Autistic and schizotypal traits exhibit similarities in their impact on mentalization and adult attachment impairments: a cross-sectional study.

BACKGROUND: Deficits in mentalizing and attachment occur in the autism and schizophrenia spectrum, and their extended traits in the general population. Parental attachment and the broader social environment highly influence the development of mentalizing. Given the similarities in the symptomatology and neurodevelopmental correlates of autism spectrum disorder (ASD) and schizophrenia (SCH), it is crucial to identify their overlaps and differences to support screening, differential diagnosis, and intervention. METHODS: This cross-sectional study utilized questionnaire data from 2203 adults (65.1% female, mean age[SD] = 37.98[9.66]), including participants diagnosed with ASD, SCH, and those exhibiting subclinical traits to investigate the associations between mentalizing, attachment, and perceived social support during adolescence across the autistic and schizotypy spectrum. RESULTS: It was revealed that both autistic and schizotypal traits have comparable effects on insecure adult attachment, primarily through challenges in mentalizing. The impact of mentalizing deficits on adult attachment slightly varies between autistic and schizotypal traits. Conversely, perceived social support during adolescence relates to improved mentalizing and secure adult attachment as a protective factor during development. CONCLUSIONS: These outcomes highlight the significance of supportive therapeutic relationships and community care while suggesting directions for further research and collaborative treatments addressing ASD and SCH, considering the differential impact of mentalizing on adult attachment.

Integrating the Memory Support Intervention into the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C): can improving memory for treatment in midlife and older adults improve patient outcomes? Study protocol for a randomized controlled trial.

BACKGROUND: Poor memory for treatment is associated with poorer treatment adherence and poorer patient outcomes. The memory support intervention (MSI) was developed to improve patient memory for treatment with the goal of improving patient outcomes. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether a new, streamlined, and potent version of the MSI improves outcomes for midlife and older adults. This streamlined MSI is comprised of constructive memory supports that will be applied to a broader range of treatment content. The platform for this study is the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C). We will focus on midlife and older adults who are low income and experiencing mobility impairments. METHODS: Participants (N = 178) will be randomly allocated to TranS-C + MSI or TranS-C alone. Both intervention arms include eight 50-min weekly sessions. Assessments will be conducted at pre-treatment, post-treatment, 6-, and 12-month follow-up (6FU and 12FU). Aim 1 will compare the effects of TranS-C + MSI versus TranS-C alone on sleep and circadian functioning, daytime functioning, well-being, and patient memory. Aim 2 will test whether patient memory for treatment mediates the relationship between treatment condition and patient outcomes. Aim 3 will evaluate if previously reported poor treatment response subgroups will moderate the relationship between treatment condition and (a) patient memory for treatment and (b) treatment outcome. Exploratory analyses will compare treatment condition on (a) patient adherence, patient-rated treatment credibility, and patient utilization of treatment contents, and (b) provider-rated acceptability, appropriateness, and feasibility. DISCUSSION: This study has the potential to provide evidence for (a) the efficacy of a new simplified version of the MSI for maintaining health, well-being, and functioning, (b) the wider application of the MSI for midlife and older adults and to the treatment of sleep and circadian problems, and (c) the efficacy of the MSI for sub-groups who are likely to benefit from the intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05986604. Registered on 2 August 2023.

Internet-based UP-A intervention on treatment of stress, anxiety, depression, and psychological flexibility among adolescents with sub-clinical diagnosis of emotional disorders during the COVID-19 pandemic: a clinical trial.

This clinical trial aims to assess the effectiveness of internet-based Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) during the COVID-19 pandemic in reducing stress, anxiety, and depression, and psychological flexibility. 40 adolescents with subclinical features of emotional disorder randomly divided into two groups of intervention and control. The participants first completed DASS-21 and AAQ-2 questionnare online. Then, the intervention group received 12 sessions of UP-A through video calls on WhatsApp, 2 days per week each for 45 min. UP-A is an emotion-focused, cognitive-behavioral therapy consisting of 5 core modules or components that target temperamental characteristics, particularly neuroticism and resulting emotion dysregulation. Eventually the stress, anxiety, and depression levels decreased in intervention group and their psychological flexibility increased immediately and 3 months after the intervention. Clinical trial registration This study was registered by Iranian Registry of Clinical Trials (Prospective, ID: IRCT20210428051113N1, Registration date: 14/06/2021; https://en.irct.ir/trial/55900 ).

