Optimizing Outcomes in Psychotherapy for Anxiety Disorders Using Smartphone-Based and Passive Sensing Features: Protocol for a Randomized Controlled Trial.

BACKGROUND: Psychotherapies, such as cognitive behavioral therapy (CBT), currently have the strongest evidence of durable symptom changes for most psychological disorders, such as anxiety disorders. Nevertheless, only about half of individuals treated with CBT benefit from it. Predictive algorithms, including digital assessments and passive sensing features, could better identify patients who would benefit from CBT, and thus, improve treatment choices. OBJECTIVE: This study aims to establish predictive features that forecast responses to transdiagnostic CBT in anxiety disorders and to investigate key mechanisms underlying treatment responses. METHODS: This study is a 2-armed randomized controlled clinical trial. We include patients with anxiety disorders who are randomized to either a transdiagnostic CBT group or a waitlist (referred to as WAIT). We index key features to predict responses prior to starting treatment using subjective self-report questionnaires, experimental tasks, biological samples, ecological momentary assessments, activity tracking, and smartphone-based passive sensing to derive a multimodal feature set for predictive modeling. Additional assessments take place weekly at mid- and posttreatment and at 6- and 12-month follow-ups to index anxiety and depression symptom severity. We aim to include 150 patients, randomized to CBT versus WAIT at a 3:1 ratio. The data set will be subject to full feature and important features selected by minimal redundancy and maximal relevance feature selection and then fed into machine leaning models, including eXtreme gradient boosting, pattern recognition network, and k-nearest neighbors to forecast treatment response. The performance of the developed models will be evaluated. In addition to predictive modeling, we will test specific mechanistic hypotheses (eg, association between self-efficacy, daily symptoms obtained using ecological momentary assessments, and treatment response) to elucidate mechanisms underlying treatment response. RESULTS: The trial is now completed. It was approved by the Cantonal Ethics Committee, Zurich. The results will be disseminated through publications in scientific peer-reviewed journals and conference presentations. CONCLUSIONS: The aim of this trial is to improve current CBT treatment by precise forecasting of treatment response and by understanding and potentially augmenting underpinning mechanisms and personalizing treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03945617; https://clinicaltrials.gov/ct2/show/results/NCT03945617. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42547.

Lavender oil preparation Silexan is effective in mild-to-moderate major depression: a randomized, placebo- and reference-controlled trial.

Anxiety and depressive disorders have overlapping symptoms and share common neurobiological pathways. Antidepressant drugs have been demonstrated to be efficacious in anxiety as well. Vice versa, it may also be promising to investigate the efficacy of anxiolytic drugs such as silexan in major depressive disorder (MDD). Patients with a mild or moderate, single or recurrent episode of MDD and a total score of 19-34 points on the Montgomery Åsberg Depression Rating Scale (MADRS) were randomized to receive 1 × 80 mg/d silexan, 1 × 50 mg/d sertraline, or placebo double-blind, double-dummy for 56 days. The primary outcome measure was the MADRS total score change between baseline and treatment end. Treatment groups were compared using a treatment policy estimand. 498 subjects (silexan 170, sertraline 171, placebo 157) were treated and analyzed. After 8 weeks, silexan and sertraline were superior to placebo for MADRS total score reduction, with absolute differences to placebo of 2.17 (95% confidence interval: 0.58; 3.76) points and 2.59 (1.02; 4.17) points, respectively (p < 0.01). Moreover, silexan was superior to placebo for alleviation of functional impairment according to the Sheehan Disability Scale with a difference of 2.40 (1.04; 3.76) points (p < 0.001). Both treatments were well tolerated; eructation was the most frequent adverse effect of silexan. The study confirms the antidepressant efficacy of silexan in mild or moderate MDD, including significant improvements in the subjects' functional capacity. The results for sertraline confirm the assay sensitivity of the trial. Both drugs were well tolerated.Trial registrationEudraCT2020-000688-22 first entered on 12/08/2020.

The boon and bane of nitrous oxide.

