Changes in pain during a depressive episode and relationship to cytokine levels in major depressive disorder.

BACKGROUND: Depressed patients have an increased incidence of pain. A pathophysiological connection between depression and pain is still not revealed. Immunological activation has been found in both depression and pain. There are few studies of pain and immune activation in patients with depression, without inflammatory and autoimmune disorders. METHODS: This is a naturalistic follow-up study of 50 patients with a major depressive disorder (MDD) depressive episode, without any inflammatory or autoimmune conditions. We have previously reported on the relationship between depression and cytokine levels. In this study, we obtained data of depression, pain and cytokine levels before and after 12 weeks of depression treatment. All patients were medication-free at inclusion. RESULTS: At inclusion three out of four patients experienced pain, and the pain scores correlated with the depression scores. After treatment, as depression was relieved, the pain scores dropped significantly and were no longer correlated to the depression scores. There were no correlations between pain scores and cytokine levels. Pain level at inclusion did not correlate with depression treatment outcome. CONCLUSION: Our findings indicate that pain is a feature of depression. Pain levels and cytokine values didn't correlate. Pain at inclusion did not predict depression treatment outcome.

"No association between disease modifying treatment and fatigue in multiple sclerosis".

BACKGROUND: Fatigue affects 60-90% of people with multiple sclerosis (MS). It reduces quality of life and the ability to work. The cause of fatigue in MS remains unknown. Several disease-modifying treatments (DMTs) slow the disease process in relapsing MS by suppressing neuroinflammation. We aimed to investigate if treatment with a DMT is associated with lower rates of fatigue. METHODS: In this cross-sectional study of the MS population in three counties in Norway, we used the Fatigue Scale for Motor and Cognitive Functions (FSMC) and the Hospital Anxiety and Depression Scale (HADS) to assess patient-reported fatigue, anxiety and depression. Clinical data were retrieved from the electronic patient record system. We categorized DMTs as high-efficacy therapy or moderate-efficacy therapy. High-efficacy drugs included fingolimod, natalizumab, ocrelizumab, rituximab, alemtuzumab, daclizumab, and autologous hematopoietic stem cell transplantation. Moderate-efficacy drugs included interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. We included persons with relapsing MS only. RESULTS: Of 1142 patients, 80% had fatigue. Fifty-six percent of the patients were on DMTs (25% on moderate-efficacy treatment and 30% on high-efficacy treatment), 18% had discontinued treatment and 26% had never received any DMT. Sex, level of disability as measured by the Multiple Sclerosis Severity Score, anxiety and depression were independently associated with fatigue. Moderate-efficacy treatment was associated with less fatigue, but not after adjustment for other variables. There was no association between high-efficacy treatment and fatigue. CONCLUSION: We found no independent relationship between the use of disease-modifying treatment and fatigue in MS.

Fatigue in multiple sclerosis is associated with socioeconomic factors.

OBJECTIVES: Fatigue is one of the leading causes of reduced quality of life and inability to work in people with multiple sclerosis (pwMS). Currently, no treatment effectively ameliorates fatigue. We still know little about what causes fatigue and which factors may contribute to fatigue. Knowledge about socioeconomic factors' role in fatigue might help us recognize strategies for the management of fatigue. Our aim was to explore whether socioeconomic factors are associated with the presence or level of perceived fatigue. METHODS: This is a cross-sectional study of the MS population in three Norwegian counties. We used the Fatigue Scale for Motor and Cognitive Functions to assess self-reported fatigue, and obtained socioeconomic data from Statistics Norway and questionnaires. To assess self-reported anxiety and depression, we employed the Hospital Anxiety and Depression Scale. Clinical data were gathered from the hospital record system. RESULTS: The response rate was 64% (1599/2512). Seventy percent of the respondents were female, and the mean age was 52 years. Higher levels of education were associated with lower levels of fatigue. Receiving a disability pension, being divorced and having children were all factors associated with higher levels of fatigue, as were low parental education, low income, current smoking, and autoimmune comorbidities. We found a higher prevalence of anxiety and depression in pwMS with fatigue compared to those without fatigue CONCLUSION: Female sex, high level of disability, anxiety, depression and socioeconomic factors were independently associated with fatigue in contemporary patients with MS. These factors should be considered when devising management strategies.

