Machine learning classification of functional neurological disorder using structural brain MRI features.

BACKGROUND: Brain imaging studies investigating grey matter in functional neurological disorder (FND) have used univariate approaches to report group-level differences compared with healthy controls (HCs). However, these findings have limited translatability because they do not differentiate patients from controls at the individual-level. METHODS: 183 participants were prospectively recruited across three groups: 61 patients with mixed FND (FND-mixed), 61 age-matched and sex-matched HCs and 61 age, sex, depression and anxiety-matched psychiatric controls (PCs). Radial basis function support vector machine classifiers with cross-validation were used to distinguish individuals with FND from HCs and PCs using 134 FreeSurfer-derived grey matter MRI features. RESULTS: Patients with FND-mixed were differentiated from HCs with an accuracy of 0.66 (p=0.005; area under the receiving operating characteristic (AUROC)=0.74); this sample was also distinguished from PCs with an accuracy of 0.60 (p=0.038; AUROC=0.56). When focusing on the functional motor disorder subtype (FND-motor, n=46), a classifier robustly differentiated these patients from HCs (accuracy=0.72; p=0.002; AUROC=0.80). FND-motor could not be distinguished from PCs, and the functional seizures subtype (n=23) could not be classified against either control group. Important regions contributing to statistically significant multivariate classifications included the cingulate gyrus, hippocampal subfields and amygdalar nuclei. Correctly versus incorrectly classified participants did not differ across a range of tested psychometric variables. CONCLUSIONS: These findings underscore the interconnection of brain structure and function in the pathophysiology of FND and demonstrate the feasibility of using structural MRI to classify the disorder. Out-of-sample replication and larger-scale classifier efforts incorporating psychiatric and neurological controls are needed.

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.

Expanding our view of the cold-water coral niche and accounting of the ecosystem services of the reef habitat.

Coral reefs are iconic ecosystems that support diverse, productive communities in both shallow and deep waters. However, our incomplete knowledge of cold-water coral (CWC) niche space limits our understanding of their distribution and precludes a complete accounting of the ecosystem services they provide. Here, we present the results of recent surveys of the CWC mound province on the Blake Plateau off the U.S. east coast, an area of intense human activity including fisheries and naval operations, and potentially energy and mineral extraction. At one site, CWC mounds are arranged in lines that total over 150 km in length, making this one of the largest reef complexes discovered in the deep ocean. This site experiences rapid and extreme shifts in temperature between 4.3 and 10.7 °C, and currents approaching 1 m s-1. Carbon is transported to depth by mesopelagic micronekton and nutrient cycling on the reef results in some of the highest nitrate concentrations recorded in the region. Predictive models reveal expanded areas of highly suitable habitat that currently remain unexplored. Multidisciplinary exploration of this new site has expanded understanding of the cold-water coral niche, improved our accounting of the ecosystem services of the reef habitat, and emphasizes the importance of properly managing these systems.

Toward a Precision Medicine Approach to the Outpatient Assessment and Treatment of Functional Neurological Disorder.

Functional neurological disorder (FND) is a neuropsychiatric condition. In this field, prospective psychotherapy trials and consensus recommendations for physiotherapy, occupational therapy, and speech language therapy have been published. However, significant clinical complexities remain. "Rule in" signs - while critical for making a positive diagnosis - do not equate to a personalized treatment plan in many instances. Here, we propose that the neuropsychiatric assessment and real-time development of a work-in-progress biopsychosocial clinical formulation aids the development of a patient-centered outpatient treatment plan. This precision medicine approach is based on the literature, expert opinions and our clinical experience working in an interdisciplinary FND service.

Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Neuropsychiatric Treatment Approaches for Functional Neurological Disorder: A How to Guide.

There is a growing body of knowledge regarding management of functional neurological disorder (FND). The aim of this article is to guide the clinician through FND clinical management, from delivery of the diagnosis, to creation of a biopsychosocially-informed treatment plan, to troubleshooting common issues that arise throughout longitudinal care. We review the evidence and core principles of both rehabilitative therapies (physical therapy, occupational therapy, and speech and language therapy) and psychological therapies for the treatment of FND, and discuss the benefits of engaging a multidisciplinary and interdisciplinary team. The optimal timing of specific therapeutic interventions is also discussed, emphasizing a patient-centered perspective. Resources for further reading, for both patients and clinicians, are provided throughout. Additional research is needed to further optimize the therapeutic approach to patients with FND, including the need to develop novel treatments for those that do not positively respond to currently available interventions.

Structural alterations in functional neurological disorder and related conditions: a software and hardware problem?

