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The Relationships among Tryptophan, Kynurenine, Indoleamine 2,3-Dioxygenase, Depression, and Neuropsychological Performance
Get PDFResearch articleIt has been suggested that the metabolic enzyme indoleamine 2,3-dioxygenase (IDO) is a biological mediator of inflammation related to the psychopathology of depression, with a Kynurenine (KYN) increase in the Tryptophan (TRP) metabolic pathway, resulting in reduced Serotonin. In this study, we examined KYN, TRP, and the ratio of KYN to TRP concentrations × 103 (KT Ratio) in serum and cerebrospinal fluid (CSF) in (a) a group of depressed patients and (b) a control group of patients referred to a neurologic outpatient clinic for whom no specific diagnosis could be established. The KT Ratio is considered an index that represents IDO. The participants were examined with the Beck Depression Inventory II (BDI-II), the Montgomery Aasberg Depression Rating Scale (MADRS), and a neuropsychological test battery. We found no significant differences between the two study groups with respect to TRP, KYN, or KT Ratio in serum or CSF. Differences in neuropsychological performance between the two patient groups could be seen in the following tests: Animal Fluency, Digit Symbol, the DKEFS Color-Interference Test (Naming Part), Trail Making Test A and B, and the Grooved Pegboard Non-dominant Hand. KYN in serum correlated highly with KYN in CSF. KYN in serum correlated significantly with both age and gender. When analyzing males and females separately, we found that women had a lower level of TRP in both serum (Mann-Whitney U-test: TRP in Serum; p = 0.001) and CSF (Mann-Whitney U-test: TRP in CSF; p = 0.003). Women had a lower level of KYN in serum (p = 0.029) than men did. Age was positively associated with KYN. KYN in CSF correlated only with age, however; there were no gender differences. No significant relationship was seen between BDI-II and MADRS on the one hand, and KYN and TRP on the other. KYN in CSF as the KT Ratio in both serum and CSF was associated with neuropsychological performance. Thus, we suggest that KYN and KT Ratio are related more strongly to neuropsychological performance than to affective symptoms in depression.We are grateful for the support from the Inland Hospital trust and from Innland Norway University of Applied Sciences.publishedVersio
First-person experiences of recovery in co-occurring mental health and substance use conditions
Get PDFThis is the author`s Version of the article published in Advances in Dual DiagnosisPurpose The purpose of this paper is to explore and describe experiences of recovery among people with co-occurring mental health and substance use conditions (co-occurring conditions) in a rural community in Norway. Design/methodology/approach In-depth individual interviews with eight persons with co-occurring conditions were conducted, audiotaped, transcribed and analysed using a phenomenological approach. This study is part of a research project investigating recovery orientation of services in a Norwegian district. Findings The analysis yielded four dimensions of recovery: feeling useful and accepted; coming to love oneself; mastering life; and emerging as a person. Insecure and inadequate housing and limited solutions to financial problems were described as major obstacles to recovery. Research limitations/implications Further research into the facilitation of recovery as defined by persons with concurrent disorders is needed, particularly regarding the facilitation of community participation. Practical implications This study supports an increased focus on societal and community factors in promoting recovery for persons with co-occurring conditions, as well as service designs that allow for an integration of social services and health care, and for collaboration among services. Social implications The results suggest that the community can aid recovery by accepting persons with co-occurring conditions as fellow citizens and welcoming their contributions. Originality/value The paper provides an enhanced understanding of how persons with co-occurring conditions may experience recovery.acceptedVersio
High levels of anomalous self-experience are associated with longer duration of untreated psychosis
Get PDFCitation: Elisabeth Haug, Merete G. Øie, Ole A. Andreassen, Unni Bratlien, Kristin L. Romm, Paul Møller and Ingrid Melle, The Association between Anomalous Self-experiences, Self-esteem and Depressive Symptoms in First Episode Schizophrenia, Frontiers in Human Neuroscience, 10, (2016).Aim
To investigate the relationship between anomalous self-experiences and duration of untreated psychosis in a sample of patients with first episode schizophrenia spectrum disorders.
