Jeffrey P. Staab

Threat assessment and locomotion: clinical applications of an integrated model of anxiety and postural control.

Interactions between anxiety and vestibular symptoms have been described since the late 1800s. Typically, they have been conceptualized as bidirectional effects of one condition on the other (i.e., anxiety disorders as a cause of vestibular symptoms and vestibular disorders as a cause of anxiety symptoms). Over the past 30 years, however, a steady progression of neurophysiological investigations of gait and stance under conditions of postural threat, neuroanatomical studies of connections between threat assessment and vestibular pathways in the brain, and clinical research on anxiety-related vestibular conditions has offered the building blocks of a more integrated model. In this newer concept, threat assessment is an integral component of spatial perception, postural control, and locomotion in health and disease. It is not imposed on the vestibular system from the outside or simply reactive to vestibular dysfunction, but an inherently necessary part of every aspect of mobility. In this article, the authors review evidence that supports this model and then use it to examine common neurotologic conditions in which anxiety-related processes play important roles-fear of falling, primary and secondary anxiety disorders in patients with vestibular symptoms, and chronic subjective dizziness.

Visual Dependency and Dizziness after Vestibular Neuritis

Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques.

Diagnostic criteria for persistent postural-perceptual dizziness (PPPD): Consensus document of the committee for the Classification of Vestibular Disorders of the Bárány Society

This paper presents diagnostic criteria for persistent postural-perceptual dizziness (PPPD) to be included in the International Classification of Vestibular Disorders (ICVD). The term PPPD is new, but the disorder is not. Its diagnostic criteria were derived by expert consensus from an exhaustive review of 30 years of research on phobic postural vertigo, space-motion discomfort, visual vertigo, and chronic subjective dizziness. PPPD manifests with one or more symptoms of dizziness, unsteadiness, or non-spinning vertigo that are present on most days for three months or more and are exacerbated by upright posture, active or passive movement, and exposure to moving or complex visual stimuli. PPPD may be precipitated by conditions that disrupt balance or cause vertigo, unsteadiness, or dizziness, including peripheral or central vestibular disorders, other medical illnesses, or psychological distress. PPPD may be present alone or co-exist with other conditions. Possible subtypes await future identification and validation. The pathophysiologic processes underlying PPPD are not fully known. Emerging research suggests that it may arise from functional changes in postural control mechanisms, multi-sensory information processing, or cortical integration of spatial orientation and threat assessment. Thus, PPPD is classified as a chronic functional vestibular disorder. It is not a structural or psychiatric condition.

Personality traits modulate subcortical and cortical vestibular and anxiety responses to sound-evoked otolithic receptor stimulation

OBJECTIVE Strong links between anxiety, space-motion perception, and vestibular symptoms have been recognized for decades. These connections may extend to anxiety-related personality traits. Psychophysical studies showed that high trait anxiety affected postural control and visual scanning strategies under stress. Neuroticism and introversion were identified as risk factors for chronic subjective dizziness (CSD), a common psychosomatic syndrome. This study examined possible relationships between personality traits and activity in brain vestibular networks for the first time using functional magnetic resonance imaging (fMRI). METHODS Twenty-six right-handed healthy individuals underwent fMRI during sound-evoked vestibular stimulation. Regional brain activity and functional connectivity measures were correlated with personality traits of the Five Factor Model (neuroticism, extraversion-introversion, openness, agreeableness, consciousness). RESULTS Neuroticism correlated positively with activity in the pons, vestibulo-cerebellum, and para-striate cortex, and negatively with activity in the supra-marginal gyrus. Neuroticism also correlated positively with connectivity between pons and amygdala, vestibulo-cerebellum and amygdala, inferior frontal gyrus and supra-marginal gyrus, and inferior frontal gyrus and para-striate cortex. Introversion correlated positively with amygdala activity and negatively with connectivity between amygdala and inferior frontal gyrus. CONCLUSIONS Neuroticism and introversion correlated with activity and connectivity in cortical and subcortical vestibular, visual, and anxiety systems during vestibular stimulation. These personality-related changes in brain activity may represent neural correlates of threat sensitivity in posture and gaze control mechanisms in normal individuals. They also may reflect risk factors for anxiety-related morbidity in patients with vestibular disorders, including previously observed associations of neuroticism and introversion with CSD.

