[CBT administered via the internet]. / Internetförmedlad psykologisk egenvård.

Cognitive behavioral therapy (CBT) can be administered clinically to individuals and in group settings. More recently, CBT has been administered successfully via the internet (ICBT). We provide a concept aiming at further developing ICBT in a self-care format. We use recent development in user interface (UI) design in order to optimize the user interface and allow easy and flexible use via smartphone, tablet, or computer. Preliminary evidence indicates that an optimized user interface and adjusted information facilitate increased use of training programs compared to a traditional ICBT interface. Our aims are to allow increased availability of evidence-based CBT tools for self-care to improve people's health and recovery from disease. So far, evidence for effects and safe use is indicated for atopic dermatitis, insomnia and high-risk use of alcohol.

Transforming guided internet interventions into simplified and self-guided digital tools - Experiences from three recent projects.

Introduction: Therapist-guided internet interventions are often more efficacious than unguided ones. However, the guidance itself requires clinician time, and some research suggests that self-guided interventions could potentially be equally effective. The concept of digital psychological self-care, self-guided internet interventions based on the use of digital tools and provided within a structured clinical process, is presented. Methods: Three new self-care interventions, a sleep diary-based intervention for insomnia, an alcohol diary-based intervention for problematic alcohol use and an intervention with exposure and mindfulness tools for atopic dermatitis (eczema), were developed. Newly developed digital self-care interventions were compared to the earlier therapist-guided interventions they were based on, using published results from three feasibility trials (n's = 30, 36 and 21) and three randomized trials (n's = 148, 166 and 102). The comparison included type of content, duration, length of written material and within-group effect-sizes. Results: In comparison to the guided interventions, clinician time was greatly reduced and the new interventions involved much less reading for participants. The digital self-care tools also showed within-group effect sizes and response rates on par with the more comprehensive guided internet interventions. Discussion: Preliminary results suggest that some guided internet interventions can be transformed into self-guided digital tools. These three examples show that digital psychological self-care, if provided with telephone interviews before and after the intervention, can be viable alternatives to more comprehensive guided internet interventions. Although these examples are promising, further studies, including randomized experiments, are needed to compare treatment efficacies, and to identify which groups of patients may need more comprehensive guided internet interventions.

Brief digital self-care intervention for health anxiety in a Swedish Medical University Clinic: a prospective single-group feasibility study.

OBJECTIVES: In routine psychiatric care in Stockholm, Sweden, a comprehensive therapist-guided intervention for clinically significant health anxiety is implemented. However, there is a need for more easily accessible self-care interventions to improve treatment dissemination. This study aimed to transform an existing therapist-guided digital intervention into a self-care intervention, reducing patient burden and used clinical resources while maintaining quality and safety. DESIGN: An uncontrolled feasibility study. SETTING: Conducted at Karolinska Institutet, a medical university in Sweden, with nationwide recruitment trough online advertisements. PARTICIPANTS: Twenty-five adults used the self-care intervention and underwent telephone assessments, along with completing self-rated questionnaires. INTERVENTION: The newly developed 8-week self-care intervention was designed to be user-friendly without therapist guidance, and to facilitate high levels of behavioural engagement. PRIMARY AND SECONDARY OUTCOME MEASURES: Indicators of quality and safety, including changes in health anxiety severity (primary), clinician time, participant adherence, perceived credibility/satisfaction with the intervention and adverse events, were benchmarked against a previous study of the more comprehensive intervention it was based on. RESULTS: Compared with the original guided intervention, the self-care intervention was condensed in terms of text (up to 70% less reading), duration (8 weeks instead of 12) and number of exercises. Quality indicators were similar to the original version. Most participants worked actively with core components in the self-care intervention. Within-group effects on health anxiety from pretreatment to the 3-month follow-up were large (g=1.37; 95% CI 0.74 to 2.00). No serious adverse events were reported. CONCLUSIONS: This brief digital self-care intervention shows potential for increasing access to treatment for individuals with health anxiety while reducing the burden on patients and clinical resources. Future studies should investigate the optimal type of intervention and support for different individuals, and if non-inferiority can be established. TRIAL REGISTRATION NUMBER: NCT05446766.

Swedish multimodal cohort of patients with anxiety or depression treated with internet-delivered psychotherapy (MULTI-PSYCH).

