Mechanistic studies in pathological health anxiety: A systematic review and emerging conceptual framework.

BACKGROUND: Pathological health anxiety (PHA) (e.g., hypochondriasis and illness anxiety disorder) is common in medical settings and associated with increased healthcare costs. However, the psychological and neurobiological mechanisms contributing to the development and maintenance of PHA are incompletely understood. METHODS: We performed a systematic review to characterize the mechanistic understanding of PHA. PubMed, PsycINFO, and Embase databases were searched to find articles published between 1/1/1990 and 12/31/2022 employing a behavioral task and/or physiological measures in individuals with hypochondriasis, illness anxiety disorder, and PHA more broadly. RESULTS: Out of 9141 records identified, fifty-seven met inclusion criteria. Article quality varied substantially across studies, and was overall inadequate. Cognitive, behavioral, and affective findings implicated in PHA included health-related attentional and memory recall biases, a narrow health concept, threat confirming thought patterns, use of safety-seeking behaviors, and biased explicit and implicit affective processing of health-related information among other observations. There is initial evidence supporting a potential overestimation of interoceptive stimuli in those with PHA. Neuroendocrine, electrophysiology, and brain imaging research in PHA are particularly in their early stages. LIMITATIONS: Included articles evaluated PHA categorically, suggesting that sub-threshold and dimensional health anxiety considerations are not contextualized. CONCLUSIONS: Within an integrated cognitive-behavioral-affective and predictive processing formulation, we theorize that sub-optimal illness and health concepts, altered interoceptive modeling, biased illness-based predictions and attention, and aberrant prediction error learning are mechanisms relevant to PHA requiring more research. Comprehensively investigating the pathophysiology of PHA offers the potential to identify adjunctive diagnostic biomarkers and catalyze new biologically-informed treatments.

Speech and language therapy: A treatment case series of 20 patients with functional speech disorder.

BACKGROUND: While expert consensus recommendations support the use of speech and language therapy (SLT) for patients with functional speech disorder (FND-speech), there are limited published data on clinical outcomes. OBJECTIVE: To retrospectively report the treatment outcomes and clinical characteristics of patients with FND-speech that attended outpatient SLT as part of a multidisciplinary program for functional neurological disorder (FND). METHODS: In this case series, we included adult patients with FND-speech that consecutively participated in outpatient SLT at our institution between October 2014 and September 2021. Baseline demographic and neuropsychiatric characteristics were extracted from the medical records, along with data on FND-speech phenotypes, number of treatment sessions received, and clinician-determined outcomes. Only descriptive statistics were used to report findings. RESULTS: Twenty patients met inclusion criteria; ages ranged from 21-77, with a mean of 51.6±16.2 years. 85% of the cohort presented with mixed FND-speech symptoms. Patients attended a range of 2-37 visits, with an average of 9.2±8.0 visits over 4.4±3.5 months. At the last treatment session, 3 patients were asymptomatic, 15 had improved, and 2 had not improved; 8 individuals that improved received video telehealth interventions. CONCLUSION: This case series lends additional support for outpatient SLT in the assessment and management of individuals with FND-speech, and may help clarify patient and provider treatment expectations. Additional prospective research is needed to investigate baseline predictors of treatment response and further define the optimal frequency, intensity, duration, and clinical setting for SLT delivery in this population.

Corrigendum: Toward a possible trauma subtype of functional neurological disorder: impact on symptom severity and physical health.

[This corrects the article DOI: 10.3389/fpsyt.2022.1040911.].

Toward a possible trauma subtype of functional neurological disorder: Impact on symptom severity and physical health.