Through the eyes of the parents: a transdiagnostic psychiatric perspective for children with differences of sexual development.

PURPOSE: Existing literature lacks data on a subgroup exhibiting psychiatric symptoms below the DSM-5 diagnostic threshold within DSD cases. Our study aims to assess parental knowledge, attitudes toward DSD, and parental perceptions of emotional and behavioral states through a transdiagnostic perspective. METHODS: The study was conducted with a total of 35 parents of children with DSD. Two groups were established via k-means clustering, based on psychiatric symptomatology levels, derived from The Strength and Difficulties Questionnaire - Parent Form and The Revised Children's Anxiety and Depression Scale - Parent Form: with one group exhibiting lower reported psychiatric symptoms (LPS=27) and the other demonstrating higher psychiatric symptoms (HPS=8) by parents. RESULTS: Our study found that many parents were hesitant to disclose DSD diagnoses to their children, believing them to be too young to comprehend the information (42.9 %) and that they were unaware of the available support that could be provided by the medical team in disclosing the diagnosis (25.7 %). Our study found no differences in DSM-5 diagnoses between HPS and LPS groups (p>0.05), with ADHD being the most prevalent diagnosis (21.7 %) and a significant overrepresentation of children with a discrepancy between assigned gender at birth and gender upbringing in the HPS group compared to the LPS group (p<0.001). CONCLUSIONS: Our study emphasizes the necessity of a transdiagnostic approach in psychiatry to move beyond binary conceptualizations and better understand the complexities of individuals with DSD.

Classification of psychosis spectrum disorders using graph convolutional networks with structurally constrained functional connectomes.

This article considers the problem of classifying individuals in a dataset of diverse psychosis spectrum conditions, including persons with subsyndromal psychotic-like experiences (PLEs) and healthy controls. This task is more challenging than the traditional problem of distinguishing patients with a diagnosed disorder from controls using brain network features, since the neurobiological differences between PLE individuals and healthy persons are less pronounced. Further, examining a transdiagnostic sample compared to controls is concordant with contemporary approaches to understanding the full spectrum of neurobiology of psychoses. We consider both support vector machines (SVMs) and graph convolutional networks (GCNs) for classification, with a variety of edge selection methods for processing the inputs. We also employ the MultiVERSE algorithm to generate network embeddings of the functional and structural networks for each subject, which are used as inputs for the SVMs. The best models among SVMs and GCNs yielded accuracies >63%. Investigation of network connectivity between persons with PLE and controls identified a region within the right inferior parietal cortex, called the PGi, as a central region for communication among modules (network hub). Class activation mapping revealed that the PLE group had salient regions in the dorsolateral prefrontal, orbital and polar frontal cortices, and the lateral temporal cortex, whereas the controls did not. Our study demonstrates the potential usefulness of deep learning methods to distinguish persons with subclinical psychosis and diagnosable disorders from controls. In the long term, this could help improve accuracy and reliability of clinical diagnoses, provide neurobiological bases for making diagnoses, and initiate early intervention strategies.

Patterns of abnormal activations in severe mental disorders a transdiagnostic data-driven meta-analysis of task-based fMRI studies.

BACKGROUND: Studies suggest severe mental disorders (SMDs), such as schizophrenia, major depressive disorder and bipolar disorder, are associated with common alterations in brain activity, albeit with a graded level of impairment. However, discrepancies between study findings likely to results from both small sample sizes and the use of different functional magnetic resonance imaging (fMRI) tasks. To address these issues, data-driven meta-analytic approach designed to identify homogeneous brain co-activity patterns across tasks was conducted to better characterize the common and distinct alterations between these disorders. METHODS: A hierarchical clustering analysis was conducted to identify groups of studies reporting similar neuroimaging results, independent of task type and psychiatric diagnosis. A traditional meta-analysis (activation likelihood estimation) was then performed within each of these groups of studies to extract their aberrant activation maps. RESULTS: A total of 762 fMRI study contrasts were targeted, comprising 13 991 patients with SMDs. Hierarchical clustering analysis identified 5 groups of studies (meta-analytic groupings; MAGs) being characterized by distinct aberrant activation patterns across SMDs: (1) emotion processing; (2) cognitive processing; (3) motor processes, (4) reward processing, and (5) visual processing. While MAG1 was mostly commonly impaired, MAG2 was more impaired in schizophrenia, while MAG3 and MAG5 revealed no differences between disorder. MAG4 showed the strongest between-diagnoses differences, particularly in the striatum, posterior cingulate cortex, and ventromedial prefrontal cortex. CONCLUSIONS: SMDs are characterized mostly by common deficits in brain networks, although differences between disorders are also present. This study highlights the importance of studying SMDs simultaneously rather than independently.