Role of the Insula and Vestibular System in Patients with Chronic Subjective Dizziness: An fMRI Study Using Sound-Evoked Vestibular Stimulation

Chronic subjective dizziness (CSD) is a common vestibular disorder characterized by persistent non-vertiginous dizziness, unsteadiness, and heightened sensitivity to motion stimuli that may last for months to years after events that cause acute vestibular symptoms or disrupt balance. CSD is not associated with abnormalities of basic vestibular or oculomotor reflexes. Rather, it is thought to arise from persistent use of high-threat postural control strategies and greater reliance on visual cues for spatial orientation (i.e., visual dependence), long after triggering events resolve. Anxiety-related personality traits confer vulnerability to CSD. Anomalous interactions between the central vestibular system and neural structures related to anxiety may sustain it. Vestibular- and anxiety-related processes overlap in the brain, particularly in the insula and hippocampus. Alterations in activity and connectivity in these brain regions in response to vestibular stimuli may be the neural basis of CSD. We examined this hypothesis by comparing brain activity from 18 patients with CSD and 18 healthy controls measured by functional magnetic resonance imaging during loud short tone bursts, which are auditory stimuli that evoke robust vestibular responses. Relative to controls, patients with CSD showed reduced activations to sound-evoked vestibular stimulation in the parieto-insular vestibular cortex (PIVC) including the posterior insula, and in the anterior insula, inferior frontal gyrus, hippocampus, and anterior cingulate cortex. Patients with CSD also showed altered connectivity between the anterior insula and PIVC, anterior insula and middle occipital cortex, hippocampus and PIVC, and anterior cingulate cortex and PIVC. We conclude that reduced activation in PIVC, hippocampus, anterior insula, inferior frontal gyrus, and anterior cingulate cortex, as well as connectivity changes among these regions, may be linked to long-term vestibular symptoms in patients with CSD. Furthermore, altered connectivity between the anterior insula and middle occipital cortex may underlie the greater reliance on visual cues for spatial orientation in CSD patients relative to controls.

Considerations on Safety Concerns About Citalopram Prescribing

Citalopram (Celexa, Forest Laboratories, New York, NY) is one of the most widely prescribed selective serotonin reuptake inhibitors (SSRIs) in our practice. It has had good tolerability and low discontinuation rates in practice and in clinical trials.1-3 The recent US Food and Drug Administration (FDA) recommendation to not use doses higher than 40 mg/d because of potential QTc prolongation has been causing various difficulties.4 This warning has raised concerns from both psychiatrists and generalists at our institution both in regard to continuation of therapy that has been effective for patients that have responded to doses over 40 mg/d and in regard to the potential to use this medication above that dose range in future patients. Specifically, in our practices, there are patients who are doing well on higher doses. These patients are predominantly in our general and subspecialty psychiatry practices. Further, in our primary care practices, large numbers of patients take citalopram, and drug-drug interactions with agents such as proton pump inhibitors (PPIs), which can increase blood levels in patients taking 40 mg/d or less of citalopram, have also caused substantial prescribing problems. Members of the Mayo Clinic Neurology/Psychiatry Task Force as well as selected members from the Heart Rhythm Services group reviewed factors that should be communicated to prescribers in relation to citalopram prescribing in light of these new warnings regarding QTc prolongation and the risk for potential morbidity and mortality from drug-induced arrhythmias including torsades de pointes and sudden cardiac arrest.

Clinical clues to a dizzying headache.

Recent years have witnessed an upsurge of interest in migraine as a cause of vestibular symptoms. Starting with 1970s case reports linking migraine to childhood vertigo, neurotologists worldwide have increasingly diagnosed migraine. Various syndromes of vestibular migraine (VM) have been described, diagnostic criteria proposed, epidemiologic data collected, and neurophysiologic models developed. Yet, the concept that migraine causes vestibular symptoms rests on a surprisingly thin research database. Current concepts of VM are based on expert opinion, not empirical data. No general consensus exists about the definition of VM. No studies have analyzed its essential features. Just one well-controlled medication trial has been published. No biomarkers are known. To stimulate more rigorous research, this paper poses three questions about clinical investigations into migraine and vestibular symptoms: What variables should be measured? What patients should be studied? How might clinical trials yield both clinically useful results and greater insights into pathophysiologic processes? Using these questions, the limits of current knowledge are explored. Applicable research methods from epidemiology to genetics are examined. Pilot data demonstrating pharmacologic and genetic dissection techniques are presented. Ambitious, but practical, near-term clinical research goals are enumerated, including rigorous validation of diagnostic criteria and development of empirically derived management guidelines.

Long-term dizziness handicap in patients with vestibular schwannoma: a multicenter cross-sectional study.