PURPOSE: Depression and anxiety afflict millions worldwide causing considerable disability. MULTI-PSYCH is a longitudinal cohort of genotyped and phenotyped individuals with depression or anxiety disorders who have undergone highly structured internet-based cognitive-behaviour therapy (ICBT). The overarching purpose of MULTI-PSYCH is to improve risk stratification, outcome prediction and secondary preventive interventions. MULTI-PSYCH is a precision medicine initiative that combines clinical, genetic and nationwide register data. PARTICIPANTS: MULTI-PSYCH includes 2668 clinically well-characterised adults with major depressive disorder (MDD) (n=1300), social anxiety disorder (n=640) or panic disorder (n=728) assessed before, during and after 12 weeks of ICBT at the internet psychiatry clinic in Stockholm, Sweden. All patients have been blood sampled and genotyped. Clinical and genetic data have been linked to several Swedish registers containing a wide range of variables from patient birth up to 10 years after the end of ICBT. These variable types include perinatal complications, school grades, psychiatric and somatic comorbidity, dispensed medications, medical interventions and diagnoses, healthcare and social benefits, demographics, income and more. Long-term follow-up data will be collected through 2029. FINDINGS TO DATE: Initial uses of MULTI-PSYCH include the discovery of an association between PRS for autism spectrum disorder and response to ICBT, the development of a machine learning model for baseline prediction of remission status after ICBT in MDD and data contributions to genome wide association studies for ICBT outcome. Other projects have been launched or are in the planning phase. FUTURE PLANS: The MULTI-PSYCH cohort provides a unique infrastructure to study not only predictors or short-term treatment outcomes, but also longer term medical and socioeconomic outcomes in patients treated with ICBT for depression or anxiety. MULTI-PSYCH is well positioned for research collaboration.

A Digital Self-help Intervention for Atopic Dermatitis: Analysis of Secondary Outcomes From a Feasibility Study.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease characterized by dry skin, eczematous lesions, and an often severe pruritus. The disease may have a negative effect on quality of life and is also associated with symptoms of anxiety and depression. Few individuals with AD receive any form of behavioral intervention. Behavioral interventions for AD are potentially efficacious but need to be constructed so that they are safe, credible, and user-friendly. We have previously reported on a feasibility study that demonstrated that a self-management version of a digital intervention based on cognitive behavioral therapy (CBT) for AD can potentially be effective in reducing AD symptoms. The aim of this secondary report was to further examine treatment feasibility and preliminary effects on dermatological quality of life, itching sensations, depressive symptoms, and perceived stress. OBJECTIVE: This is a secondary report on intervention credibility, usability, adverse events, and preliminary effects on secondary measures of a self-management digital intervention for atopic dermatitis. METHODS: In total, 21 adults with AD, recruited nationwide in Sweden, were assessed by telephone, and used the digital intervention for 8 weeks. Participants were also assessed directly afterward and 3 months after the end of the intervention. There was no therapist guidance. Feasibility indicators included intervention credibility, usability, and possible adverse effects. Other measures included preliminary effects on dermatological quality of life, itching sensations, depressive symptoms, and perceived stress. RESULTS: The intervention was regarded as credible and no serious adverse events were reported. System usability was, however, found to be below the predetermined cutoff for acceptable usability. Preliminary effects at 3-month follow-up were in the moderate to large range for dermatological quality of life (Cohen d=0.89, 95% CI 0.18-1.56), itching sensations (Cohen d=0.85, 95% CI 0.15-1.52), depressive symptoms (Cohen d=0.78, 95% CI 0.1-1.45), and perceived stress (Cohen d=0.75, 95% CI 0.01-1.36). CONCLUSIONS: This 8-week self-management digital CBT-based intervention was, together with telephone calls before and after, a feasible intervention for participants with AD. Preliminary effects were promising and should be explored further in a randomized controlled trial. Intervention usability was, however, rated below cutoff scores. Efforts should be made to improve written material to increase usability.

Internet delivered cognitive behavioral therapy for adults with ADHD - A randomized controlled trial.

