Treating anxiety and depression in older adults: Randomised controlled trial comparing guided V. Self-guided internet-delivered cognitive-behavioural therapy

© 2016 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. Background Symptoms of anxiety and depression are prevalent in older adults. Aims To compare clinician-guided and self-guided versions of a transdiagnostic internet-delivered cognitive-behavioural therapy (iCBT) intervention for adults aged 60 years and above. Method Adults (n=433) with symptoms of anxiety and depression were randomly allocated to: (1) clinician-guided treatment (n=153); (2) initial clinician interview followed by self-guided treatment (n=140); or (3) self-guided treatment without interview (n=140). Results Large reductions (d ≥1.00) in symptoms of depression and anxiety were observed across groups, and sustained at follow-up. No differences were observed in clinical outcomes or satisfaction ratings. Age did not affect outcomes. Conclusions Carefully developed iCBT interventions may significantly reduce symptoms of anxiety and depression in older adults when delivered in either clinician-guided or self-guided formats

The pain course: A randomised controlled trial examining an internet-delivered pain management program when provided with different levels of clinician support

© 2015 International Association for the Study of Pain. The present study evaluated an internet-delivered pain management program, the Pain Course, when provided with different levels of clinician support. Participants (n5490) were randomised to 1 of 4 groups: (1) Regular Contact (n5143), (2) Optional Contact (n5 141), (3) No Contact (n 5 131), and (4) a treatment-As-usual Waitlist Control Group (n 5 75). The treatment program was based on the principles of cognitive behaviour therapy and comprised 5 internet-delivered lessons provided over 8 weeks. The 3 Treatment Groups reported significant improvements (between-group Cohen's d; avg. reduction) in disability (ds ≤ 0.50; avg. reduction ≤ 18%), anxiety (ds≤0.44; avg. reduction≤32%), depression (ds≤0.73; avg. reduction≤36%), and average pain (ds≤0.30; avg. reduction ≤ 12%) immediately posttreatment, which were sustained at or further improved to 3-month follow-up. High treatment completion rates and levels of satisfaction were reported, and no marked or consistent differences were observed between the Treatment Groups. The mean clinician time per participant was 67.69 minutes (SD533.50), 12.85 minutes (SD524.61), and 5.44 minutes (SD 5 12.38) for those receiving regular contact, the option of contact, and no clinical contact, respectively. These results highlight the very significant public health potential of carefully designed and administered internet-delivered pain management programs and indicate that these programs can be successfully administered with several levels of clinical support

User characteristics and outcomes from a national digital mental health service: an observational study of registrants of the Australian MindSpot Clinic.

Background:Interest is growing in digital and telehealth delivery of mental health services, but data are scarce on outcomes in routine care. The federally funded Australian MindSpot Clinic provides online and telephone psychological assessment and treatment services to Australian adults. We aimed to summarise demographic characteristics and treatment outcomes of patients registered with MindSpot over the first 7 years of clinic operation. Methods:We used an observational design to review all patients who registered for assessment with the MindSpot Clinic between Jan 1, 2013, and Dec 31, 2019. We descriptively analysed the demographics, service preferences, and baseline symptoms of patients. Among patients enrolled in a digital treatment course, we evaluated scales of depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder 7-Item Scale [GAD-7]), as primary measures of treatment outcome, from the screening assessment to post-treatment and a 3 month follow-up. The Kessler Psychological Distress 10-Item Plus Scale was also used to assess changes in general distress and disability, and course satisfaction was measured post-treatment. Outcomes:A total of 121 652 screening assessments were started, of which 96 018 (78·9%) were completed. The mean age of patients was 35·7 years (SD 13·8) and 88 702 (72·9%) were women. Based on available assessment data, 36 866 (34·5%) of 106 811 participants had never previously spoken to a health professional about their symptoms, and most people self-reported symptoms of anxiety (88 879 [81·9%] of 108 494) or depression (78 803 [72·6%] of 108 494), either alone or in combination, at baseline. 21 745 patients started treatment in a therapist-guided online course, of whom 14 503 (66·7%) completed treatment (≥four of five lessons). Key trends in service use included an increase in the proportion of people using MindSpot primarily for assessment and information, from 52·6% in 2013 to 66·7% in 2019, while the proportion primarily seeking online treatment decreased, from 42·6% in 2013 to 26·7% in 2019. Effect sizes and percentage changes were large for estimated mean scores on the PHQ-9 and GAD-7 from assessment to post-treatment (PHQ-9, Cohen's d effect size 1·40 [95% CI 1·37-1·43]; and GAD-7, 1·45 [1·42-1·47]) and the 3 month follow-up (PHQ-9, 1·36 [1·34-1·38]; and GAD-7, 1·42 [1·40-1·44]); proportions of patients with reliable symptom deterioration (score increase of ≥6 points [PHQ-9] or ≥5 points [GAD-7]) were low post-treatment (of 13 058 respondents, 184 [1·4%] had symptom deterioration on the PHQ-9 and 282 [2·2%] on the GAD-7); and patient satisfaction rates were high (12 452 [96·6%] of 12 895 respondents would recommend the course and 12 433 [96·7%] of 12 860 reported the course worthwhile). We also observed small improvements in disability following treatment as measured by days out of role. Interpretation:Our findings indicate improvement in psychological symptoms and positive reception among patients receiving online mental health treatment. These results support the addition of digital services such as MindSpot as a component in contemporary national mental health systems. Funding:None