Background: As a group, individuals with functional neurological disorder (FND) report an approximately 3-fold increase in adverse life experiences (ALEs) compared to healthy controls. In patients with FND, studies have identified a positive correlation between symptom severity and the magnitude of ALEs. While not all individuals with FND report ALEs, such findings raise the possibility of a trauma-subtype of FND. Objective: This study investigated if patients with FND, with or without probable post-traumatic stress disorder (PTSD) and/or significant childhood maltreatment, differed in their symptom severity and physical health. Materials and methods: Seventy-eight patients with FND were recruited (functional seizures, n = 34; functional movement disorder, n = 56). Participants completed self-report measures of symptom severity [Somatoform Dissociation Questionniare-20 (SDQ-20), Screening for Somatoform Disorders: Conversion Disorder subscale (SOMS:CD), Patient Health Questionniare-15 (PHQ-15)], physical health [Short Form Health Survey-36 (SF36-physical health)], childhood maltreatment [Childhood Trauma Questionnaire (CTQ)], and PTSD [PTSD Checklist-5 (PCL-5)]; a psychometric battery of other common predisposing vulnerabilities was also completed. To adjust for multiple comparisons, a Bonferroni correction was applied to all univariate analyses. Results: Patients with FND and probable PTSD (n = 33) vs. those without probable PTSD (n = 43) had statistically significant increased scores on all symptom severity measures - as well as decreased physical health scores. In secondary post-hoc regression analyses, these findings remained significant adjusting for age, sex, race, college education, and: pathological dissociation; alexithymia; attachment styles; personality characteristics; resilience scores; functional seizures subtype; or moderate-to-severe childhood abuse and neglect scores; SOMS:CD and SDQ-20 findings also held adjusting for depression and anxiety scores. In a separate set of analyses, patients with FND and moderate-to-severe childhood abuse (n = 46) vs. those without moderate-to-severe childhood abuse (n = 32) showed statistically significant increased SDQ-20 and PHQ-15 scores; in post-hoc regressions, these findings held adjusting for demographic and other variables. Stratification by childhood neglect did not relate to symptom severity or physical health scores. Conclusion: This study provides support for a possible trauma-subtype of FND. Future research should investigate the neurobiological and treatment relevance of a FND trauma-subtype, as well as continuing to delineate clinical characteristics and mechanisms in individuals with FND that lack a history of ALEs.

A new science of emotion: implications for functional neurological disorder.

Functional neurological disorder reflects impairments in brain networks leading to distressing motor, sensory and/or cognitive symptoms that demonstrate positive clinical signs on examination incongruent with other conditions. A central issue in historical and contemporary formulations of functional neurological disorder has been the mechanistic and aetiological role of emotions. However, the debate has mostly omitted fundamental questions about the nature of emotions in the first place. In this perspective article, we first outline a set of relevant working principles of the brain (e.g. allostasis, predictive processing, interoception and affect), followed by a focused review of the theory of constructed emotion to introduce a new understanding of what emotions are. Building on this theoretical framework, we formulate how altered emotion category construction can be an integral component of the pathophysiology of functional neurological disorder and related functional somatic symptoms. In doing so, we address several themes for the functional neurological disorder field including: (i) how energy regulation and the process of emotion category construction relate to symptom generation, including revisiting alexithymia, 'panic attack without panic', dissociation, insecure attachment and the influential role of life experiences; (ii) re-interpret select neurobiological research findings in functional neurological disorder cohorts through the lens of the theory of constructed emotion to illustrate its potential mechanistic relevance; and (iii) discuss therapeutic implications. While we continue to support that functional neurological disorder is mechanistically and aetiologically heterogenous, consideration of how the theory of constructed emotion relates to the generation and maintenance of functional neurological and functional somatic symptoms offers an integrated viewpoint that cuts across neurology, psychiatry, psychology and cognitive-affective neuroscience.

Sensory Processing Difficulties in Patients with Functional Neurological Disorder: Occupational Therapy Management Strategies and Two Cases.

Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry, with some patients experiencing sensory hypersensitivities and other sensory processing difficulties. It has been postulated that poor integration and modulation of sensory information with cognitive, affective and behavioral processes may play a role in the pathophysiology of FND. In this article, we first succinctly review the role for occupational therapy (OT) in the multidisciplinary therapeutic approach to managing patients with FND. After highlighting previously published data identifying sensory processing difficulties in patients with FND, we subsequently outline the components of the sensory-based outpatient OT program for FND at the Massachusetts General Hospital. Here, we detail how occupational therapists assess and treat sensory modulation difficulties with the aid of resources like the Adolescent/Adult Sensory Profile (AASP), The Canadian Occupational Performance Measure (COPM), and the Sensory-Motor Preference Checklist. We then report on 2 clinical cases representative of the sensory modulation difficulties endorsed by some patients with FND, illustrating how developing an individualized, sensory-based treatment plan can help improve functional neurological symptoms and overall participation in activities of daily living. Prospective, controlled research is needed to further operationalize OT-based sensory modulation interventions, as well as define the tolerability and efficacy of this intervention for pediatric and adult populations with FND.