Methods
Anomalous self-experiences were assessed by means of the Examination of Anomalous Self-Experience manual in 55 patients referred to their first adequate treatment for schizophrenia. Diagnoses, symptom severity, functioning and childhood trauma were assessed using the Structured Clinical Interview for the Positive and Negative Syndrome Scale, Premorbid Adjustment Scale, Social Functioning Scale and Childhood trauma questionnaire. Substance misuse was measured with the Drug Use Disorder Identification Test, and alcohol use was measured with the Alcohol Use Disorder Identification Test. Duration of untreated psychosis was measured in accordance with a standardized procedure.
Results
High levels of anomalous self-experiences are significantly associated with longer duration of untreated psychosis, an association which held after correcting for other variables associated with long duration of untreated psychosis.
Conclusions
The field of early detection in psychosis is in need of additional clinical perspectives to make further progress. Improved understanding and assessment of anomalous self-experiences may help clinicians to detect these important phenomena and provide earlier help, and thus reduce treatment delay.This work was supported by Innlandet Hospital Trust (grant number 150229)acceptedVersio
MRI-based classification models in prediction of mild cognitive impairment and dementia in late-life depression
Get PDFObjective: Late-life depression (LLD) is associated with development of different types of dementia. Identification of LLD patients, who will develop cognitive decline, i.e., the early stage of dementia would help to implement interventions earlier. The purpose of this study was to assess whether structural brain magnetic resonance imaging (MRI) in LLD patients can predict mild cognitive impairment (MCI) or dementia 1 year prior to the diagnosis. Methods: LLD patients underwent brain MRI at baseline and repeated clinical assessment after 1-year. Structural brain measurements were obtained using Freesurfer software (v. 5.1) from the T1W brain MRI images. MRI-based Random Forest classifier was used to discriminate between LLD who developed MCI or dementia after 1-year follow-up and cognitively stable LLD. Additionally, a previously established Random Forest model trained on 185 patients with Alzheimer’s disease (AD) vs. 225 cognitively normal elderly from the Alzheimer’s disease Neuroimaging Initiative was tested on the LLD data set (ADNI model). Results: MCI and dementia diagnoses were predicted in LLD patients with 76%/68%/84% accuracy/sensitivity/specificity. Adding the baseline Mini-Mental State Examination (MMSE) scores to the models improved accuracy/sensitivity/specificity to 81%/75%/86%. The best model predicted MCI status alone using MRI and baseline MMSE scores with accuracy/sensitivity/specificity of 89%/85%/90%. The most important region for all the models was right ventral diencephalon, including hypothalamus. Its volume correlated negatively with the number of depressive episodes. ADNI model trained on AD vs. Controls using SV could predict MCI-DEM patients with 67% accuracy. Conclusion: LDD patients developing MCI and dementia can be discriminated from LLD patients remaining cognitively stable with good accuracy based on baseline structural MRI alone. Baseline MMSE score improves prediction accuracy. Ventral diencephalon, including the hypothalamus might play an important role in preservation of cognitive functions in LLD.publishedVersio
Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome
Get PDFAbstract Impairments in cognition, pain intolerance, and physical inactivity characterize adolescent chronic fatigue syndrome (CFS), yet little is known about its neurobiology. The right dorsal anterior insular (dAI) connectivity of the salience network provides a motivational context to stimuli. In this study, we examined regional functional connectivity (FC) patterns of the right dAI in adolescent CFS patients and healthy participants. Eighteen adolescent patients with CFS and 18 aged-matched healthy adolescent control participants underwent resting-state functional magnetic resonance imaging. The right dAI region of interest was examined in a seed-to-voxel resting-state FC analysis using SPM and CONN toolbox. Relative to healthy adolescents, CFS patients demonstrated reduced FC of the right dAI to the right posterior parietal cortex (PPC) node of the central executive network. The decreased FC of the right dAI–PPC might indicate impaired cognitive control development in adolescent CFS. Immature FC of the right dAI–PPC in patients also lacked associations with three known functional domains: cognition, pain and physical activity, which were observed in the healthy group. These results suggest a distinct biological signature of adolescent CFS and might represent a fundamental role of the dAI in motivated behavior.Norwegian Research Council, http:// www.forskningsradet.no/en (VBW, grant number 228874); South-Eastern Norway Regional Health Authority, https://www.helse-sorost.no/south- eastern-norway-regional-health-authority (VBW); and the University of Oslo, http://www.uio.no/ english/ (VBW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.acceptedVersio
Risk assessment of "other substances" – L-threonine. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food Safety
Get PDFShort summary
At the request of the Norwegian Food Safety Authority, the Norwegian Scientific Committee for Food Safety (VKM) has characterised the risk of specified doses of L-threonine in food supplements. VKM concludes that:
In adults (≥18 years), the specified doses 1000, 1200, 1500, 2000 and 2400 mg/day L-threonine in food supplements are unlikely to cause adverse health effects.
