Exploring Psychosis in Neurodegenerative Dementia: Connecting Symptoms to Neurobiology.

The following commentary discusses a review by Cressot et al. entitled: 'Psychosis in Neurodegenerative Dementias: A Systematic Comparative Review'. The authors describe the epidemiology and phenomenology of psychosis across neurodegenerative dementias. Dementia with Lewy bodies had the highest reported prevalence of psychosis at 74% followed by Alzheimer's disease, 54% and frontotemporal degeneration, 42%. Detailed characterization of psychosis shows differences in the types of hallucinations and delusions by dementia type. These findings suggest that different types of dementia related pathology are associated with high rates of psychosis with more specific symptom profiles than previously appreciated. Understanding the differences and variety of psychotic experiences across dementia types may have diagnostic and therapeutic implications for treating hallucinations and delusions in populations suffering from neurodegenerative diseases.

Effects of a novel, brief psychological therapy (Managing Unusual Sensory Experiences) for hallucinations in first episode psychosis (MUSE FEP): Findings from an exploratory randomised controlled trial.

Hallucinations are a common feature of psychosis, yet access to effective psychological treatment is limited. The Managing Unusual Sensory Experiences for First-Episode-Psychosis (MUSE-FEP) trial aimed to establish the feasibility and acceptability of a brief, hallucination-specific, digitally provided treatment, delivered by a non-specialist workforce for people with psychosis. MUSE uses psychoeducation about the causal mechanisms of hallucinations and tailored interventions to help a person understand and manage their experiences. We undertook a two-site, single-blind (rater) Randomised Controlled Trial and recruited 82 participants who were allocated 1:1 to MUSE and treatment as usual (TAU) (n = 40) or TAU alone (n = 42). Participants completed assessments before and after treatment (2 months), and at follow up (3-4 months). Information on recruitment rates, adherence, and completion of outcome assessments was collected. Analyses focussed on feasibility outcomes and initial estimates of intervention effects to inform a future trial. The trial is registered with the ISRCTN registry 16793301. Criteria for the feasibility of trial methodology and intervention delivery were met. The trial exceeded the recruitment target, had high retention rates (87.8%) at end of treatment, and at follow up (86.6%), with good acceptability of treatment. There were 3 serious adverse events in the therapy group, and 5 in the TAU group. Improvements were evident in both groups at the end of treatment and follow up, with a particular benefit in perceived recovery in the MUSE group. We showed it was feasible to increase access to psychological intervention but a definitive trial requires further changes to the trial design or treatment.

Predicting the onset of psychotic experiences in daily life with the use of ambulatory sensor data - A proof-of-concept study.

INTRODUCTION: Predictive models of psychotic symptoms could improve ecological momentary interventions by dynamically providing help when it is needed. Wearable sensors measuring autonomic arousal constitute a feasible base for predictive models since they passively collect physiological data linked to the onset of psychotic experiences. To explore this potential, we investigated whether changes in autonomic arousal predict the onset of hallucination spectrum experiences (HSE) and paranoia in individuals with an increased likelihood of experiencing psychotic symptoms. METHOD: For 24 h of ambulatory assessment, 62 participants wore electrodermal activity and heart rate sensors and were provided with an Android smartphone to answer questions about their HSE-, and paranoia-levels every 20 min. We calculated random forests to detect the onset of HSEs and paranoia. The generalizability of our models was tested using leave-one-assessment-out and leave-one-person-out cross-validation. RESULTS: Leave-one-assessment-out models that relied on physiological data and participant ID yielded balanced accuracy scores of 80 % for HSE and 66 % for paranoia. Adding baseline information about lifetime experiences of psychotic symptoms increased balanced accuracy to 82 % (HSE) and 70 % (paranoia). Leave-one-person-out models yielded lower balanced accuracy scores (51 % to 58 %). DISCUSSION: Using passively collectible variables to predict the onset of psychotic experiences is possible and prediction models improve with additional information about lifetime experiences of psychotic symptoms. Generalizing to new individuals showed poor performance, so including personal data from a recipient may be necessary for symptom prediction. Completely individualized prediction models built solely with the data of the person to be predicted might increase accuracy further.

