Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer's disease.

BACKGROUND: Brain innate immune activation is associated with Alzheimer's disease (AD), but degrees of activation may vary between disease stages. Thus, brain innate immune activation must be assessed in longitudinal clinical studies that include biomarker negative healthy controls and cases with established AD pathology. Here, we employ longitudinally sampled cerebrospinal fluid (CSF) core AD, immune activation and glial biomarkers to investigate early (predementia stage) innate immune activation levels and biomarker profiles. METHODS: We included non-demented cases from a longitudinal observational cohort study, with CSF samples available at baseline (n = 535) and follow-up (n = 213), between 1 and 6 years from baseline (mean 2.8 years). We measured Aß42/40 ratio, p-tau181, and total-tau to determine Ab (A+), tau-tangle pathology (T+), and neurodegeneration (N+), respectively. We classified individuals into these groups: A-/T-/N-, A+/T-/N-, A+/T+ or N+, or A-/T+ or N+. Using linear and mixed linear regression, we compared levels of CSF sTREM2, YKL-40, clusterin, fractalkine, MCP-1, IL-6, IL-1, IL-18, and IFN-γ both cross-sectionally and longitudinally between groups. A post hoc analysis was also performed to assess biomarker differences between cognitively healthy and impaired individuals in the A+/T+ or N+ group. RESULTS: Cross-sectionally, CSF sTREM2, YKL-40, clusterin and fractalkine were higher only in groups with tau pathology, independent of amyloidosis (p < 0.001, A+/T+ or N+ and A-/T+ or N+, compared to A-/T-/N-). No significant group differences were observed for the cytokines CSF MCP-1, IL-6, IL-10, IL18 or IFN-γ. Longitudinally, CSF YKL-40, fractalkine and IFN-γ were all significantly lower in stable A+/T-/N- cases (all p < 0.05). CSF sTREM2, YKL-40, clusterin, fractalkine (p < 0.001) and MCP-1 (p < 0.05) were all higher in T or N+, with or without amyloidosis at baseline, but remained stable over time. High CSF sTREM2 was associated with preserved cognitive function within the A+/T+ or N+ group, relative to the cognitively impaired with the same A/T/N biomarker profile (p < 0.01). CONCLUSIONS: Immune hypoactivation and reduced neuron-microglia communication are observed in isolated amyloidosis while activation and increased fractalkine accompanies tau pathology in predementia AD. Glial hypo- and hyperactivation through the predementia AD continuum suggests altered glial interaction with Ab and tau pathology, and may necessitate differential treatments, depending on the stage and patient-specific activation patterns.

Reduction in manual asymmetry and decline in fine manual dexterity in right-handed older adults with mild cognitive impairment.

Research in Parkinson's or Alzheimer's disease suggests that hand function is affected by neurodegenerative diseases. However, little is known about the relationship between hand function and mild cognitive impairment (MCI). Therefore, we conducted a kinematic analysis of unimanual hand movements in MCI patients to answer whether manual asymmetries and manual dexterity are affected or preserved in this condition. Forty-one MCI patients and fifty healthy controls were tested with the Purdue Pegboard test. All participants were right-handed. Kinematic analyses (by hand) were calculated for path length, angle, and linear and angular velocities during reaching, grasping, transport and inserting. Group differences were tested by with factorial MANOVAs and laterality indexes (LI) were assessed. Groups were compared on "Right-Left" hand correlations to identify kinematics that best single-out patients. Kinematics from grasping and inserting were significantly more deteriorated in the MCI group, while outcomes for reaching and transport denoted superior performance. LIs data showed symmetry of movements in the MCI group, during reaching and transport. Comparisons of "Right-Left" hand correlations revealed that kinematics in reaching and transport were more symmetrical in patients. This study showed a deterioration of fine manual dexterity, an enhancement in gross dexterity of upper-limbs, and symmetrical movements in MCI patients.

What does hand motor function tell us about our aging brain in association with WMH?

