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.

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.

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.

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.

Neurocognitive dysfunction is a transdiagnostic finding in psychopathology, but relationships among cognitive domains and general and specific psychopathology dimensions remain unclear. This study aimed to examine associations between cognition and psychopathology dimensions in a large youth cohort.

The sample (N = 9350; age 8–21 years) was drawn from the Philadelphia Neurodevelopmental Cohort. Data from structured clinical interviews were modeled using bifactor confirmatory factor analysis (CFA), resulting in an overall psychopathology (‘p’) factor score and six orthogonal psychopathology dimensions: dysphoria/distress, obsessive-compulsive, behavioral/externalizing, attention-deficit/hyperactivity, phobias, and psychosis. Neurocognitive data were aggregated using correlated-traits CFA into five factors: executive functioning, memory, complex cognition, social cognition, and sensorimotor speed. We examined relationships among specific and general psychopathology dimensions and neurocognitive factors.

The final model showed both overall and specific associations between cognitive functioning and psychopathology, with acceptable fit (CFI = 0.91; TLI = 0.90; RMSEA = 0.024; SRMR = 0.054). Overall psychopathology and most psychopathology dimensions were negatively associated with neurocognitive functioning (phobias [p < 0.0005], behavioral/externalizing [p < 0.0005], attention-deficit/hyperactivity [p < 0.0005], psychosis [p < 0.0005 to p < 0.05]), except for dysphoria/distress and obsessive-compulsive symptoms, which were positively associated with complex cognition (p < 0.05 and p < 0.01, respectively).

By modeling a broad range of cognitive and psychopathology domains in a large, diverse sample of youth, we found aspects of neurocognitive functioning shared across clinical phenotypes, as well as domain-specific patterns. Findings support transdiagnostic examination of cognitive performance to parse variability in the link between neurocognitive functioning and clinical phenotypes.

The DSM Level 1 Cross-Cutting Symptom Measure (DSM-XC) allows for assessing multiple psychopathological domains. However, its capability to screen for mental disorders in a population-based sample and the impact of adverbial framings (intensity and frequency) on its performance are unknown.

The study was based on cross-sectional data from the 1993 Pelotas birth cohort in Brazil. Participants with completed DSM-XC and structured diagnostic interviews (n = 3578, aged 22, 53.6% females) were included. Sensitivity, specificity, positive (LR+), and negative (LR−) likelihood ratios for each of the 13 DSM-XC domains were estimated for detecting five internalizing disorders (bipolar, generalized anxiety, major depressive, post-traumatic stress, and social anxiety disorders) and three externalizing disorders (antisocial personality, attention-deficit/hyperactivity, and alcohol use disorders). Sensitivities and specificities >0.75, LR+ > 2 and LR− < 0.5 were considered meaningful. Values were calculated for the DSM-XC's original scoring and for adverbial framings.

Several DSM-XC domains demonstrated meaningful screening properties. The anxiety domain exhibited acceptable sensitivity and LR− values for all internalizing disorders. The suicidal ideation, psychosis, memory, repetitive thoughts and behaviors, and dissociation domains displayed acceptable specificity for all disorders. Domains also yielded small but meaningful LR+ values for internalizing disorders. However, LR+ and LR− values were not generally meaningful for externalizing disorders. Frequency-framed questions improved screening properties.

The DSM-XC domains showed transdiagnostic screening properties, providing small but meaningful changes in the likelihood of internalizing disorders in the community, which can be improved by asking frequency of symptoms compared to intensity. The DSM-XC is currently lacking meaningful domains for externalizing disorders.

Emotion regulation tendencies are well-known transdiagnostic markers of psychopathology, but their neurobiological foundations have mostly been examined within the theoretical framework of cortical–subcortical interactions.

We explored the connectome-wide neural correlates of emotion regulation tendencies using functional and diffusion magnetic resonance images of healthy young adults (N = 99; age 20–30; 28 females). We first tested the importance of considering both the functional and structural connectome through intersubject representational similarity analyses. Then, we employed a canonical correlation analysis between the functional–structural hybrid connectome and 23 emotion regulation strategies. Lastly, we sought to externally validate the results on a transdiagnostic adolescent sample (N = 93; age 11–19; 34 females).

First, interindividual similarity of emotion regulation profiles was significantly correlated with interindividual similarity of the functional–structural hybrid connectome, more so than either the functional or structural connectome. Canonical correlation analysis revealed that an adaptive-to-maladaptive gradient of emotion regulation tendencies mapped onto a specific configuration of covariance within the functional–structural hybrid connectome, which primarily involved functional connections in the motor network and the visual networks as well as structural connections in the default mode network and the subcortical–cerebellar network. In the transdiagnostic adolescent dataset, stronger functional signatures of the found network were associated with higher general positive affect through more frequent use of adaptive coping strategies.