In adolescents (14 to <18 years), the specified doses 1000, 1200, 1500, 2000 and 2400 mg/day L-threonine in food supplements are unlikely to cause adverse health effects.
In children (10 to <14 years), the specified doses 1000, 1200, 1500, 2000 and 2400 mg/day L-threonine in food supplements are unlikely to cause adverse health effects.publishedVersio
MRI-assessed atrophy subtypes in Alzheimer’s disease and the cognitive reserve hypothesis
Get PDFBackground/Aims MRI assessment of the brain has demonstrated four different patterns of atrophy in patients with Alzheimer’s disease dementia (AD): typical AD, limbic-predominant AD, hippocampal-sparing AD, and a subtype with minimal atrophy, previously referred to as no-atrophy AD. The aim of the present study was to identify and describe the differences between these four AD subtypes in a longitudinal memory-clinic study. Methods The medial temporal lobes, the frontal regions, and the posterior regions were assessed with MRI visual rating scales to categorize 123 patients with mild AD according to ICD-10 and NINCDS-ADRDA criteria and the clinical dementia rating scale (CDR) into atrophy subtypes. Demographic data, neuropsychological measures, cerebrospinal-fluid biomarkers, and progression rate of dementia at two-year follow-up were compared between the groups. Results Typical AD was found in 59 patients (48%); 29 (24%) patients had limbic-predominant AD; 19 (15%) had hippocampal-sparing AD; and 16 (13%) belonged to the group with minimal atrophy. No differences were found regarding cognitive test results or progression rates between the different subtypes. Using adjusted logistic regression analysis, we found that the patients in the minimal-atrophy group were less educated, had a lower baseline CDR sum of boxes score, and had higher levels of amyloid β in the cerebrospinal fluid. Conclusion Previous results concerning the prevalence and the similar phenotypic expressions of the four AD subtypes were confirmed. The main finding was that patients with minimal atrophy as assessed by MRI had less education than the other AD subtypes and that this could support the cognitive reserve hypothesis and, at least in part, explain the lower degree of atrophy in this group. Patients with less formal education might present with clinically typical AD symptoms before they have positive biomarkers of AD and this finding might challenge suggested biomarker-based criteria for AD.Southern and Eastern Norway Regional Health Authority for providing funding for KP with an unrestricted grant, grant number 2013058 (https://www.helse-sorost.no/south-eastern- norway-regional-health-authority). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Norwegian ExtraFoundation for Health and Rehabilitation through the Norwegian Health Association for funding of coauthors RSE and MLB. (https://www.extrastiftelsen.no/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Liason Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology (NTNU) for funding of coauthor RSE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.publishedVersio
Factors associated with consumption of alcohol in older adults - a comparison between two cultures, China and Norway: the CLHLS and the HUNT-study
Get PDFBackground There is little knowledge about the consumption of alcohol among Chinese and Norwegian older adults aged 65 years and over. The aim of this study was to investigate the prevalence and factors related to alcohol consumption among older adults in China and Norway. Methods The Chinese Longitudinal Healthy Longevity Survey (CLHLS) data in 2008–2009 conducted in China and The Nord-Trøndelag Health Study data in 2006–2008 (HUNT3) conducted in Norway were used. Mulitvariable logistic regression was used to test the factors related to alcohol consumption. Results The prevalence of participants who drink alcohol in the Chinese and Norwegian sample were 19.88% and 46.2%, respectively. The weighted prevalence of participants with consumption of alcohol in the Chinese sample of women and men were 7.20% and 34.14%, respectively. In the Norwegian sample, the prevalence of consumption of alcohol were 43.31% and 65.35% for women and men, respectively. Factors such as younger age, higher level of education, living in urban areas, living with spouse or partner, and better health status were related to higher likelihood of alcohol consumption among Norwegian older women and men; while reported better health status and poorer life satisfaction were related to higher likelihood of alcohol consumption among Chinese. In addition, rural males and older females with higher level of education were more likely to consume alcohol. Conclusion The alcohol consumption patterns were quite different between China and Norway. Besides economic development levels and cultures in the two different countries, demographic characteristics, socioeconomic status, overall health status, and life satisfaction were associated with alcohol consumption as well.Factors associated with consumption of alcohol in older adults - a comparison between two cultures, China and Norway: the CLHLS and the HUNT-studyNonepublishedVersio