BACKGROUND: White matter hyperintensities (WMH) are a common cerebral finding in older people. WMH are usually asymptomatic, but excessive WMH are associated with cognitive decline and dementia. WMH are also among the neurological findings most consistently associated with declining motor performance in healthy ageing. AIMS: To determine if WMH load is associated with simple and complex motor movements in dominant and non-dominant hands in cognitively intact older subjects. METHODS: Hand motor performance was assessed with the Purdue Pegboard and Finger-tapping tests on 44 healthy right-handed participants, mean age 70.9 years (range 59-84 years). Participants also underwent magnetic resonance (MR) imaging, which were used to quantify WMH volume. The effect of WMH on the motor parameters was assessed via mediation analyses. RESULTS: WMH load increased significantly with age, while the motor scores decreased significantly with age. WMH load mediated only the relationship between age and left-hand pegboard scores. DISCUSSION: WMH mediated only the more complex Purdue Pegboard task for the non-dominant hand. This is likely because complex movements in the non-dominant hand recruit a larger cerebral network, which is more vulnerable to WMH. CONCLUSIONS: Complex hand movements in the non-dominant hand are mediated by WMH. Subtle loss of motor movements of non-dominant hand might predict future excessive white matter atrophy.

Glial activation and inflammation along the Alzheimer's disease continuum.

BACKGROUND: Neuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer's disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD continuum, to reveal putative protective or harmful stage-dependent patterns of activation. METHODS: We included healthy controls (n = 36) and Aß-positive (Aß+) cases (as defined by pathological CSF amyloid beta 1-42 (Aß42)) with either subjective cognitive decline (SCD, n = 19), mild cognitive impairment (MCI, n = 39), or AD dementia (n = 27). The following CSF markers were measured: a microglial activation marker-soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a marker of microglial inflammatory reaction-monocyte chemoattractant protein-1 (MCP-1), two astroglial activation markers-chitinase-3-like protein 1 (YKL-40) and clusterin, a neuron-microglia communication marker-fractalkine, and the CSF AD biomarkers (Aß42, phosphorylated tau (P-tau), total tau (T-tau)). Using ANOVA with planned comparisons, or Kruskal-Wallis tests with Dunn's pairwise comparisons, CSF levels were compared between clinical groups and between stages of biomarker severity using CSF biomarkers for classification based on amyloid pathology (A), tau pathology (T), and neurodegeneration (N) giving rise to the A/T/N score. RESULTS: Compared to healthy controls, sTREM2 was increased in SCD (p < .01), MCI (p < .05), and AD dementia cases (p < .001) and increased in AD dementia compared to MCI cases (p < .05). MCP-1 was increased in MCI (p < .05) and AD dementia compared to both healthy controls (p < .001) and SCD cases (p < .01). YKL-40 was increased in dementia compared to healthy controls (p < .01) and MCI (p < .05). All of the CSF activation markers were increased in subjects with pathological CSF T-tau (A+T-N+ and A+T+N+), compared to subjects without neurodegeneration (A-T-N- and A+T-N-). DISCUSSION: Microglial activation as indicated by increased sTREM2 is present already at the preclinical SCD stage; increased MCP-1 and astroglial activation markers (YKL-40 and clusterin) were noted only at the MCI and AD dementia stages, respectively, and in Aß+ cases (A+) with pathological T-tau (N+). Possible different effects of early and later glial activation need to be explored.

Coping, thought suppression, and perceived stress in currently depressed, previously depressed, and never depressed individuals.

BACKGROUND: Previous research shows that depression is associated with an increase in stressful life events and perceived stress as well as dysfunctional ways of coping with stress. However, knowledge about coping in previously depressed individuals is scant. METHODS: This study compared perceived stress, coping, and thought suppression in a sample of 30 currently depressed, 63 previously depressed, and 42 never depressed individuals. RESULTS: Analysis of variance revealed that previously depressed individuals showed less wishful thinking and thought suppression than the currently depressed individuals, but scored significantly higher on these strategies than the never depressed individuals. However, the group differences became nonsignificant when controlling for perceived stress and intrusions. CONCLUSIONS: This study shows that both current depression and previous depression is related to avoidant coping (wishful thinking and thought suppression). However, these associations might be explained by the higher level of perceived stress among individuals with current or previous depression.

Metacognitions and Mindful Attention Awareness in Depression: A Comparison Of Currently Depressed, Previously Depressed and Never Depressed Individuals.