Nitrous oxide (N2O) has been known since the end of the eighteenth century. Today, N2O plays a huge role as a greenhouse gas and an ozone-depleting stratospheric molecule. The main sources of anthropogenic N2O emissions are agriculture, fuel combustion, wastewater treatment, and various industrial processes. By contrast, the contribution of medical N2O to the greenhouse effect appears to be small. The recreational and medical uses of N2O gradually diverged over time. N2O has analgesic and anesthetic effects, making it widely used in modern dentistry and surgery. New research has also begun studying N2O's antidepressant actions. N-methyl-D-aspartate (NMDA) antagonism and opioid effects are believed to be the main underlying biochemical mechanisms. At this point, numerous questions remain open and, in particular, the conduct of larger clinical trials will be essential to confirm N2O's use as a rapid-acting antidepressant. The N2O concentration delivered, the duration of a single inhalation, as well as the number of inhalations ultimately required, deserve to be better understood. Finally, the non-medical use of N2O has gained significant attention in recent years. Sudden deaths directly attributed to N2O are primarily due to asphyxia. Heavy, chronic N2O use may result in vitamin B12 deficiency, which, among other things, may cause megaloblastic anemia, venous thrombosis, myeloneuropathy, and skin pigmentation. Helpful biochemical tests include homocysteine and methylmalonic acid. The centerpiece of treatment is complete cessation of N2O use together with parenteral administration of vitamin B12.

Linguistic and (micro)cultural differences in the global debate about re-naming 'schizophrenia': A mixed-methods survey from Switzerland.

BACKGROUND AND HYPOTHESIS: This survey explores Swiss mental health professionals', users', and relatives' opinions on re-naming schizophrenia exploiting Switzerland's specific multilingualism to examine possible effects of linguistic and microcultural differences on the issue. STUDY DESIGN: Opinions on 'schizophrenia' were collected using a self-rated online questionnaire incl. Freetext answers available in the three main Swiss languages, German, French and Italian. It was distributed to the main professional and self-help organizations in Switzerland between June and October 2021. STUDY RESULTS: Overall, 449 persons completed the questionnaire, 263 in German, 172 in French and 14 in Italian. Of the total sample, 339 identified as mental health professionals, 81 as relatives and 29 as users. Considering the whole sample, almost half favored a name-change with a significant difference between stakeholder- and between language groups. Also, the name 'schizophrenia' was evaluated more critically than the diagnostic concept. Qualitative analysis of freetext answers showed a highly heterogenous argumentation, but no difference between language groups. CONCLUSIONS: Our results suggest the attitude towards re-naming might itself be subject to (micro)cultural difference, and they highlight the nature of 'schizophrenia' as not only a scientific, but also a linguistic and cultural object. Such local factors ought to be taken into consideration in the global debate.

Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.

Background: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets. Results: We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine's data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. Conclusions: These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry. Funding: This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1-190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016-0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 - 2056) (FXV). Clinical trial number: NCT03842800.

Ketamine is a widely used anesthetic as well as a popular illegal recreational drug. Recently, it has also gained attention as a potential treatment for depression, particularly in cases that don't respond to conventional therapies. However, individuals can vary in their response to ketamine. For example, the drug can alter some people's perception, such as seeing objects as larger or small than they are, while other individuals are unaffected. Although a single dose of ketamine was shown to improve depression symptoms in approximately 65% of patients, the treatment does not work for a significant portion of patients. Understanding why ketamine does not work for everyone could help to identify which patients would benefit most from the treatment. Previous studies investigating ketamine as a treatment for depression have typically included a group of individuals given ketamine and a group given a placebo drug. Assuming people respond similarly to ketamine, the responses in each group were averaged and compared to one another. However, this averaging of results may have masked any individual differences in response to ketamine. As a result, Moujaes et al. set out to investigate whether individuals show differences in brain activity and behavior in response to ketamine. Moujaes et al. monitored the brain activity and behavior of 40 healthy individuals that were first given a placebo drug and then ketamine. The results showed that brain activity and behavior varied significantly between individuals after ketamine administration. Genetic analysis revealed that different gene expression patterns paired with differences in ketamine response in individuals ­ an effect that was hidden when the results were averaged. Ketamine also caused greater differences in brain activity and behavior between individuals than other drugs, such as psychedelics, suggesting ketamine generates a particularly complex response in people. In the future, extending these findings in healthy individuals to those with depression will be crucial for determining whether differences in response to ketamine align with how effective ketamine treatment is for an individual.