Study protocol TransTAM: Transdiagnostic research into emotional disorders and cognitive-behavioral therapy of the adaptive mind.

BACKGROUND: Emotional disorders such as depression and anxiety disorders share substantial similarities in their etiology and treatment. In recent decades, these commonalities have been increasingly recognized in classification systems and treatment programs crossing diagnostic boundaries. METHODS: To examine the prospective effects of different transdiagnostic markers on relevant treatment outcomes, we plan to track a minimum of N = 200 patients with emotional disorders during their routine course of cognitive behavioral therapy at two German outpatient clinics. We will collect a wide range of transdiagnostic markers, ranging from basic perceptual processes and self-report measures to complex behavioral and neurobiological indicators, before entering therapy. Symptoms and psychopathological processes will be recorded before entering therapy, between the 20th and 24th therapy session, and at the end of therapy. DISCUSSION: Our results could help to identify transdiagnostic markers with high predictive power, but also provide deeper insights into which patient groups with which symptom clusters are less likely to benefit from therapy, and for what reasons. TRIAL REGISTRATION: The trial was preregistered at the German Clinical Trial Register (DRKS-ID: DRKS00031206; 2023-05-09).

Update and validation of the Beliefs about Losing Control Inventory-II (BALCI-II): a psychometric investigation.

The Beliefs about Losing Control Inventory (BALCI) was developed to assess negative beliefs about losing control in obsessive-compulsive disorder (OCD). Since its creation, research and theoretical work support negative beliefs about losing control as a potential transdiagnostic construct. The present study revised and expanded the original BALCI to be more inclusive of control-related concerns beyond those that would be expected in OCD (e.g. concerns about losing control over how one comes across to others in social anxiety disorder; SAD). Undergraduate students (N = 440) completed a questionnaire battery including the BALCI-II item pool. An exploratory factor analysis of the 32-item BALCI-II supported a four-factor solution. Three of the identified factors capture the feared consequences of losing control: 1) overwhelming emotions, 2) dangerous behaviour, and 3) madness. The fourth factor captures inflated beliefs about probability/severity of those losses. The BALCI-II was found to have good convergent and divergent validity, good to excellent internal, and retest reliability and was shown to have predictive utility in both OCD and SAD, above and beyond existing disorder-specific maladaptive belief domains. Results suggest the BALCI-II is an improvement over the previous version and supports the relevance of these beliefs beyond OCD.

A 'Problematic' Pattern of Power-system Functioning and its Association with psychopathological Symptoms.

Following the well-researched two-dimensional model of attachment-system functioning, based on the concepts of hyperactivation and deactivation, a two-dimensional model of the power behavioral system has recently been proposed. The power system is aimed at activating, organizing, and implementing action patterns that protect or restore a sense of power or dominance. Here, we tested predictions derived from the two-dimensional model of power-system functioning regarding the contribution of a 'problematic' high-high pattern, characterized by the coexistence of both hyperactivating and deactivating strategies, to psychopathological symptoms. A non-clinical sample of Italian adults (N = 385) completed the Power Behavioral System Scale together with self-report measures of anxiety and depression symptoms and difficulties in executive control. Multiple regression analyses showed that higher deactivation and hyperactivation scores, characteristic of the 'problematic' pattern, significantly predicted anxiety and depression symptoms as well as executive function difficulties. These results provide initial support for the pathogenic implications of the 'problematic' high-high pattern of power-system functioning.

The Unified Protocol or Dialectical Behaviour Therapy? Considerations for Choosing Between Two Evidence-Based Transdiagnostic Psychotherapies for Complex Patients.