Evidence-based psychological interventions for adults with attention deficit hyperactivity disorder (ADHD) are seldom available in clinical settings. Medication is often offered as the sole treatment, with non-optimal effects for a majority of patients. The objective was to compare internet-based cognitive behavioral therapy (iCBT) to an active control treatment of internet-based applied relaxation training (iART), and to treatment as usual only (TAU) in adult outpatients with ADHD. One hundred and four patients, of which 67 % used ADHD medication, were randomized to 12 weeks of iCBT (n = 36), iART (n = 37), or TAU (n = 31). Primary outcome was change in the Adult ADHD Self Report Scale (ASRS) up to 3 (FU3) and 12 months (FU12) after treatment. ASRS improved more for iCBT (p < .01; Cohen's d = 0.42 at post-treatment and 0.67 at FU3) and iART (p < .01; Cohen's d = 0.57 at post-treatment and 0.66 at FU3) than for TAU. The effects sustained over 12 months for iCBT (p < .001) and iART (p < .001). No significant difference was found when comparing iCBT to iART (p = .53). Treatment responders reached 25 % for both treatments, which was superior to the 3 % responders in TAU (p < .05). iCBT and iART could both be promising add-ons to medication and increase availability to psychological treatment with sustained symptom reductions after one year.

Brief self-guided digital intervention versus a comprehensive therapist-guided online cognitive behavioural therapy for atopic dermatitis: a trial protocol for a randomised non-inferiority trial.

INTRODUCTION: Our aim is to investigate whether a shortened digital self-care intervention is non-inferior to, and cost-effective compared with, a comprehensive and therapist-guided cognitive behavioural therapy treatment for atopic dermatitis (AD). METHODS AND ANALYSIS: This is a single-blind, randomised clinical non-inferiority trial at Karolinska Institutet, a medical university in Stockholm, Sweden. We will recruit 174 adult participants with AD through self-referral. Participants will be randomised 1:1 to the two experimental conditions. Participants randomised to guided care will receive internet-delivered cognitive behavioural therapy for 12 weeks. Participants randomised to digital self-care will have access to this self-guided intervention for 12 weeks. At post-treatment (primary endpoint), non-inferiority will be tested and resource use will be compared between the two treatment groups. Cost-effectiveness will be explored at 1-year follow-up. Potential mediators will be investigated. Data will be analysed intention to treat. We define non-inferiority as a three-point difference on the primary outcome measure (Patient-oriented Eczema Measure). Recruitment started in November 2022. ETHICS AND DISSEMINATION: This study is approved by the Swedish ethics authority (reg. no 2021-06704-01) and is preregistered at ClinicalTrials.gov. The study will be reported according to the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. The results of the study will be published in peer-reviewed scientific journals and disseminated to patient organisations and media. TRIAL REGISTRATION NUMBER: NCT05517850.

Treatment feasibility of a digital tool for brief self-help behavioural therapy for insomnia (FastAsleep).

Cognitive behavioural therapy for insomnia is efficacious and recommended for insomnia, but availability is scarce. Cognitive behavioural therapy for insomnia self-help interventions could increase availability, especially if unguided. Optimizing cognitive behavioural therapy for insomnia methods and system user-friendliness, we developed a short, digital, self-help programme-FastAsleep-based on the behavioural components of sleep restriction and stimulus control. This study investigated its feasibility and preliminary effects. Thirty media-recruited participants with moderate to severe insomnia were assessed via telephone before using FastAsleep for 4 weeks, and were interviewed afterwards. Self-ratings with web questionnaires were conducted at screening, pre-, mid- and post-treatment, and at 3-month follow-up. Primary outcomes were feasibility (credibility, adherence, system user-friendliness and adverse effects), and secondary outcomes were changes in symptom severity (insomnia, depression and anxiety). Adherence was generally high, participants' feasibility ratings were favourable, and adverse effects matched previously reported levels for cognitive behavioural therapy for insomnia. Symptoms of insomnia decreased after the treatment period (Hedge's g = 1.79, 95% confidence interval = 1.20-2.39), as did symptoms of depression and anxiety. FastAsleep can be considered feasible and promising for alleviating insomnia symptoms among patients fit for self-care. Future controlled trials are needed to establish the efficacy of FastAsleep and its suitability in a stepped care model.

The 14-item short health anxiety inventory (SHAI-14) used as a screening tool: appropriate interpretation and diagnostic accuracy of the Swedish version.