Exploring the Spectrum of Visual Illusions and Other Minor Hallucinations in Patients with Parkinson's Disease in Lithuania.

Background and Objectives: Parkinson's disease (PD) is associated with various non-motor symptoms, including minor hallucinations, comprising visual illusions and presence and passage hallucinations. Despite their occurrence, even in newly diagnosed PD patients, data regarding the prevalence and characteristics of minor hallucinations, visual illusions in particular, remain limited. The aim of this study was to address this knowledge gap by assessing the prevalence of minor hallucinations in PD patients, with a focus on visual illusions. Materials and Methods: In this prospective pilot study, we enrolled 35 PD patients without dementia and 35 age- and gender-matched PD-unaffected individuals. Cognitive function was assessed using the Montreal Cognitive Assessment, clinical data were collected, and all subjects were assessed via questionnaires regarding 20 types of visual illusions and other minor hallucinations. Results: The prevalence of minor hallucinations was significantly higher among PD patients compared to controls (45.7% vs. 11.4%, p = 0.003). PD patients reported visual illusions and presence hallucinations more frequently than the controls (37.1% vs. 8.6% and 22.9% vs. 2.9%, p = 0.009 and p = 0.028, respectively), with no significant difference in passage hallucinations (20% vs. 8.6%, p = 0.306). In the PD group, the most frequently observed visual illusions were complex visual illusions, kinetopsia, and pelopsia; the latter was also the most common visual illusion in the control group. PD patients experiencing visual illusions were more likely to report presence hallucinations compared to patients without visual illusions (53.8% vs. 4.5%, p = 0.002); no significant differences in other clinical characteristics were found. Conclusions: Minor hallucinations are a common phenomenon among PD patients without dementia, with a higher prevalence than among healthy controls. Visual illusions are the most prevalent type of minor hallucinations, affecting more than a third of PD patients, with complex visual illusions, kinetopsia, and pelopsia being the most frequently reported types.

Clearing the Fog: A Review of Antipsychotics for Parkinson's-Related Hallucinations: A Focus on Pimavanserin, Quetiapine and Clozapine.

Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care.

Prodromal period of psychosis: diagnostic criteria.

OBJECTIVE: Aim: To study the psychopathological mechanisms of the development of the prodromal stage of psychosis in order to identify risk factors for the formation of psychosis. PATIENTS AND METHODS: Materials and Methods: In this research 137 patients with newly diagnosed psychosis were examined: 65 patients with a diagnosis of paranoid schizophrenia; 72 patients - with a diagnosis of acute polymorphic psychotic disorder. RESULTS: Results: According to the analysis of symptoms using the PANSS, the absence of signs of an anxious state, conceptual disorganization of thinking, emotional withdrowal are reliable signs of PPP in PS, and unusual thought content, absence of signs of stereotyped thinking, tension, anxiety, and hallucinations are reliable signs of PPP in APPD. According to the analysis of symptoms using the SOPS, unusual thought content/delusional ideas, bizarre thinking, social anhedonia, suspiciousness/persecutory ideas, decrease in expressiveness of emotions are reliable signs of PPP in PS, and bizarre thinking, impaired tolerance to normal stress, sleep disturbance, perceptual abnormalities/hallucinations, trouble with focus and attention are reliable signs of PPP in APPD. CONCLUSION: Conclusions: In the process of studying the clinical-psychopathological and pathopsychological aspects of the development of the PPP, a number of risk factors for the formation of psychosis were identified. We found that he most important diagnostic signs of PPP in PS patients are: stereotyped thinking, social isolation, disorganizational thinking disorders, passive-apathetic social detachment, suspiciousness. The most informative prodromal symptoms of HP in PS patients are: conceptual disorganization of thinking, bizzare thinking, social isolation, suspiciousness/persecutory ideas, reduced expression of emotions.

Safety Profile of Pimavanserin Therapy in Elderly Patients with Neurodegenerative Disease-Related Neuropsychiatric Symptoms: A Phase 3B Study.