The advent of multiple transdiagnostic treatments in recent decades has advanced the field of clinical psychology while also raising questions for clinicians and patients about how to decide between treatments and how to best deliver a chosen treatment. The purpose of this paper is to review two prominent transdiagnostic treatments that target emotion dysregulation: dialectical behaviour therapy and the unified protocol for transdiagnostic treatment for emotional disorders. First, we review the theoretical underpinnings, research support and proposed mechanisms of action for these treatments. Next, we discuss patient and therapist variables that might indicate which treatment is more appropriate for a given patient and discuss decision-making guidelines to help make this determination with an emphasis on complex patients who may present with risk and/or clinical comorbidities. Finally, we discuss areas for future research that can help further ensure we work to match patients to the treatment that is most likely to benefit them.

Elevations in depression and anxiety symptoms prior to discharge from partial hospitalization.

Discharge from psychiatric treatment has been established as an emotionally intense and vulnerable time for patients; however, to date no studies have investigated symptoms directly preceding discharge and the impact on post-discharge outcomes. Our primary aim was to assess the prevalence of elevations in depression and anxiety symptoms prior to discharge from a partial hospitalization program (PHP). Our secondary aim was to assess whether these pre-discharge elevations predict post-discharge outcomes. We analyzed daily depression and anxiety symptom severity from 4211 patients attending a PHP. Two subsamples (n = 113 and n = 70) completed post-discharge outcome measures of symptom severity, well-being, and/or functional impairment at two-weeks, one-month, and three-months post-discharge. Approximately two-thirds of patients demonstrated a significant increase in depression (p < .001) and anxiety (p < .001) symptom severity prior to discharge. These pre-discharge elevations did not significantly predict post-discharge measures when controlling for symptom severity at discharge. Our results suggest patients experience an increase in symptom severity preceding discharge, even after improvement; however, these elevations do not provide additional prognostic information. Clinicians may consider sharing these results with patients to normalize the experience of symptom elevation prior to discharge and highlight that it is not a prognostic indicator.

Cognitive remediation therapy for patients with eating disorders: a qualitative study.

BACKGROUND: Transdiagnostic Cognitive Remediation Therapy (TCRT) is a new adaptation of cognitive remediation therapy for eating disorders (EDs) developed to address common cognitive difficulties across ED diagnoses (i.e., cognitive flexibility, central coherence, and impulsivity). This is the first evaluation of this novel treatment. The aim of this study was to explore acceptability and patients' experience of TCRT. METHODS: Thirteen patients diagnosed with restrictive or binge/purge subtypes of EDs and concurrent cognitive difficulties completed semi-structured qualitative interviews after receiving TCRT. Interview transcripts were analyzed using reflexive thematic analysis. RESULTS: The analysis resulted in four main themes: (1) Treatment fit (2), Treatment experience (3), Perceived outcomes, and (4) Future recommendations. Eleven of the thirteen patients evaluated the treatment positively, found the focus relevant and expressed how it contributed to new insights related to thinking style. Seven of the patients also described it as a starting point for making changes and using new strategies. Importantly, experiencing some challenges related to the cognitive difficulties addressed in the treatment seemed essential for engagement. CONCLUSION: Offering TCRT as an adjunctive treatment for patients with EDs and concurrent cognitive difficulties can be a way to engage patients in treatment, build therapeutic alliances and provide important awareness and strategies to handle challenges related to thinking style. TRIAL REGISTRATION: This study is part of a larger randomized controlled trial, ClinicalTrials.gov Id: NCT03808467.

Cognitive difficulties are thought to be one of several factors contributing to the development and maintenance of eating disorders (ED), but are rarely addressed in ED treatments. Cognitive remediation therapy (CRT) for EDs is a supplementary treatment originally developed for patients with anorexia nervosa (AN) that specifically targets cognitive difficulties. However, cognitive difficulties are found across ED diagnoses and not only in patients with AN. In this study, we have adapted CRT to address cognitive difficulties across ED diagnoses. The goal of this study was to explore patients' experiences of this novel transdiagnostic CRT. We interviewed 13 individuals with various eating disorders after they had received the treatment. Eleven of the participants rated the treatment positively, expressed that it was engaging, offered something new and made them more aware of their thought processes. Seven participants also reported using new strategies to handle challenges related to cognitive difficulties. Importantly, one participant expressed that she did not experience cognitive difficulties and chose to drop out of the treatment, highlighting the importance of finding the treatment relevant to foster engagement.

Sleep disturbance and other co-occurring conditions in autistic children: A network approach to understanding their inter-relationships.