Taken together, our study illustrates a gradient of emotion regulation tendencies that is best captured when simultaneously considering the functional and structural connections across the whole brain.

To evaluate the clinical efficacy of COMPASS, a therapist-supported digital therapeutic for reducing psychological distress (anxiety/depression) in people living with long-term physical health conditions (LTCs).

A two-armed randomized-controlled trial recruiting from LTC charities. Participants with anxiety and/or depression symptoms related to their LTC(s) were randomized (concealed allocation via independent administrator) to COMPASS (access to 11 tailored modules plus five thirty-minute therapist support sessions) or standard charity support (SCS). Assessments were completed online pre-randomization, at 6- and 12-weeks post-randomization. Primary outcome was Patient Health Questionnaire Anxiety and Depression Scale; PHQ-ADS measured at 12-weeks. Analysis used intention-to-treat principles with adjusted mean differences estimated using linear mixed-effects models. Data-analyst was blinded to group allocation.

194 participants were randomized to COMPASS (N = 94) or SCS (N = 100). At 12-weeks, mean level of psychological distress was 6.82 (95% confidence interval; CI 4.55–9.10) points lower (p < 0.001) in the COMPASS arm compared with SCS (standardized mean difference of 0.71 (95% CI 0.48–0.95)). The COMPASS arm also showed moderate significant treatment effects on secondary outcomes including depression, anxiety and illness-related distress and small significant effects on functioning and quality-of-life. Rates of adverse events were comparable across the arms. Deterioration in distress at 12-weeks was observed in 2.2% of the SCS arm, and no participants in the COMPASS arm.

Compared with SCS, COMPASS digital therapeutic with minimal therapist input reduces psychological distress at post-treatment (12-weeks). COMPASS offers a potentially scalable implementation model for health services but its translation to these contexts needs further evaluating.

NCT04535778

1. (1) Integrating psychological services into physical health services has the potential to improve access to psychological support for minority groups facing multi-morbidity, such as Irish Travellers. This approach offers a less stigmatised route for individuals to receive help and involves fewer administrative processes, which may pose challenges for those with varying levels of literacy ability.

2. (2) This case example presents initial evidence that short-term transdiagnostic cognitive behavioural therapy can be an effective intervention for reducing depression and anxiety symptoms in older people from an Irish Traveller background.

3. (3) Successful outcomes in this case example hinged on:

   1. (a) A comprehensive formulation that considered the client’s full identity (e.g. cultural identity, intergenerational connections, cohort beliefs, physical health needs) in addition to their presenting problem.

   2. (b) Adapting the intervention to accommodate for culturally relevant aspects of the individual’s presentation. This involved modifying homework to reduce the literacy requirements, involving a trusted family member as a co-therapist, and integrating culturally relevant language into the therapy.

4. (4) This case report underscores the scarcity of rigorous research involving Irish Traveller populations and emphasises the need for further exploration of their experiences of mental health difficulties and engagement with mental health services. Further research should actively involve Irish Travellers to identify unmet needs and explore potential adaptations for therapeutic interventions. This would help to ensure accurate representation and prevent the homogenisation of this diverse group of individuals.

Convergent evidence has suggested atypical relationships between brain structure and function in major psychiatric disorders, yet how the abnormal patterns coincide and/or differ across different disorders remains largely unknown. Here, we aim to investigate the common and/or unique dynamic structure–function coupling patterns across major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ).

We quantified the dynamic structure–function coupling in 452 patients with psychiatric disorders (MDD/BD/SZ = 166/168/118) and 205 unaffected controls at three distinct brain network levels, such as global, meso-, and local levels. We also correlated dynamic structure–function coupling with the topological features of functional networks to examine how the structure–function relationship facilitates brain information communication over time.

The dynamic structure–function coupling is preserved for the three disorders at the global network level. Similar abnormalities in the rich-club organization are found in two distinct functional configuration states at the meso-level and are associated with the disease severity of MDD, BD, and SZ. At the local level, shared and unique alterations are observed in the brain regions involving the visual, cognitive control, and default mode networks. In addition, the relationships between structure–function coupling and the topological features of functional networks are altered in a manner indicative of state specificity.

These findings suggest both transdiagnostic and illness-specific alterations in the dynamic structure–function relationship of large-scale brain networks across MDD, BD, and SZ, providing new insights and potential biomarkers into the neurodevelopmental basis underlying the behavioral and cognitive deficits observed in these disorders.

Obsessive–compulsive disorder (OCD) is a classic disorder on the compulsivity spectrum, with diverse comorbidities. In the current study, we sought to understand OCD from a dimensional perspective by identifying multimodal neuroimaging patterns correlated with multiple phenotypic characteristics within the striatum-based circuits known to be affected by OCD.

