Gregory A Fonzo

The University of Texas at Austin Dell Medical School · Department of Psychiatry

Objective: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure...

Objective: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms. Method:...

A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disor...

The efficacy of antidepressant treatment for depression is controversial due to only modest superiority demonstrated over placebo. However, neurobiological heterogeneity within depression may limit overall antidepressant efficacy. We sought to identify a neurobiological phenotype responsive to antidepressant treatment by testing pretreatment brain...

Intimate-partner violence (IPV) is one of the most common causes of posttraumatic stress disorder (PTSD) among women. PTSD neuroimaging studies have identified functional differences in the amygdala and anterior cingulate cortex (ACC)/medial prefrontal cortex during emotion processing. Recent investigations of the limbic sensory system and its asso...

Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning an...

Discerning functional brain network variations related to neuropathological aggregates in Alzheimer's disease (AD), including amyloid-beta (Abeta) and phosphorylated tau (p-tau), is crucial for understanding their link to cognitive decline and underlying molecular mechanisms. However, these variations are often confounded by normal aging-related ch...

Background: Major depressive disorder (MDD) is a prevalent psychiatric disorder characterized by substantial clinical and neurobiological heterogeneity. Conventional studies that solely focus on clinical symptoms or neuroimaging metrics often fail to capture the intricate relationship between these modalities, limiting their ability to disentangle...

Neuroimaging techniques including functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) have shown promise in detecting functional abnormalities in various brain disorders. However, existing studies often focus on a single domain or modality, neglecting the valuable complementary information offered by multiple domains from bo...

Major depressive disorder (MDD) is a global health challenge with high prevalence. Further, many diagnosed with MDD are treatment resistant to traditional antidepressants. Repetitive transcranial magnetic stimulation (rTMS) offers promise as an alternative solution, but identifying objective biomarkers for predicting treatment response remains unde...

Psychedelics are natural or synthetic compounds, some with long histories of religious and cultural practice, which can induce remarkable changes in the human consciousness. After decades of suppression, the use and research of psychedelics are witnessing a new renaissance. At our new psychedelics research and therapy center, we are studying if cer...

Importance Understanding the heterogeneity of neuropsychiatric symptoms (NPSs) and associated brain abnormalities is essential for effective management and treatment of dementia. Objective To identify dementia subtypes with distinct functional connectivity associated with neuropsychiatric subsyndromes. Design, Setting, and Participants Using data...

Psychedelics (hallucinogenic 5-HT2A agonists such as psilocybin) are gaining recognition for their potential to treat a range of conditions, including anxiety-related psychopathology. Despite early promising results, the mechanisms by which psychedelic therapy alleviates anxiety are not well understood. Here, we review neural and cognitive mechanis...

Major depressive disorder (MDD) is a common and often severe condition that profoundly diminishes quality of life for individuals across ages and demographic groups. Unfortunately, current antidepressant and psychotherapeutic treatments exhibit limited efficacy and unsatisfactory response rates in a substantial number of patients. The development o...

Since 2009, the ENIGMA Consortium has brought together neuroimaging researchers from over 45 countries to perform some of the largest international studies of over 30 major brain disorders. The ENIGMA working groups tackle the growing challenge of data harmonization and standardization in analytic workflows, and address the need for well-powered, m...

Neurodevelopmental disorders, such as Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD), are characterized by comorbidity and heterogeneity. Identifying distinct subtypes within these disorders can illuminate the underlying neurobiological and clinical characteristics, paving the way for more tailored treatments. We...

Cocaine use disorder (CUD) is prevalent, and repetitive transcranial magnetic stimulation (rTMS) shows promise in reducing cravings. However, the association between a consistent CUD-specifc functional connectivity signature and treatment response remains unclear. Here we identify a validated functional connectivity signature from functional magnet...

In recent years, psychedelics have generated considerable excitement and interest as potential novel therapeutics for an array of conditions, with the most advanced evidence base in the treatment of certain severe and/or treatment-resistant psychiatric disorders. An array of clinical and pre-clinical evidence has informed our current understanding...

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we buil...

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we buil...

BACKGROUND Dementia is highly heterogeneous, with pronounced individual differences in neuropsychiatric symptoms (NPS) and neuroimaging findings. Understanding the heterogeneity of NPS and associated brain abnormalities is essential for effective management and treatment of dementia. METHODS Using large-scale neuroimaging data from the Open Access...

Trauma exposure, particularly interpersonal violence (IPV) traumas, are significant risk factors for development of mental health disorders, particularly posttraumatic stress disorder (PTSD). Studies attempting to disentangle mechanisms by which trauma confers risk and maintenance of PTSD have often investigated threat or reward learning in isolati...

Antidepressant medications yield unsatisfactory treatment outcomes in patients with major depressive disorder (MDD) with modest advantages over the placebo. This modest efficacy is partly due to the elusive mechanisms of antidepressant responses and unexplained heterogeneity in patient’s response to treatment — the approved antidepressants only ben...

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by social interaction deficits, communication difficulties, and restricted/repetitive behaviors or fixated interests. Despite its high prevalence, development of effective therapy for ASD is hindered by its symptomatic and neurophysiological heterogeneities. To col...

Cocaine use disorder (CUD) is a prevalent substance abuse disorder, and repetitive transcranial magnetic stimulation (rTMS) has shown potential in reducing cocaine cravings. However, a robust and replicable biomarker for CUD phenotyping is lacking, and the association between CUD brain phenotypes and treatment response remains unclear. Our study su...

Background Adolescent internalizing symptoms and trauma exposure have been linked with altered reward learning processes and decreased ventral striatal responses to rewarding cues. Recent computational work on decision-making highlights an important role for prospective representations of the imagined outcomes of different choices. This study teste...