The primary aim of the study was to test (1) how metacognition relates to the concept of mindful attention awareness, and (2) whether metacognitions or mindful attention awareness best predicted symptoms of depression. Data was collected from three samples: currently depressed (n = 37), previously depressed (n = 81) and never depressed controls (n = 50). There was a moderate correlation between mindful attention awareness and three of five metacognitive subscales. Both mindful attention awareness and metacognition were significantly correlated with depression severity scores after controlling for anxiety. The depressed group had significantly more dysfunctional metacognitions and less mindful attention awareness than the never depressed group. Negative beliefs about worry and mindful attention awareness were also significantly different in the previously depressed group compared with the never depressed. This suggests that metacognitions and mindful attention awareness can be vulnerability factors for depression. The results also indicated that anxiety symptoms and negative beliefs about worry were the most important factors in predicting depression. In conclusion, the study shows that metacognitions and mindful attention awareness are two related but separate constructs and that metacognitions emerged as the best predictor of depression. These results provide support for the metacognitive model of emotional disorders. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Metacognitions and mindful attention awareness are related but separate constructs Both mindful attention awareness and metacognition are associated with depression Anxiety and negative beliefs about worry (metacognitions) are most important in predicting depression Addressing metacognitions in therapy should be considered in treatment of depression.

Outcome prediction in chronic unilateral lumbar radiculopathy: prospective cohort study.

BACKGROUND: Identification of prognostic factors for persistent pain and disability are important for better understanding of the clinical course of chronic unilateral lumbar radiculopathy and to assist clinical decision-making. There is a lack of scientific evidence concerning prognostic factors. The aim of this study was to identify clinically relevant predictors for outcome at 52 weeks. METHODS: 116 patients were included in a sham controlled clinical trial on epidural injection of glucocorticoids in patients with chronic unilateral lumbar radiculopathy. Success at follow-up was ≤ 17.5 for visual analogue scale (VAS) leg pain, ≤ 22.5 for VAS back pain and ≤ 20 for Oswestry Disability Index (ODI). Fifteen clinically relevant variables included demographic, psychosocial, clinical and radiological data and were analysed using a logistic multivariable regression analysis. RESULTS: At follow-up, 75 (64.7%) patients had reached a successful outcome with an ODI score ≤ 20, 54 (46.6%) with a VAS leg pain score ≤ 17.5, and 47 (40.5%) with a VAS back pain score ≤ 22.5. Lower age (OR 0.94 (CI 0.89-0.99) for each year decrease in age) and FABQ Work ≥ 34 (OR 0.16 (CI 0.04-0.61)) were independent variables predicting a successful outcome on the ODI. Higher education (OR 5.77 (CI 1.46-22.87)) and working full-time (OR 2.70 (CI 1.02-7.18)) were statistically significant (P <0.05) independent predictors for successful outcome (VAS score ≤ 17.5) on the measure of leg pain. Lower age predicted success on ODI (OR 0.94 (95% CI 0.89 to 0.99) for each year) and less back pain (OR 0.94 (0.90 to 0.99)), while higher education (OR 5.77 (1.46 to 22.87)), working full-time (OR 2.70 (1.02 to 7.18)) and muscle weakness at baseline (OR 4.11 (1.24 to 13.61) predicted less leg pain, and reflex impairment at baseline predicted the contrary (OR 0.39 (0.15 to 0.97)). CONCLUSIONS: Lower age, higher education, working full-time and low fear avoidance beliefs each predict a better outcome of chronic unilateral lumbar radiculopathy. Specifically, lower age and low fear avoidance predict a better functional outcome and less back pain, while higher education and working full-time predict less leg pain. These results should be validated in further studies before being used to inform patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12574253 . Registered 18 May 2005.

Predictors of Response to Web-Based Cognitive Behavioral Therapy With High-Intensity Face-to-Face Therapist Guidance for Depression: A Bayesian Analysis.

