Efficacy of Cognitive-Behavioral Therapy Targeting Severe Fatigue Following Coronavirus Disease 2019: Results of a Randomized Controlled Trial.

BACKGROUND: Severe fatigue following coronavirus disease 2019 (COVID-19) is prevalent and debilitating. This study investigated the efficacy of cognitive-behavioral therapy (CBT) for severe fatigue following COVID-19. METHODS: A multicenter, 2-arm randomized controlled trial was conducted in the Netherlands with patients being severely fatigued 3-12 months following COVID-19. Patients (N = 114) were randomly assigned (1:1) to CBT or care as usual (CAU). CBT, targeting perpetuating factors of fatigue, was provided for 17 weeks. The primary outcome was the overall mean difference between CBT and CAU on the fatigue severity subscale of the Checklist Individual Strength, directly post-CBT or CAU (T1), and after 6 months (T2). Secondary outcomes were differences in proportions of patients meeting criteria for severe and/or chronic fatigue, differences in physical and social functioning, somatic symptoms, and problems concentrating between CBT and CAU. RESULTS: Patients were mainly nonhospitalized and self-referred. Patients who received CBT were significantly less severely fatigued across follow-up assessments than patients receiving CAU (-8.8 [95% confidence interval {CI}, -11.9 to -5.8]); P < .001), representing a medium Cohen's d effect size (0.69). The between-group difference in fatigue severity was present at T1 (-9.3 [95% CI, -13.3 to -5.3]) and T2 (-8.4 [95% CI, -13.1 to -3.7]). All secondary outcomes favored CBT. Eight adverse events were recorded during CBT, and 20 during CAU. No serious adverse events were recorded. CONCLUSIONS: Among patients, who were mainly nonhospitalized and self-referred, CBT was effective in reducing fatigue. The positive effect was sustained at 6-month follow-up. CLINICAL TRIALS REGISTRATION: Netherlands Trial Register NL8947.

The relationship between types of life events and the onset of functional neurological (conversion) disorder in adults: a systematic review and meta-analysis.

Adverse life events precede the onset of functional neurological disorder (FND, also known as conversion disorder) more commonly than other neuropsychiatric conditions, but their aetiological role is unclear. We conducted a systematic review and quantitative analysis of the type, timing and number of life events preceding the onset of FND in adults, and a meta-analysis of the proportions of types of events in controlled studies. Fifty-one studies of different designs, covering 4247 patients, were eligible for inclusion. There was no clear majority of any type of preceding event. Family problems were the most common category of events, followed by relationship problems. Females were more likely to experience preceding family/relationship problems than males, who reported more work problems. Family problems were the commonest type of preceding event in studies in developing countries, whereas family and health problems were equally common in developed countries. Abuse was associated with early symptom onset, while patients with later onset were more likely to report family problems. The median number of events was one, and the events occurred closer to onset than in controls. Meta-analysis found that family, relationship and work events were all relatively more common in patients than pathological controls, as were events where symptoms might provide a solution to the stressor. In conclusion, although a range of events precede the onset of FND, they do not appear to do so uniformly. This may support a different aetiological role for stressors than in other disorders, although the support is indirect and the quality generally low.

Clinical differences between patients with psychogenic nonepileptic seizures and functional motor disorder.

OBJECTIVES: Why a patient might present with psychogenic nonepileptic seizures (PNES) as opposed to another functional neurological symptom is unknown. A recent review suggested that patients with PNES and functional motor disorders (FMD) differ on demographic and clinical factors of potential aetiological and mechanistic significance, arguing they might represent different disorders, though direct comparisons are limited. We sought to determine whether these factors differed in patients presenting with FMD and PNES at our clinic, as well as whether preceding medical complaints would differ between the two, particularly those affecting the limbs or head. METHODS: A retrospective chart review of all presentations with FMD or PNES patients to a functional neurology clinic, collecting demographic and clinical data, including medical and surgical history. RESULTS: Fifty-six patients with FMD and 52 with PNES were included. Significantly more patients with FMD had functional somatic syndromes (46% vs 27%, p = 0.036) and preceding medical events that affected their limbs than patients with PNES (34% vs 14%, p = 0.013); significantly more patients with PNES had dissociative symptoms (31% vs 4%, p < 0.001) and lifetime suicidal ideation (56% vs 32%, p = 0.013). SIGNIFICANCE: These results highlight the substantial comorbidities affecting FMD and PNES, but find clinical differences between the two groups that may be of aetiological or mechanistic significance.

