Marilla Geraci

National Institutes of Health | NIH · NIH Clinical Center (CC)

Background: The central nucleus of the amygdala and bed nucleus of the stria terminalis are involved primarily in phasic and sustained aversive states. Although both structures have been implicated in pathological anxiety, few studies with a clinical population have specifically focused on them, partly because of their small size. Previous work in...

Background Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder. Method Unmedicated individuals with GAD ( n = 18) an...

Objective: Deficits in reinforcement-based decision making have been reported in generalized anxiety disorder. However, the pathophysiology of these deficits is largely unknown; published studies have mainly examined adolescents, and the integrity of core functional processes underpinning decision making remains undetermined. In particular, it is...

Background: Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related fun...

Background: Delineating specific clinical phenotypes of anxiety disorders is a crucial step toward better classification and understanding of these conditions. The present study sought to identify differential aversive responses to predictable and unpredictable threat of shock in healthy comparisons and in non-medicated anxiety patients with and w...

There is preliminary data indicating that patients with generalized anxiety disorder (GAD) show impairment on decision-making tasks requiring the appropriate representation of reinforcement value. The current study aimed to extend this literature using the passive avoidance (PA) learning task, where the participant has to learn to respond to stimul...

Sustaining change in the behaviors and habits of experienced practicing nurses can be frustrating and daunting, even when changes are based on evidence. Partnering with an active shared governance structure to communicate change and elicit feedback is an established method to foster partnership, equity, accountability, and ownership. Few recent exe...

Meta-analytic results of fear-conditioning studies in the anxiety disorders implicate generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of anxiety pathology. Due to the absence of conditioning studies assessing generalization in generalized anxiety disorder (GAD), resu...

Generalized social phobia (GSP) and generalized anxiety disorder (GAD) are both associated with emotion dysregulation. Research implicates dorsal anterior cingulate cortex in both explicit emotion regulation (EER) and top-down attentional control (TAC). Although studies have examined these processes in GSP or GAD, no work compares findings across t...

Few studies have addressed whether the use of avoidance-oriented coping strategies is related to the development of panic in patients with panic disorder(PD). Self-report, clinician-rated, and physiological data were collected from 42 individuals who participated in a yohimbine biological challenge study, performed under double-blind, placebo-contr...

Generalized social phobia (GSP) involves the fear of being negatively evaluated. Previous work suggests that self-referentiality, mediated by the medial prefrontal cortex (MFPC), plays an important role in the disorder. However, it is not clear whether this anomalous MPFC response to self-related information in patients with GSP concerns an increas...

While social phobia in adolescence predicts the illness in adulthood, no study has directly compared the neural responses in social phobia in adults and adolescents. The authors examined neural responses to facial expressions in adults and adolescents with social phobia to determine whether the neural correlates of adult social phobia during face p...

Little is known about the neural underpinnings of generalized social phobia, which is defined by a persistent heightened fear of social disapproval. Using event-related functional MRI (fMRI), the authors examined whether the intent of an event, which mediates the neural response to social disapproval in healthy individuals, differentially affects r...

Classical conditioning features prominently in many etiological accounts of panic disorder. According to such accounts, neutral conditioned stimuli present during panic attacks acquire panicogenic properties. Conditioned stimuli triggering panic symptoms are not limited to the original conditioned stimuli but are thought to generalize to stimuli re...

Generalized social phobia (GSP) involves the fear/avoidance of social situations whereas generalized anxiety disorder (GAD) involves an intrusive worry about everyday life circumstances. It remains unclear whether these, highly co-morbid, conditions represent distinct disorders or alternative presentations of a single underlying pathology. In this...

We investigated whether performance on a reward processing task differs between fully remitted patients with major depressive disorder (MDD) and healthy control subjects after catecholamine depletion. Seventeen unmedicated subjects with remitted MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral alpha-methyl-para...

Positron emission tomography (PET) can localize and quantify neurokinin-1 (NK(1)) receptors in brain using the nonpeptide antagonist radioligand, [(18)F]SPA-RQ. We sought to determine if patients with panic disorder have altered density of NK(1) receptors in brain because of their history of recurrent panic attacks. We also sought to determine if a...