'If we don't assess the patient's vision, we risk starting at the wrong end': a qualitative evaluation of a stroke service knowledge translation project.

BACKGROUND: Visual impairments (VIs) affect 60% of stroke survivors and have negative consequences for rehabilitation and quality of life poststroke. Symptoms of VIs post stroke are difficult to identify for stroke survivors and health care professionals without using a structured vision assessment. In this study, we qualitatively evaluate the implementation outcomes after implementing a structured visual assessment with the Competence, Rehabilitation of Sight after Stroke Vision (KROSS) assessment tool in stroke care services. METHODS: This is a qualitative study comprising four focus group interviews. The health care personnel (HCP) involved in the implementation or with experience using the KROSS assessment tool in practice were invited to participate. We used Proctor et al.'s definitions of implementation outcomes as a framework, which informed the interview guide and analysis. We used a deductive - inductive content analysis, as described by Elo and Kyngäs. RESULTS: The participants found the structured vision assessment with the KROSS tool as being acceptable; they expressed a motivation and intention to use the new routine in practice. They believed it was important to assess their patient's visual function because it influenced other rehabilitation activities and activities of daily living. Most of the participants reported having adopted the vision assessment in their practice, except for those participants from the home care services who experienced that they have few stroke survivors to follow up on. The assessment was believed to be more appropriate to perform within the rehabilitation services where there is more of a focus on functional assessments. Although vision assessment was new to all the participants, they felt that they improved their vision assessment skills by regularly using the assessment tool. Together with sufficient instructions and supervision, they believed that vison assessment was feasible for their practise. Including the vison assessment in the existing routines and systems was important to promote sustainable implementation. CONCLUSION: Implementing a structured vision assessment with the KROSS tool in health care services was experienced as acceptable and feasible. The new routine led to increased attention towards poststroke VIs and increased collaboration with vision experts. Tailoring the routine to each practice and how they organise their work can support the integration of a vision assessment in their routines. To promote better vision care poststroke vision assessment and follow up should be included in the stroke care pathways.

The Bridge Building Model: connecting evidence-based practice, evidence-based research, public involvement and needs led research.

This paper describes a model developed by an interdisciplinary team of research and public engagement specialists, with backgrounds in health and social care research, higher education, evidence-based practice, leadership, commissioning research and public involvement and engagement. The model we propose combines evidence-based practice, evidence-based research, public involvement and needs led research. Our aim is to capitalise on the joining of the rationale and methods for these approaches, which have all been highlighted as important, but for which there has been a lack of models for integration. Our ambition is to argue for and show an effective and evidence-based way of working that bridges health and social care needs identification, evidence-based practice and research.

This paper describes a model that combines different concepts in healthcare research that the authors suggest belong together. The concepts are; Evidence Based Practice, where healthcare is based on the best research evidence, Evidence Based Research, where new research is developed in the context of what research already exists, public involvement in research, where service users, carers and health and social care professionals engage with research, and Needs Led Research, where new research addresses the needs of people that use healthcare services.Combining these important approaches in our model is new and we argue for and show a way of working that 'builds bridges' between health and social care needs, healthcare practice and research.The Bridge Building Model has been developed by a team of research and public involvement specialists, with a variety of backgrounds in health and social care research. These include education, healthcare leadership using evidence in healthcare and research funding.

Barriers and facilitators to the implementation of a structured visual assessment after stroke in municipal health care services.