Neuroimaging measurements of local functional and structural features and clinical information were collected from 110 subjects, including 51 patients with OCD and 59 healthy control subjects. Linked independent component analysis (LICA) and correlation analysis were applied to identify associations between local neuroimaging patterns across modalities (including gray matter volume, white matter integrity, and spontaneous functional activity) and clinical factors.

LICA identified eight multimodal neuroimaging patterns related to phenotypic variations, including three related to symptoms and diagnosis. One imaging pattern (IC9) that included both the amplitude of low-frequency fluctuation measure of spontaneous functional activity and white matter integrity measures correlated negatively with OCD diagnosis and diagnostic scales. Two imaging patterns (IC10 and IC27) correlated with compulsion symptoms: IC10 included primarily anatomical measures and IC27 included primarily functional measures. In addition, we identified imaging patterns associated with age, gender, and emotional expression across subjects.

We established that data fusion techniques can identify local multimodal neuroimaging patterns associated with OCD phenotypes. The results inform our understanding of the neurobiological underpinnings of compulsive behaviors and OCD diagnosis.

Affective disturbances in schizophrenia and bipolar disorder may represent a transdiagnostic etiological process as well as a target of intervention. Hypotheses on similarities and differences in various parameters of affective dynamics (intensity, successive/acute changes, variability, and reactivity to stress) between the two disorders were tested.

Experience sampling method was used to assess dynamics of positive and negative affect, 10 times a day over 6 consecutive days. Patients with schizophrenia (n = 46) and patients with bipolar disorder (n = 46) were compared against age-matched healthy controls (n = 46).

Compared to controls, the schizophrenia group had significantly more intense momentary negative affect, a lower likelihood of acute changes in positive affect, and reduced within-person variability of positive affect. The bipolar disorder group was not significantly different from either the schizophrenia group or the healthy control group on any affect indexes. Within the schizophrenia group, level of depression was associated with weaker reactivity to stress for negative affect. Within the bipolar disorder group, level of depression was associated with lower positive affect.

Patients with schizophrenia endured a more stable and negative affective state than healthy individuals, and were less likely to be uplifted in response to happenings in daily life. There is little evidence that these affective constructs characterize the psychopathology of bipolar disorder; such investigation may have been limited by the heterogeneity within group. Our findings supported the clinical importance of assessing multiple facets of affective dynamics beyond the mean levels of intensity.

1. (1) To understand misophonic distress from a CBT perspective.

2. (2) To learn a formulation-driven approach to misophonia.

3. (3) To apply transdiagnostic interventions to misophonia.

4. (4) To learn about misophonia-specific interventions.

5. (5) To consider the value of a multi-dimensional measure of misophonia.

Anxiety disorders are highly prevalent and debilitating conditions that show high comorbidity rates in adolescence. The present article illustrates how Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) was adapted for Iranian adolescents with anxiety disorders.

A total of 54 adolescents with comorbid anxiety disorders participated in a randomized, waitlist-controlled trial of group weekly sessions of either UP-A or waitlist control (WLC). Primary and process of change outcomes were assessed at baseline, posttreatment, and 1-month follow-up.

Significant changes were observed over time on major DSM-5 anxiety disorder symptoms (F(2, 51) = 117.09, p < 0.001), phobia type symptoms (F(2, 51) = 100.67, p < 0.001), and overall anxiety symptoms (F(2, 51) = 196.29, p < 0.001), as well as on emotion regulation strategies of reappraisal (F(2, 51) = 17.03, p < 0.001), and suppression (F(2, 51) = 21.13, p < 0.001), as well as on intolerance of uncertainty dimensions including prospective (F(2, 51) = 74.49, p < 0.001), inhibitory (F(2, 51) = 45.94, p < 0.001), and total intolerance of uncertainty (F(2, 51) = 84.42, p < 0.001), in favor of UP-A over WLC.

Overall, results provide a cultural application of the UP-A and support the protocol as useful for improving anxiety disorders as well as modifying of emotion regulation strategies and intolerance of uncertainty dimensions in Iranian adolescents. Future directions and study limitations are discussed.

Growing research indicates that death anxiety is implicated in many mental health conditions. This increasing evidence highlights a need for scalable, accessible and cost-effective psychological interventions to reduce death anxiety.

The present study outlines the results of a phase I trial for one such treatment: Overcome Death Anxiety (ODA). ODA is the first CBT-based online intervention for fears of death, and is an individualised program requiring no therapist guidance.

A sample of 20 individuals with various mental health diagnoses commenced the ODA program. Death anxiety was assessed at baseline and at post-intervention. Depression, anxiety and stress were also measured.