Predicting Progression of IgA Nephropathy: New Clinical Progression Risk Score

IgA nephropathy (IgAN) is a common cause of end-stage renal disease (ESRD) in Asia. In this study, based on a large cohort of Chinese patients with IgAN, we aim to identify independent predictive factors associated with disease progression to ESRD. We collected retrospective clinical data and renal outcomes on 619 biopsy-diagnosed IgAN patients with a mean follow-up time of 41.3 months. In total, 67 individuals reached the study endpoint defined by occurrence of ESRD necessitating renal replacement therapy. In the fully adjusted Cox proportional hazards model, there were four baseline variables with a significant independent effect on the risk of ESRD. These included: eGFR [HR = 0.96(0.95–0.97)], serum albumin [HR = 0.47(0.32–0.68)], hemoglobin [HR = 0.79(0.72–0.88)], and SBP [HR = 1.02(1.00–1.03)]. Based on these observations, we developed a 4-variable equation of a clinical risk score for disease progression. Our risk score explained nearly 22% of the total variance in the primary outcome. Survival ROC curves revealed that the risk score provided improved prediction of ESRD at 24th, 60th and 120th month of follow-up compared to the three previously proposed risk scores. In summary, our data indicate that IgAN patients with higher systolic blood pressure, lower eGFR, hemoglobin, and albumin levels at baseline are at a greatest risk of progression to ESRD. The new progression risk score calculated based on these four baseline variables offers a simple clinical tool for risk stratification

Behavioral and Endocrine Consequences of Simultaneous Exposure to Two Different Stressors in Rats: Interaction or Independence?

Although behavioral and endocrine consequences of acute exposure to stressors have been extensively studied, little is known about how simultaneous exposure to two different stressors interacts to induce short- and long-term effects. In the present experiment we studied this interaction in adult male rats exposed to cat fur odor (impregnated cloth) or immobilization on boards either separately or simultaneously. We reasoned that exposure to the odor of a potential predator while immobilized, may potentiate its negative consequences as compared to exposure to only one of the stressors. Exposure to cat odor elicited the expected reduction of activity and avoidance of the area where the impregnated cloth was located. The endocrine response (plasma levels of ACTH and corticosterone, as a measure of the hypothalamic-pituitary-adrenal axis, HPA) was markedly greater after immobilization than after cat fur odor and no additive effects were found by simultaneous exposure to both stressors. Cat odor, but not immobilization, increased anxiety-like behavior as evaluated in the elevated plus-maze 7 days after the stressors, with no evidence of enhanced HPA activation. In addition, cat odor exposure resulted in long-lasting (8 days later) fear conditioning to the box containing a clean cloth, which was reflected by hypoactivity, avoidance of the cloth area and enhanced HPA activation. All these effects were similarly observed in rats exposed simultaneously to cat odor and immobilization. In rats only exposed to immobilization, only some weak behavioral signs of fear conditioning were found, but HPA activation in response to the context paired to immobilization was enhanced to the same extent as in cat odor-exposed animals, supporting a certain degree of endocrine conditioning. The present results did not reveal important behavioral interactions between the two stressors when animals experienced both simultaneously, whereas some interactions were found regarding HPA activation. Theoretical implications are discussed

Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge

<p>Abstract</p> <p>Background</p> <p>There is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown.</p> <p>Methods</p> <p>To address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation.</p> <p>Results</p> <p>Adolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors.</p> <p>Conclusion</p> <p>Our results demonstrate that predatory stress, an ethologically relevant stressor, can elicit changes in neuroinflammation and behavior. The predatory stress model may be useful in elucidating mechanisms by which psychological stress modulates diseases with an inflammatory component.</p