BACKGROUND: Stroke is a leading cause of disability worldwide. Visual impairments (VIs) affect 60% of stroke survivors, and have negative consequences for rehabilitation and post-stroke life. VIs after stroke are often overlooked and undertreated due to lack of structured routines for visual care after stroke. This study aims to identify and assess barriers and facilitators to the implementation of structured visual assessment after stroke in municipal health care services. The study is part of a larger knowledge translation project. METHODS: Eleven leaders and municipal interdisciplinary health care professionals participated in qualitative interviews. During two workshops, results from the interviews were discussed with 26 participants from municipal health care services and user representatives. Data from interviews and workshops were collected before the intervention was implemented and analyzed using content analysis. RESULTS: The analysis identified individual and contextual barriers and facilitators. The individual barriers were related to the participants' experiences of having low competence of visual functions and vision assessment skills. They considered themselves as generalists, not stroke experts, and some were reluctant of change because of previous experiences of unsuccessful implementation projects. Individual facilitators were strong beliefs that including vision in stroke care would improve health care services. If experienced as useful and evidence based, the new vision routine would implement easier. Contextual barriers were experiences of unclear responsibility for vision care, lack of structured interdisciplinary collaboration and lack of formal stroke routines. Time constraints and practical difficulties with including the vision tool in current medical records were also expressed barriers. Contextual facilitators were leader support and acknowledgement, in addition to having a flexible work schedule. CONCLUSIONS: This study shows that improving competence about VIs after stroke and skills in assessing visual functions are particularly important to consider when planning implementation of new vision routines in municipal health care services. Increased knowledge about the consequences of living with VIs after stroke, and the motivation to provide best possible care, were individual facilitators for changing clinical practice. Involving knowledge users, solutions for integrating new knowledge in existing routines, along with easily accessible supervision in own practise, are essential facilitators for promoting a successful implementation.

High prevalence of fatigue in contemporary patients with multiple sclerosis.

OBJECTIVE: The prevalence of multiple sclerosis (MS)-related fatigue may have changed due to new diagnostic criteria and new disease modifying drugs. We aimed to assess the prevalence of fatigue in a contemporary MS cohort, and to explore associations between fatigue and clinical and demographic factors. METHODS: This is a cross-sectional study of the MS population in three Norwegian counties. Fatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions (FSMC). We also assessed self-reported anxiety, depression and daytime sleepiness. RESULTS: The response rate was 64% (1599/2512). The mean age of the participants was 52 ± 13 years, median EDSS was 2.5 (IQR 1.5-3.0) and median disease duration from onset was 16 years (IQR 8-25). We found a prevalence of fatigue of 81%. Women had a higher prevalence of fatigue than men (83% vs 78%, p = 0.02). The prevalence increased with age (p < 0.001) and with increasing disease severity (p < 0.001), but in multivariate analyses, only sex and disease severity remained independent determinants of fatigue. Anxiety, depression, and daytime sleepiness were more prevalent in patients with fatigue than in those without fatigue (all p-values < 0.001). CONCLUSION: The prevalence of fatigue is high in contemporary patients with MS. Fatigue is associated with female sex and level of disability, as well as with anxiety, depression and excessive daytime sleepiness.

Frailty assessment of older adults, first-time applicants of public home care service in Norway.