BACKGROUND: Several studies have demonstrated the effect of guided Internet-based cognitive behavioral therapy (ICBT) for depression. However, ICBT is not suitable for all depressed patients and there is a considerable level of nonresponse. Research on predictors and moderators of outcome in ICBT is inconclusive. OBJECTIVE: This paper explored predictors of response to an intervention combining the Web-based program MoodGYM and face-to-face therapist guidance in a sample of primary care patients with mild to moderate depressive symptoms. METHODS: Participants (N=106) aged between 18 and 65 years were recruited from primary care and randomly allocated to a treatment condition or to a delayed treatment condition. The intervention included the Norwegian version of the MoodGYM program, face-to-face guidance from a psychologist, and reminder emails. In this paper, data from the treatment phase of the 2 groups was merged to increase the sample size (n=82). Outcome was improvement in depressive symptoms during treatment as assessed with the Beck Depression Inventory-II (BDI-II). Predictors included demographic variables, severity variables (eg, number of depressive episodes and pretreatment depression and anxiety severity), cognitive variables (eg, dysfunctional thinking), module completion, and treatment expectancy and motivation. Using Bayesian analysis, predictors of response were explored with a latent-class approach and by analyzing whether predictors affected the slope of response. RESULTS: A 2-class model distinguished well between responders (74%, 61/82) and nonresponders (26%, 21/82). Our results indicate that having had more depressive episodes, being married or cohabiting, and scoring higher on a measure of life satisfaction had high odds for positively affecting the probability of response. Higher levels of dysfunctional thinking had high odds for a negative effect on the probability of responding. Prediction of the slope of response yielded largely similar results. Bayes factors indicated substantial evidence that being married or cohabiting predicted a more positive treatment response. The effects of life satisfaction and number of depressive episodes were more uncertain. There was substantial evidence that several variables were unrelated to treatment response, including gender, age, and pretreatment symptoms of depression and anxiety. CONCLUSIONS: Treatment response to ICBT with face-to-face guidance may be comparable across varying levels of depressive severity and irrespective of the presence and severity of comorbid anxiety. Being married or cohabiting, reporting higher life satisfaction, and having had more depressive episodes may predict a more favorable response, whereas higher levels of dysfunctional thinking may be a predictor of poorer response. More studies exploring predictors and moderators of Internet-based treatments are needed to inform for whom this treatment is most effective. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry number: ACTRN12610000257066; https://www.anzctr.org.au/trial_view.aspx?id=335255 (Archived by WebCite at http://www.webcitation.org/6GR48iZH4).

Uptake and adherence of a self-directed internet-based mental health intervention with tailored e-mail reminders in senior high schools in Norway.

BACKGROUND: Internet-based cognitive behavioural therapy (ICBT) is a promising approach to the prevention and reduction of depressive symptoms among adolescents. This study aimed to evaluate the feasibility and efficacy of disseminating a self-directed internet-based mental health intervention (MoodGYM) in senior high schools. It also sought to investigate possible effects of tailored and weekly e-mail reminders on initial uptake and adherence to the intervention. METHOD: A baseline survey was conducted in four senior high schools in two Norwegian municipalities (n = 1337). 52.8% (707/1337) of the students consented to further participation in the trial and were randomly allocated to one of three MoodGYM intervention groups (tailored weekly e-mail reminder (n = 175), standardized weekly e-mail reminder (n = 176 ) or no e-mail reminder (n = 175)) or a waitlist control group (n = 180). We tested for effects of the intervention on depression and self-esteem using multivariate analysis of variance, effects of tailored e-mail and self-reported current need of help on initial uptake of the intervention using logistic regression and the effect of weekly e-mails on adherence using ordinal regression. RESULTS: There was substantial non-participation from the intervention, with only 8.5% (45/527) participants logging on to MoodGYM, and few proceeding beyond the first part of the programme. No significant effect on depression or self-esteem was found among the sample as a whole or among participants with elevated depression scores at baseline. Having a higher average grade in senior high school predicted initial uptake of the intervention, but tailored e-mail and self-reported current need of help did not. Weekly e-mail prompts did not predict adherence. The main reasons for non-use reported were lack of time/forgetting about it and doubt about the usefulness of the program. CONCLUSION: Overall, disseminating a self-directed internet-based intervention to a school population proved difficult despite steps taken to reduce barriers in terms of tailoring feedback and dispatching weekly e-mail reminders. Providing mental health interventions within the school environment is likely to ensure better uptake among senior high school students, but there is a need to effectively communicate that such programmes can be helpful. TRIAL REGISTRATION: The trial was registered retrospectively as ACTRN12612001106820.

Norwegian general practitioners' perspectives on implementation of a guided web-based cognitive behavioral therapy for depression: a qualitative study.