The relationship between psychosocial trauma type and conversion (functional neurological) disorder symptoms: a cross-sectional study.

OBJECTIVE: Psychosocial trauma was associated with developing conversion disorder (also known as functional neurological disorder) before Freud, though why a particular symptom should arise is unknown. We aimed to determine if there was a relationship between trauma type and symptom. METHODS: We retrospectively reviewed the medical records of patients attending Australia's first functional neurology clinic, including referral, clinic letters and a clinic questionnaire. RESULTS: There were 106 females, 43 males and five transgender patients. Sensory (51%), motor (47%) and seizures (39%) were the commonest functional symptoms. Most patients (92%) reported stressors associated with symptom onset. Multiple trauma/symptom type associations were found: patients with in-law problems experienced more cognitive symptoms (p = .036), for example, while expressive speech problems more commonly followed relationship difficulties (p = .021). CONCLUSION: Associations were found between type of traumatic events and type of symptoms in conversion disorder. This will require verification in a larger sample.

Preictal autonomic dynamics in psychogenic nonepileptic seizures.

OBJECTIVES: Psychogenic nonepileptic seizures (PNES) resemble seizures but are psychological in origin. The etiology of PNES remains poorly understood, yet several theories argue for the importance of autonomic dysregulation in its pathophysiology. We therefore conducted a retrospective study to investigate autonomic dynamics leading up to a seizure to inform their mechanistic relevance. METHODS: One hundred one patients with PNES and 45 patients with epileptic seizure (ES) were analyzed for preictal heart rate (HR) and respiratory rate (RR) at baseline and at minute intervals from 5 min to onset. RESULTS: Patients with PNES showed rising HR (p < 0.001, repeated-measures analysis of variance (ANOVA)) and rising RR (p = 0.012, repeated-measures ANOVA) from baseline to the onset of their seizures. Patients with ES did not exhibit significant preictal HR or RR increase. Patients with PNES had nonsignificantly higher preictal HR and RR than patients with ES. SIGNIFICANCE: Patients with PNES exhibit increasing autonomic arousal prior to seizure events unlike patients with epilepsy. This may reflect increasing levels of preictal anxiety, and future studies could study patients' subjective experiences of the preictal period, and more definitive measures of ventilation to see if this supported a model of PNES as "panic without panic".

Are psychogenic non-epileptic seizures just another symptom of conversion disorder?

BACKGROUND: Psychogenic non-epileptic seizures (PNES) are classified with other functional neurological symptoms as 'Conversion Disorder', but there are reasons to wonder whether this symptomatology constitutes a distinct entity. METHODS: We reviewed the literature comparing PNES with other functional neurological symptoms. RESULTS: We find eight studies that directly examined this question. Though all but one found significant differences-notably in presenting age, trauma history, and dissociation-they were divided on whether these differences represented an important distinction. CONCLUSION: We argue that the aetiological and mechanistic distinctions they support, particularly when bolstered by additional data, give reason to sustain a separation between these conditions.

Misidentification of mental health symptoms in presence of organic diseases and delirium during psychiatric liaison consulting.

OBJECTIVE: To identify predictors of misidentification of organic mental disorders and delirium in patients undergoing psychiatric liaison consultation. METHODS: Data were collected at Santa Casa de São Paulo between July of 2009 and March of 2013. We included in our analysis all inpatients for whom the requesting service judged that a psychiatric consultation was required for a possible mental health condition. Outcomes of interest were the instances of misidentification where a condition was initially deemed to be of a psychiatric nature, whereas the final diagnosis by the liaison psychiatric team was of an organic disease or delirium. Our predictors were the clinical specialty of the requesting service, requester and patient characteristics. A series of generalised linear models were used to evaluate misidentification risks. RESULTS: A total of 947 subjects met our inclusion criteria, 14.6% having a final liaison diagnosis of organic mental disorder and 8.1% of delirium. Older patients were significantly associated with increased risk of misidentification for both organic conditions (OR 3.01 - 95% CI 2.01, 4.5) and delirium (OR 3.92 - 2.4, 6.39). CONCLUSIONS: Educational interventions in general hospitals focused on preventing psychiatric misdiagnosis should target in-hospital services where patients tend to be older.