Plasma neurofilament light, glial fibrillary acid protein, and phosphorylated tau 181 as biomarkers for neuropsychiatric symptoms and related clinical disease progression.

BACKGROUND: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. METHODS: One hundred and fifty-one participants with normal cognition (n=76) or mild cognitive impairment (n=75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Linear regression and ROC analyses were used to address the associations of interest. RESULTS: Higher GFAP levels were associated with NPS at baseline (ß=0.23, p=.008). Higher NfL and GFAP levels were associated with the presence of NPS at follow-up (ß=0.29, p=.007 and ß=0.28, p=.007, respectively) and with an increase in the NPI-Q severity score over time (ß=0.23, p=.035 and ß=0.27, p=.011, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.73 to 0.84, p=.007) and AD pathology (AUC 0.79 to 0.86, p=.006), but not of cognitive decline (AUC 0.79 to 0.84, p=.068). CONCLUSION: Plasma GFAP is associated with NPS while NfL and GFAP are both associated with future NPS and NPS severity. Considering the presence of NPS along with blood-based AD-biomarkers may improve diagnosis and prediction of clinical progression of NPS and inform clinical decision-making in non-demented older people.

Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.

In this study, for the first time, we explored a dataset of functional magnetic resonance images collected during focused attention and open monitoring meditation before and after a five-day psilocybin-assisted meditation retreat using a recently established approach, based on the Mapper algorithm from topological data analysis. After generating subject-specific maps for two groups (psilocybin vs. placebo, 18 subjects/group) of experienced meditators, organizational principles were uncovered using graph topological tools, including the optimal transport (OT) distance, a geometrically rich measure of similarity between brain activity patterns. This revealed characteristics of the topology (i.e. shape) in space (i.e. abstract space of voxels) and time dimension of whole-brain activity patterns during different styles of meditation and psilocybin-induced alterations. Most interestingly, we found that (psilocybin-induced) positive derealization, which fosters insightfulness specifically when accompanied by enhanced open-monitoring meditation, was linked to the OT distance between open-monitoring and resting state. Our findings suggest that enhanced meta-awareness through meditation practice in experienced meditators combined with potential psilocybin-induced positive alterations in perception mediate insightfulness. Together, these findings provide a novel perspective on meditation and psychedelics that may reveal potential novel brain markers for positive synergistic effects between mindfulness practices and psilocybin.

Introducing neurofilament light chain measure in psychiatry: current evidence, opportunities, and pitfalls.

The recent introduction of new-generation immunoassay methods allows the reliable quantification of structural brain markers in peripheral matrices. Neurofilament light chain (NfL), a neuron-specific cytoskeletal component released in extracellular matrices after neuroaxonal impairment, is considered a promising blood marker of active brain pathology. Given its sensitivity to a wide range of neuropathological alterations, NfL has been suggested for the use in clinical practice as a highly sensitive, but unspecific tool to quantify active brain pathology. While large efforts have been put in characterizing its clinical profile in many neurological conditions, NfL has received far less attention as a potential biomarker in major psychiatric disorders. Therefore, we briefly introduce NfL as a marker of neuroaxonal injury, systematically review recent findings on cerebrospinal fluid and blood NfL levels in patients with primary psychiatric conditions and highlight the opportunities and pitfalls. Current evidence suggests an elevation of blood NfL levels in patients with major depression, bipolar disorder, psychotic disorders, anorexia nervosa, and substance use disorders compared to physiological states. However, blood NfL levels strongly vary across diagnostic entities, clinical stage, and patient subgroups, and are influenced by several demographic, clinical, and analytical factors, which require accurate characterization. Potential clinical applications of NfL measure in psychiatry are seen in diagnostic and prognostic algorithms, to exclude neurodegenerative disease, in the assessment of brain toxicity for different pharmacological compounds, and in the longitudinal monitoring of treatment response. The high inter-individual variability of NfL levels and the lack of neurobiological understanding of its release are some of the main current limitations. Overall, this primer aims to introduce researchers and clinicians to NfL measure in the psychiatric field and to provide a conceptual framework for future research directions.

