Voice phenomenology as a mirror of the past.

BACKGROUND: Post-traumatic mechanisms are theorised to contribute to voice-hearing in people with psychosis and a history of trauma. Phenomenological links between trauma and voices support this hypothesis, as they suggest post-traumatic processes contribute to the content of, and relationships with, voices. However, research has included small samples and lacked theory-based comprehensive assessments. METHOD: In people with distressing voices (n = 73) who experienced trauma prior to voice-hearing, trauma-voice links were assessed both independently and dependently (descriptions were presented and rated separately and together, respectively) by both participants and researchers. A structured coding frame assessed four types of independent links (i.e. victimisation type, physiological-behavioural, emotional, and cognitive response themes including negative self-beliefs) and three types of dependent links: relational (similar interaction with/response to, voice and trauma); content (voice and trauma content are exactly the same); and identity (voice identity is the same as perpetrator). RESULTS: Independent links were prevalent in participants (51-58%) and low to moderately present in researcher ratings (8-41%) for significant themes. Identification of negative self-beliefs in trauma was associated with a significantly higher likelihood of negative self-beliefs in voices [participants odds ratio (OR) 9.8; researchers OR 4.9]. Participants and researchers also reported many dependent links (80%, 66%, respectively), most frequently relational links (75%, 64%), followed by content (60%, 25%) and identity links (51%, 22%). CONCLUSION: Trauma appears to be a strong shaping force for voice content and its psychological impact. The most common trauma-voice links involved the experience of cognitive-affective psychological threat, embodied in relational experiences. Trauma-induced mechanisms may be important intervention targets.

Networks underpinning emotion: A systematic review and synthesis of functional and effective connectivity.

Existing models of emotion processing are based almost exclusively on brain activation data, yet make assumptions about network connectivity. There is a need to integrate connectivity findings into these models. We systematically reviewed all studies of functional and effective connectivity employing tasks to investigate negative emotion processing and regulation in healthy participants. Thirty-three studies met inclusion criteria. A quality assessment tool was derived from prominent neuroimaging papers. The evidence supports existing models, with primarily limbic regions for salience and identification, and frontal areas important for emotion regulation. There was mixed support for the assumption that regulatory influences on limbic and sensory areas come predominantly from prefrontal areas. Rather, studies quantifying effective connectivity reveal context-dependent dynamic modulatory relationships between occipital, subcortical, and frontal regions, arguing against purely top-down regulatory theoretical models. Our quality assessment tool found considerable variability in study design and tasks employed. The findings support and extend those of previous syntheses focused on activation studies, and provide evidence for a more nuanced view of connectivity in networks of human emotion processing and regulation.

Testing the combination of Feeling Safe and peer counselling against formulation-based cognitive behaviour therapy to promote psychological wellbeing in people with persecutory delusions: study protocol for a randomized controlled trial (the Feeling Safe-NL Trial).

BACKGROUND: Persecutory delusions are strong threat beliefs about others' negative intentions. They can have a major impact on patients' day-to-day life. The Feeling Safe Programme is a new translational cognitive-behaviour therapy that helps patients modify threat beliefs and relearn safety by targeting key psychological causal factors. A different intervention approach, with growing international interest, is peer counselling to facilitate personal recovery. Combining these two approaches is a potential avenue to maximize patient outcomes. This combination of two different treatments will be tested as the Feeling Safe-NL Programme, which aims to promote psychological wellbeing. We will test whether Feeling Safe-NL is more effective and more cost-effective in improving mental wellbeing and reducing persecutory delusions than the current guideline intervention of formulation-based CBT for psychosis (CBTp). METHODS: A single-blind parallel-group randomized controlled trial for 190 out-patients who experience persecutory delusions and low mental wellbeing. Patients will be randomized (1:1) to Feeling Safe-NL (Feeling Safe and peer counselling) or to formulation-based CBTp, both provided over a period of 6 months. Participants in both conditions are offered the possibility to self-monitor their recovery process. Blinded assessments will be conducted at 0, 6 (post-treatment), 12, and 18 months. The primary outcome is mental wellbeing. The overall effect over time (baseline to 18-month follow-up) and the effects at each timepoint will be determined. Secondary outcomes include the severity of the persecutory delusion, general paranoid ideation, patient-chosen therapy outcomes, and activity. Service use data and quality of life data will be collected for the health-economic evaluation. DISCUSSION: The Feeling Safe-NL Trial is the first to evaluate a treatment for people with persecutory delusions, while using mental wellbeing as the primary outcome. It will also provide the first evaluation of the combination of a peer counselling intervention and a CBT-based program for recovery from persecutory delusions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25766661 (retrospectively registered 7 July 2022).