Using the Biopsychosocial Model to Guide Patient-Centered Neurological Treatments.

The biopsychosocial model was defined by George L. Engel to propose a holistic approach to patient care. Through this model, physicians can understand patients in their context to aid the development of tailored, individualized treatment plans that consider relevant biological, psychological, and social-cultural-spiritual factors impacting health and longitudinal care. In this article, we advocate for the use of the biopsychosocial model in neurology practice across outpatient and inpatient clinical settings. To do so, we first present the history of the biopsychosocial model, and its relationships to precision medicine and deep phenotyping. Then, we bring the neurologist up-to-date information on the components of the biopsychosocial clinical formulation, including predisposing, precipitating, perpetuating, and protective factors. We conclude by detailing illustrative neurological case examples using the biopsychosocial model, emphasizing the importance of considering relevant psychological and social factors to aid the delivery of patient-centered clinical care in neurology.

Are Functional (Psychogenic Nonepileptic) Seizures the Sole Expression of Psychological Processes?

Functional [psychogenic nonepileptic/dissociative] seizures (FND-seiz) and related functional neurological disorder subtypes were of immense interest to early founders of modern-day neurology and psychiatry. Unfortunately, the divide that occurred between the both specialties throughout the mid-twentieth century placed FND-seiz at the borderland between the two disciplines. In the process, a false Cartesian dualism emerged that labeled psychiatric conditions as impairments of the mind and neurological conditions as disturbances in structural neuroanatomy. Excitingly, modern-day neuropsychiatric perspectives now consider neurologic and psychiatric conditions as disorders of both brain and mind. In this article, we aim to integrate neurologic and psychiatric perspectives in the conceptual framing of FND-seiz. In doing so, we explore emerging relationships between symptoms, neuropsychological constructs, brain networks, and neuroendocrine/autonomic biomarkers of disease. Evidence suggests that the neuropsychological constructs of emotion processing, attention, interoception, and self-agency are important in the pathophysiology of FND-seiz. Furthermore, FND-seiz is a multi-network brain disorder, with evidence supporting roles for disturbances within and across the salience, limbic, attentional, multimodal integration, and sensorimotor networks. Risk factors, including the magnitude of previously experienced adverse life events, relate to individual differences in network architecture and neuroendocrine profiles. The time has come to use an integrated neuropsychiatric approach that embraces the closely intertwined relationship between physical health and mental health to conceptualize FND-seiz and related functional neurological disorder subtypes.

Autonomic, Endocrine, and Inflammation Profiles in Functional Neurological Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: Functional neurological disorder (FND) is a core neuropsychiatric condition. To date, promising yet inconsistently identified neural circuit profiles have been observed in patients with FND, suggesting that gaps remain in our systems-level neurobiological understanding. As such, other important physiological variables, including autonomic, endocrine, and inflammation findings, need to be contextualized for a more complete mechanistic picture. METHODS: The investigators conducted a systematic review and meta-analysis of available case-control and cohort studies of FND. PubMed, PsycINFO, and Embase databases were searched for studies from January 1, 1900, to September 1, 2020, that investigated autonomic, endocrine, and inflammation markers in patients with FND. Sixty-six of 2,056 screened records were included in the review, representing 1,699 patients; data from 20 articles were used in the meta-analysis. RESULTS: Findings revealed that children and adolescents with FND, compared with healthy control subjects (HCs), have increased resting heart rate (HR); there is also a tendency toward reduced resting HR variability in patients with FND across the lifespan compared with HCs. In adults, peri-ictal HR differentiated patients with functional seizures from those with epileptic seizures. Other autonomic and endocrine profiles for patients with FND were heterogeneous, with several studies highlighting the importance of individual differences. CONCLUSIONS: Inflammation research in FND remains in its early stages. Moving forward, there is a need for the use of larger sample sizes to consider the complex interplay between functional neurological symptoms and behavioral, psychological, autonomic, endocrine, inflammation, neuroimaging, and epigenetic/genetic data. More research is also needed to determine whether FND is mechanistically (and etiologically) similar or distinct across phenotypes.

Seroprevalence of Antitransglutaminase and Antiendomysium Antibodies in Adult Colombian Blood Bank Donors.