BACKGROUND: The 14-item Short Health Anxiety Inventory (SHAI-14) is a common measure of health anxiety but its screening properties have not been studied. The aims of this study were to evaluate the SHAI-14 as a screening instrument, identify cut-offs for clinically significant health anxiety and investigate which scores correspond to different severity levels. METHOD: The study included 1729 psychiatric patients and 85 healthy controls. Participants completed the SHAI-14 and underwent a diagnostic interview. Cut-off scores were evaluated in three scenarios to approximate screening 1) in a psychiatric clinic, 2) in a low prevalence setting and, 3) of healthy volunteers (cut-off for remission). Receiver operating characteristics were used. Classification of severity was based on the distribution of SHAI-14 scores reported by patients with clinically significant health anxiety. RESULTS: The area under the curve (AUC) values were high in all scenarios (above 0.95). The optimal cut-off scores on the SHAI-14 were 22 in the psychiatric context, 29 in a setting with low prevalence of psychiatric disorders and 18 versus healthy controls. SHAI-14 scores of 0-27 represented no or mild health anxiety, 28-32 moderate health anxiety and 33-42 substantial health anxiety. CONCLUSION: Brief self-report measures used as screening instruments are a simple way of gathering information about the presence of specific symptoms and thus a way to detect the likelihood of a diagnosis. The SHAI-14 shows evidence of good diagnostic utility in both clinical and non-clinical settings. However, which cut-off score is to be used, depends on the intended purpose and the setting where the cut-off is used.

Optimized User Experience, Efficiency, and Resource Use in Online Self-Management of Atopic Dermatitis.

This quality improvement study describes the revision of an internet-delivered, self-guided psychological treatment for atopic dermatitis.

Corrigendum to "The effect of user interface on treatment engagement in a self-guided digital problem-solving intervention: A randomized controlled trial" [Internet Interv. 26 (2021) 1-10/100448].

[This corrects the article DOI: 10.1016/j.invent.2021.100448.].

Online Guided Self-help Cognitive Behavioral Therapy With Exposure to Anxiety and Problem Solving in Type 1 Diabetes Mellitus: Case Study.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is dependent on self-care to avoid short- and long-term complications. There are several problem areas in diabetes that could be addressed by psychological interventions, such as suboptimal problem-solving strategies and fear of hypoglycemia. There is empirical support for a few psychological interventions, most often cognitive behavioral therapy, with various treatment aims. However, these interventions are largely unavailable in regular diabetes health care. Online guided self-help cognitive behavioral therapy could help achieve greater outreach. OBJECTIVE: We tested a manualized treatment in the early stage for further development, with the long-term aim to increase access to care. The purpose of this report was to show the potential of this newly developed online intervention by describing 2 illustrative cases. METHODS: An online guided self-help cognitive behavioral therapy protocol featuring problem solving and exposure was developed. The treatment was administered from a secure online platform and lasted for 8 weeks. Case 1 was a male participant. He had a number of diabetes-related complications and was worried about his future. He reported that he had a general idea that he needed to change his lifestyle but found it difficult to get started. Case 2 was a female participant. She had fear of hypoglycemia and unhelpful avoidance behaviors. She kept her blood glucose levels unhealthily high in order to prevent hypoglycemic episodes. Furthermore, she avoided contact with diabetes health care. RESULTS: The 2 participants showed clinically significant improvements in their most relevant problem areas. In case 1, the participant's blood glucose levels reduced, and he was able to establish healthy routines, such as increase physical exercise and decrease overeating. In case 2, the participant's fear of hypoglycemia greatly decreased, and she was able to confront many of her avoided situations and increase necessary visits to her diabetes clinic. Treatment satisfaction was high, and no adverse events were reported. CONCLUSIONS: It is possible to deliver a cognitive behavioral therapy intervention aimed at problem areas in diabetes online. Problem solving appears to help with problems in everyday routines and lifestyle choices. Exposure to aversive stimuli appears to be a plausible intervention specifically aimed at the fear of hypoglycemia. Larger and controlled studies are needed.

A self-guided and monitored digital problem-solving intervention for patients with symptoms of depression or anxiety on the waiting list for treatment in routine psychiatric care: feasibility study.

