Effects of stress and relaxation on central pain modulation in chronic whiplash and fibromyalgia patients compared to healthy controls

Background: Compelling evidence has demonstrated that impaired central pain modulation contributes to persistent pain in patients with chronic whiplash associated disorders (WAD) and fibromyalgia (FM). However, there is limited research concerning the influence of stress and relaxation on central pain modulation in patients with chronic WAD and FM. Objectives: The present study aims to investigate the effects of acute cognitive stress and relaxation on central pain modulation in chronic WAD and FM patients compared to healthy individuals. Study Design: A randomized crossover design was employed. Setting: The present study took place at the University of Brussels, the University Hospital Brussels, and the University of Antwerp. Methods: Fifty-nine participants (16 chronic WAD patients, 21 FM, 22 pain-free controls) were enrolled and subjected to various pain measurements. Temporal summation (TS) of pain and conditioned pain modulation (CPM) were evaluated. Subsequently, participants were randomly allocated to either a group that received progressive relaxation therapy or a group that performed a battery of cognitive tests (= cognitive stressor). Afterwards, all pain measurements were repeated. One week later participant groups were switched. Results: A significant difference was found between the groups in the change in TS in response to relaxation (P = 0.008) and cognitive stress (P = 0.003). TS decreased in response to relaxation and cognitive stress in chronic WAD patients and controls. In contrast, TS increased after both interventions in FM patients. CPM efficacy decreased in all 3 groups in response to relaxation (P = 0.002) and cognitive stress (P = 0.001). Limitations: The obtained results only apply for a single session of muscle relaxation therapy and cognitive stress, whereby no conclusions can be made for effects on pain perception and modulation of chronic cognitive stress and long-term relaxation therapies. Conclusions: A single relaxation session as well as cognitive stress may have negative acute effects on pain modulation in patients with FM, while cognitive stress and relaxation did not worsen bottom-up sensitization in chronic WAD patients and healthy persons. However, endogenous pain inhibition, assessed using a CPM paradigm, worsened in chronic WAD and FM patients, as well as in healthy people following both interventions

Relationship between exercise-induced oxidative stress changes and parasympathetic activity in chronic fatigue syndrome : an observational study in patients and healthy subjects

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Individualized prediction of three- and six-year outcomes of psychosis in a longitudinal multicenter study:a machine learning approach

Schizophrenia and related disorders have heterogeneous outcomes. Individualized prediction of long-term outcomes may be helpful in improving treatment decisions. Utilizing extensive baseline data of 523 patients with a psychotic disorder and variable illness duration, we predicted symptomatic and global outcomes at 3-year and 6-year follow-ups. We classified outcomes as (1) symptomatic: in remission or not in remission, and (2) global outcome, using the Global Assessment of Functioning (GAF) scale, divided into good (GAF &gt;= 65) and poor (GAF &lt; 65). Aiming for a robust and interpretable prediction model, we employed a linear support vector machine and recursive feature elimination within a nested cross-validation design to obtain a lean set of predictors. Generalization to out-of-study samples was estimated using leave-one-site-out cross-validation. Prediction accuracies were above chance and ranged from 62.2% to 64.7% (symptomatic outcome), and 63.5-67.6% (global outcome). Leave-one-site-out cross-validation demonstrated the robustness of our models, with a minor drop in predictive accuracies of 2.3% on average. Important predictors included GAF scores, psychotic symptoms, quality of life, antipsychotics use, psychosocial needs, and depressive symptoms. These robust, albeit modestly accurate, long-term prognostic predictions based on lean predictor sets indicate the potential of machine learning models complementing clinical judgment and decision-making. Future model development may benefit from studies scoping patient's and clinicians' needs in prognostication.</p

Neurovisceral phenotypes in the expression of psychiatric symptoms

This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brainbody mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in 'emotional' brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognised factors causing vasodilatation (as noted post prandially, post exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety

The outcome of psychosis

Schizophrenia spectrum disorders, or psychotic disorders, are considered among the most serious life shortening, burdening mental illnesses worldwide, at a personal, familial and societal level, with approximately a 2- to 3-fold mortality risk as compared to the general population. The symptoms associated with psychosis tend to have devastating effects on global, social, occupational and daily functioning, quality of life and physical health. Illness outcome is an important measure in health care planning. Moreover, patients (and their families) presenting with a psychotic episode at the clinic want to know what to expect regarding the course of the disease. Many factors, including premorbid, clinical, demographic, environmental and genetic characteristics may contribute to the likelihood of a poor outcome after a first psychosis. But to what extent do these factors together explain outcome? At present little is understood of mechanisms leading to an unfavorable but also to a favorable outcome. In the first part of the thesis, studies are presented examining determinants in childhood and determinants after the development of psychotic illness in relation to clinical outcomes and global functioning. In the second part of the thesis the emphasis is on physical outcomes, in particular metabolic disturbances and smell processing, and its relation to clinical variables, cognition and brain volumes. By examining precursors that play a role in mental health and physical outcomes of psychotic disorders, it becomes clear that the underlying mechanisms are multifaceted. Taken together, research presented in this thesis highlights that predictors of mental health outcomes and physical outcomes include an interaction of many factors concerning the (intermediate) phenotype such as structural brain integrity (grey matter volumes and white matter pathways wiring), premorbid functioning, demographic characteristics, psychiatric symptomatology, need of care, and (social) cognitive functioning. Some predictor modalities hold special promise, such as reward processing in health outcome prediction; premorbid functioning and (social) cognition in predicting metabolic syndrome and olfactory identification deficit; connectome organization,patients’ needs and present state/lifetime psychotic symptoms in symptomatic and global functioning outcome prediction. Furthermore, it can be concluded that mental health and physical wellbeing are not separable in schizophrenia spectrum disorders. Much of the same predictive factors of mental health outcomes also seem to apply to physical outcomes. The studies presented in this thesis confirm the necessity of a multidisciplinary approach in health care, using mental health and physical outcome as integral treatment target. Future focus should be on personalized outcome prediction. We used machine learning techniques to predict outcome in individual patients with schizophrenia, and although our results are promising, these prediction models need to become more accurate before they can be translated into clinically useful tools. Even more elaborate sets of predictors are necessary, as well as larger multicenter prospective cohort studies for replication, before individualized prediction tools can be developed, tested and implemented in the clinic