BACKGROUND: Previous research suggests that Internet-based cognitive behavioral therapy (ICBT) has a positive effect on symptoms of depression. ICBT appears to be more effective with therapist support, but it is unclear what this support should comprise. General practitioners (GPs) have positive attitudes toward ICBT. However, ICBT is rarely used in regular care in general practice. More research is warranted to integrate the potential of ICBT as part of regular care. OBJECTIVE: The aim of this study was to explore aspects perceived by GPs to affect the implementation of guided ICBT in daily practice. Understanding their perspectives may contribute to improving the treatment of depression in the context of general practice. METHODS: A training package (3-day course) introducing a Norwegian translation of the ICBT program MoodGYM was developed and presented to GPs in Norway. Following training, GPs were asked to include guided ICBT in their regular care of patients with symptoms of depression by providing brief, face-to-face follow-up consultations between modules. We interviewed 11 GPs who had taken the course. Our interview guide comprised open questions that encouraged GPs to frame their responses using examples from their experiences when implementing ICBT. Thematic analysis was chosen to explore patterns across the data. RESULTS: An overall belief that ICBT would benefit both the patients' health and the GPs' own work satisfaction prompted the GPs to take the ICBT course. ICBT motivated them to invest time and effort in improving treatment. The most important motivating aspects in MoodGYM were that a program based on cognitive behavioral therapy could add a structured agenda to their consultations and empower depressed patients. Organizational aspects, such as a lack of time and varied practice, inhibited the use of ICBT. Inadequate knowledge, recalling the program, and changing own habits were also challenging. The GPs were ambivalent about whether ICBT had a negative impact on the doctor-patient interaction in the module follow-ups. Generally, GPs made an effort to recommend MoodGYM, but the expected module follow-ups were often not provided to patients and instead the GPs returned to standard treatment. CONCLUSIONS: GPs' feedback in the present study contribute to our understanding of the challenges of changing treatment for depression. Our findings indicated that recommending ICBT could add to the GP's toolkit. Offering training and highlighting the following aspects may increase recommendation of ICBT by GPs: (1) ICBT is theory-based and credible, (2) ICBT increases the GPs' work satisfaction by having a tool to offer, and (3) ICBT facilitates empowerment of patients in their own health. In addition, the present study also indicated that complex aspects must be accommodated before module follow-ups can be incorporated into GPs' treatment of depression.

A study of the psychometric properties of the Beck Depression Inventory-II, the Montgomery and Åsberg Depression Rating Scale, and the Hospital Anxiety and Depression Scale in a sample from a healthy population.

The objective of this study is to evaluate internal consistency and psychometric properties of the Hospital Anxiety and Depression Scale (HADS), the Beck Depression inventory-II (BDI-II) and the Montgomery and Åsberg Depression Rating Scale (MADRS) for screening for major depressive episode (MDE) in a selected sample from a healthy population. Participants answered the BDI-II and the HADS questionnaires and were interviewed with MADRS. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I Disorders-Clinician Version (SCID-CV) was used to diagnose MDE. Current MDE was diagnosed in 20 (6%) of the 357 participants. All three scales including the depression sub-scale for HADS had high area under the receiver operating characteristics curve (ROC) (AUC) (0.84-0.87), and internal consistency was also high for all scales (0.75-0.89). Optimal cut-off for MDE was ≥ 12 for BDI-II, MADRS ≥ 8, HADS total ≥ 9, and HADS-D ≥ 4, which all resulted in sensitivities = 85% and specificities > 78%. Diagnostic accuracy was low on all depression scales (Cohen's kappa = 0.20-0.40). Reports of the properties of depression scales in a healthy population are limited. We found BDI-II, HADS and MADRS to be acceptable as screening instruments for MDE in a selected sample from healthy population with recommend cut-offs as mentioned above.

Depressive Symptoms Are Not Associated with Predementia Cerebrospinal Fluid Amyloid Pathology.

Introduction: Depressive symptoms are associated with Alzheimer's disease (AD), but their neurobiological and neuropsychological correlates remain poorly understood. We investigate if depressive symptoms are associated with amyloid (Aß) pathology and cognition in predementia AD. Methods: We included subjective cognitive decline (SCD, n = 160) and mild cognitive impairment (MCI, n = 192) from the dementia disease initiation cohort. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15). Aß pathology was determined using cerebrospinal fluid (CSF) Aß42/40 ratio. Associations between depressive symptoms and cognition were assessed with logistic regression. Results: Only the Aß negative MCI group (MCI-Aß-) was associated with depressive symptoms (odds ratio [OR] = 2.65, p = 0.005). Depressive symptoms were associated with worse memory in MCI-Aß- (OR = 0.94, p = 0.039), but with better performance in MCI-Aß+ (OR = 1.103, p = 0.001). Conclusion: Our results suggest that depressive symptoms in MCI are neither associated with Aß pathology, nor AD-associated memory impairment. However, memory impairment in non-AD MCI may relate to depressive symptoms.