In total, 50% (10/20) reached the end of the program and completed post-treatment questionnaires. Of these, 60% (6/10) showed a clinically reliable reduction in their overall death anxiety, and 90% (9/10) showed a reduction on at least one facet of death anxiety. There were no adverse events noted.

ODA appears to be a safe and potentially effective treatment for death anxiety. The findings have provided initial evidence to support a randomised controlled trial using a larger sample, to further examine the efficacy of ODA.

This economic evaluation supplements a pragmatic randomized controlled trial conducted in community care settings, which showed superior improvement in the symptoms of adults with anxiety disorders who received 12 sessions of transdiagnostic cognitive-behavioural group therapy in addition to treatment as usual (tCBT + TAU) compared to TAU alone.

This study evaluates the cost-utility and cost-effectiveness of tCBT + TAU over an 8-month time horizon. For the reference case, quality-adjusted life years (QALYs) obtained using the EQ-5D-5L, and the health system perspective were chosen. Alternatively, anxiety-free days (AFDs), derived from the Beck Anxiety Inventory, and the limited societal perspective were considered. Unadjusted incremental cost-effectiveness/utility ratios were calculated. Net-benefit regressions were done for a willingness-to-pay (WTP) thresholds range to build cost-effectiveness acceptability curves (CEAC). Sensitivity analyses were included.

Compared to TAU (n = 114), tCBT + TAU (n = 117) generated additional QALYs, AFDs, and higher mental health care costs from the health system perspective. From the health system and the limited societal perspectives, at a WTP of Can$ 50 000/QALY, the CEACs showed that the probability of tCBT + TAU v. TAU being cost-effective was 97 and 89%. Promising cost-effectiveness results using AFDs are also presented. The participation of therapists from the public health sector could increase cost-effectiveness.

From the limited societal and health system perspectives, this first economic evaluation of tCBT shows favourable cost-effectiveness results at a WTP threshold of Can$ 50 000/QALY. Future research is needed to replicate findings in longer follow-up studies and different health system contexts to better inform decision-makers for a full-scale implementation.

Studies investigating the long-term effect of attention bias modification (ABM) in clinical samples are lacking. This study investigates the 6-months follow-up effect of ABM on depressive symptoms in participant with major depressive disorder with and without comorbid disorders.

We conducted a double-blind randomized sham-controlled trial in 101 participants between 19 November 2019, and 17 August 2021. Follow-up ended 3 April 2022. Participants were allocated to ABM or sham condition twice daily for 14 consecutive days. Primary outcomes were the total score on the Beck Depression Inventory-II (BDI-II) at 6 months, mean Brief State Rumination Inventory (BSRI) score post-treatment and reduction in BSRI post-treatment. Secondary outcome was change in attentional bias (AB). The trial was preregistered in ClinicalTrials.gov (#NCT 04137367).

A total of 118 patients aged 18–65 years were assessed for eligibility, and 101 were randomized and subjected to intention-to-treat analyses. At 6 months, ABM had no effect on depression and anxiety compared to a sham condition. While rumination decreased during the intervention, there was no effect of condition on rumination and AB. Predictor analysis did not reveal differences between participants with ongoing major depressive episode or comorbid anxiety.

Compared to sham training, there was no effect of ABM on depressive symptoms at 6-months follow-up. Since the intervention failed at modifying AB, it is unclear whether changes in AB are related to long-term outcomes.

Quantitatively derived dimensional models of psychopathology enjoy overwhelming empirical support, and a large and active community of psychopathology researchers has been establishing an empirically based dimensional hierarchical taxonomy of psychopathology (or HiTOP) as a strong candidate replacement for the current categorical classification system. The hierarchical nature of this taxonomy implies that different levels of resolution are likely to be optimal for different purposes. Our aim was to identify which level of detail is likely to provide optimal validity and explanatory power with regard to relevant clinical variables.

In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we used data from a sample of 2900 psychiatric outpatients to compare different levels from a bass-ackwards model of psychopathology in relation to psychosocial impairment across different domains (global functioning, inability to work, social functioning, suicidal ideation, history of suicide attempts, history of psychiatric hospitalization).

All functioning indices were significantly associated with general psychopathology, but more complex levels provided significant incremental validity. The optimal level of complexity varied across functioning indices, suggesting that there is no single ‘best’ level for understanding relations between psychopathology and functioning.

Results support the hierarchical organization of psychopathology dimensions with regard to validity considerations and downstream implications for applied assessment. It would be fruitful to develop and implement measurement of these dimensions at the appropriate level for the purpose at hand. These findings can be used to guide HiTOP-consistent assessment in other research and clinical settings.