To my family Josefin, Selma and Oskar. Not only did they put up with me during the entire PhD journey, but they also spent the last two weeks of it in quarantine with me because of the coronavirus pandemic of 2020.ABSTRACT Background: Internet-delivered Cognitive Behavior Therapy (ICBT) is efficacious for a number of psychiatric disorders and can be successfully implemented in routine psychiatric care. Still, only about half of patients experience a good enough treatment outcome. Using data from the early part of treatment to identify patients with high risk of not benefitting from it, and target them with additional resources to prevent the predicted failure is a potential way forward. We call this an Adaptive Treatment Strategy, and a very important part of it is the ability to predict the outcome for a specific patient. Aims:To establish a proof of concept for an Adaptive Treatment Strategy in ICBT, and explore outcome prediction further by evaluating the accuracy of an empirically supported classification algorithm, the time point in treatment when acceptable accuracy can be reached, and the accuracy of ICBT-therapists' own predictions. Preliminary benchmarks regarding the clinical usefulness of prediction will be established. Studies:Four studies were performed: Study I was a randomized controlled trial (RCT; n=251) where patients' risk of treatment Failure (Red=high risk of failure, Green=low risk) was predicted during week 4 out of 9 in ICBT for Insomnia. Red patients (n=102) were then randomized to either continuing with standard treatment (n=51) or having their treatment individually adapted (n=51). In Study II, the classification algorithm from Study I was evaluated in terms of classification accuracy and the contribution of the different predictors used. In Study III, data from 4310 regular care ICBT-patients having received treatment for either Depression, Social anxiety disorder or Panic disorder were analyzed in a series of multiple regression models using weekly observations of the primary symptom measure as predictors to classify risk of Failure. As a contrast, Study IV examines ICBT therapists' own predictions on both categorical and continuous treatment outcomes, as they made predictions for each of their patients (n=897) during week 4 in the same three treatments as in Study III. Results:The RCT was successful in that Red patients receiving Adapted treatment improved significantly more than Red patients receiving standard treatment, and their odds of failure were nearly cut in half. Green patients did better than Red patients, indicating that the accuracy of the classification algorithm was clinically useful. Study II showed that the balanced accuracy of the classifier was 67% and that only 11 of 21 predictors correlated significantly with Failure. Notable predictors were symptom levels as well as different markers of treatment engagement. Study III and IV showed that acceptable predictions could be made halfway through treatment using only symptom scores and basic statistics, and that ICBT-...

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This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder (MDD) after psychotherapy. Genotyped adult patients (n = 894, 65.5% women, age 18–75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008–2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off ≤10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and (iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730, P = 0.084) but not vs XGBoost (D = 0.463, P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness.

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Objective Investigating unique and shared aspects of measures of emotion regulation (ER) advances our understanding of ER as a multidimensional construct. This study aimed to investigate psychometric properties of three ER‐measures: Difficulties in Emotion Regulation Scale (DERS‐36), the abbreviated version DERS‐16, and Emotion Regulation Questionnaire (ERQ). Methods In a community sample (N = 843; 56% females) we investigated their internal consistency, factor structure, convergence, and association with symptoms of depression, anxiety, stress and substance abuse. Results The proposed factor structures of the DERS‐16 and the ERQ demonstrated an adequate fit. There were moderate correlations between the two DERS versions (36 and 16) and ERQ subscales Reappraisal and Suppression. Total scores of DERS‐36 and DERS‐16 demonstrated preferential associations with depression and anxiety. Corresponding associations between ERQ subscales and psychiatric symptoms were weak. Conclusion The results indicate that DERS‐16 could be useful as an alternative, easily administered measure of ER difficulties.

A learning machine, in the form of a gating network that governs a finite number of different machine learning methods, is described at the conceptual level with examples of concrete prediction subtasks. A historical data set with data from over 5000 patients in Internet-based psychological treatment will be used to equip healthcare staff with decision support for questions pertaining to ongoing and future cases in clinical care for depression, social anxiety, and panic disorder. The organizational knowledge graph is used to inform the weight adjustment of the gating network and for routing subtasks to the different methods employed locally for prediction. The result is an operational model for assisting therapists in their clinical work, about to be subjected to validation in a clinical trial.

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