlighted a number of urgent challenges facing today’s clinical interns. They provid...

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 lit...

Understanding the neurobiological systems involved in psychopathology has been hindered by the limitations of categorical nosologies, spurring the development of alternative dimensional systems for characterizing psychopathology. The Hierarchical Taxonomy of Psychopathology (HiTOP) is one such system, derived from quantitative studies of covariatio...

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 diso...

Fear and anxiety play a central role in the lives of humans and other animals, and there is considerable interest in clarifying their nature, identifying their biological underpinnings, and determining their consequences for health and disease. Although important strides have been made over the past half-century, it has become clear that our unders...

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 re...

Elevated levels of Neuroticism/Negative Emotionality (N/NE) and, less consistently, lower levels of Extraversion/Positive Emotionality (E/PE) confer risk for pathological depression and anxiety. To date, most prospective-longitudinal research has narrowly focused on traditional diagnostic categories, creating uncertainty about the precise nature of...

Our capacity to measure diverse aspects of human biology in vivo has developed rapidly in the past decades, but the rate at which these techniques have generated translatable insights into the biology of psychopathological conditions has lagged far behind. This slow progress is partly due to the poor sensitivity, specificity, and replicability of m...

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 man...

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),...

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. Furt...

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 aff...

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 a...

Anxiety and depression are common and challenging to treat. Yet our understanding of the dynamic emotional processes that underlie internalizing illness remains incomplete, thwarting treatment development. Here, we used ecological momentary assessment to understand relations between real-world affective dynamics and specific internalizing facets in...

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...

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a quantitative nosological system that addresses shortcomings of traditional mental disorder diagnoses, including arbitrary boundaries between psychopathology and normality, frequent disorder co-occurrence, substantial heterogeneity within disorders, and diagnostic unreliability over time and...

The central goal of clinical psychology is to reduce the suffering caused by mental health conditions. Anxiety, depression, 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...

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 ge...

Older adults comprise the fastest growing global demographic and are at increased risk of poor mental health outcomes. Although aerobic exercise and sleep are critical to the preservation of emotional well-being, few studies have examined their combined mood-enhancing effects, or the potential neural mechanisms underlying these effects. Here, we us...

When extreme, anxiety—a state of distress and arousal prototypically evoked by uncertain danger—can be debilitating. Uncertain anticipation is a shared feature of situations that elicit signs and symptoms of anxiety across psychiatric disorders, species, and assays. Despite the profound significance of anxiety for human health and wellbeing, the ne...

Steeper rates of temporal discounting—the degree to which smaller-sooner (SS) rewards are preferred over larger-later (LL) ones—have been associated with impulsive and ill-advised behaviors in adolescence. Yet, the underlying neural systems remain poorly understood. Here we used a well-established temporal discounting paradigm and functional MRI (f...

One in every five fatalities in the United States is caused by smoking, causing an estimated 480,000 deaths each year. While tobacco use is the leading preventable cause of mortality in the United States, the habit of tobacco use stems from the addictive nicotine content in cigarettes. Although the addictive and physiological health effects of toba...

Background:Retrospective studies have found that people with elevated social anxiety (SA) show a preference for digital/online communication, which may be due to perceptions of enhanced emotional safety. Whether these preferences for/benefits of digital compared to face-to-face communication manifest in the real world has yet to be explored. Method...

Understanding how individuals with varying levels of social anxiety respond to daily positive events is important. Psychological processes that increase positive emotions are being widely used as strategies to not only enhance well-being but also reduce the symptoms and impairment tied to negative emotional dispositions and conditions, including ex...

Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorder...

Objective: Diagnosis is a cornerstone of clinical practice for mental health care providers, yet traditional diagnostic systems have well-known shortcomings, including inadequate reliability, high comorbidity, and marked within-diagnosis heterogeneity. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a data-driven, hierarchically based alter...

Background Social anxiety lies on a continuum, and young adults with elevated symptoms are at risk for developing a range of psychiatric disorders. Yet relatively little is known about the factors that govern the hour-by-hour experience and expression of social anxiety in the real world. Methods Here we used smartphone-based ecological momentary a...

Understanding how individuals with varying levels of social anxiety respond to daily positive events is important. Psychological processes that increase positive emotions are being widely used as strategies to not only enhance well-being but reduce the symptoms and impairment tied to negative emotional dispositions and conditions, including excessi...

For more than a century, research on psychopathology has focused on categorical diagnoses. Although this work has produced major discoveries, growing evidence points to the superiority of a dimensional approach to the science of mental illness. Here we outline one such dimensional system-the Hierarchical Taxonomy of Psychopathology (HiTOP)-that is...

Borsboom et al. confuse biological approaches with extreme biological reductionism and common-cause models of psychopathology. In muddling these concepts, they mistakenly throw the baby out with the bathwater. Here, we highlight recent work underscoring the unique value of clinical and translational neuroscience approaches for understanding the nat...

Social anxiety lies on a continuum, and young adults with elevated symptoms are at risk for developing a range of debilitating psychiatric disorders. Yet, relatively little is known about the factors that govern the momentary expression of social anxiety in daily life, close to clinically significant end-points. Here, we used smartphone-based ecolo...

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the underlying mechanisms have only recently begun to come into focus. Here, we review new insights into the nature and biological bases of dispositional negativity, a fundamental dimension of chi...

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the underlying mechanisms have only recently begun to come into focus. Here, we review new insights into the nature and biological bases of dispositional negativity, a fundamental dimension of chi...

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the underlying mechanisms have only recently begun to come into focus. Here, we review new insights into the nature and biological bases of dispositional negativity, a fundamental dimension of chi...