The benzodiazepine (BZD) receptor system has been implicated in the pathophysiologic mechanism of panic disorder (PD) by indirect evidence from pharmacological challenge studies and by direct evidence from single-photon emission computed tomography and positron emission tomography neuroimaging studies. However, the results of previous neuroimaging...

Generalized social phobia (GSP) is characterized by fear/avoidance of social situations. Previous studies have examined the neural responses in GSP to one class of social stimuli, facial expressions. However, studies have not examined the neural response in GSP to another equally important class of social stimuli, the communication of praise or cri...

Classical fear-conditioning is central to many etiologic accounts of panic disorder (PD), but few lab-based conditioning studies in PD have been conducted. One conditioning perspective proposes associative-learning deficits characterized by deficient safety learning among PD patients. The current study of PD assesses acquisition and retention of di...

Panic disorder (PD) is hypothesized to be associated with altered function of the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Previous proton magnetic resonance spectroscopy (MRS) studies found lower GABA concentrations in the occipital cortex of subjects with PD relative to healthy control subjects. The current study is the...

Generalized social phobia involves fear/avoidance, specifically of social situations, whereas generalized anxiety disorder involves intrusive worry about diverse circumstances. It remains unclear the degree to which these two, often comorbid, conditions represent distinct disorders or alternative presentations of a single, core underlying pathology...

The pathophysiologic mechanism of major depressive disorder (MDD) has been consistently associated with altered catecholaminergic function, especially with decreased dopamine neurotransmission, by various sources of largely indirect evidence. An instructive paradigm for more directly investigating the relationship between catecholaminergic function...

Treatment for anxiety and post-traumatic stress disorder (PTSD) includes exposure therapy and medications, but some patients are refractory. Few studies of repetitive transcranial magnetic stimulation (rTMS) for anxiety or PTSD exist. In this preliminary report, rTMS was combined with exposure therapy for PTSD. Nine subjects with chronic, treatment...

Generalized social phobia (GSP) is characterized by a marked fear of most social situations. It is associated with an anomalous neural response to emotional stimuli, and individuals with the disorder frequently show interpretation bias in social situations. From this it might be suggested that GSP involves difficulty in accurately perceiving, using...

Neuropeptide Y (NPY) and serotonergic systems have been implicated in the pathophysiology of depression but have not yet been linked together. In a randomized, double-blind crossover study, 28 medication-free patients with remitted depression and 26 healthy control subjects underwent tryptophan depletion (TD) and sham depletion. Plasma NPY concentr...

CONTEXT: The benzodiazepine (BZD) receptor system has been implicated in the pathophysiologic mechanism of panic disorder (PD) by indirect evidence from pharmacological challenge studies and by direct evidence from single-photon emission computed tomography and positron emission tomography neuroimaging studies. However, the results of previous neur...

The causes of paroxysmal hypertension in patients in whom pheochromocytoma has been excluded ('pseudopheochromocytoma') usually remain unclear. Blood pressure disturbances and symptoms of catecholamine excess in these patients may reflect activation of the sympathetic nervous and adrenal medullary systems. We therefore examined sympathoadrenal func...

Neuropsychological studies have provided evidence for deficits in psychiatric disorders, such as schizophrenia and mood disorders. However, neuropsychological function in Panic Disorder (PD) or PD with a comorbid diagnosis of Major Depressive Disorder (MDD) has not been comprehensively studied. The present study investigated neuropsychological func...

alpha2-Adrenoreceptors restrain sympathetic nervous outflows and inhibit release of noradrenaline from sympathetic nerves. In-frame deletion of the alpha2C-adrenoreceptor subtype (alpha2CDel322-325) increases the risk of congestive heart failure. Increased delivery of catecholamines to cardiovascular receptors might explain this increased risk. Twe...

An instructive paradigm for investigating the relationship between brain serotonin function and major depressive disorder (MDD) is the response to tryptophan depletion (TD) induced by oral loading with all essential amino acids except the serotonin precursor tryptophan. To determine whether serotonin dysfunction represents a trait abnormality in MD...

It has been suggested that pharmacological challenges that induce panic attacks are confounded by effects of environmental stress, elevated baseline arousal, and expectancy bias. To control for effects of arousal and cognition on the panicogenic effects of pentagastrin, pharmacological challenges were conducted during sleep in seven patients with p...