Autistic children frequently have one or more co-occurring psychological, behavioral, or medical conditions. We examined relationships between child behaviors, sleep, adaptive behavior, autistic traits, mental health conditions, and health in autistic children using network analysis. Network analysis is hypothesis generating and can inform our understanding of relationships between multiple conditions and behaviors, directing the development of transdiagnostic treatments for co-occurring conditions. Participants were two child cohorts from the Autism Treatment Network registry: ages 2-5 years (n = 2372) and 6-17 years (n = 1553). Least absolute-shrinkage and selection operator (LASSO) regularized partial correlation network analysis was performed in the 2-5 years cohort (35 items) and the 6-17 years cohort (36 items). The Spinglass algorithm determined communities within each network. Two-step expected influence (EI2) determined the importance of network variables. The most influential network items were sleep difficulties (2 items) and aggressive behaviors for young children and aggressive behaviors, social problems, and anxious/depressed behavior for older children. Five communities were found for younger children and seven for older children. Of the top three most important bridge variables, night-waking/parasomnias and anxious/depressed behavior were in both age-groups, and somatic complaints and sleep initiation/duration were in younger and older cohorts respectively. Despite cohort differences, sleep disturbances were prominent in all networks, indicating they are a transdiagnostic feature across many clinical conditions, and thus a target for intervention and monitoring. Aggressive behavior was influential in the partial correlation networks, indicating a potential red flag for clinical monitoring. Other items of strong network importance may also be intervention targets or screening flags.

Efficacy of the unified protocol for transdiagnostic treatment of comorbid emotional disorders in patients with ultra high risk for psychosis: Results of a randomized controlled trial.

BACKGROUND: The most common reason for help-seeking in ultra-high risk (UHR) for psychosis patients is comorbid symptoms, mainly anxiety and depression. However, psychological interventions are mainly focused on subthreshold psychotic symptoms. There is a growing push to include transdiagnostic therapies in specialized intervention teams for psychosis in young people. The Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders (UP) has demonstrated efficacy in emotional disorders, and its application has recently expanded to other pathologies such as borderline personality disorder (BPD) and bipolar disorder (BD). METHODS: This pilot study was conducted with 36 patients with UHR for psychosis and symptoms of comorbid emotional disorders who were receiving treatment in an early intervention programme for psychosis. This is a randomised control trial (RCT) with two conditions: treatment as usual (TAU) with the group and online application of the UP (UP+TAU) (n = 18) and TAU (n = 18). Evaluations were conducted at baseline, after treatment, and at the three-month follow-up. RESULTS: Comorbid anxiety and depression symptoms improved significantly in patients in the UP+TAU group compared to those in the TAU. Significant improvements in negative affect, emotional dysregulation, neuroticism, extraversion, functioning, and quality of life were also observed, and satisfaction with the intervention was high. CONCLUSIONS: UP may be an acceptable and effective intervention for the treatment of symptoms of comorbid emotional disorders in patients with UHR for psychosis. LIMITATIONS: The sample size was small, and further studies are needed to test this intervention with larger samples of patients with UHR for psychosis with emotional comorbidities.

Characterization of neural networks involved in transdiagnostic emotion dysregulation from a pilot randomized controlled trial of a neurostimulation-enhanced behavioral intervention.