Age-adjusted CSF t-tau and NfL do not improve diagnostic accuracy for prodromal Alzheimer's disease.

Cerebrospinal fluid total-tau (t-tau) and neurofilament light chain (NfL) are biomarkers of neurodegeneration and are increased in Alzheimer's disease (AD). In order to adjust for age-related increases in t-tau and NfL, cross-sectional age-adjusted norms were developed based on amyloid negative cognitively normal (CN) adults aged 41-78 years (CN, n = 137). The age-adjusted norms for t-tau and NfL did not improve receiver operating curve based diagnostic accuracies in individuals with mild cognitive impairment (MCI) due to AD (AD-MCI, n = 144). Furthermore, while NfL was correlated with higher age in AD-MCI, no significant correlation was found for t-tau. The cox proportional hazard models, applied in 429 participants with baseline t-tau and NfL, showed higher hazard ratio of progression to MCI or dementia without age-adjustments (HR = 3.39 for t-tau and HR = 3.17 for NfL), as compared to using our norms (HR = 2.29 for t-tau and HR = 1.89 for NfL). Our results indicate that utilizing normative reference data could obscure significant age-related increases in these markers associated with neurodegeneration and AD leading to a potential loss of overall diagnostic accuracy.

Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer's disease.

Staging amyloid-beta (Aß) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer's disease (AD). In blood, phosphorylated tau (p-tau) associates with Aß pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n = 1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aß ("A") and neurodegeneration ("N") abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aß-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aß therapies.

Motivation to persist with internet-based cognitive behavioural treatment using blended care: a qualitative study.

BACKGROUND: The prevalence of depression is high and results in huge costs for society. Internet-based cognitive behavioural treatment (ICBT) has been suggested for use in primary care and has been shown to be more effective when combined with human support. However, non-completion rates remain a challenge. Current recommendations state that steps to improve persistence with ICBT should be determined and the impact of therapist support on persistence explored. A few earlier studies have explored motivations to persist with ICBT without face-to-face therapist support. The present study explored the motivation to persist as experienced by a group of patients who sought help in primary care and used "blended care", i.e. ICBT supported by short face-to-face consultations. METHODS: To elucidate motivation in an everyday context and the meaning of patients' experiences we chose a phenomenological hermeneutical approach. We interviewed participants in the intervention group of a randomized controlled trial that evaluated the efficacy of an ICBT programme called MoodGYM, an eHealth intervention used to treat depression. Fourteen participants, both completers and non-completers, went through individual, semi-structured interviews after they ended their treatment. RESULTS: Hope of recovery and a desire to gain control of one's life were identified as intrinsic motivators. The feeling of being able to freely choose how, when and where to complete the ICBT modules was identified as an important supporting condition and satisfied the participants' need for autonomy. Furthermore, the importance of a sense of belonging towards partners, friends or family was essential for motivation as was the ability to identify with ICBT content. Another supporting condition was the experience of connectedness when met with acknowledgement, flexibility and feedback from a qualified therapist in the face-to-face consultations. CONCLUSIONS: A key finding was that participants were motivated to persist with ICBT when their overall need for relatedness was satisfied. This was achieved through a sense of belonging towards partners, friends and family. Connectedness with the therapist and the participant's ability to identify with the ICBT modules also gave a sense of relatedness. Improving these motivational aspects may increase patients' persistence with ICBT.

The Norwegian Junior Temperament and Character Inventory (JTCI): an assessment of its psychometric properties.