Background: Pimavanserin, a 5-HT2A receptor inverse agonist/antagonist, is the only medication approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Further expanding knowledge of the safety profile of pimavanserin in PDP and neurodegenerative diseases (NDD) such as Alzheimer's disease is of great interest for informing its use in patients with PDP (with or without dementia), given this population is highly sensitive to adverse effects following antipsychotic use. Objective: This trial evaluated the effects of pimavanserin compared to placebo in frail older adults and elderly patients with neuropsychiatric symptoms related to NDD, such as hallucinations and delusions, to better understand the safety of pimavanserin in this population. Methods: This was a phase 3b, 8-week treatment (study duration of up to 16 weeks), multicenter, randomized, double-blind, placebo-controlled, two-arm parallel-group trial (NCT03575052). The primary endpoint was safety and tolerability, measured by treatment-emergent adverse events (TEAEs). Secondary safety endpoints were change from baseline in motor and cognitive function; exploratory endpoints included suicidality, sleep quality, and neuropsychiatric symptoms. Results: Incidences of TEAEs were similar between treatment groups; 29.8% reported ≥1 TEAE (pimavanserin: 30.4%; placebo: 29.3%), and 1.8% reported serious TEAEs (pimavanserin: 2.0%; placebo: 1.5%). Pimavanserin did not impact motor- or cognitive-related function. Conclusions: Pimavanserin was well tolerated and not associated with motor or cognitive impairment. Together, these findings highlight the manageable and generally favorable safety profile of pimavanserin in patients with NDD, contributing to our knowledge on the safety of pimavanserin as it generalizes to patients with PDP.

Self-assessment scale of auditory verbal hallucinations (SAVH): A novel tool for patients with schizophrenia.

BACKGROUND: A scale for self-assessment of auditory verbal hallucinations (SAVH) was developed for patients, and this study aimed to validate the scale by investigating its psychometric properties. METHODS: Forty one patients with schizophrenia or schizoaffective disorders (DSM-5) self-assessed their hallucinations using nine SAVH questions. Each question was scored from 0 to 5, indicating the severity of the symptoms. Patients were also evaluated with the Brief Psychiatric Rating Scale (BPRS), Auditory Hallucination Rating Scale (AHRS), and Birchwood Insight Scale (BIS). The psychometric properties of the SAVH were assessed by the face, internal consistency, construct, convergent and discriminant validities. RESULTS: SAVH scores were used to examine the psychometric properties. Cronbach's α and Guttman's Lambda-6 were 0.67 and 0.73 respectively. Significant correlations were observed between SAVH and AHRS total scores, as well as BPRS hallucinatory behavior subscores. No significant correlations were found between total SAVH scores and (i) levels of insight or (ii) negative BPRS subscores. Factor analysis on SAVH revealed three factors accounting for 59.3 % of the variance. Most patients found the questions clear, appropriate, and of adequate length. CONCLUSIONS: SAVH demonstrated good psychometric properties, suggesting its utility in assessing auditory verbal hallucinations (AVH). This self-assessment could be valuable in evaluating AVH treatment efficacy, monitoring AVH, and empowering patients.

Functional and structural effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations in schizophrenia: A systematic review.

BACKGROUND: Auditory verbal hallucinations (AVH) are a disabling symptom for people with schizophrenia (SCZ), and do not always respond to antipsychotics. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for medication-refractory AVH, though the underlying neural mechanisms by which rTMS produces these effects remain unclear. This systematic review evaluated the structural and functional impact of rTMS for AVH in SCZ, and its association with clinical outcomes. METHODS: A systematic search was conducted in Medline, PsychINFO, and PubMed using terms for four key concepts: AVH, SCZ, rTMS, neuroimaging. Using PRISMA guidelines, 18 studies were identified that collected neuroimaging data of an rTMS intervention for AVH in SCZ. Risk of bias assessments was conducted. RESULTS: Low frequency (<5 Hz) rTMS targeting left hemispheric language processing regions may normalize brain abnormalities in AVH patients at structural, functional, electrophysiological, and topological levels, with concurrent symptom improvement. Amelioration of aberrant neural activity in frontotemporal networks associated with speech and auditory processing was commonly observed, as well as in cerebellar and emotion regulation regions. Neuroimaging analyses identified neural substrates with direct correlations to post-rTMS AVH severity, propounding their use as therapeutic targets. DISCUSSION: Combined rTMS-neuroimaging highlights the multidimensional alterations of rTMS on brain activity and structure in treatment-resistant AVH, which may be used to develop more efficacious therapies. Larger randomized, sham-controlled studies are needed. Future studies should explore alternate stimulation targets, investigate the neural effects of high-frequency rTMS and evaluate long-term neuroimaging outcomes.