Functional neurological (conversion) disorder (FND) is a condition at the interface of neurology and psychiatry. A "software" vs. "hardware" analogy describes abnormal neurobiological mechanisms occurring in the context of intact macroscopic brain structure. While useful for explanatory and treatment models, this framework may require more nuanced considerations in the context of quantitative structural neuroimaging findings in FND. Moreover, high co-occurrence of FND and somatic symptom disorders (SSD) as defined in DSM-IV (somatization disorder, somatoform pain disorder, and undifferentiated somatoform disorder; referred to as SSD for brevity in this article) raises the possibility of a partially overlapping pathophysiology. In this systematic review, we use a transdiagnostic approach to review and appraise the structural neuroimaging literature in FND and SSD. While larger sample size studies are needed for definitive characterization, this article highlights that individuals with FND and SSD may exhibit sensorimotor, prefrontal, striatal-thalamic, paralimbic, and limbic structural alterations. The structural neuroimaging literature is contextualized within the neurobiology of stress-related neuroplasticity, gender differences, psychiatric comorbidities, and the greater spectrum of functional somatic disorders. Future directions that could accelerate the characterization of the pathophysiology of FND and DSM-5 SSD are outlined, including "disease staging" discussions to contextualize subgroups with or without structural changes. Emerging neuroimaging evidence suggests that some individuals with FND and SSD may have a "software" and "hardware" problem, although if structural alterations are present the neural mechanisms of functional disorders remain distinct from lesional neurological conditions. Furthermore, it remains unclear whether structural alterations relate to predisposing vulnerabilities or consequences of the disorder.

You've made the diagnosis of functional neurological disorder: now what?

Patients with functional neurological disorders (FND)/conversion disorder commonly present to outpatient clinics. FND is now a 'rule in' diagnosis based on neurological examination findings and semiological features. While neurologists may be more comfortable diagnosing patients with FND, there is only limited guidance as to how to conduct follow-up outpatient visits. Using clinical vignettes, we provide practical suggestions that may help guide clinical encounters including how to: (1) explore illness beliefs openly; (2) enquire longitudinally about predisposing vulnerabilities, acute precipitants and perpetuating factors that may be further elucidated over time; (3) facilitate psychotherapy engagement by actively listening for potentially unhelpful or maladaptive patterns of thoughts, behaviours, fears or psychosocial stressors that can be reflected back to the patient and (4) enquire about the fidelity of individual treatments and educate other providers who may be less familiar with FND. These suggestions, while important to individualise, provide a blueprint for follow-up FND clinical care.

The Inpatient Assessment and Management of Motor Functional Neurological Disorders: An Interdisciplinary Perspective.

BACKGROUND: Motor functional neurologic disorders (FND)-previously termed "hysteria" and later "conversion disorder"-are exceedingly common and frequently encountered in the acute hospital setting. Despite their high prevalence, patients with motor FND can be challenging to diagnose accurately and manage effectively. To date, there is limited guidance on the inpatient approach to the neuropsychiatric evaluation of patients with functional (psychogenic) neurologic symptoms. OBJECTIVE: The authors outline an inpatient multidisciplinary approach, involving neurology, psychiatry, and physical therapy, for the assessment and acute inpatient management of motor FND. METHODS: A vignette of a patient with motor FND is presented followed by a discussion of general assessment principles. Thereafter, a detailed description of the neurologic and psychiatric assessments is outlined. Delivery of a "rule-in" diagnosis is emphasized and specific guidance for what can be accomplished postdiagnosis in the hospital is suggested. DISCUSSION: We encourage an interdisciplinary approach beginning at the early stages of the diagnostic assessment once an individual is suspected of having motor FND. CONCLUSIONS: Practical suggestions for the inpatient assessment of motor FND are presented. It is also important to individualize the diagnostic assessment. Future research should be conducted to test best practices for motor FND management in the acute inpatient hospital setting.

A randomized trial of an optimism training intervention in patients with heart disease.

OBJECTIVE: Optimism is prospectively and independently associated with superior cardiac outcomes, but there has been minimal study of optimism-specific interventions in persons with cardiovascular illness. We aimed to examine the feasibility and impact of an optimism-promoting program among patients with heart disease in a randomized controlled trial. METHODS: Participants (N=61) were outpatients, age 35-60, with coronary artery disease who were randomized to an 8-week in-person group-based optimism training intervention or an attention-matched educational control condition. Feasibility was assessed via rates of session attendance and exercise completion, and acceptability was assessed via weekly participant ratings of exercise ease, utility, and likelihood of continuation. The impact of the intervention was assessed via between-group differences in change from baseline optimism (Life Orientation Test-Revised [LOT-R]) and other psychological self-report outcomes at 8weeks (primary time point) and 16weeks, using random effects regression models. RESULTS: Participants completed a mean of 6.8 (SD 1.2) sessions and 13.9 (SD 2.4) exercises, with mean ratings all >3.5/5 on measures of acceptability. The intervention was associated with greater improvement in optimism at 8weeks (ß=5.13; 95% confidence interval [CI]=3.55, 6.70; p<0.001) and 16weeks; the intervention was also associated with greater improvements in life satisfaction, hope, and anxiety at both time points, though not with positive or negative affect. CONCLUSIONS: A group-based optimism training program was feasible, acceptable, and associated with improvements in optimism and other psychological measures in cardiac patients. Future larger studies should examine effects on major clinical outcomes.