BACKGROUND: There is often a waiting period for people who seek psychiatric treatment for depression or anxiety. As this delay risks worsening symptoms, an alternative could be to provide an intervention that requires minimal resources during the waiting period. AIMS: The aim was to investigate if a digital problem-solving intervention delivered in a self-guided format with automated features is feasible to provide for patients on the waiting list in routine psychiatric care. METHOD: A total of 12 patients with symptoms of depression or anxiety on the waiting list for treatment in routine psychiatric care were given access to a self-guided and monitored digital problem-solving intervention over 4 weeks. Primary outcome measures were treatment credibility and usability. Secondary outcome measures were behavioural engagement, symptoms of depression and anxiety, and negative effects. RESULTS: A majority of participants rated the intervention as both credible and usable. The intervention was used at least once by nine out of 12 individuals, with an average of 11 logins. The participants did, on average, initiate 2.8 problem-solving attempts and 10.1 solutions. A few participants reached a clinically relevant symptom improvement of depression and anxiety. No serious negative effects were reported. CONCLUSIONS: The credibility and usability of the intervention was perceived as good, and the behavioural engagement with the intervention was deemed sufficient compared with similar self-guided interventions. A self-guided and monitored digital problem-solving intervention may be a beneficial option for patients waiting for or receiving treatment in routine psychiatric care, and should be further evaluated.

The effect of user interface on treatment engagement in a self-guided digital problem-solving intervention: A randomized controlled trial.

BACKGROUND: Resources are spent worldwide on the development of digital platforms and their user interfaces (UIs) for digital mental health services (DMHS). However, studies investigating the potential benefits of different UIs for DMHS are currently lacking. To fill this knowledge gap, the aim of this study was to investigate differences in treatment engagement between two different UIs for DMHS. METHODS: A total of 397 participants from the Swedish general public were randomized (1:1) to use a self-guided digital problem-solving intervention during one week, either with an optimized UI (N = 198), based on user experience (UX) design principles and with automated features, or a basic UI (N = 199), analogous with a UI used in Swedish regular health care comprising elementary UI features and less automation. Primary outcome measures were self-rated usability, on the System Usability Scale, and treatment credibility, on the Credibility/Expectancy Questionnaire. Secondary outcome measures included behavioral engagement with the intervention. FINDINGS: There were no significant differences between the UIs in ratings of usability or treatment credibility. However, participants who used the optimized UI were significantly more engaged with the intervention as measured by usage of the intervention at least once (odds ratio 2.54, 95% CI [1.67, 3.85]), total number of generated solutions (mean difference 1.41, 95% CI [0.72, 2.11]), and mean number of generated solutions per initiated problem-solving attempt (mean difference 1.45, 95% CI [1.06, 1.85]). Other findings included participants using the optimized UI rating the intervention as easier to understand, while feeling more overwhelmed, than those using the basic UI. INTERPRETATION: Our findings indicate that an optimized UI based on UX design principles, in comparison to a basic UI comprising elementary UI features, do not affect overall self-rated usability or treatment credibility but increases some measures of behavioral engagement with a digital intervention. FUNDING: Funded by the Government of Sweden, Ministry of Health and Social Affairs.

Return on investment of internet delivered exposure therapy for irritable bowel syndrome: a randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a debilitating and costly disorder. Cognitive behavior therapy (CBT) is effective in the treatment of IBS, both when delivered over the internet and in face-to-face settings. CBT consists of different components and little is known about their relative importance. We have in an earlier study showed that inclusion of exposure in the CBT for IBS makes it even more effective. In the present study we wanted to evaluate the economic effects for society of inclusion vs exclusion of exposure in an internet delivered CBT for IBS. METHODS: We used data from a previous study with 309 participants with IBS. Participants were randomized to internet delivered CBT with (ICBT) or without exposure (ICBT-WE). We compared direct and indirect costs at baseline, after treatment, and 6 months after treatment (primary endpoint; 6MFU). Data was also collected on symptom severity and time spent by therapists and participants. The relative Incremental Cost Effectiveness Ratio (ICER) was calculated for the two treatment conditions and the return on investment (ROI). RESULTS: Results showed that ICBT cost $213.5 (20%) more than ICBT-WE per participant. However, ICBT was associated with larger reductions regarding both costs and symptoms than ICBT-WE at 6MFU. The ICER was - 301.69, meaning that for every point improvement on the Gastrointestinal Symptom Rating Scale-IBS version in ICBT, societal costs would be reduced with approximately $300. At a willingness to pay for a case of clinically significant improvement in IBS symptoms of $0, there was an 84% probability of cost-effectiveness. ROI analysis showed that for every $1 invested in ICBT rather than ICBT-WE, the return would be $5.64 six months after treatment. Analyses of post-treatment data showed a similar pattern although cost-savings were smaller. CONCLUSIONS: Including exposure in Cognitive Behavior Treatment for IBS is more cost-effective from a societal perspective than not including it, even though it may demand more therapist and patient time in the short term. TRIAL REGISTRATION: This study is reported in accordance with the CONSORT statement for non-pharmacological trials [1]. Clinicaltrials.gov registration ID: NCT01529567 (14/02/2013).