Celiac disease (CD) is an autoimmune enteropathy induced by the ingestion of gluten from wheat, barley, and rye in genetically susceptible individuals. The global prevalence of CD is 1.4%. However, most of the prevalence studies have been conducted in Caucasian populations; few studies have been performed in Latin America. The aim of this study is to determine the seroprevalence of auto-antibodies used as markers for CD in a Colombian cohort. In this cross-sectional study, the serum samples from Colombian donors of the National Red Cross Blood Bank were collected between June and September 2017 in Bogotá, Colombia. All sera were tested for IgA antitissue transglutaminase (TTG) by enzyme-linked immunosorbent assay. Seropositive sera were tested for IgA antiendomysium (EMA) using indirect immunofluorescence assay. The ancestral genetic composition was determined in donor samples with antibody assay reactivity. Those with two seroreactive assays were typed for HLA class II DQ2 and DQ8. In total, 228 blood donors participated in the study. Among them, 113 were females (49.56%) with an average age of 31.63 years (SD ± 12.99); males had an average of 34.71 years (SD ± 13.01). Only 3 (1.31%) donors reported chronic diarrhea and nonintentional weight loss; 11 (4.82%) had a family history of CD. For the serological assays, 11 donors (4.82%) were seroreactive to IgA anti-TTG: 3 had high reactivity and 8 had low reactivity. Of those seroreactive to IgA anti-TTG, 3 (1.32%) were also seroreactive to anti-EMA, and they were typed as HLA-DQ8 or HLA-DQ2. The baseline ancestral percentage of the seroreactive donors was higher for European and Native American than for African genes. The seroprevalence for anti-TTG and anti-EMA with the presence of HLA-DQ8 and HLA-DQ2 was 1.32%. Additionally, 4.82% donor participants were reactive only for anti-TTG. Compared with other studies, our findings suggest that Colombia has a high prevalence of CD markers.

Briquet syndrome revisited: implications for functional neurological disorder.

With the creation of the Somatic Symptom and Related Disorders category of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition in 2013, the functional neurological (symptom) disorder diagnostic criteria underwent transformative changes. These included an emphasis on 'rule-in' physical examination signs/semiological features guiding diagnosis and the removal of a required proximal psychological stressor to be linked to symptoms. In addition, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder, somatoform pain disorder and undifferentiated somatoform disorder conditions were eliminated and collapsed into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder diagnosis. With somatic symptom disorder, emphasis was placed on a cognitive-behavioural (psychological) formulation as the basis for diagnosis in individuals reporting distressing bodily symptoms such as pain and/or fatigue; the need for bodily symptoms to be 'medically unexplained' was removed, and the overall utility of this diagnostic criteria remains debated. A consequence of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition restructuring is that the diagnosis of somatization disorder that encompassed individuals with functional neurological (sensorimotor) symptoms and prominent other bodily symptoms, including pain, was eliminated. This change negatively impacts clinical and research efforts because many patients with functional neurological disorder experience pain, supporting that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition would benefit from an integrated diagnosis at this intersection. We seek to revisit this with modifications, particularly since pain (and a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder comorbidity, more specifically) is associated with poor clinical prognosis in functional neurological disorder. As a first step, we systematically reviewed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder literature to detail epidemiologic, healthcare utilization, demographic, diagnostic, medical and psychiatric comorbidity, psychosocial, neurobiological and treatment data. Thereafter, we propose a preliminary revision to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition allowing for the specifier functional neurological disorder 'with prominent pain'. To meet this criterion, core functional neurological symptoms (e.g. limb weakness, gait difficulties, seizures, non-dermatomal sensory loss and/or blindness) would have 'rule-in' signs and pain (>6 months) impairing social and/or occupational functioning would also be present. Two optional secondary specifiers assist in characterizing individuals with cognitive-behavioural (psychological) features recognized to amplify or perpetuate pain and documenting if there is a pain-related comorbidity. The specifier of 'with prominent pain' is etiologically neutral, while secondary specifiers provide additional clarification. We advocate for a similar approach to contextualize fatigue and mixed somatic symptoms in functional neurological disorder. While this preliminary proposal requires prospective data and additional discussion, these revisions offer the potential benefit to readily identify important functional neurological disorder subgroups-resulting in diagnostic, treatment and pathophysiology implications.