Voice-hearers' beliefs about the causes of their voices.

Despite empirical evidence for multifactorial causes of voice-hearing, people's own beliefs about what caused their voices are understudied. People with distressing voices (n=125) completed measures of trauma, post-traumatic stress disorder (PTSD) symptoms, and beliefs about causality. Most participants reported trauma in the past (97%) and PTSD symptoms were prevalent. Traumatic experiences were the most commonly endorsed causal factor of voice-hearing (64%), followed by distress (62%). Beliefs about biological causes, including drug use (22%), were least endorsed. Those who experienced more traumatic events and more PTSD symptoms were more likely to endorse trauma as a causal factor of voice-hearing (R2=0.38).

Deep brain stimulation response in obsessive-compulsive disorder is associated with preoperative nucleus accumbens volume.

BACKGROUND: Deep brain stimulation (DBS) is a new treatment option for patients with therapy-resistant obsessive-compulsive disorder (OCD). Approximately 60% of patients benefit from DBS, which might be improved if a biomarker could identify patients who are likely to respond. Therefore, we evaluated the use of preoperative structural magnetic resonance imaging (MRI) in predicting treatment outcome for OCD patients on the group- and individual-level. METHODS: In this retrospective study, we analyzed preoperative MRI data of a large cohort of patients who received DBS for OCD (n = 57). We used voxel-based morphometry to investigate whether grey matter (GM) or white matter (WM) volume surrounding the DBS electrode (nucleus accumbens (NAc), anterior thalamic radiation), and whole-brain GM/WM volume were associated with OCD severity and response status at 12-month follow-up. In addition, we performed machine learning analyses to predict treatment outcome at an individual-level and evaluated its performance using cross-validation. RESULTS: Larger preoperative left NAc volume was associated with lower OCD severity at 12-month follow-up (pFWE < 0.05). None of the individual-level regression/classification analyses exceeded chance-level performance. CONCLUSIONS: These results provide evidence that patients with larger NAc volumes show a better response to DBS, indicating that DBS success is partly determined by individual differences in brain anatomy. However, the results also indicate that structural MRI data alone does not provide sufficient information to guide clinical decision making at an individual level yet.

Using fMRI and machine learning to predict symptom improvement following cognitive behavioural therapy for psychosis.

Cognitive behavioural therapy for psychosis (CBTp) involves helping patients to understand and reframe threatening appraisals of their psychotic experiences to reduce distress and increase functioning. Whilst CBTp is effective for many, it is not effective for all patients and the factors predicting a good outcome remain poorly understood. Machine learning is a powerful approach that allows new predictors to be identified in a data-driven way, which can inform understanding of the mechanisms underlying therapeutic interventions, and ultimately make predictions about symptom improvement at the individual patient level. Thirty-eight patients with a diagnosis of schizophrenia completed a social affect task during functional MRI. Multivariate pattern analysis assessed whether treatment response in those receiving CBTp (n = 22) could be predicted by pre-therapy neural responses to facial affect that was either threat-related (ambiguous 'neutral' faces perceived as threatening in psychosis, in addition to angry and fearful faces) or prosocial (happy faces). The models predicted improvement in psychotic (r = 0.63, p = 0.003) and affective (r = 0.31, p = 0.05) symptoms following CBTp, but not in the treatment-as-usual group (n = 16). Psychotic symptom improvement was predicted by neural responses to threat-related affect across sensorimotor and frontal-limbic regions, whereas affective symptom improvement was predicted by neural responses to fearful faces only as well as prosocial affect across sensorimotor and frontal regions. These findings suggest that CBTp most likely improves psychotic and affective symptoms in those endorsing more threatening appraisals and mood-congruent processing biases, respectively, which are explored and reframed as part of the therapy. This study improves our understanding of the neurobiology of treatment response and provides a foundation that will hopefully lead to greater precision and tailoring of the interventions offered to patients.