BACKGROUND: Emotional dysregulation is a serious and impairing mental health problem. We examined functional activity and connectivity of neural networks involved in emotional dysregulation at baseline and following a pilot neurostimulation-enhanced cognitive restructuring intervention in a transdiagnostic clinical adult sample. METHODS: Neuroimaging data were analyzed from adults who scored 89 or higher on the Difficulties with Emotion Regulation (DERS) scale and had at least one DSM-5 diagnosis. These participants were part of a pilot randomized, double-blind, placebo-controlled trial combining a single therapeutic session of cognitive restructuring with active or sham transcranial magnetic stimulation over the dorsolateral prefrontal cortex. During the study, participants engaged in an emotional regulation task using personalized autobiographical stressors while undergoing functional magnetic resonance imaging (fMRI) before and after the pilot intervention. The fMRI task required participants to either experience the emotions associated with the memories or apply cognitive restructuring strategies to reduce their distress. RESULTS: Whole-brain fMRI results during regulation at baseline revealed increased activation in the dorsal frontoparietal network but decreased activation in the supplementary motor area, cingulate cortex, insula, and ventrolateral prefrontal cortex (vlPFC). Emotion dysregulation was associated with greater vmPFC and amygdala activation and functional connectivity between these regions. The strength of functional connectivity between the dlPFC and other frontal regions was also a marker of emotional dysregulation. Preliminary findings from a subset of participants who completed the follow-up fMRI scan showed that active neurostimulation improved behavioral indices of emotion regulation more than sham stimulation. A whole-brain generalized psychophysiological interaction analysis indicated that active neurostimulation selectively increased occipital cortex connectivity with both the insula and the dlPFC. Region-of-interest functional connectivity analyses showed that active neurostimulation selectively increased dlPFC connectivity with the insula and orbitofrontal cortex (OFC). CONCLUSION: Insufficient neural specificity during the emotion regulation process and over-involvement of frontal regions may be a marker of emotional dysregulation across disorders. OFC, vlPFC, insula activity, and connectivity are associated with improved emotion regulation in transdiagnostic adults. In this pilot study, active neurostimulation led to neural changes in the emotion regulation network after a single session; however, the intervention findings are preliminary, given the small sample size. These functional network properties can inform future neuroscience-driven interventions and larger-scale studies.

Contrast avoidance as a diagnostic feature of OCD: A receiver-operator characteristic curve analysis of the contrast avoidance questionnaires.

BACKGROUND: Models focusing on transdiagnostic mechanisms, such as repetitive negative thinking, may be of additive value to existing conceptualizations of obsessive-compulsive disorder (OCD). One such model is the Contrast Avoidance Model (CAM), which posits that individuals with generalized anxiety disorder (GAD) are sensitive to sharp increases in emotions, and use worry to maintain heightened states of negative arousal to avoid these emotional shifts. The current study used receiver operator characteristic (ROC) curve analyses to examine the predictive utility of two contrast avoidance questionnaires in detecting probable OCD. METHODS: Undergraduate students (N = 2880) completed measures of contrast avoidance (CAQ-GE and CAQ-W) and obsessive-compulsive symptoms. A subset of participants were selected for the probable OCD group (n = 431) and the non-OCD group (n = 433). RESULTS: Results showed significant differences in total CAQ-GE and CAQ-W scores between the probable OCD group and the non-OCD group. Area under the curve values demonstrated excellent accuracy in predicting probable OCD on the CAQ-GE and CAQ-W, (.87 and .88, respectively). Correlation analyses for the entire screening sample revealed that certain OC symptom dimensions (e.g., Unacceptable Thoughts; Responsibility for Harm) were more closely associated with the CAQ-GE and the CAQ-W relative to other symptom dimensions. LIMITATIONS: The study had a cross-sectional design and relied on an undergraduate sample. CONCLUSION: Identifying shared mechanisms across OCD and its comorbidities is an important and novel approach to understanding the etiology and maintenance of symptoms.

Common threads: Altered interoceptive processes across affective and anxiety disorders.

There is growing attention towards atypical brain-body interactions and interoceptive processes and their potential role in psychiatric conditions, including affective and anxiety disorders. This paper aims to synthesize recent developments in this field. We present emerging explanatory models and focus on brain-body coupling and modulations of the underlying neurocircuitry that support the concept of a continuum of affective disorders. Grounded in theoretical frameworks like peripheral theories of emotion and predictive processing, we propose that altered interoceptive processes might represent transdiagnostic mechanisms that confer common vulnerability traits across multiple disorders. A deeper understanding of the interplay between bodily states and neural processing is essential for a holistic conceptualization of mental disorders.

Dissecting depression symptoms: Multi-omics clustering uncovers immune-related subgroups and cell-type specific dysregulation.