Altered corollary discharge in the auditory cortex could reflect louder inner voice experience in patients with verbal hallucinations, a pilot fMRI study.

INTRODUCTION: Wide range of evidence associates auditory verbal hallucinations (AVH) with frontotemporal corollary discharge deficit. AVH likely reflect altered experiences of the inner voice and are phenomenologically diverse. The aspects of hallucinations (and related inner voice experiences) that could be explained by this deficit remain unclear. To address this important subject, we examined the temporal cortex activity during two tasks with and without corollary discharge. METHODS: We carried out an event-related BOLD fMRI study to examine temporal cortex activity in seven patients and eight healthy controls during two tasks with and without corollary discharge: reading aloud and hearing, respectively. Data were denoised by removing independent components related to head movement and subsequently processed using finite impulse response basis function to address hemodynamic response variations. To mitigate the small sample size, final analyses were carried out using permutation-based analysis of variance. RESULTS: There was a significant group interaction in the Read relative to Hear condition during the early post-stimulus stage in the left Heschl's Gyrus (p<0.01, corrected for multiple comparisons, at peak voxel [-72,53,41]). This effect was driven by a higher activity in the Read relative to the Hear condition in the same area in the patients (p<0.02, corrected). CONCLUSIONS: Our results are consistent with prior literature indicating abnormal frontotemporal disconnection in participants with hallucinations. The functional repercussions of this deficit were limited to the primary auditory cortex in early post-stimulus stage, which suggests louder experience of the inner voice in patients and could account for the loudness of their hallucinations.

Low-frequency rTMS induces modifications in cortical structural connectivity - functional connectivity coupling in schizophrenia patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC-FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC-FC coupling compared to healthy controls. Notably, SC-FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC-FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC-FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low-frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.

Psychopathology and psychosocial functioning among young people with first-episode psychosis and/or first-presentation borderline personality disorder.

BACKGROUND: One in five young people with first-episode psychosis (FEP) also presents with borderline personality disorder (BPD) features. Among people diagnosed with BPD, auditory verbal hallucinations occur in 29-50 % and delusions in 10-100 %. Co-occurrence of psychotic symptoms and BPD is associated with greater clinical severity and greater difficulty accessing evidence based FEP care. This study aimed to investigate psychotic symptoms and psychosocial functioning among young people presenting to an early intervention mental health service. METHOD: According to the presence or absence of either FEP or BPD, 141 participants, aged 15-25 years, were assigned to one of four groups: FEP, BPD, combined FEP + BPD, or clinical comparison (CC) participants with neither FEP nor BPD. Participants completed semi-structured diagnostic interviews and interviewer and self-report measures of psychopathology and psychosocial functioning. RESULTS: The FEP + BPD group had significantly more severe psychopathology and poorer psychosocial functioning than the FEP group on every measure, apart from intensity of hallucinations. Comparing the FEP or BPD groups, the BPD group had greater psychopathology, apart from intensity of psychotic symptoms, which was significantly greater in the FEP group. These two groups did not significantly differ in their overall psychosocial functioning. Compared with CC young people, both the FEP + BPD and BPD groups differed significantly on every measure, with medium to large effect sizes. CONCLUSIONS: Young people with co-occurring FEP and BPD experience more severe difficulties than young people with either diagnosis alone. This combination of psychosis and severe personality pathology has been longitudinally associated with poorer outcomes among adults and requires specific clinical attention.

Interplay between childhood trauma, bodily self-disturbances, and clinical phenomena in schizophrenia spectrum disorders: A network analysis.