Startle potentiation is a well validated translational measure of negative affect. Startle potentiation is widely used in clinical and affective science and there are multiple approaches for its quantification. The three most commonly used approaches quantify startle potentiation as the increase in startle response from a neutral to threat conditio...

Alcohol use is common, imposes a staggering burden on public health, and often resists treatment. The central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (Ce)—plays a key role in prominent neuroscientific models of alcohol drinking, but the relevance of these regions to acu...

Emotion is a core feature of the human condition, with profound consequences for health, wealth, and wellbeing. Over the past quarter-century, improved methods for manipulating and measuring different features of emotion have yielded steady advances in our scientific understanding emotional states, traits, and disorders. Yet, it is clear that most...

Children with an extremely inhibited, anxious temperament (AT) are at increased risk for anxiety disorders and depression. Using a rhesus monkey model of early-life AT, we previously demonstrated that metabolism in the central extended amygdala (EAc), including the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST),...

Alcohol abuse is common, imposes a staggering burden on public health, and is challenging to treat, underscoring the need to develop a deeper understanding of the underlying neurobiology. When administered acutely, ethyl alcohol reduces threat reactivity in humans and other animals, and there is growing evidence that threat-dampening and related ne...

Spatial normalization—the process of aligning anatomical or functional data acquired from different individuals to a common stereotaxic atlas—is routinely used in the vast majority of functional neuroimaging studies, with important consequences for scientific inference and reproducibility. Although several approaches exist, multi-step techniques th...

The central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a critical role in triggering fear and anxiety and is implicated in the development of a range of debilitating neuropsychiatric disorders. Although it is widely believed that these disorders reflect the coordina...

Dispositional anxiety is a trait-like phenotype that confers increased risk for a range of debilitating neuropsychiatric disorders. Like many patients with anxiety disorders, individuals with elevated levels of dispositional anxiety are prone to intrusive and distressing thoughts in the absence of immediate threat. Recent electrophysiological resea...

Anxiety disorders impose a staggering burden on public health, underscoring the need to develop a deeper understanding of the distributed neural circuits underlying extreme fear and anxiety. Recent work highlights the importance of the central extended amygdala, including the central nucleus of the amygdala (Ce) and neighboring bed nucleus of the s...

The central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a key role in orchestrating states of fear and anxiety and is implicated in the development and maintenance of anxiety disorders, depression, and substance abuse. Although it is widely thought that these disorde...

The internalizing spectrum of psychiatric disorders-depression and anxiety-are common, highly comorbid, and challenging to treat. Individuals with childhood onset depression have a particularly poor prognosis. There is compelling evidence that individuals with depression display reduced resting-state EEG activity at sensors overlying the left prefr...

Dispositional negativity—the tendency to experience more frequent or intense negative emotions—is a fundamental dimension of temperament and personality. Elevated levels of dispositional negativity have profound consequences for public health and wealth, drawing the attention of researchers, clinicians, and policymakers. Yet, relatively little is k...

Dispositional negativity—the tendency to experience more frequent or intense negative emotions—is a fundamental dimension of temperament and personality. Elevated levels of dispositional negativity have profound consequences for public health and wealth, drawing the attention of researchers, clinicians, and policy makers. Yet, relatively little is...

The central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), two nuclei within the central extended amygdala, function as critical relays within the distributed neural networks that coordinate sensory, emotional, and cognitive responses to threat. These structures have overlapping anatomical projections to downstream ta...

Dispositional negativity—the propensity to experience and express more frequent, intense, or enduring negative affect—is a fundamental dimension of childhood temperament and adult personality. Elevated levels of dispositional negativity can have profound consequences for health, wealth, and happiness, drawing the attention of clinicians, researcher...

Children with an anxious temperament are prone to heightened shyness and behavioral inhibition (BI). When chronic and extreme, this anxious, inhibited phenotype is an important early-life risk factor for the development of anxiety disorders, depression and co-morbid substance abuse. Individuals with extreme anxious temperament often show persistent...

It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated in...

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the neurocognitive mechanisms that confer increased risk have only recently begun to come into focus. Here we review recent work highlighting the importance of neural circuits centered on the amyg...

Lieberman and Eisenberger (1) claim that the “dorsal anterior cingulate cortex (dACC) is selective for pain.” This surprising conclusion contradicts a large body of evidence showing robust dACC responses to nonpainful conditions. Electrophysiological and optogenetic studies have identified neuronal populations activated during foraging behavior, at...

Startle potentiation is a well-validated translational measure of negative affect. Startle potentiation is widely used in clinical and affective science, and there are multiple approaches for its quantification. The three most commonly used approaches quantify startle potentiation as the increase in startle response from a neutral to threat conditi...

perception loops might be reused for more advanced cognitive abilities such as planning, mindreading, and executive function). This suggests that the same " affective tuning " of neuronal hierarchies naturally biases higher cognitive abilities, too. In sum, various active inference mechanisms reviewed here – embodied predictive coding, precision dy...

Significance According to the World Health Organization, anxiety and depressive disorders are a leading source of disability, affecting hundreds of millions of people. Children can inherit an extremely anxious temperament, which is a prominent risk factor for the later development of anxiety, depression, and comorbid substance abuse. This study use...

Recent years have witnessed the emergence of powerful new tools for assaying the brain and a remarkable acceleration of research focused on the interplay of emotion and cognition. This work has begun to yield new insights into fundamental questions about the nature of the mind and important clues about the origins of mental illness. In particular,...

Dispositional anxiety is a well-established risk factor for the development of anxiety and other emotional disorders. These disorders are common, debilitating, and challenging to treat, pointing to the need to understand the more elementary neurocognitive mechanisms that confer elevated risk. Importantly, many of the maladaptive behaviors character...

Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment