The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder

Genome-wide association studies in bipolar disorder (BD)1 have implicated a single-nucleotide polymorphism (rs1006737, G right arrow A) in the CACNA1C gene, which encodes for the alpha 1c (CAV1.2) subunit of the voltage-gated, L-type calcium channel. Neuroimaging studies of healthy individuals report that this risk allele modulates brain function within limbic (amygdala, anterior cingulate gyrus) and hippocampal regions during tasks of reward processing2, 3 and episodic memory. Moreover, animal studies suggest that the CaV1.2 L-type calcium channels influence emotional behaviour through enhanced neurotransmission via the lateral amygdala pathway. On the basis of this evidence, we tested the hypotheses that the CACNA1C rs1006737 risk allele will modulate neural responses within predefined prefrontal and subcortical regions of interest during emotional face processing and that this effect would be amplified in BD patients

Accuracy of magnetic resonance imaging in detecting lumbo-sacral nerve root compromise: A systematic literature review

Background: MRI is considered to be the diagnostic tool of choice in diagnosing nerve root compromise among patients presenting with clinical suspicion of lumbo-sacral radiculopathy. There exists controversy among researchers and clinicians regarding the diagnostic utility and accuracy of MRI in detecting nerve root compromise and radiculopathy. This review evaluated 4 primary diagnostic accuracy studies that specifically assessed the accuracy of MRI in detecting nerve root compromise, as established in the current literature. Methods: Eight electronic data bases were searched for relevant articles from inception until January 2014. All primary diagnostic studies which investigated the accuracy of MRI in diagnosing nerve root compromise among patients with low back and referred leg symptoms were screened for inclusion. Qualifying studies were retrieved and independently assessed for methodological quality using the 'Quality Assessment of Diagnostic tests Accuracy Studies' criteria. Results: Four studies qualified for inclusion in this review. The sensitivity of MRI in detecting lumbar nerve root compromise was very low at 0.25 (95 % CI) while the specificity was relatively high at 0.92 (95 % CI). Conclusions: There is lack of sufficient high quality scientific evidence in support or against the use of MRI in diagnosing nerve root compression and radiculopathy. Therefore, clinicians should always correlate the findings of MRI with the patients' medical history and clinical presentation in clinical decision making.IS

Physical characteristics of the back are not predictive of low back pain in healthy workers: A prospective study

Background. In the working population, back disorders are an important reason for sick leave and permanent work inability. In the context of fitting the job to the worker, one of the primary tasks of the occupational health physician is to evaluate the balance between work-related and individual variables. Since this evaluation of work capacity often consists of a physical examination of the back, the objective of this study was to investigate whether a physical examination of the low back, which is routinely performed in occupational medicine, predicts the development of low back pain (LBP). Methods. This study is part of the Belgian Low Back Cohort (BelCoBack) Study, a prospective study to identify risk factors for the development of low back disorders in occupational settings. The study population for this paper were 692 young healthcare or distribution workers (mean age of 26 years) with no or limited back antecedents in the year before inclusion. At baseline, these workers underwent a standardised physical examination of the low back. One year later, they completed a questionnaire on the occurrence of LBP and some of its characteristics. To study the respective role of predictors at baseline on the occurrence of LBP, we opted for Cox regression with a constant risk period. Analyses were performed separately for workers without any back antecedents in the year before inclusion ('asymptomatic' workers) and for workers with limited back antecedents in the year before inclusion ('mildly symptomatic' workers). Results. In the group of 'asymptomatic' workers, obese workers showed a more than twofold-increased risk on the development of LBP as compared to non-obese colleagues (RR 2.57, 95%CI: 1.09 - 6.09). In the group of 'mildly symptomatic' workers, the self-reports of pain before the examination turned out to be most predictive (RR 3.89, 95%CI: 1.20 - 12.64). Conclusion. This study showed that, in a population of young workers wh no or limited antecedents of LBP at baseline, physical examinations, as routinely assessed in occupational medicine, are not useful to predict workers at risk for the development of back disorders one year later