BACKGROUND: Bodily self-disturbances have long been considered central to schizophrenia. Exposure to childhood trauma has been linked to the development of both psychosis and bodily self-disturbances, yet little work has examined the role of bodily self-disturbances in the relationship between childhood trauma and schizophrenia symptomatology. This study uses network analysis to bridge this gap. METHODS: Networks were constructed to examine relationships between schizophrenia symptoms (Positive and Negative Symptom Scale; PANSS), bodily self-disturbances (Perceptual Aberration Scale; PAS), and self-reported exposure to childhood trauma (Childhood Trauma Questionnaire, Short-Form; CTQ-SF) in 152 people with a schizophrenia-spectrum disorder. Shortest path and bridge analyses were conducted to assess the role of bodily self-disturbances in linking childhood trauma to schizophrenia symptomatology. Three networks were constructed: 1) PAS, childhood trauma, and PANSS sub-scale composites (positive, negative, general); 2) PAS, childhood trauma, and positive symptoms, 3) PAS, childhood trauma, and distress symptoms. RESULTS: Shortest path analysis revealed that bodily self-disturbances were on the shortest path between childhood trauma and positive and general symptoms (Network 1), between trauma and hallucinations (Network 2), and between trauma and depression (Network 3). Bodily self-disturbances were also found to serve as a bridge between childhood trauma and positive symptoms of schizophrenia, particularly delusions and hallucinations. CONCLUSIONS: Using a novel, data-driven approach, we showed that bodily self-disturbances play a key role in linking childhood trauma to positive and co-morbid affective symptoms of schizophrenia. Threat experiences (i.e., abuse) specifically relate to bodily self-disturbances and psychotic symptoms.

Sleep-Related Hallucinations.

The diagnostic category of sleep-related hallucinations (SRH) replaces the previous category of Terrifying Hypnagogic Hallucinations in the 2001 edition of International Classification of Sleep Disorders-R. Hypnagogic and hypnopompic hallucinations (HHH) that occur in the absence of other symptoms or disorder and, within the limits of normal sleep, are most likely non-pathological. By contrast, complex nocturnal visual hallucinations (CNVH) may reflect a dimension of psychopathology reflecting different combinations of etiologic influences. The identification and conceptualization of CNVH is relatively new, and more research is needed to clarify whether CNVH share common mechanisms with HHH.

Abnormal effective connectivity of reward network in first-episode schizophrenia with auditory verbal hallucinations.

OBJECTIVE: Auditory verbal hallucinations (AVHs) in schizophrenia is proved to be associated with dysfunction of mesolimbic-cortical circuits, especially during abnormal salient and internal verbal resource monitoring processing procedures. However, the information flow among areas involved in coordinated interaction implicated the pathophysiology of AVHs remains unclear. METHODS: We used spectral dynamic causal modeling (DCM) to quantify connections among eight critical hubs of reward network in 86 first-episode drug-naïve schizophrenia patients with AVHs (AVH), 93 patients without AVHs (NAVH), and 88 matched normal controls (NC) using resting-state functional magnetic resonance imaging. Group-level connection coefficients, between-group differences and correlation analysis between image measures and symptoms were performed. RESULT: DCM revealed weaker effective connectivity (EC) from right ventral striatum (RVS) to ventral tegmental area (VTA) in AVH compared to NAVH. AVH showed stronger EC from left anterior insula (AI) to RVS, stronger EC from RVS to anterior cingulate cortex (ACC), and stronger EC from VTA to posterior cingulate cortex (PCC) compared to NC. The correlation analysis results were mostly visible in the negative correlation between EC from right AI to ACC and positive sub-score, P1 sub-score, and P3 sub-score of PNASS in group-level. CONCLUSION: These findings suggest that neural causal interactions between the reward network associated with AVHs are disrupted, expanding the evidence for potential neurobiological mechanisms of AVHs. Particularly, dopamine-dependent salience attribution and top-down monitoring impairments and compensatory effects of enhanced excitatory afferents to ACC, which may provide evidence for a therapeutic target based on direct in vivo of AVHs in schizophrenia.