In a subset of patients with mental disorders, such as depression, low-grade inflammation and altered immune marker concentrations are observed. However, these immune alterations are often assessed by only one data type and small marker panels. Here, we used a transdiagnostic approach and combined data from two cohorts to define subgroups of depression symptoms across the diagnostic spectrum through a large-scale multi-omics clustering approach in 237 individuals. The method incorporated age, body mass index (BMI), 43 plasma immune markers and RNA-seq data from peripheral mononuclear blood cells (PBMCs). Our initial clustering revealed four clusters, including two immune-related depression symptom clusters characterized by elevated BMI, higher depression severity and elevated levels of immune markers such as interleukin-1 receptor antagonist (IL-1RA), C-reactive protein (CRP) and C-C motif chemokine 2 (CCL2 or MCP-1). In contrast, the RNA-seq data mostly differentiated a cluster with low depression severity, enriched in brain related gene sets. This cluster was also distinguished by electrocardiography data, while structural imaging data revealed differences in ventricle volumes across the clusters. Incorporating predicted cell type proportions into the clustering resulted in three clusters, with one showing elevated immune marker concentrations. The cell type proportion and genes related to cell types were most pronounced in an intermediate depression symptoms cluster, suggesting that RNA-seq and immune markers measure different aspects of immune dysregulation. Lastly, we found a dysregulation of the SERPINF1/VEGF-A pathway that was specific to dendritic cells by integrating immune marker and RNA-seq data. This shows the advantages of combining different data modalities and highlights possible markers for further stratification research of depression symptoms.

"So Many Other Things Improve" with Transdiagnostic Treatment for Sleep and Circadian Problems: Interviews with Community Providers on Treating Clients with Serious Mental Illness.

Community mental health centers (CMHCs) offer invaluable, publicly-funded treatment for serious mental illness (SMI). Unfortunately, evidence-based psychological treatments are often not delivered at CMHCs, in part due to implementation barriers, such as limited time, high caseloads, and complex clinical presentations. Transdiagnostic treatments may help address these barriers, because they allow providers to treat symptoms across multiple disorders concurrently. However, little research has investigated CMHC providers' experiences of delivering transdiagnostic treatments "on the ground," particularly for adults with SMI. Thus, the aim of the present study was to assess CMHC providers' perspectives on delivering a transdiagnostic treatment - the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) - to adults diagnosed with SMI. In the context of a larger parent trial, providers were randomized to deliver a standard version of TranS-C (Standard TranS-C) or a version adapted to the CMHC context (Adapted TranS-C). Twenty-five providers from the parent trial participated in a semi-structured interview (n = 10 Standard TranS-C; n = 15 from Adapted TranS-C). Responses were deductively and inductively coded to identify themes related to Proctor's taxonomy of implementation outcomes. Four novel "transdiagnostic take homes" were identified: (1) transdiagnostic targets, such as sleep, can be perceived as motivating and appropriate when treating SMI, (2) strategies to bolster client motivation/adherence and address a wider range of symptom severity may improve transdiagnostic treatments, (3) balancing feasibility with offering in-depth resources is an important challenge for transdiagnostic treatment development, and (4) adapting transdiagnostic treatments to the CMHC context may improve provider perceptions of implementation outcomes.

Sensitivity of the familial high-risk approach for the prediction of future psychosis: a total population study.

Children who have a parent with a psychotic disorder present an increased risk of developing psychosis. It is unclear to date, however, what proportion of all psychosis cases in the population are captured by a familial high-risk for psychosis (FHR-P) approach. This is essential information for prevention research and health service planning, as it tells us the total proportion of psychosis cases that this high-risk approach would prevent if an effective intervention were developed. Through a prospective cohort study including all individuals born in Finland between January 1, 1987 and December 31, 1992, we examined the absolute risk and total proportion of psychosis cases captured by FHR-P and by a transdiagnostic familial risk approach (TDFR-P) based on parental inpatient hospitalization for any mental disorder. Outcomes of non-affective psychosis (ICD-10: F20-F29) and schizophrenia (ICD-10: F20) were identified in the index children up to December 31, 2016. Of the index children (N=368,937), 1.5% (N=5,544) met FHR-P criteria and 10.3% (N=38,040) met TDFR-P criteria. By the study endpoint, 1.9% (N=6,966) of the index children had been diagnosed with non-affective psychosis and 0.5% (N=1,846) with schizophrenia. In terms of sensitivity, of all non-affective psychosis cases in the index children, 5.2% (N=355) were captured by FHR-P and 20.6% (N=1,413) by TDFR-P approaches. The absolute risk of non-affective psychosis was 6.4% in those with FHR-P, and 3.7% in those with TDFR-P. There was notable variation in the sensitivity and total proportion of FHR-P and TDFR-P cases captured based on the age at which FHR-P/TDFR-P were determined. The absolute risk for psychosis, however, was relatively time invariant. These metrics are essential to inform intervention strategies for psychosis risk requiring pragmatic decision-making.