OBJECTIVE: Early detection of frailty is essential to prevent or delay disability. The most appropriate screening tool for frailty among home-dwelling older adults is under debate. The present study estimates the prevalence of frailty among older adults, first-time applicants of public home care service in Norway, and investigates the appropriateness of gait speed and Short Physical Performance Battery as screening-tools for frailty. DESIGN AND SETTING: We conducted a cross-sectional study of 116 older adults >65 years applying for public home care service for the first time. Frailty was assessed by an adapted version of the Fried Frailty Phenotype. The test accuracies of gait speed and Short Physical Performance Battery to detect frailty were calculated for a general population >70 years in Norway. RESULTS: 62.1% of the participants were frail, 29.3% were prefrail, and 8.6% were robust. Mean gait speed and Short Physical Performance Battery-scores were significantly lower in frail compared to prefrail individuals, and significantly lower in prefrail compared to robust individuals. The sensitivity and specificity of gait speed at a cut point of 0.8 m/s to detect physical frailty phenotype was 99% and 68%, respectively. CONCLUSIONS: The high prevalence of frailty in the present study indicates that screening for frailty should be considered at an earlier time point than when older adults apply for public home care service for the first time. Gait speed may be an appropriate screening tool for frailty in a general population >70 years in Norway.KEY POINTSThe prevalence of frailty among older adults, first-time applicants of public home care services in Norway is major.Screening for frailty should be considered before older adults apply for public home care service for the first time.Gait speed at a cut point at 0.8 m/s may be an appropriate screening tool for frailty in a general population >70 years in Norway.

Chronic fatigue and depression due to multiple sclerosis: Immune-inflammatory pathways, tryptophan catabolites and the gut-brain axis as possible shared pathways.

Chronic fatigue and major depression (MDD)-like symptoms are common manifestations of multiple sclerosis (MS), both with huge impact on quality of life. Depression can manifest itself as fatigue, and depressive symptoms are often mistaken for fatigue, and vice versa. The two conditions are sometimes difficult to differentiate, and their relationship is unclear. Whether chronic fatigue and depression occur primarily, secondarily or coincidentally with activated immune-inflammatory pathways in MS is still under debate. We have carried out a descriptive review aiming to gain a deeper understanding of the relationship between chronic fatigue and depression in MS, and the shared pathways that underpin both conditions. This review focuses on immune-inflammatory pathways, the kynurenine pathway and the gut-brain axis. It seems likely that proinflammatory cytokines, tryptophan catabolites (the KYN pathway) and the gut-brain axis are involved in the mechanisms causing chronic fatigue and MDD-like symptoms in MS. However, the evidence base is weak, and more research is needed. In order to advance our understanding of the underlying pathological mechanisms, MS-related fatigue and depression should be examined using a longitudinal design and both immune-inflammatory and KYN pathway biomarkers should be measured, relevant clinical characteristics judiciously registered, and self-report instruments for both fatigue and depression should be used.

"Invisible" visual impairments. A qualitative study of stroke survivors` experience of vision symptoms, health services and impact of visual impairments.

BACKGROUND: Visual impairments (VIs) have a negative impact on life and affect up to 60% of stroke survivors. Despite this, VIs are often overlooked. This paper explores how persons with VIs experience vision care within stroke health services and how VIs impact everyday life the first 3 months post stroke. METHODS: Individual semi-structured interviews were conducted with 10 stroke survivors 3 months post stroke, and analyzed using qualitative content analysis. RESULTS: The main theme, "Invisible" visual impairments, represents how participants experience VIs as an unknown and difficult symptom of stroke and that the lack of attention and appropriate visual care leads to uncertainty about the future. VIs were highlighted as a main factor hindering the participants living life as before. The lack of acknowledgement, information, and systematic vision rehabilitation leads to feelings of being unsupported in the process of coping with VIs. CONCLUSION: VIs are unknown symptoms pre stroke and sequelas after stroke that significantly affect everyday life. VIs and vision rehabilitation needs more attention through all phases of stroke health services. We request a greater awareness of VIs as a presenting symptom of stroke, and that visual symptoms should be included in stroke awareness campaigns. Further, we suggest increased competence and standardized evidence-based clinical pathways for VIs to advance all stroke health services including rehabilitation in order to improve outcomes and adaptation to future life for stroke survivors with VIs.

Personality traits and the risk of becoming lonely in old age: A 5-year follow-up study.