Disrupted global metastability and static and dynamic brain connectivity across individuals in the Alzheimer's disease continuum
Get PDFAs findings on the neuropathological and behavioral components of Alzheimer's disease (AD) continue to accrue, converging evidence suggests that macroscale brain functional disruptions may mediate their association. Recent developments on theoretical neuroscience indicate that instantaneous patterns of brain connectivity and metastability may be a key mechanism in neural communication underlying cognitive performance. However, the potential significance of these patterns across the AD spectrum remains virtually unexplored. We assessed the clinical sensitivity of static and dynamic functional brain disruptions across the AD spectrum using resting-state fMRI in a sample consisting of AD patients (n = 80) and subjects with either mild (n = 44) or subjective (n = 26) cognitive impairment (MCI, SCI). Spatial maps constituting the nodes in the functional brain network and their associated time-series were estimated using spatial group independent component analysis and dual regression, and whole-brain oscillatory activity was analyzed both globally (metastability) and locally (static and dynamic connectivity). Instantaneous phase metrics showed functional coupling alterations in AD compared to MCI and SCI, both static (putamen, dorsal and default-mode) and dynamic (temporal, frontal-superior and default-mode), along with decreased global metastability. The results suggest that brains of AD patients display altered oscillatory patterns, in agreement with theoretical premises on cognitive dynamics
Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens
Get PDFAbstract
Background
Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism.
Reports also indicate anti-inflammatory and antioxidative effects. The concentrations
of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are
involved in both the antioxidative defense and the inflammatory response, the present study
aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations
of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular
mortality following such supplementation.
Methods
215 elderly individuals were included and given the intervention for four years. A clinical
examination was performed and blood samples were taken at the start and after 48 months.
Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using
group mean values, and repeated measures of variance.
Findings
After supplementation with selenium and coenzyme Q10, applying group mean evaluations,
significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group,
whereas a decrease in concentration could be seen of the same biomarkers in the placebo
group.
Applying the repeated measures of variance evaluations, the same significant increase
in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; P<0.0001) and
of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme
Q10 also on the expression of IGF-1 as one of the mechanistic effects of the
intervention.
Conclusion
Supplementation with selenium and coenzyme Q10 over four years resulted in increased
levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1
SD score, compared with placebo. The effects could be part of the mechanistic explanation
behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality
reported earlier. However, as the effects of IGF-1 are complex, more research on the result
of intervention with selenium and coenzyme Q10 is needed.Funding: Part of the analysis costs was supported by grants from Family Erling-Persson Foundation, Medical Research Council, Pharma Nord Aps, Denmark, the County Council ofOÈ stergoÈtland, LinkoÈping University. The selenium tablets and coenzyme Q10 capsules were kindly donated by Pharma Nord Aps. The funding organizations had no role in the design, management, analysis, interpretation of the data, preparation, review or approval of the manuscript.publishedVersio