Collaborative Care and Related Interventions in Patients With Heart Disease: An Update and New Directions.

BACKGROUND: Psychiatric disorders, such as depression, are very common in cardiac patients and are independently linked to adverse cardiac outcomes, including mortality. Collaborative care and other integrated care models have been used successfully to manage psychiatric conditions in patients with heart disease, with beneficial effects on function and other outcomes. Novel programs using remote delivery of mental health interventions and promotion of psychological well-being may play an increasingly large role in supporting cardiovascular health. METHODS: We review prior studies of standard and expanded integrated care programs among patients with cardiac disease, examine contemporary intervention delivery methods (e.g., Internet or mobile phone) that could be adapted for these programs, and outline mental health-related interventions to promote healthy behaviors and overall recovery across all cardiac patients. RESULTS: Standard integrated care models for mental health disorders are effective at improving mood, anxiety, and function in patients with heart disease. Novel, "blended" collaborative care models may have even greater promise in improving cardiac outcomes, and interfacing with cardiac patients via mobile applications, text messages, and video visits may provide additional benefit. A variety of newer interventions using stress management, mindfulness, or positive psychology have shown promising effects on mental health, health behaviors, and overall cardiac outcomes. CONCLUSIONS: Further study of novel applications of collaborative care and related interventions is warranted given the potential of these programs to increase the reach and effect of mental health interventions in patients with heart disease.

QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update.

BACKGROUND: Some psychotropic medications have been associated with prolongation of the QT interval and QT prolongation, especially in those with medical illness, and are linked to lethal ventricular arrhythmias, such as Torsades de Pointes (TdP). In 2013, we published a review of QT prolongation, TdP, and psychotropic medications. OBJECTIVE: We provide an update over the past 5 years on the specific concerns most relevant to clinicians who see medically ill patients. METHODS: In this nonsystematic review, we aimed to carefully and intensively identify new articles by utilizing a structured PubMed search from 2012-present. RESULTS: QT prolongation remains an imperfect, though well-established marker of risk for TdP. Among antidepressant medications, citalopram does appear to prolong the QT interval more than other selective serotonin reuptake inhibitors, though the clinical significance of this prolongation remains unclear. Escitalopram appears to prolong the QT interval to a lesser extent. Haloperidol carries a risk for QT prolongation, but the assertion that intravenous haloperidol is inherently riskier may be confounded by its primary use in medically ill populations. Among atypical antipsychotic agents, ziprasidone-and possibly iloperidone-is associated with the greatest QT prolongation, whereas aripiprazole appears safest from this standpoint. CONCLUSIONS: The evidence for clinically meaningful QT prolongation with most classes of psychiatric agents remains minimal. The most important risk-reducing intervention clinicians can make is undertaking a careful analysis of other QT risk factors when prescribing psychiatric medications.

Improved Metabolic and Psychiatric Outcomes with Discontinuation of Atypical Antipsychotics in Youth Hospitalized in a State Psychiatric Facility.

OBJECTIVES: To assess the impact of antipsychotic tapering and discontinuation on measures of metabolic functioning and psychiatric symptom severity in severely impaired youth hospitalized in a psychiatric state hospital. METHODS: The study examined psychiatric and metabolic measures in 67 hospitalized children and adolescents (mean age 11.9; 56 with discontinued use of antipsychotics, 10 with continued use of antipsychotics, and 1 started on an antipsychotic) from admission to discharge. RESULTS: Upon admission, 56 youth were tapered off of antipsychotic medications, started on other forms of pharmacotherapy (92.9% were started on medications used to treat attention-deficit/hyperactivity disorder), and received evidence-based behavioral programming and were ultimately discharged from the hospital. The mean duration of treatment was 228 days for the discontinuation group and 204 days for the continuation group. Significant decreases in body mass index [BMI; t(53) = 7.12, p = 0.0001] and BMI percentile [t(53) = 6.73, p = 0.0001] were found from admission to discharge in the antipsychotic discontinuation group. Changes in BMI, BMI percentile, or systolic blood pressure were not found in the group (n = 10) who were maintained on antipsychotics. Both groups experienced a significant increase in their Global Assessment of Functioning score [t(52) = 19.98, p = 0.0001 for discontinued; t(8) = 5.092, p = 0.001 for maintained]. Psychiatric symptom severity scores significantly improved in many subscales relevant to disruptive behaviors and mood disorders for those who were removed from the medications. For those maintained on the antipsychotics, there were fewer changes in psychiatric symptom scores. CONCLUSION: Discontinuation of atypical antipsychotic medications in conjunction with tailoring treatment to presenting diagnoses resulted in metabolic and psychiatric symptom improvement among severely impaired state hospital inpatient youth. These results serve as a feasibility demonstration that discontinuation of antipsychotics does not provoke psychiatric destabilization, particularly among disruptive behavior disordered youth.