Prognosis of acute low back pain: design of a prospective inception cohort study

BACKGROUND: Clinical guidelines generally portray acute low back pain as a benign and self-limiting condition. However, evidence about the clinical course of acute low back pain is contradictory and the risk of subsequently developing chronic low back pain remains uncertain. There are few high quality prognosis studies and none that have measured pain, disability and return to work over a 12 month period. This study aims to provide the first estimates of the one year prognosis of acute low back pain (pain of less than 2 weeks duration) in patients consulting primary care practitioners. A secondary aim is to identify factors that are associated with the prognosis of low back pain. METHODS/DESIGN: The study is a prospective inception cohort study. Consecutive patients consulting general medical practitioners, physiotherapists and chiropractors in the Sydney metropolitan region will complete a baseline questionnaire regarding their back pain. Subsequently these patients will be followed up by telephone 6 weeks, 3 months and 12 months after the initial consultation. Patients will be considered to have recovered from the episode of back pain if they have no pain and no limitation of activity, and have returned to pre-injury work status. Life tables will be generated to determine the one year prognosis of acute low back pain. Prognostic factors will be assessed using Cox regression. DISCUSSION: This study will provide the first estimates of the one year prognosis of acute low back pain in a representative sample of primary care patients

Changes in the incidence of occupational disability as a result of back and neck pain in the Netherlands

BACKGROUND: Back pain (including neck pain) is one of the most prevalent health problems for which physicians are consulted. Back pain can decrease the quality of life considerably during a great part of the lives of those who suffer from it. At the same time it has an enormous economic impact, mainly through sickness absence and long-term disability. The objective of this paper is to compare the incidence of occupational disability as a result of back and neck pain in 1980–1985 to 1999–2000 and to explain the findings. METHODS: A descriptive study was performed at population level of changes in incidence of occupational disability as a result of back and neck pain. Statistics from the National Institute of Social Insurance in the Netherlands are used to calculate age and gender specific incidence rates for back pain diagnoses based on the ICD-classification. Incidence rate ratios stratified according to gender and adjusted for age were calculated to indicate changes over time. RESULTS: The incidence of occupational disability as a result of back pain decreased significantly by 37% (95% CI 37%–38%) in men and with 21% (95% CI 20%–24%) in women, after adjustment for age. For overall occupational disability as a result of all diagnoses this was 18% (95% CI 18%–19%) and 34% (95% CI 33%–35%) respectively. Changes were not homogeneous over diagnostic subcategories and age groups. Spondylosis decreased most in men by 59% (95% CI 57%–61%). The incidence of non-specific back pain and neck pain increased most by 196% (95% CI 164%–215%). Post-laminectomy syndrome increased over all age categories both for men (85%, 95% CI 61%–113%) and women (113%, 95% CI 65%–179%). CONCLUSION: The decrease in occupational disability as a result of back pain was larger than the decrease in occupational disability over all diagnoses. However, time trends were not homogeneous over age-, nor over sex- nor back pain categories. Most of this decrease was due to general changes such as legal and economic changes. One of several additional explanations for a decrease is the changed view on management of back pain

How can chiropractic become a respected mainstream profession? The example of podiatry

<p>Abstract</p> <p>Background</p> <p>The chiropractic profession has succeeded to remain in existence for over 110 years despite the fact that many other professions which had their start at around the same time as chiropractic have disappeared. Despite chiropractic's longevity, the profession has not succeeded in establishing cultural authority and respect within mainstream society, and its market share is dwindling. In the meantime, the podiatric medical profession, during approximately the same time period, has been far more successful in developing itself into a respected profession that is well integrated into mainstream health care and society.</p> <p>Objective</p> <p>To present a perspective on the current state of the chiropractic profession and to make recommendations as to how the profession can look to the podiatric medical profession as a model for how a non-allopathic healthcare profession can establish mainstream integration and cultural authority.</p> <p>Discussion</p> <p>There are several key areas in which the podiatric medical profession has succeeded and in which the chiropractic profession has not. The authors contend that it is in these key areas that changes must be made in order for our profession to overcome its shrinking market share and its present low status amongst healthcare professions. These areas include public health, education, identity and professionalism.</p> <p>Conclusion</p> <p>The chiropractic profession has great promise in terms of its potential contribution to society and the potential for its members to realize the benefits that come from being involved in a mainstream, respected and highly utilized professional group. However, there are several changes that must be made within the profession if it is going to fulfill this promise. Several lessons can be learned from the podiatric medical profession in this effort.</p

Differential response of human basophil activation markers: a multi-parameter flow cytometry approach

<p>Abstract</p> <p>Background</p> <p>Basophils are circulating cells involved in hypersensitivity reactions and allergy but many aspects of their activation, including the sensitivity to external triggering factors and the molecular aspects of cell responses, are still to be focused. In this context, polychromatic flow cytometry (PFC) is a proper tool to investigate basophil function, as it allows to distinguish the expression of several membrane markers upon activation in multiple experimental conditions. </p> <p>Methods</p> <p>Cell suspensions were prepared from leukocyte buffy coat of K2-EDTA anticoagulated blood specimens; about 1500-2500 cellular events for each tested sample, gated in the lymphocyte CD45dim area and then electronically purified as HLADRnon expressing/CD123bright, were identified as basophilic cells. Basophil activation with fMLP, anti-IgE and calcium ionophore A23187 was evaluated by studying up-regulation of the indicated membrane markers with a two-laser six-color PFC protocol.</p> <p>Results</p> <p>Following stimulation, CD63, CD13, CD45 and the ectoenzyme CD203c up-regulated their membrane expression, while CD69 did not; CD63 expression occurred immediately (within 60 sec) but only in a minority of basophils, even at optimal agonist doses (in 33% and 14% of basophils, following fMLP and anti-IgE stimulation respectively). CD203c up-regulation occurred in the whole basophil population, even in CD63non expressing cells. Dose-dependence curves revealed CD203c as a more sensitive marker than CD63, in response to fMLP but not in response to anti-IgE and to calcium ionophore.</p> <p>Conclusion</p> <p>Use of polychromatic flow cytometry allowed efficient basophil electronic purification and identification of different behaviors of the major activation markers. The simultaneous use of two markers of activation and careful choice of activator are essential steps for reliable assessment of human basophil functions.</p

A systematic review of associations between functional MRI activity and polygenic risk for schizophrenia and bipolar disorder

Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data. Results indicate that the effect of genetic load for SCZ and BD on brain function affects task-related recruitment, with frontal areas having a more prominent role, independent of task. Additionally, the results suggest that the polygenic architecture of psychotic disorders is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions. Future imaging genetics studies with large samples, especially population studies, would be uniquely informative in mapping the spatial distribution of the genetic risk to psychiatric disorders on brain processes during various cognitive tasks and may lead to the discovery of biological pathways that could be crucial in mediating the link between genetic factors and alterations in brain networks

Novel Primate Model of Serotonin Transporter Genetic Polymorphisms Associated with Gene Expression, Anxiety and Sensitivity to Antidepressants