BACKGROUND: Although many people experience loneliness in old age, there is little knowledge of predisposing personality factors. The aim of the present study was to explore to what extent personality traits are associated with the risk of becoming lonely, in women and men aged 60-79 years at baseline. METHODS: The panel data are from The Norwegian study on Life course, Ageing and Generations (NorLAG). Our sample consisted of 516 men and 419 women aged 60-79 years, who were surveyed in both 2002-2003 (baseline) and 2007-2008 (follow-up), and who reported not being lonely at baseline. Personality traits were measured by the Big Five scale. Multivariable logistic regression analyses were used to investigate the association between a personality trait and the risk of becoming lonely, with adjustment for age, mental health and living with a partner. RESULTS: At follow-up 59 women and 54 men reported loneliness (14.1% vs. 10.5%, p = 0.092). Among women, high agreeableness at baseline was significantly associated with a higher risk of becoming lonely. Among men, low agreeableness, low conscientiousness and high neuroticism at baseline were significantly associated with a higher risk of becoming lonely. CONCLUSIONS: Personality traits related differently to loneliness depending on gender. These findings may be useful when developing strategies for preventing loneliness in old age.

Associations between gait speed and well-known fall risk factors among community-dwelling older adults.

BACKGROUND AND PURPOSE: Exercise interventions are effective at preventing falls in community-dwelling older adults, especially before disability is present. Gait speed below 1.0 m/s is a strong predictor for falls in the elderly. However, evidence is sparse for gait speed alone being sufficient to identify individuals at a high risk of falling. This study aimed to describe the prevalence of fall risk factors among community-dwelling older adults in their late 70s and to investigate the associations between these risk factors and low gait speed in this population. METHODS: This cross-sectional cohort study comprised 108 elderly living in a small Norwegian municipality, born between 1936 and 1938. Exclusion criteria were living in residential care, inability to walk 4 m, and severe cognitive impairment. Measurements included gait speed, depressive symptoms, executive functions, fear of falling, vision function, fall history, body mass index, medications, and comorbidity. Gait speed was dichotomized using a cut-off of 1 m/s, and associations between different risk factors and low gait speed was explored using logistic regression analysis. RESULTS: Mean gait speed was 1.0 ± 0.3 m/s. In 44.4% of the participants, gait speed was below 1.0 m/s, indicating increased fall risk. Low gait speed was significantly associated with a history of multiple falls (odds ratio [OR] = 3.70, 95% CI [1.18, 11.65]), low educational level (OR = 3.58, 95% CI [1.10, 11.66]), higher number of medications (OR = 4.28, 95% CI [1.63, 11.2]), and higher number of depressive symptoms (OR = 1.31, 95% CI [1.09, 1.58]). We found no significant associations between gait speed and comorbidity, sex, vision, executive functions, or fear of falling. CONCLUSION: Our results indicate that gait speed with cut-off 1.0 m/s could represent a useful tool for identifying individuals who are vulnerable but not yet disabled and could benefit from fall-preventive exercise. However, extended assessment is probably needed to personalize interventions.

Role of the Immune System in Autism Spectrum Disorders (ASD).

BACKGROUND: The evidence based supports that multifactorial and complex immune interactions play a role in autism spectrum disorders (ASD), but contradictory findings are also reported. OBJECTIVE: The aim of this selective review was to identify trends in the research literature on this topic, focusing on immunology and other aberrations with respect to the different ASD subtypes. METHODS: This selective review is based on original and review articles written in English and identified in literature searches of PubMed. RESULTS: Several studies have found that the risk of ASD is greater among children whose mothers suffered from autoimmune diseases while pregnant. Moreover, individuals with ASD show increased levels of antibodies that are specific for several specific proteins. Studies also show that mothers of children with ASD have antibodies against fetal brain proteins. There are also reports on the associations between increased levels of proinflammatory cytokines and ASD. Finally, infections in mothers during pregnancy are linked to an increased risk of ASD. CONCLUSION: We propose that the large inconsistencies in findings among studies in the field are due to differences in subdiagnoses among the included children with ASD. Well-phenotyped ASD samples are needed to understand the biological and immunological mechanisms underpinning ASD and its subdiagnoses. Future research should apply new strategies to scrutinize the link between ASD and changes in immune responsivity. Important new research avenues are to investigate the associations (a) between different ASD phenotypes and aberrations in (auto)immune pathways and (b) between reduced natural regulatory autoimmune responses during pregnancy, which are in turn associated with increased oxidative and nitrosative stress in maternal blood and putative detrimental effects in the offspring.

Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders.

BACKGROUND: There is evidence that changes in neuro-immune responses coupled with dysfunctions in serotonin metabolism underpin the pathophysiology of autism spectrum disorders (ASD). OBJECTIVE: This study aimed to delineate whether ASD subgroups or characteristics show aberrations in tryptophan and brain-derived neurotrophic factor (BDNF) metabolism. METHODS: 65 individuals with ASD (diagnosed according to ICD criteria) and 30 healthy control patients were included. Measured were serum levels of tryptophan, kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), BDNF and PRO-BDNF and total blood 5-HT and 5-OH-tryptophan (5-HTP). RESULTS: Elevated BDNF levels and lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder, whilst elevated tryptophan and lower 5-HT synthesis were hallmarks of Asperger syndrome. A pathological MRI was associated with elevated tryptophan and lowered KA. Abnormal EEG results and dysmorphology were both associated with an elevated BDNF/ PRO-BDNF ratio. Any brain pathology and gastro-intestinal symptoms were accompanied by lowered KA. CONCLUSIONS: Increased BDNF production and changes in the metabolism of tryptophan are associated with many ASD characteristics, showing particularly strong associations with childhood autism and Intellectual and Developmental Disabilities. Peripheral BDNF and tryptophan metabolism appear to take part in the pathophysiology of autism spectrum disorders and their phenotypes.

Mechanisms of poststroke fatigue.

Poststroke fatigue is a debilitating symptom and is poorly understood. Here we summarise molecular, behavioural and neurophysiological changes related to poststroke fatigue and put forward potential theories for mechanistic understanding of poststroke fatigue.

Deficit, but Not Nondeficit, Schizophrenia Is Characterized by Mucosa-Associated Activation of the Tryptophan Catabolite (TRYCAT) Pathway with Highly Specific Increases in IgA Responses Directed to Picolinic, Xanthurenic, and Quinolinic Acid.

Evidence suggests that activation of the tryptophan catabolite (TRYCAT) pathway is involved in the pathophysiology of schizophrenia. However, no previous study examined whether TRYCAT pathway activation is associated with deficit schizophrenia. We measured IgA responses to TRYCATs, namely quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, and anthranilic acid and 3-OH-kynurenine, in 40 healthy controls and in schizophrenic patients with (n = 40) and without (n = 40) deficit, defined according to the Schedule for the Deficit Syndrome (SDS). Primary deficit schizophrenia is accompanied by an activated TRYCAT pathway as compared to controls and nondeficit schizophrenia. Participants with deficit schizophrenia show increased IgA responses to xanthurenic acid, picolinic acid, and quinolinic acid and relatively lowered IgA responses to kynurenic and anthranilic acids, as compared to patients with nondeficit schizophrenia. Both schizophrenia subgroups show increased IgA responses to 3-OH-kynurenine as compared to controls. The IgA responses to noxious TRYCATs, namely xanthurenic acid, picolinic acid, quinolinic acid, and 3-OH-kynurenine, but not protective TRYCATS, namely anthranilic acid and kunyrenic acid, are significantly higher in deficit schizophrenia than in controls. The negative symptoms of schizophrenia are significantly and positively associated with increased IgA responses directed against picolinic acid and inversely with anthranilic acid, whereas no significant associations between positive symptoms and IgA responses to TRYCATs were found. In conclusion, primary deficit schizophrenia is characterized by TRYCAT pathway activation and differs from nondeficit schizophrenia by a highly specific TRYCAT pattern suggesting increased excitotoxicity, cytotoxicity, and neurotoxicity, as well as inflammation and oxidative stress. The specific alterations in IgA responses to TRYCATs provide further insight for the biological delineation of deficit versus nondeficit schizophrenia.