The challenges of living with Debilitating Symptom Complexes Attributed to Ticks (DSCATT) - A qualitative study.

OBJECTIVE: We sought to explore the lived experience of people with Debilitating Symptom Complexes Attributed to Ticks (DSCATT) to inform the development of a potential treatment intervention. METHODS: We conducted one-to-one in-depth, semi-structured interviews with 13 people living in Australia affected by DSCATT. Interviews were transcribed and analysed using thematic analysis. RESULTS: Although participants attributed the origin of their illness to tick bites, not all were adamant they had Lyme disease. Negative experiences in conventional healthcare were marked and were reported to exacerbate the impact of the illness and affect mental health. Further, these negative experiences propelled participants to seek unapproved treatments (by Australian standards). The desire for the illness to be acknowledged and causative agents identified was pronounced among the participant group. CONCLUSIONS: Individuals with DSCATT experience significant challenges amid a contentious healthcare landscape surrounding chronic symptoms attributed to ticks in Australia. Our findings suggest the need for empathetic, supportive and patient-centred treatments for this cohort. IMPLICATIONS FOR PUBLIC HEALTH: DSCATT results in a considerable burden across multiple domains for those affected. Negative experiences with healthcare exacerbate the suffering of people with DSCATT in Australia. New approaches that acknowledge the illness experience of people with DSCATT, alongside evidence-based treatments that encompass biopsychosocial models of care, are needed to tackle this debilitating condition.

A growing understanding of the role of muscarinic receptors in the molecular pathology and treatment of schizophrenia.

Pre-clinical models, postmortem and neuroimaging studies all support a role for muscarinic receptors in the molecular pathology of schizophrenia. From these data it was proposed that activation of the muscarinic M1 and/or M4 receptor would reduce the severity of the symptoms of schizophrenia. This hypothesis is now supported by results from two clinical trials which indicate that activating central muscarinic M1 and M4 receptors can reduce the severity of positive, negative and cognitive symptoms of the disorder. This review will provide an update on a growing body of evidence that argues the muscarinic M1 and M4 receptors have critical roles in CNS functions that are dysregulated by the pathophysiology of schizophrenia. This realization has been made possible, in part, by the growing ability to visualize and quantify muscarinic M1 and M4 receptors in the human CNS using molecular neuroimaging. We will discuss how these advances have provided evidence to support the notion that there is a sub-group of patients within the syndrome of schizophrenia that have a unique molecular pathology driven by a marked loss of muscarinic M1 receptors. This review is timely, as drugs targeting muscarinic receptors approach clinical use for the treatment of schizophrenia and here we outline the background biology that supported development of such drugs to treat the disorder.

Feedback-loop between psychotic symptoms and brain volume: A cross-lagged panel model study.

Brain structural changes are known to be associated with psychotic symptoms, with worse symptoms consistently associated with brain volume loss in some areas. It is not clear whether volume and symptoms interfere with each other over the course of psychosis. In this paper, we analyse the temporal relationships between psychosis symptom severity and total gray matter volume. We applied a cross-lagged panel model to a public dataset from the NUSDAST cohorts. The subjects were assessed at three-time points: baseline, 24 months, and 48 months. Psychosis symptoms were measured by SANS and SAPS scores. The cohort contained 673 subjects with schizophrenia, healthy subjects and their siblings. There were significant effects of symptom severity on total gray matter volume and vice-versa. The worse the psychotic symptoms, the smaller the total gray volume, and the smaller the volume, the worse the symptomatology. There is a bidirectional temporal relationship between symptoms of psychosis and brain volume.

Anaesthesia and the development of functional neurological disorder: A systematic review and case series.