Internet-Delivered Cognitive Behavior Therapy for Atopic Dermatitis: A Randomized Clinical Trial.

IMPORTANCE: Atopic dermatitis is a common and debilitating skin condition characterized by intense itching and chronic inflammation. Research on behavioral treatments with high accessibility is needed. OBJECTIVE: To investigate the efficacy of a highly scalable internet-delivered cognitive behavior therapy (CBT) for adults with atopic dermatitis. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial from a medical university in Stockholm, Sweden, included 102 adults with atopic dermatitis, recruited from across Sweden, who received 12 weeks of internet-delivered CBT (March 29, 2017, to February 16, 2018). The first participant provided screening data on November 27, 2016, and the last 1-year follow-up assessment was conducted on June 28, 2019. INTERVENTIONS: Participants were randomized in a 1:1 ratio to 12 weeks of therapist-guided internet-delivered CBT (n = 51) or a control condition (n = 51) that gave instructions about standard care. MAIN OUTCOMES AND MEASURES: The primary outcome was the between-group difference in mean reduction of atopic dermatitis symptoms as measured by the Patient-Oriented Eczema Measure and modeled intention to treat during the 12-week treatment period. RESULTS: A total of 102 participants (mean [SD] age, 37 [11] years; 83 [81%] female) were recruited and randomized. The primary analysis indicated that participants receiving internet-delivered CBT, relative to the controls, had a significantly larger mean weekly reduction in symptoms of atopic dermatitis as measured with the Patient-Oriented Eczema Measure (B = 0.32; 95% CI, 0.14-0.49; P < .001), with a moderate to large, controlled effect size after treatment (d = 0.75; 95% CI, 0.32-1.16). Secondary analyses indicated that internet-delivered CBT also produced significantly larger reductions in itch intensity, perceived stress, sleep problems, and depression. Gains were sustained at 12 months of follow-up. Treatment satisfaction was high, and therapists spent a mean (SD) of 39.7 (34.7) minutes per treated patient providing internet-delivered CBT. CONCLUSIONS AND RELEVANCE: Internet-delivered CBT appears to be efficacious for reducing symptoms of atopic dermatitis, despite requiring minimal therapist resources. Thus, internet-delivered CBT has the potential to increase access to effective adjunct behavioral treatment for patients with this common skin condition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03051958.

Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders: A meta-analysis.

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.

Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression.

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

Individually Tailored Internet-Based Cognitive-Behavioral Therapy for Daily Functioning in Patients with Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Parkinson's disease (PD) is often associated with psychological distress and lowered daily functioning. The availability of psychological interventions tailored for people with Parkinson is very limited. OBJECTIVE: To study if guided individually-tailored internet-based cognitive behavioral therapy (ICBT) provide additional value to standard medical treatment for PD. METHODS: Seventy-seven individuals with PD and self-reported problems with general function measured with the Work and Social Adjustment Scale (WSAS > 15) were randomized to 10 weeks of either ICBT combined with standard medical treatment, or standard medical treatment plus being on waitlist to ICBT (CONTROL). Change in the main outcome WSAS, as well as secondary measures such as quality of life, depression, anxiety and insomnia symptoms were investigated post treatment. RESULTS: Participants receiving ICBT reported significantly higher functioning after treatment (WSAS group difference -4.56, controlled effect size g = 0.69, significant group by time interaction, Wχ2= 26.23, p = 0.001). However, only around one third of participants in the treatment group were classified as treatment responders, defined as having a 30% reduction on the WSAS post treatment. Patient involvement and ratings of ICBT credibility were high. Symptoms of anxiety, depression and insomnia symptoms were significantly lower after treatment compared to CONTROL. There were also positive effects on Parkinson-specific function and quality of life in the treatment group. CONCLUSIONS: ICBT as an addition to standard medical treatment was credible and improved functioning for some individuals with PD. Still, the treatment needs further development in order to help a larger proportion of individuals with PD. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02627885.