Baseline symptom severity and efficacy of Silexan in patients with anxiety disorders: A symptom-based, patient-level analysis of randomized, placebo-controlled trials.

The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80 mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n = 587; placebo, n = 585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p < 0.001). HAMA items from the somatic domain scored lower at baseline and showed less improvement than items from the psychic domain, particularly in patients with mild or moderate baseline symptoms. For CGI item 2 (global improvement), significant efficacy favoring Silexan were observed in mild, moderate, and severe baseline symptom severity. Although significant improvements were found for all subsets, the more severe the initial symptoms, the greater the treatment effects documented by the HAMA. Overall this analysis confirms that Silexan is an effective treatment option in early or mild stages of anxiety disorder. Given its favorable safety profile, Silexan can thus fill a therapeutic gap in the treatment of (subsyndromal) anxiety disorders.

Mental Health in Elite Coaches.

CONTEXT: Coaches play an important role in promoting mental health in elite sports. However, they themselves are exposed to risks affecting their mental health, and their fears and worries are often overlooked. Moreover, it remains unclear how coaches' mental health affects their athletes' mental health. OBJECTIVE: To create a compilation of the literature on (1) elite coaches' mental health and (2) how coaches' mental health influences elite athletes' mental health. Building on this, recommendations for improving coaches' psychological well-being should be elaborated upon and discussed. DATA SOURCES: A literature search was conducted up to November 30, 2021, using the following databases: PubMed, PsycINFO, Scopus, Web of Science, and SportDiscus. STUDY SELECTION: Studies reporting elite coaches' mental health symptoms and disorders and the influence of elite coaches' mental health on elite athletes' mental health were included. STUDY DESIGN: Scoping review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Data regarding elite coaches' mental health, as well as their influence on athletes' mental health and performance, were included in a descriptive analysis. The PRISMA guidelines were used to guide this review. RESULTS: Little research has been done on elite coaches' mental health disorders, although studies confirm that they do experience, for example, symptoms of burnout, anxiety, and depression. The influence of coaches' mental health on their athletes is underinvestigated, with research focused mainly on the influence of coaches' stress. CONCLUSION: Knowledge about coaches' mental health is still limited. Coaches' poor mental health diminishes coaching performance and might impair athletes' mental health. Coaches should receive more support, including sports psychiatric care and education on the importance of mental health. This could improve the mental health of both coaches and athletes, and positively affect athlete performance.

Neurometabolic profile of the amygdala in smokers assessed with 1H-magnetic resonance spectroscopy.

Tobacco smoking is one of the main causes of premature death worldwide and quitting success remains low, highlighting the need to understand the neurobiological mechanisms underlying relapse. Preclinical models have shown that the amygdala and glutamate play an important role in nicotine addiction. The aims of this study were to compare glutamate and other metabolites in the amygdala between smokers and controls, and between different smoking states. Furthermore, associations between amygdalar metabolite levels and smoking characteristics were explored. A novel non-water-suppressed proton magnetic resonance spectroscopy protocol was applied to quantify neurometabolites in 28 male smokers (≥15 cigarettes/day) and 21 non-smoking controls, matched in age, education, verbal IQ, and weekly alcohol consumption. Controls were measured once (baseline) and smokers were measured in a baseline state (1-3 h abstinence), during withdrawal (24 h abstinence) and in a satiation state (directly after smoking). Baseline spectroscopy data were compared between groups by independent t-tests or Mann-Whitney-U tests. Smoking state differences were investigated by repeated-measures analyses of variance (ANOVAs). Associations between spectroscopy data and smoking characteristics were explored using Spearman correlations. Good spectral quality, high anatomical specificity (98% mean gray matter) and reliable quantification of most metabolites of interest were achieved in the amygdala. Metabolite levels did not differ between groups, but smokers showed significantly higher glutamine levels at baseline than satiation. Glx levels were negatively associated with pack-years and smoking duration. In summary, this study provides first insights into the neurometabolic profile of the amygdala in smokers with high anatomical specificity. By applying proton magnetic resonance spectroscopy, neurometabolites in smokers during different smoking states and non-smoking controls were quantified reliably. A significant shift in glutamine levels between smoking states was detected, with lower concentrations in satiation than baseline. The negative association between Glx levels and smoking quantity and duration may imply altered glutamate homeostasis with more severe nicotine addiction.