On hallucinations and memory: the relationship between hallucinations and autobiographical overgenerality in Alzheimer's Disease.

OBJECTIVES: Alzheimer's disease (AD) has been associated with autobiographical overgenerality (i.e. a tendency of patients to retrieve general rather than specific personal memories). AD has also been associated with hallucinations. We investigated the relationship between autobiographical overgenerality and hallucinations in AD. METHODS: We invited 28 patients with mild AD to retrieve autobiographical memories, and we also evaluated the occurrence of hallucinations in these patients. RESULTS: Analysis demonstrated significant correlations between hallucinations and autobiographical overgenerality in the patients. CONCLUSION: AD patients who are distressed by hallucinations may demonstrate autobiographical overgenerality as a strategy to avoid retrieving distressing information that may be related with hallucinations. However, hallucinations as observed in our study can be attributed to other factors such as the general cognitive decline in AD.

Does insecure attachment lead to psychosis via dissociation? A systematic review of the literature.

PURPOSE: Insecure attachment may constitute a vulnerability factor for psychosis, and dissociation may be a key mechanism in the development of auditory hallucinations specifically. While there is good evidence for the role of these processes in isolation, it is unclear whether dissociation accounts for the association between insecure attachment and psychosis. This systematic review takes a theory-driven approach to examine proposed causal relationships across the clinical and nonclinical literature. METHODS: We searched five databases (PubMeD, Web of Science, PsycINFO, CINAHL and ETHOS) for published and unpublished research examining attachment, dissociation and psychosis. Two independent reviewers extracted the data and assessed the quality of all included studies. RESULTS: We identified 242 potential articles and included 13 in the final review (2096 participants). We found that (1) disorganised attachment was consistently associated with dissociation and inconsistently associated with voices and paranoia, (2) dissociation was associated with voices and paranoia, and these links were stronger in clinical samples, and (3) dissociation played a role in the impact of insecure attachment on voice hearing and paranoia in clinical groups. CONCLUSIONS: This is the first review to synthesise the research examining attachment, dissociation, and psychosis. The evidence is consistent with proposed causal hypotheses and raises conceptual and measurement issues, for example, the need to clarify the relative contributions of different insecure attachment styles, and utilise behavioural/observational measures to strengthen study designs. Most importantly, we need experimental and longitudinal studies to confirm causal links and targets for treatment.

Eight-month intensive meditation-based intervention improves refractory hallucinations and delusions and quality of life in male inpatients with schizophrenia: a randomized controlled trial.

AIM: This study investigated the impact of an 8-month daily-guided intensive meditation-based intervention (iMI) on persistent hallucinations/delusions and health-related quality of life (QoL) in male inpatients with schizophrenia with treatment-refractory hallucinations and delusions (TRHDs). METHODS: A randomized controlled trial assigned 64 male inpatients with schizophrenia and TRHD equally to an 8-month iMI plus general rehabilitation program (GRP) or GRP alone. Assessments were conducted at baseline and the third and eighth months using the Positive and Negative Syndrome Scale (PANSS), 36-Item Short Form-36 (SF-36), and Five Facet Mindfulness Questionnaire (FFMQ). Primary outcomes measured PANSS reduction rates for total score, positive symptoms, and hallucinations/delusions items. Secondary outcomes assessed PANSS, SF-36, and FFMQ scores for psychotic symptoms, health-related QoL, and mindfulness skills, respectively. RESULTS: In the primary outcome, iMI significantly improved the reduction rates of PANSS total score, positive symptoms, and hallucination/delusion items compared with GRP at both the third and eighth months. Treatment response rates (≥25% reduction) for these measures significantly increased in the iMI group at the eighth month. Concerning secondary outcomes, iMI significantly reduced PANSS total score and hallucination/delusion items, while increasing scores in physical activity and mindfulness skills at both the third and eighth months compared with GRP. These effects were more pronounced with an 8-month intervention compared with a 3-month intervention. CONCLUSIONS: An iMI benefits patients with TRHDs by reducing persistent hallucinations/delusions and enhancing health-related QoL. Longer iMI duration yields superior treatment outcomes.