Objective (1) To characterize long-term dizziness following observation, microsurgery, and stereotactic radiosurgery (SRS) for small to medium-sized vestibular schwannoma (VS) using a validated self-assessment inventory; and (2) to identify clinical variables associated with long-term dizziness handicap. Study Design Cross-sectional observational study. Setting Two independent tertiary academic referral centers: one located in the United States and one in Norway. Subjects and Methods All patients with sporadic VS of less than 3 cm who underwent primary microsurgery, SRS, or observation between 1998 and 2008 were identified. Subjects were surveyed via a postal questionnaire using the Dizziness Handicap Inventory (DHI) and a VS symptom questionnaire. Results The overall survey response rate was 79%. A total of 538 respondents (mean age, 64 years; 56% female) were analyzed, and the mean time interval between treatment and survey was 7.7 years. Pretreatment variables associated with greater dizziness handicap included female sex, older age, larger tumor size, preexisting diagnosis of headache or migraine, and symptoms of dizziness predating treatment. Significant posttreatment features strongly associated with poor long-term DHI scores included frequency and severity of ongoing headache. On multivariable analysis, treatment modality did not influence long-term dizziness handicap. Conclusion At a mean of approximately 8 years following treatment, over half of patients with VS reported ongoing dizziness. The authors have identified several baseline features that may help predict the risk of lasting dizziness. Treatment modality does not appear to influence long-term DHI score. We found a strong association between posttreatment headache and poor dizziness handicap. Future study is needed to further define this relationship.

Serotonin transporter gene promotor polymorphism (5-HTTLPR) associations with number of psychotropic medication trials in a tertiary care outpatient psychiatric consultation practice.

OBJECTIVE The authors tested the hypothesis that the short allele of 5-HTTLPR is associated with number of psychotropic medication trials as a measure of treatment-resistance or intolerance in psychosomatic medicine (PM) outpatients. METHODS Review of Mayo Clinic PM outpatient 2008 records identified 44 (20.6%) who had 5-HTTLPR genotype tests. A univariate analysis screened for factors that could account for number of medication trials. Logistic regression then determined degree of association between 5-HTTLPR genotype category and number of pharmacological trials. RESULTS Univariate analysis revealed significant differences across the ordinal genotype spectrum long/long, short/long, short/short in mean number of overall psychotropic medication trials (8.9, 14.8, 18.0, P = 0.002), mean number of antidepressant trials (4.3, 7.2, 8.1, P = 0.018), mean number of mood stabilizer trials (0.8, 1.9, 2.3, P = 0.008), percent living alone (7%, 25%, 50%, P = 0.020), reported family history of depression (93%, 65%, 40%, P = 0.006), and reported family history of chemical dependency treatment (50%, 35%, 10%, P = 0.050). There were trends for differences in consultation reason for unexplained symptoms (14%, 25%, 50%, P = 0.063), and diagnoses of somatoform disorder (7%, 30%, 40%, P = 0.060), and generalized anxiety disorder (43%, 65%, 80%, P = 0.064). After controlling for other differences, presence of the short allele remained associated with number of psychotropic medication trials (OR 4.779, 95% CI 2.263-6.771, P = 0.004), and number of antidepressant trials (OR 1.591, 95% CI 1.072-2.762, P = 0.019). CONCLUSION 5-HTTLPR testing may identify PM outpatients at higher relative risk for pharmacotherapy treatment non-response or intolerance who may benefit from alternative or augmentative medication recommendations or non-pharmacological interventions.

Neuroticism modulates brain visuo-vestibular and anxiety systems during a virtual rollercoaster task

Different lines of research suggest that anxiety‐related personality traits may influence the visual and vestibular control of balance, although the brain mechanisms underlying this effect remain unclear. To our knowledge, this is the first functional magnetic resonance imaging (fMRI) study that investigates how individual differences in neuroticism and introversion, two key personality traits linked to anxiety, modulate brain regional responses and functional connectivity patterns during a fMRI task simulating self‐motion. Twenty‐four healthy individuals with variable levels of neuroticism and introversion underwent fMRI while performing a virtual reality rollercoaster task that included two main types of trials: (1) trials simulating downward or upward self‐motion (vertical motion), and (2) trials simulating self‐motion in horizontal planes (horizontal motion). Regional brain activity and functional connectivity patterns when comparing vertical versus horizontal motion trials were correlated with personality traits of the Five Factor Model (i.e., neuroticism, extraversion‐introversion, openness, agreeableness, and conscientiousness). When comparing vertical to horizontal motion trials, we found a positive correlation between neuroticism scores and regional activity in the left parieto‐insular vestibular cortex (PIVC). For the same contrast, increased functional connectivity between the left PIVC and right amygdala was also detected as a function of higher neuroticism scores. Together, these findings provide new evidence that individual differences in personality traits linked to anxiety are significantly associated with changes in the activity and functional connectivity patterns within visuo‐vestibular and anxiety‐related systems during simulated vertical self‐motion. Hum Brain Mapp 38:715–726, 2017.