EEG-vigilance regulation is associated with and predicts ketamine response in major depressive disorder.

Ketamine offers promising new therapeutic options for difficult-to-treat depression. The efficacy of treatment response, including ketamine, has been intricately linked to EEG measures of vigilance. This research investigated the interplay between intravenous ketamine and alterations in brain arousal, quantified through EEG vigilance assessments in two distinct cohorts of depressed patients (original dataset: n = 24; testing dataset: n = 24). Clinical response was defined as a decrease from baseline of >33% on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 h after infusion. EEG recordings were obtained pre-, start-, end- and 24 h post- infusion, and the resting EEG was automatically scored using the Vigilance Algorithm Leipzig (VIGALL). Relative to placebo (sodium chloride 0.9%), ketamine increased the amount of low-vigilance stage B1 at end-infusion. This increase in B1 was positively related to serum concentrations of ketamine, but not to norketamine, and was independent of clinical response. In contrast, treatment responders showed a distinct EEG pattern characterized by a decrease in high-vigilance stage A1 and an increase in low-vigilance B2/3, regardless of whether placebo or ketamine had been given. Furthermore, pretreatment EEG differed between responders and non-responders with responders showing a higher percentage of stage A1 (53% vs. 21%). The logistic regression fitted on the percent of A1 stages was able to predict treatment outcomes in the testing dataset with an area under the ROC curve of 0.7. Ketamine affects EEG vigilance in a distinct pattern observed only in responders. Consequently, the percentage of pretreatment stage A1 shows significant potential as a predictive biomarker of treatment response.Clinical Trials Registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000952-17/CZ Registration number: EudraCT Number: 2013-000952-17.

Predictors for early and long-term readmission in involuntarily admitted patients.

BACKGROUND: It is a common aim to reduce psychiatric readmissions. Although risk factors for readmissions were described, specific data in the group of patients with potentially aversively experienced involuntary admissions are lacking. To better understand underlying mechanisms, it is important to identify factors that are linked to readmissions in this specific patient group, which is the purpose of the current paper. METHODS: A four-year cohort of N = 3575 involuntary admissions (IA) was followed-up for subsequent re-hospitalization. Demographic, administrative and clinical factors associated with short- (within 30 days) or long-term (> 30 days) readmissions were examined using logistic regression modelling. RESULTS: Almost half of all IA cases were readmitted within the observation period, whereof every fifth readmission was within the first month after discharge from the involuntary index hospitalization. Adjusted regression modelling revealed problematic substance use at admission and assisted living or homelessness as risk factors for readmission, while high functioning at discharge, anxiety disorders, no subsequent treatment after discharge or IA due to danger to others were negatively associated with readmission. Factors specifically linked to short-term readmission were substance use and personality disorders, abscondence or discharge by initiation of the clinic, as well as being discharged to any place except the patient's home. There were no specific risk-factors for long-term readmission. CONCLUSIONS: To prevent readmissions after IA, especially for patients at risk, the aim of treatment strategies should be to focus on intensive discharge planning, enable continuous treatment in the outpatient setting, and provide social support.

Outcomes of electroconvulsive therapy in patients with depressive symptoms with versus without comorbid personality disorders/traits: A systematic review and meta-analysis.