Physical function of elderly patients with multimorbidity upon acute hospital admission versus 3 weeks post-discharge.

PURPOSE: To evaluate the change in activities of daily living, grip strength and functional mobility in very old patients >75 years old with multimorbidity upon admission to hospital versus 3 weeks after discharge. A second aim was to explore which baseline variables could predict personal activities of daily living 3 weeks after discharge. METHODS: This prospective cohort study included 115 home-dwelling older adults (mean 86 years, standard deviation 5.9). Participants were measured with the Timed Up and Go, grip strength and Barthel Index in hospital (T1) and 3 weeks after discharge (T2). RESULTS: After 3 weeks, the participants had significantly improved their activities of daily living, mobility and muscle strength, but were still physically reduced compared to reference values for age-matched elderly home dwellers and were at high risk of falls and further loss of independence. In the multivariate regression analysis, baseline cognitive function and mobility were independently associated with Barthel Index at T2 and explained 47% of the variance three weeks after discharge. CONCLUSIONS: Our findings highlight the importance of applying performance-based assessments for elderly in hospital. The result indicates that frail old adults acutely admitted to hospital are in need of rehabilitation 3 weeks after hospitalization. Implications for Rehabilitation Older people with multimorbidity improve their physical function 3 weeks after hospitalization. Nevertheless, they still are physically reduced with respect to reference values for age-matched elderly home dwellers and far below the cutoff score for their risk of falls, continued health decline and loosing their independence. The results imply that older people with multimorbidity are in need of early rehabilitation program during hospitalization and after hospitalization. The use of performance-based measurements enables us to identify older adults at highest risk of decline in health and function and is a key of identifying frail older peoples need for rehabilitation. The Time up and Go test, Grip Strength test and the Barthel Index are considered to complement each other and regarded as useful assessments for frail older people in hospital with acute illness.

Kynurenine Pathway in Autism Spectrum Disorders in Children.

BACKGROUND: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. METHODS: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. RESULTS: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 µM, p = 0.020). CONCLUSION: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD.

Cytokine Profile in Autism Spectrum Disorders in Children.

The pathogenesis of autism spectrum disorders (ASD) is not completely understood, but there is evidence of associations with altered immune responses. The aim of this study was to determine the serum levels of various cytokines in children with ASD and in healthy controls, in order to determine their role in ASD and its diagnostic subgroups. Sixty-five ASD patients were enrolled from an epidemiological survey in Norway, of which 30 were diagnosed with childhood autism, 16 with Asperger syndrome, 12 with atypical autism, 1 with Rett syndrome, and 6 with another ASD diagnosis. The serum levels of 12 cytokines were measured in all of the patients and in 30 healthy children. The cytokine levels did not differ significantly between the ASD group and the healthy controls. However, the interleukin-8 (IL-8) level was significantly higher (6.82 vs 4.58 pg/ml, p = 0.017) while that of IL-10 was significantly lower (2.24 vs 6.49 pg/ml, p = 0.009) in patients with childhood autism than in controls. Furthermore, the IL-8 level was significantly higher in childhood autism than in Asperger syndrome (6.82 vs 4.05 pg/ml, p = 0.013). Our study shows that the cytokine profile of children diagnosed with ASD, regardless of the subdiagnosis, does not differ from healthy controls. However, differentiation into different diagnostic subgroups reveals significantly different levels of IL-8 and IL-10. This indicates that different mechanisms may underlie the different ASD subdiagnoses. Future research into the pathophysiological mechanisms of ASD should pay more attention to the different subdiagnoses of ASD.