Though sertraline is commonly prescribed in patients with major depressive disorder (MDD), its superiority over placebo is only marginal. This is in part due to the neurobiological heterogeneity of the individuals. Characterizing individual-unique functional architecture of the brain may help better dissect the heterogeneity, thereby defining treat...

Depressive episodes are more common and last longer in patients with bipolar disorder relative to manic or hypomanic episodes. They are often refractory to current pharmacologic treatment strategies, resulting in increased morbidity and mortality. There has been increased interest in neuromodulatory treatments, namely repetitive transcranial magnet...

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a gl...

Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level infere...

IMPORTANCE: Though sertraline is commonly prescribed in patients with major depressive disorder (MDD), its superiority over placebo is only marginal. This is in part due to the neurobiological heterogeneity of the individuals. Characterizing individual-unique functional architecture of the brain may help better dissect the heterogeneity, thereby de...

Medication and other therapies for psychiatric disorders show unsatisfying efficacy, in part due to the significant clinical/ biological heterogeneity within each disorder and our over-reliance on categorical clinical diagnoses. Alternatively, dimensional transdiagnostic studies have provided a promising pathway toward realizing personalized medici...

Post-traumatic stress disorder (PTSD) is a debilitating mental illness composed of a heterogeneous collection of symptom clusters. The unique nature of PTSD as arising from a precipitating traumatic event helps simplify cross-species translational research modeling the neurobehavioral effects of stress and fear. However, the neurobiological progres...

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging meth...

This chapter explores the connection between trauma and personality disorders (PDs). The mindset of a survivor of trauma is examined to elucidate how patterns of behavior evolve after trauma that may lead to the development of character pathology. Psychological etiologic theories coupled with neuroanatomical changes from neuroimaging research are r...

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through th...

Background Exposure-based psychotherapy is a first-line treatment for posttraumatic stress disorder (PTSD), but its mechanisms are poorly understood. Functional brain connectivity is a promising metric for identifying treatment mechanisms and bio-signatures of therapeutic response. To this end, we assessed amygdala and insula treatment-related conn...

There is limited research exploring attachment style and defenses in adolescents. The purpose of the current research is to explore the relationship between adolescent attachment style and development of defense mechanisms, as well as attachment style and problem behaviors. A total of 1487 students from two California high-schools completed three s...

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA‐Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega‐analysis of a large number of brain structural scans. In this process, the group was confronted with many methodolo...

Purpose of review This review aims to synthesize existing research regarding the definition of treatment resistance in posttraumatic stress disorder (PTSD), predictors of treatment non-response to first-line interventions, and emerging second-line PTSD treatment options into an accessible resource for the practicing clinician. Recent findings The...

Antidepressants are widely prescribed, but their efficacy relative to placebo is modest, in part because the clinical diagnosis of major depression encompasses biologically heterogeneous conditions. Here, we sought to identify a neurobiological signature of response to antidepressant treatment as compared to placebo. We designed a latent-space mach...

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodolo...

Repetitive transcranial magnetic stimulation (rTMS) is a commonly-used treatment for major depressive disorder (MDD). However, our understanding of the mechanism by which TMS exerts its antidepressant effect is minimal. Furthermore, we lack brain signals that can be used to predict and track clinical outcome. Such signals would allow for treatment...

Importance Despite the widespread awareness of functional magnetic resonance imaging findings suggesting a role for cortical connectivity networks in treatment selection for major depressive disorder, its clinical utility remains limited. Recent methodological advances have revealed functional magnetic resonance imaging–like connectivity networks u...

Objective: Major depressive disorder is associated with aberrant resting-state functional connectivity across multiple brain networks supporting emotion processing, executive function, and reward processing. The purpose of this study was to determine whether patterns of resting-state connectivity between brain regions predict differential outcome...

For better or worse, human beings are irrevocably shaped by the developmental environment via biological imprinting of early experience. The brain mechanisms by which stressful early experiences, such as childhood maltreatment, lead to later mental and physical health challenges have been extensively sought yet remain elusive. This work has largely...

Treatment of posttraumatic stress disorder (PTSD) is time and cost-intensive. New, readily implementable interventions are needed. Two parallel randomized clinical trials tested if cognitive/affective computerized training improves cognitive/affective functions and PTSD symptoms in acute (N = 80) and chronic PTSD (N = 84). Adults age 18–65 were rec...

Background: Major Depressive Disorder (MDD) has been associated with brain-related changes. However, biomarkers have yet to be defined that could "accurately" identify antidepressant-responsive patterns and reduce the trial-and-error process in treatment selection. Cerebral blood perfusion, as measured by Arterial Spin Labelling (ASL), has been us...

Introduction: Post-Traumatic Stress Disorder (PTSD) is a prevalent, severe and tenacious psychopathological consequence of traumatic events. Neurobehavioral mechanisms underlying PTSD pathogenesis have been identified, and may serve as risk-resilience factors during the early aftermath of trauma exposure. Longitudinally documenting the neurobehavio...

Post-traumatic stress manifests in disturbed affect and emotion, including exaggerated severity and frequency of negative valence emotions, e.g., fear, anxiety, anger, shame, and guilt. However, another core feature of common post-trauma psychopathologies, i.e. post-traumatic stress disorder (PTSD) and major depression, is diminished positive affec...

Affective neuroimaging has contributed to our knowledge of generalized anxiety disorder (GAD) through measurement of blood oxygenation level-dependent (BOLD) responses, which facilitate inference on neural responses to emotional stimuli during task-based functional magnetic resonance imaging (fMRI). In this article, the authors provide an integrate...