The role of adolescent personality concerning mental health, well-being, self development, and academic performance is an interesting aspect that needs more attention. The use of the JTCI (Junior Temperament and Character Inventory) can contribute to more knowledge and a better understanding of a possible influence of personality in this context. The aim of this study was to assess the psychometric properties of the Norwegian version of the JTCI among an adolescent sample in terms of factor analysis, reliability and validity. The sample included 2075 subjects in the age from 15-18years. We analyzed the factor structure, internal consistency, and validity of the measure. The Norwegian version of the JTCI was found to have good psychometric properties in terms of internal consistency, a reasonable factor structure and significant correlations with depression, self-esteem, and self-efficacy. However, further research on its differentiation of Harm Avoidance and Self-directedness is needed. The JTCI appears as a useful tool in addressing issues ranging from scholastic performance to developmental issues, mental health and well-being.

Accuracy of physical examination for chronic lumbar radiculopathy.

BACKGROUND: Clinical examination of patients with chronic lumbar radiculopathy aims to clarify whether there is nerve root impingement. The aims of this study were to investigate the association between findings at clinical examination and nerve root impingement, to evaluate the accuracy of clinical index tests in a specialised care setting, and to see whether imaging clarifies the cause of chronic radicular pain. METHODS: A total of 116 patients referred with symptoms of lumbar radiculopathy lasting more than 12 weeks and at least one positive index test were included. The tests were the straight leg raising test, and tests for motor muscle strength, dermatome sensory loss, and reflex impairment. Magnetic resonance imaging (n = 109) or computer tomography (n = 7) were imaging reference standards. Images were analysed at the level of single nerve root(s), and nerve root impingement was classified as present or absent. Sensitivities, specificities, and positive and negative likelihood ratios (LR) for detection of nerve root impingement were calculated for each individual index test. An overall clinical evaluation, concluding on the level and side of the radiculopathy, was performed. RESULTS: The prevalence of disc herniation was 77.8%. The diagnostic accuracy of individual index tests was low with no tests reaching positive LR >4.0 or negative LR <0.4. The overall clinical evaluation was slightly more accurate, with a positive LR of 6.28 (95% CI 1.06-37.21) for L4, 1.74 (95% CI 1.04-2.93) for L5, and 1.29 (95% CI 0.97-1.72) for S1 nerve root impingement. An overall clinical evaluation, concluding on the level and side of the radiculopathy was also performed, and receiver operating characteristic (ROC) analysis with area under the curve (AUC) calculation for diagnostic accuracy of this evaluation was performed. CONCLUSIONS: The accuracy of individual clinical index tests used to predict imaging findings of nerve root impingement in patients with chronic lumbar radiculopathy is low when applied in specialised care, but clinicians' overall evaluation improves diagnostic accuracy slightly. The tests are not very helpful in clarifying the cause of radicular pain, and are therefore inaccurate for guidance in the diagnostic workup of the patients. The study population was highly selected and therefore the results from this study should not be generalised to unselected patient populations in primary care nor to even more selected surgical populations.

Evaluating the translation process of an Internet-based self-help intervention for prevention of depression: a cost-effectiveness analysis.

BACKGROUND: Depression is common and treatable with cognitive behavior therapy (CBT), for example. However, access to this therapy is limited. Internet-based interventions have been found to be effective in reducing symptoms of depression. The International Society for Research on Internet Interventions has highlighted the importance of translating effective Internet programs into multiple languages to enable worldwide dissemination. OBJECTIVE: The aim of the current study was to determine if it would be cost effective to translate an existing English-language Internet-based intervention for use in a non-English-speaking country. METHODS: This paper reports an evaluation of a trial in which a research group in Norway translated two English-language Internet-based interventions into Norwegian (MoodGYM and BluePages) that had previously been shown to reduce symptoms of depression. The translation process and estimates of the cost-effectiveness of such a translation process is described. Estimated health effect was found by using quality-adjusted life years (QALY). RESULTS: Conservative estimates indicate that for every 1000 persons treated, 16 QALYs are gained. The investment is returned 9 times and the cost-effectiveness ratio (CER) is 3432. The costs of the translation project totaled to approximately 27% of the estimated original English-language version development costs. CONCLUSIONS: The economic analysis shows that the cost-effectiveness of the translation project was substantial. Hopefully, these results will encourage others to do similar analyses and report cost-effectiveness data in their research reports.

The clinical effectiveness of web-based cognitive behavioral therapy with face-to-face therapist support for depressed primary care patients: randomized controlled trial.

