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

Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study

Background Preliminary evidence suggests cancer- and chemotherapy-related autonomic nervous system (ANS) dysfunction may contribute to the increased cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However, the reliability of these findings may have been jeopardized by inconsistent participant screening and assessment methods. Therefore, good laboratory practices must be established before the presence and nature of cancer-related autonomic dysfunction can be characterized. The purpose of this study was to assess the feasibility of conducting concurrent ANS and cardiovascular evaluations in young adult cancer patients, according to the following criteria: i) identifying methodological pitfalls and proposing good laboratory practice criteria for ANS testing in cancer, and ii) providing initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS). Methods Thirteen patients (mixed diagnoses) were assessed immediately before and after 4 cycles of chemotherapy. Their results were compared to 12 sex- and age-matched controls. ANS function was assessed using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test) reactivity. Cardiovascular reactivity during exercise was assessed using a modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication. T-tests and repeated measures ANOVAs were used to assess between- and within-group differences at baseline and follow-up. Results The overall success rate in achieving our feasibility criteria was 98.4 %. According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up. Conclusions Results from our feasibility assessment suggest that the investigation of ANS function in young adult cancer patients undergoing chemotherapy is possible. To the best of our knowledge, this is the first study to report CASS-based evidence of ANS impairment and sudomotor dysfunction in any cancer population. Moreover, we provide evidence of cancer- and chemotherapy-related parasympathetic dysfunction – as a possible contributor to the pathogenesis of CV disease in cancer survivors

Not saying, not doing: Convergences, contingencies and causal mechanisms of state reform and decentralisation in Hollande’s France

Are States in contemporary Europe subject to new forms of convergence under the impact of economic crisis, enhanced European steering and international monitoring? Or is the evolution of governance (national and sub-national) driven fundamentally by diverging, mainly domestic pressures? Drawing on extensive new data, the article combines analysis of the State Modernisation and Decentralisation reform programmes of the Hollande–Ayrault administration, drawing comparisons where appropriate with the previous Sarkozy regime. The limits of President Hollande’s anti-Sarkozy method were demonstrated in the first 2 years; framing state reform and decentralisation in negative terms prevented the emergence of a coherent legitimising discourse. The empirical data is interpreted with reference to a comparative ‘States of Convergence’ framework, which is conceptualised as a heuristic device for analysing variation between places, countries and policy fields. The article concludes that the forces of hard convergence are gaining ground, as economic, epistemic and European pressures continually challenge the forces of institutional inertia

The effect of stimulation technique on sympathetic skin responses in healthy subjects

The aim of this study was to collect normative data for sympathetic skin responses (SSR) elicited by electrical stimulus of the ipsilateral and contralateral peripheral nerves, and by magnetic stimulus of cervical cord. SSRs were measured at the mid-palm of both hands following electrical stimulation of the left median nerve at the wrist and magnetic stimulation at the neck in 40 healthy adult volunteers (mean age 52.2 ± 12.2 years, 19 males). The onset latency, peak latency, amplitude and area were estimated in “P” type responses (i.e., waveforms with a larger positive, compared to negative, component). SSR onset and peak latency were prolonged when the electrical stimulus was applied at the contralateral side (i.e., the SSR recorded in the right palm P < 0.001). The onset latency was similar on both sides during cervical magnetic stimulation. However, peak latency was faster on the left side (P < 0.03). Comparison of electrical and magnetic stimulation revealed that both the onset and peak latency were shorter with magnetic stimulation (P < 0.001). The latency of a SSR varies depending on what type of stimulation is used and where the stimulus is applied. Electrically generated SSRs have a longer delay and the delay is prolonged at the contralateral side. These factors should be taken into account when interpreting SSR data

Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study

Background Preliminary evidence suggests cancer- and chemotherapy-related autonomic nervous system (ANS) dysfunction may contribute to the increased cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However, the reliability of these findings may have been jeopardized by inconsistent participant screening and assessment methods. Therefore, good laboratory practices must be established before the presence and nature of cancer-related autonomic dysfunction can be characterized. The purpose of this study was to assess the feasibility of conducting concurrent ANS and cardiovascular evaluations in young adult cancer patients, according to the following criteria: i) identifying methodological pitfalls and proposing good laboratory practice criteria for ANS testing in cancer, and ii) providing initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS). Methods Thirteen patients (mixed diagnoses) were assessed immediately before and after 4 cycles of chemotherapy. Their results were compared to 12 sex- and age-matched controls. ANS function was assessed using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test) reactivity. Cardiovascular reactivity during exercise was assessed using a modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication. T-tests and repeated measures ANOVAs were used to assess between- and within-group differences at baseline and follow-up. Results The overall success rate in achieving our feasibility criteria was 98.4 %. According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up. Conclusions Results from our feasibility assessment suggest that the investigation of ANS function in young adult cancer patients undergoing chemotherapy is possible. To the best of our knowledge, this is the first study to report CASS-based evidence of ANS impairment and sudomotor dysfunction in any cancer population. Moreover, we provide evidence of cancer- and chemotherapy-related parasympathetic dysfunction – as a possible contributor to the pathogenesis of CV disease in cancer survivors

HER-2/neu diagnostics in breast cancer

HER-2/neu status of the primary breast cancer (PBC) is determined by immunohistochemistry and fluorescent in situ hybridization. Because of a variety of technical factors, however, the PBC may not accurately reflect the metastatic tumor in terms of HER-2/neu status. Recently published guidelines recommend that tumors be defined as HER-2/neu positive if 30% or more of the cells are 3+. Circulating levels of the HER-2 extracellular domain can be measured in serum using a test cleared by the US Food and Drug Administration, and increased serum HER-2/neu levels to above 15 ng/ml can reflect tumor progression. Studies comparing tissue HER-2/neu status of the PBC and HER-2/neu levels above 15 ng/ml in metastatic breast cancer patients are also reviewed