AIMS: To assess electroconvulsive therapy (ECT) outcomes in patients affected by depressive symptoms with versus without additional comorbid personality disorders/traits. METHODS: We identified observational studies investigating ECT clinical outcomes in patients affected by depressive symptoms with versus without comorbid personality disorders/traits in Embase/Medline in 11/2022. Our protocol was registered with PROSPERO (CRD42023390833). Study quality was evaluated using the Newcastle-Ottawa-Scale. Our primary outcomes were ECT response and remission rates. Meta-regression analyses included effects of in/outpatient percentages, age, number of ECT sessions, and electrode placement; subgroup analyses included the assessment methods for personality disorders/traits. We performed sensitivity analyses after excluding poor-quality studies. RESULTS: A total of 20 studies (n = 11,390) were included in our analysis. Patients with comorbid personality disorders/traits had lower remission rates (OR = 0.42, 95% CI = 0.31, 0.58, p < 0.001) with substantial heterogeneity (I2 = 93.0%) as well as lower response rates (OR = 0.35, 95% CI = 0.24, 0.51, n = 5129, p < 0.001) with substantial heterogeneity (I2 = 93.0%) compared with patients without comorbid personality disorders/traits. Relapse rates were higher in patients with versus without comorbid personality disorders/traits (OR = 3.23, 95% CI = 1.40, 7.45, k = 4, n = 239, p = 0.006) with moderate heterogeneity (I2 = 75.0%) and post-ECT memory impairment was more frequent in patients with versus without comorbid personality disorders/traits (OR = 1.41, 95% CI = 1.36, 1.46, k = 4, n = 471, p < 0.001) with minimal heterogeneity (I2 = 0.0%). Dropout rates were higher in patients with versus without comorbid personality disorders/traits (OR = 1.58, 95% CI = 1.13, 2.21, k = 3, n = 6145, p = 0.008). CONCLUSIONS: Patients with comorbid personality disorders/traits treated with ECT are reported to have lower response and remission rates and higher rates of side effects and relapse rates compared with patients without personality disorders/traits.

Uncovering Emotions: A Pilot Study on Classifying Moods in the Valence-Arousal Space using In-the-Wild Passive Data.

Mood classification from passive data promises to provide an unobtrusive way to track a person's emotions over time. In this exploratory study, we collected phone sensor data and physiological signals from 8 individuals, including 5 healthy participants and 3 depressed patients, for a maximum of 35 days. Participants were asked to answer a digital questionnaire three times daily, resulting in a total of 334 self-reported mood state samples. Gradient-boosting classification was applied to the collected passive data to categorize 4 mood states in the Valence-Energetic Arousal space. The cross-validation results showed better classification performance compared to a baseline model, which always predicts the majority class. The classifier using passive data had an area under the precision-recall curve of 0.39 (SD = 0.1) while the baseline had 0.26 (SD = 0.03), suggesting the presence of information in the collected features that support the classification process. The model identified the entropy of the heart rate and the average physical activity in the preceding 8 hours, along with the max normal-to-normal (NN) sinus beat interval and the NN low frequency-high frequency ratio during the questionnaire completion, as the most important features in its analysis. Additionally, the time range of data collection was considered a contextual factor.

Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine.