OBJECTIVE: There are reports of functional neurological disorder (FND) developing after anaesthesia, though separating any aetiological role from other possible factors is challenging. We aimed to systematically review all published cases of post-anaesthetic FND to see if any common factors supported an anaesthetic role. We also aimed to identify all cases of post-anaesthetic FND arising in our FND clinic, to obtain an estimate of its frequency. METHODS: For the review, a systematic search for published cases of FND developing within 48 h of anaesthesia was conducted in June 2022. For the case series, the medical records of all patients attending an FND clinic in Melbourne between 2017 and 2019 were examined, and all cases with FND within 48 h of anaesthesia extracted. RESULTS: 36 published cases were identified for the review. Sixteen described preceding stressors and 16 psychiatric diagnoses, including 8 with previous FND. Thirty-two (92%) had undergone general anaesthesia, most commonly for obstetric procedures. Motor/sensory loss was the most common presentation, followed by seizures and coma. Most (80.5%) developed symptoms immediately on induction or cessation of anaesthesia. For the case series, 8 of 107 clinic patients (7.5%), developed FND within 48 h of anaesthesia. All had previous psychiatric diagnoses, including 3 with previous FND. Three underwent general anaesthesia and 3 procedural sedation, with seizures the most common presentation. All developed symptoms immediately on induction or cessation of anaesthesia. CONCLUSION: These cases provide some support for an aetiological role for anaesthesia: there is evidence for an anaesthetic 'model' for the symptoms of FND that arise, they largely arise with the onset or termination of anaesthesia, and they arise most frequently during general anaesthesia or sedation.

Conversion disorder: a problematic diagnosis.

The diagnosis of conversion disorder is problematic. Since doctors have conceptually and practically differentiated the symptoms from neurological ('organic') disease it has been presumed to be a psychological disorder, but the psychological mechanism, and how this differs from feigning (conscious simulation), has remained elusive. Although misdiagnosis of neurological disease as conversion disorder is uncommon, it remains a concern for clinicians, particularly for psychiatrists who may be unaware of the positive ways in which neurologists can exclude organic disease. The diagnosis is anomalous in psychiatry in that current diagnostic systems require that feigning is excluded and that the symptoms can be explained psychologically. In practice, feigning is very difficult to either disprove or prove, and a psychological explanation cannot always be found. Studies of childhood and adult psychological precipitants have tended to support the relevance of stressful life events prior to symptom onset at the group level but they are not found in a substantial proportion of cases. These problems highlight serious theoretical and practical issues not just for the current diagnostic systems but for the concept of the disorder itself. Psychology, physiology and functional imaging techniques have been used in attempts to elucidate the neurobiology of conversion disorder and to differentiate it from feigning, but while intriguing results are emerging they can only be considered preliminary. Such work looks to a future that could refine our understanding of the disorder. However, until that time, the formal diagnostic requirement for associated psychological stressors and the exclusion of feigning are of limited clinical value. Simplified criteria are suggested which will also encourage cooperation between neurology and psychiatry in the management of these patients.

Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda.

Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart - leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using "rule-in" examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

Differential effects of pre and post-payment on neurologists' response rates to a postal survey.

BACKGROUND: Monetary incentives are an effective way of increasing response rates to surveys, though they are generally less effective in physicians, and are more effective when the incentive is paid up-front rather than when made conditional on completion. METHODS: In this study we examine the effectiveness of pre- and post-completion incentives on the response rates of all the neurologists in the UK to a survey about conversion disorder, using a cluster randomised controlled design. A postal survey was sent to all practicing consultant neurologists, in two rounds, including either a book token, the promise of a book token, or nothing at all. RESULTS: Three hundred and fifty-one of 591 eligible neurologists completed the survey, for a response rate of 59%. While the post-completion incentive exerted no discernible influence on response rates, a pre-completion incentive did, with an odds-ratio of 2.1 (95% confidence interval 1.5-3.0). CONCLUSIONS: We conclude that neurologists, in the UK at least, may be influenced to respond to a postal survey by a pre-payment incentive but are unaffected by a promised reward.