The outcome of psychosis

Schizophrenia spectrum disorders, or psychotic disorders, are considered among the most serious life shortening, burdening mental illnesses worldwide, at a personal, familial and societal level, with approximately a 2- to 3-fold mortality risk as compared to the general population. The symptoms associated with psychosis tend to have devastating effects on global, social, occupational and daily functioning, quality of life and physical health. Illness outcome is an important measure in health care planning. Moreover, patients (and their families) presenting with a psychotic episode at the clinic want to know what to expect regarding the course of the disease. Many factors, including premorbid, clinical, demographic, environmental and genetic characteristics may contribute to the likelihood of a poor outcome after a first psychosis. But to what extent do these factors together explain outcome? At present little is understood of mechanisms leading to an unfavorable but also to a favorable outcome. In the first part of the thesis, studies are presented examining determinants in childhood and determinants after the development of psychotic illness in relation to clinical outcomes and global functioning. In the second part of the thesis the emphasis is on physical outcomes, in particular metabolic disturbances and smell processing, and its relation to clinical variables, cognition and brain volumes. By examining precursors that play a role in mental health and physical outcomes of psychotic disorders, it becomes clear that the underlying mechanisms are multifaceted. Taken together, research presented in this thesis highlights that predictors of mental health outcomes and physical outcomes include an interaction of many factors concerning the (intermediate) phenotype such as structural brain integrity (grey matter volumes and white matter pathways wiring), premorbid functioning, demographic characteristics, psychiatric symptomatology, need of care, and (social) cognitive functioning. Some predictor modalities hold special promise, such as reward processing in health outcome prediction; premorbid functioning and (social) cognition in predicting metabolic syndrome and olfactory identification deficit; connectome organization,patients’ needs and present state/lifetime psychotic symptoms in symptomatic and global functioning outcome prediction. Furthermore, it can be concluded that mental health and physical wellbeing are not separable in schizophrenia spectrum disorders. Much of the same predictive factors of mental health outcomes also seem to apply to physical outcomes. The studies presented in this thesis confirm the necessity of a multidisciplinary approach in health care, using mental health and physical outcome as integral treatment target. Future focus should be on personalized outcome prediction. We used machine learning techniques to predict outcome in individual patients with schizophrenia, and although our results are promising, these prediction models need to become more accurate before they can be translated into clinically useful tools. Even more elaborate sets of predictors are necessary, as well as larger multicenter prospective cohort studies for replication, before individualized prediction tools can be developed, tested and implemented in the clinic

Rehabilitation of chronic whiplash: treatment of cervical dysfunctions or chronic pain syndrome?

Chronic whiplash-associated disorders (WAD) remains a challenging condition for clinicians. There is substantial evidence for the presence of various cervical dysfunctions (e. g., increased cervical muscle tone and impaired cervical movement control), but their contribution to the complex clinical picture of subjects with chronic WAD seems rather limited. There is consistent evidence for increased responsiveness of the central nervous system in those with chronic WAD, and central pain processing is likely to play a crucial role in the transition from an acute whiplash trauma towards chronic WAD. The manuscript explains how our current understanding of chronic WAD can be used to steer the content of conservative interventions and how treatment of cervical dysfunctions in patients with chronic WAD should account for the processes involved in chronicity. It is recommended to prevent sensorimotor incongruence, target cognitive-emotional sensitization, and apply a cognitive behavioral therapy-guided exercise program

Reduced parasympathetic reactivation during recovery from exercise in myalgic encephalomyelitis/chronic fatigue syndrome

Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients. Although severe exercise intolerance is one of the core features of ME/CFS, little attempts have been made to study ANS responses to physical exercise. Therefore, impairments in ANS activation at rest and following exercise were examined using a case-control study in 20 ME/CFS patients and 20 healthy people. Different autonomous variables, including cardiac, respiratory, and electrodermal responses were assessed at rest and following an acute exercise bout. At rest, parameters in the time-domain represented normal autonomic function in ME/CFS, while frequency-domain parameters indicated the possible presence of diminished (para)sympathetic activation. Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS. This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS. Delayed HR recovery and/or a reduced HRV as seen in ME/CFS have been associated with poor disease prognosis, high risk for adverse cardiac events, and morbidity in other pathologies, implying that future studies should examine whether this is also the case in ME/CFS and how to safely improve HR recovery in this population