Recently, the Amazonian plant medicine "ayahuasca"-containing the psychedelic compound N,N-dimethyltryptamine (DMT) and numerous ß-carboline alkaloids, such as harmine-has been suggested to exhibit beneficial effects in patients with affective and other mental health disorders. Although ayahuasca ingestion is considered safe, its pharmacokinetics/pharmacodynamics and tolerability profile pose some challenges and may limit the clinical applicability in vulnerable patient populations. While overdosing and the admixture of intolerable plant constituents may explain some of the common adverse reactions, the peroral route of administration may represent another relevant source of gastro-intestinal intolerabilities and unpredictable pharmacokinetics across users. To overcome these challenges, the present work aimed at creating ayahuasca-analogue formulations with improved pharmacokinetics and tolerability profiles. To this end, we developed peroral formulas and compared them with parenteral formulas specifically designed to circumvent the gastro-intestinal tract. In more detail, peroral administration of a capsule (containing purified DMT and harmine) was tested against a combined administration of an oromucosal harmine tablet and an intranasal DMT spray at two dose levels in an open-label within-subject study in 10 healthy male subjects. Pharmacokinetic and pharmacodynamic profiles were assessed by means of continuous blood sampling, vital sign monitoring, and psychometric assessments. Common side effects induced by traditional herbal ayahuasca such as nausea, vomiting, and diarrhea were significantly attenuated by our DMT/harmine formulations. While all preparations were well tolerated, the combined buccal/intranasal administration of harmine and DMT yielded substantially improved pharmacokinetic profiles, indicated by significantly reduced variations in systemic exposure. In conclusion, the combined buccal/intranasal administration of harmine and DMT is an innovative approach that may pave the way towards a safe, rapid-acting, and patient-oriented administration of DMT/harmine for the treatment of affective disorders. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04716335.

Feasibility, Adherence, and Effectiveness of Blended Psychotherapy for Severe Mental Illnesses: Scoping Review.

BACKGROUND: Blended psychotherapy (bPT) combines face-to-face psychotherapy with digital interventions to enhance the effectiveness of mental health treatment. The feasibility and effectiveness of bPT have been demonstrated for various mental health issues, although primarily for patients with higher levels of functioning. OBJECTIVE: This scoping review aims to investigate the feasibility, adherence, and effectiveness of bPT for the treatment of patients with severe mental illnesses (SMIs). METHODS: Following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines, we conducted searches in PubMed, MEDLINE, Embase, PsycINFO, and PsycArticles for studies published until March 23, 2023. RESULTS: Out of 587 screened papers, we incorporated 25 studies encompassing 23 bPT interventions, involving a total of 2554 patients with SMI. The intervention formats and research designs exhibited significant variation. Our findings offer preliminary evidence supporting the feasibility of bPT for SMI, although there is limited research on adherence. Nevertheless, the summarized studies indicated promising attrition rates, spanning from 0% to 37%, implying a potential beneficial impact of bPT on adherence to SMI treatment. The quantity of evidence on the effects of bPT for SMI was limited and challenging to generalize. Among the 15 controlled trials, 4 concluded that bPT interventions were effective compared with controls. However, it is noteworthy that 2 of these studies used the same study population, and the control groups exhibited significant variations. CONCLUSIONS: Overall, our review suggests that while bPT appears promising as a treatment method, further research is necessary to establish its effectiveness for SMI. We discuss considerations for clinical implementation, directions, and future research.

Estimating multimodal brain variability in schizophrenia spectrum disorders: A worldwide ENIGMA study.

Objective: Schizophrenia is a multifaceted disorder associated with structural brain heterogeneity. Despite its relevance for identifying illness subtypes and informative biomarkers, structural brain heterogeneity in schizophrenia remains incompletely understood. Therefore, the objective of this study was to provide a comprehensive insight into the structural brain heterogeneity associated with schizophrenia. Methods: This meta- and mega-analysis investigated the variability of multimodal structural brain measures of white and gray matter in individuals with schizophrenia versus healthy controls. Using the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6139 individuals for a given brain measure, we examined variability in cortical thickness, surface area, folding index, subcortical volume and fractional anisotropy. Results: We found that individuals with schizophrenia are distinguished by higher heterogeneity in the frontotemporal network with regard to multimodal structural measures. Moreover, individuals with schizophrenia showed higher homogeneity of the folding index, especially in the left parahippocampal region. Conclusions: Higher multimodal heterogeneity in frontotemporal regions potentially implies different subtypes of schizophrenia that converge on impaired frontotemporal interaction as a core feature of the disorder. Conversely, more homogeneous folding patterns in the left parahippocampal region might signify a consistent characteristic of schizophrenia shared across subtypes. These findings underscore the importance of structural brain variability in advancing our neurobiological understanding of schizophrenia, and aid in identifying illness subtypes as well as informative biomarkers.