The Distribution of Toxoplasma gondii Cysts in the Brain of a Mouse with Latent Toxoplasmosis: Implications for the Behavioral Manipulation Hypothesis

reportedly manipulates rodent behavior to enhance the likelihood of transmission to its definitive cat host. The proximate mechanisms underlying this adaptive manipulation remain largely unclear, though a growing body of evidence suggests that the parasite-entrained dysregulation of dopamine metabolism plays a central role. Paradoxically, the distribution of the parasite in the brain has received only scant attention. at six months of age and examined 18 weeks later. The cysts were distributed throughout the brain and selective tropism of the parasite toward a particular functional system was not observed. Importantly, the cysts were not preferentially associated with the dopaminergic system and absent from the hypothalamic defensive system. The striking interindividual differences in the total parasite load and cyst distribution indicate a probabilistic nature of brain infestation. Still, some brain regions were consistently more infected than others. These included the olfactory bulb, the entorhinal, somatosensory, motor and orbital, frontal association and visual cortices, and, importantly, the hippocampus and the amygdala. By contrast, a consistently low incidence of tissue cysts was recorded in the cerebellum, the pontine nuclei, the caudate putamen and virtually all compact masses of myelinated axons. Numerous perivascular and leptomeningeal infiltrations of inflammatory cells were observed, but they were not associated with intracellular cysts. distribution stems from uneven brain colonization during acute infection and explains numerous behavioral abnormalities observed in the chronically infected rodents. Thus, the parasite can effectively change behavioral phenotype of infected hosts despite the absence of well targeted tropism

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

The Pain Course: 12- and 24-Month Outcomes From a Randomized Controlled Trial of an Internet-Delivered Pain Management Program Provided With Different Levels of Clinician Support

© 2018 the American Pain Society Little is known about the long-term outcomes of emerging Internet-delivered pain management programs. The current study reports the 12- and 24-month follow-up data from a randomized controlled trial (n = 490) of an Internet-delivered pain management program, the Pain Course. The initial results of the trial to the 3-month follow-up have been reported elsewhere. There were significant improvements in disability, depression, anxiety, and pain levels across 3 treatment groups receiving different levels of clinician support compared with a treatment as the usual control. No marked or significant differences were found between the treatment groups either after treatment or at the 3-month follow-up. The current study obtained long-term follow-up data from 78% and 79% of participants (n = 397) at the 12-month and 24-month follow-up marks, respectively. Clinically significant decreases (average percent reduction; Cohen's d effect sizes) were maintained at the 12- and 24-month follow-ups for disability (average reduction ≥27%; d ≥.67), depression (average reduction ≥36%; d ≥.80), anxiety (average reduction ≥38%; d ≥.66), and average pain levels (average reduction ≥21%; d ≥.67). No marked or consistent differences were found among the 3 treatment groups. These findings suggest that the outcomes of Internet-delivered programs may be maintained over the long term. Perspective: This article presents the long-term outcome data of an established Internet-delivered pain management program for adults with chronic pain. The clinical improvements observed during the program were found to be maintained at the 12- and 24-month follow-up marks. This finding indicates that these programs can have lasting clinical effects

The pain course: a randomised controlled trial comparing a remote-delivered chronic pain management program when provided in online and workbook formats.

This study compared a remote-delivered pain management program, the Pain Course, when delivered in online and workbook formats. Participants (n = 178) were randomised into 2 groups: (1) an Internet Group (n = 84) who were provided with secure accounts to the program in an online format; or (2) a Workbook Group (n = 94) who were mailed workbook versions of the program. The content of both programs was identical and comprised 5 core lessons, which participants were encouraged to work through over an 8-week period, according to a prescribed timetable. All participants were provided with weekly contact with a clinical psychologist through email and telephone throughout the program. The overall findings suggest that the workbook format was no less effective or acceptable than the validated online format. Significant improvements (avg. improvement; Internet Group vs Workbook Group) in levels of disability (PDI: 16% vs 24%; RMDQ: 12% vs 15%), anxiety (GAD-7: 36% vs 26%), and depression (PHQ-9: 36% vs 36%) were observed in both groups immediately posttreatment. Further improvements were observed in disability levels to 3-month follow-up, and improvements across the other primary outcomes were maintained until 12-month follow-up. High treatment completion rates and levels of satisfaction were reported in both groups, and both groups required a similarly small amount of clinician contact per participant (M = 74.85 minutes; SD = 41.03). These results highlight the public health potential of remote-delivered pain management programs, delivered in either workbook or online formats, as methods of increasing access to pain management