Nuclear imaging studies have examined cerebral blood flow (rCBF) in subjects with posttraumatic stress disorder (PTSD) using symptom evocation paradigms. To date, no such studies have investigated rCBF as related to subjects' reports of flashback intensity. Subjects with varying traumatic histories and longstanding PTSD were studied using [15O]-H2O...

The purpose of this study was to design and conduct a pilot analysis evaluating the utility of a longitudinal, graphic approach to the symptoms of posttraumatic stress disorder (PTSD). Representative patients were instructed in the use of a daily prospective life-chart; they were interviewed and their past medical records were examined for monthly...

Pentagastrin, a cholecystokinin (CCK) agonist, produces anxiety and panic in patients with panic disorder and social phobia. Preclinical data suggests that pentagastrin-induced anxiogenesis may be mediated via 5-HT3 receptors. In the present study, 14 patients with panic disorder or social phobia underwent pharmacological challenge in three conditi...

The present study sought to determine whether social phobics, like patients with panic disorder, have increased sensitivity to the panicogenic effects of pentagastrin. Intravenous pentagastrin and placebo were administered in a double-blind fashion to 19 social phobics, 11 patients with panic disorder, and 19 healthy controls while they participate...

Ten to 30 percent of patients undergoing cardiac catheterization because of chest pain are found to have normal coronary angiograms. Because these patients may have a visceral pain syndrome unrelated to myocardial ischemia, we investigated whether drugs that are useful in chronic pain syndromes might also be beneficial in such patients. Sixty conse...

A large body of data suggest that brain cholecystokinin (CCK) systems are involved in the regulation of anxiety, and numerous studies have demonstrated that CCK-4, a CCKB agonist, reliably induces panic attacks in patients with panic disorder. Recently, pentagastrin, a commercially available CCKB agonist, has been reported to have similar anxiogeni...

Diurnal changes in the frequency of panic attacks and symptoms of generalised anxiety, phobic anxiety and phobic avoidance in 34 panic-disorder patients and 40 normal controls were evaluated. The panic-disorder patients had significant diurnal changes in generalised and phobic anxiety, but not phobic avoidance. Increased severity of symptoms and pr...

Given the abrupt and time-limited nature of daytime-awake and nocturnal-sleep panic attacks, several chemical and neuroendocrine challenge tests have been employed to investigate the neurobiology of "spontaneous" panic attacks. Previously we demonstrated that panic disorder patients have blunted growth hormone (GH) responses to clonidine, an alpha...

The behavioral and neuroendocrine effects of meta-chlorophenylpiperazine (m-CPP), a serotonergic agonist, were compared with the effects of caffeine, an adenosine antagonist, in panic disorder patients. Patients with panic disorder were given single oral doses of 0.5 mg/kg m-CPP, 480 mg caffeine, and placebo on separate days under double-blind cond...

Single-dose nifedipine was given to 13 phobic patients with increased generalized anxiety. Nifedipine failed to demonstrate anxiety-reducing effects on baseline anxiety ratings. Furthermore, in a subset of four patients, the drug failed to show an anxiolytic effect in exposure-related anxiety.

Because previous studies have documented the distorting effect of time of recall on the reporting of life events over a one-year period of time, the relation between various life event measures and time of recall over time periods greater than one year was examined in 44 patients with panic disorder and 44 control subjects. For both groups, time of...

The authors examined the number, type, and effect of life events during the year before the onset of panic attacks in 44 patients with a Research Diagnostic Criteria diagnosis of panic disorder and 44 healthy control subjects matched for age, sex, and time of retrospection. The patients had significantly more life events, and these events had a mor...

Eleven panic disorder patients who had experienced a major loss or separation in the year before they had their first panic attack were significantly more likely to develop a subsequent major depression than were 22 patients who had not suffered such a loss.

Uhde, Thomas W., Jean-Philippe Boulenger, Peter P. Roy-Byrne, Macilla F. Geraci, Bernard J. Vittone, and Robert M. Post: Longitudinal course of panic disorder: clinical and biological considerations. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1985, 9(1); 39-51. 1. 1. The longitudinal course of panic disorder and its associated symptoms were inv...