BACKGROUND: Most patients with mild to moderate depression receive treatment in primary care, but despite guideline recommendations, structured psychological interventions are infrequently delivered. Research supports the effectiveness of Internet-based treatment for depression; however, few trials have studied the effect of the MoodGYM program plus therapist support. The use of such interventions could improve the delivery of treatment in primary care. OBJECTIVE: To evaluate the effectiveness and acceptability of a guided Web-based intervention for mild to moderate depression, which could be suitable for implementation in general practice. METHODS: Participants (N=106) aged between 18 and 65 years were recruited from primary care and randomly allocated to a treatment condition comprising 6 weeks of therapist-assisted Web-based cognitive behavioral therapy (CBT), or to a 6-week delayed treatment condition. The intervention included the Norwegian version of the MoodGYM program, brief face-to-face support from a psychologist, and reminder emails. The primary outcome measure, depression symptoms, was measured by the Beck Depression Inventory-II (BDI-II). Secondary outcome measures included the Beck Anxiety Inventory (BAI), the Hospital Anxiety and Depression Scale (HADS), the Satisfaction with Life Scale (SWLS), and the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D). All outcomes were based on self-report and were assessed at baseline, postintervention, and at 6-month follow-up. RESULTS: Postintervention measures were completed by 37 (71%) and 47 (87%) of the 52 participants in the intervention and 54 participants in the delayed treatment group, respectively. Linear mixed-models analyses revealed a significant difference in time trends between the groups for the BDI-II, (P=.002), for HADS depression and anxiety subscales (P<.001 and P=.001, respectively), and for the SWLS (P<.001). No differential group effects were found for the BAI and the EQ-5D. In comparison to the control group, significantly more participants in the intervention group experienced recovery from depression as measured by the BDI-II. Of the 52 participants in the treatment program, 31 (60%) adhered to the program, and overall treatment satisfaction was high. The reduction of depression and anxiety symptoms was largely maintained at 6-month follow-up, and positive gains in life satisfaction were partly maintained. CONCLUSIONS: The intervention combining MoodGYM and brief therapist support can be an effective treatment of depression in a sample of primary care patients. The intervention alleviates depressive symptoms and has a significant positive effect on anxiety symptoms and satisfaction with life. Moderate rates of nonadherence and predominately positive evaluations of the treatment also indicate the acceptability of the intervention. The intervention could potentially be used in a stepped-care approach, but remains to be tested in regular primary health care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12610000257066; http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12610000257066 (Archived by WebCite at http://www.webcitation.org/6Ie3YhIZa).

Patients' experiences of helpfulness in guided internet-based treatment for depression: qualitative study of integrated therapeutic dimensions.

BACKGROUND: Quantitative research on Internet-based cognitive behavioral therapy (ICBT) has collected substantial evidence for the effectiveness of this treatment approach on health outcomes. Less is known about how patients find ICBT to be generally meaningful and helpful for treating depression. OBJECTIVE: To explore patients' experiences of being in ICBT treatment with a focus on the treatment dimensions that they considered helpful. METHODS: Choosing a phenomenological-hermeneutical approach, 14 patients were interviewed with semistructured qualitative interviews to elicit their understanding of using ICBT. The patients took part in a clinical trial using ICBT with MoodGYM, which also featured brief consultations with a clinical psychologist. The interviews were transcribed and analyzed according to the chosen methodology and organized into significant themes. RESULTS: The phenomenological-hermeneutical analysis identified 5 themes relating overall to the meaning of this mode of treatment in terms of helpfulness. Two related to treatment in general: (1) taking action to address one's problems and (2) the value of talking to a professional. The next two themes specifically addressed guided self-help using the MoodGYM program: (3) acquiring relevant knowledge, and (4) restructuring the new knowledge acquired through ICBT. A fifth theme concerned (5) actual changes in patients' perceptions and interactions, related to either the self-help material or the face-to-face consultations with the therapist. CONCLUSIONS: Three important dimensions were made explicit: the active engagement of the patient, the guidance of the therapist, and the content of the treatment program. The findings pointed to (1) the role of MoodGYM as a source of new knowledge providing patients with a structured approach to work with their depression, (2) the patient's role as the primary agent of change through adapting relevant knowledge from MoodGYM to their situation, and (3) the dialogue with the therapist as a trusting relationship in which to share thoughts and feelings, receive feedback and advice, and to assist the patient in making use of the MoodGYM content.