This is the final version of the article. It first appeared from Nature Publishing Group via https://dx.doi.org/10.1038/npp.2016.41Genetic polymorphisms in the repeat upstream region of the serotonin transporter gene (SLC6A4) are associated with individual differences in stress reactivity, vulnerability to affective disorders and response to pharmacotherapy. However, the molecular, neurodevelopmental and psychopharmacological mechanisms underlying the link between SLC6A4 polymorphisms and the emotionally vulnerable phenotype are not fully understood. Thus, using the marmoset monkey Callithrix jacchus we characterize here a new neurobiological model to help to address these questions. We first sequenced the marmoset SLC6A4 promoter and identified a double nucleotide polymorphism (−2053AC/CT) and two single nucleotide polymorphisms (−2022C/T and −1592G/C) within the repeat upstream region. We showed their association with gene expression using in vivo quantitative PCR and with affective behavior using a primate test of anxiety (human intruder test). The low-expressing haplotype (AC/C/G) was linked with high anxiety whilst the high-expressing one (CT/T/C) was associated with an active coping strategy in response to threat. Pharmacological challenge with an acute dose of the selective serotonin reuptake inhibitor (SSRI), citalopram, revealed a genotype-dependent behavioral response. Whilst individuals homozygous for the high anxiety-related haplotype AC/C/G exhibited a dose-dependent, anxiogenic response, individuals homozygous for the low anxiety-related haplotype CT/T/C showed an opposing, dose-dependent anxiolytic effect. These findings provide a novel genetic and behavioral primate model to study the molecular, neurodevelopmental and psychopharmacological mechanisms that underlie genetic variation-associated complex behaviors, with specific implications for the understanding of normal and abnormal serotonin actions and the development of personalized pharmacological treatments for psychiatric disorders.Work was supported by an MRC Programme (ACR; G0901884) and performed within the Behavioural and Clinical Neuroscience Institute, University of Cambridge, funded jointly by the Wellcome Trust and MRC. AMS was supported by a McDonnell Foundation grant (PI’s: E. Phelps, T.W. Robbins; Co-Investigators: ACR and J. LeDoux; 22002015501) and currently supported by MRC; YS supported by the Long Term Student Support Program provided by Osaka University and the Ministry of Education, Culture, Sports, Science and Technology of Japan; HC supported by MRC Career Development Award and ACFS/MI supported by grants from the MRC and Wellcome Trust. GC supported by the Behavioural and Clinical Neuroscience Institute, Cambridge, United Kingdom. EHSS was self-funded

Brief psychosocial education, not core stabilization, reduced incidence of low back pain: results from the Prevention of Low Back Pain in the Military (POLM) cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>Effective strategies for the primary prevention of low back pain (LBP) remain elusive with few large-scale clinical trials investigating exercise and education approaches. The purpose of this trial was to determine whether core stabilization alone or in combination with psychosocial education prevented incidence of low back pain in comparison to traditional lumbar exercise.</p> <p>Methods</p> <p>The Prevention of Low Back Pain in the Military study was a cluster randomized clinical study with four intervention arms and a two-year follow-up. Participants were recruited from a military training setting from 2007 to 2008. Soldiers in 20 consecutive companies were considered for eligibility (n = 7,616). Of those, 1,741 were ineligible and 1,550 were eligible but refused participation. For the 4,325 Soldiers enrolled with no previous history of LBP average age was 22.0 years (SD = 4.2) and there were 3,082 males (71.3%). Companies were randomly assigned to receive traditional lumbar exercise, traditional lumbar exercise with psychosocial education, core stabilization exercise, or core stabilization with psychosocial education, The psychosocial education session occurred during one session and the exercise programs were done daily for 5 minutes over 12 weeks. The primary outcome for this trial was incidence of low back pain resulting in the seeking of health care.</p> <p>Results</p> <p>There were no adverse events reported. Evaluable patient analysis (4,147/4,325 provided data) indicated no differences in low back incidence resulting in the seeking of health care between those receiving the traditional exercise and core stabilization exercise programs. However, brief psychosocial education prevented low back pain episodes regardless of the assigned exercise approach, resulting in a 3.3% (95% CI: 1.1 to 5.5%) decrease over two years (numbers needed to treat (NNT) = 30.3, 95% CI = 18.2 to 90.9).</p> <p>Conclusions</p> <p>Core stabilization has been advocated as preventative, but offered no such benefit when compared to traditional lumbar exercise in this trial. Instead, a brief psychosocial education program that reduced fear and threat of low back pain decreased incidence of low back pain resulting in the seeking of health care. Since this trial was conducted in a military setting, future studies are necessary to determine if these findings can be translated into civilian populations.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00373009">NCT00373009</a> at ClinicalTrials.gov - <url>http://clinicaltrials.gov/</url></p