Psychosis is a serious comorbidity to Parkinson's disease associated with high levels of distress and disability but access to effective treatments remain limited, leading to high rates of emergency hospitalization. Here, we propose a new framework for how cognitive behavioural therapy (CBT) may be used to treat Parkinson's disease psychosis. We note specific adaptions, including aims that focus on reducing distress and disability and extending quality of life; tailored psychoeducation; assessment and formulation that additionally includes disease course, medication effects and side-effects, and Parkinson's specific social factors; addressing anxiety and depression alongside cognitive appraisals for the types of psychotic symptoms more common in Parkinson's disease; appropriate reality testing sensitive to disease progression; and trigger monitoring and management for hallucinations and delusions that carefully distinguishes this from avoidant coping. We review preliminary case study-level evidence for the successful use of CBT for Parkinson's disease psychosis and suggest a road map for its formal evaluation before integration into evidence-based healthcare.

Evidence suggests that attenuated mismatch negative (MMN) waves have a close link to auditory verbal hallucinations (AVH) and their clinical outcomes, especially impaired neural oscillations such as θ, β representing attentional control. In current study, thirty patients with schizophrenia and AVH (SZ) and twenty-nine healthy controls (HC) underwent multi-feature MMN paradigm measurements including frequency and duration deviant stimuli (fMMN and dMMN). Clinical symptoms and MMN paradigm were followed up among SZ group after 8-week treatment. Results demonstrated that hallucinating patients exhibited attenuated dMMN amplitudes across Fz (p = 0.010), F1 (p = 0.020) and F2 (p = 0.014) electrodes, which were trendily recovered after treatment. Meanwhile, θ band and TBR at frontal fMMN and right temporal dMMN were significantly reduced in SZs. After treatment, SZs showed reduced scores of Hoffman's Auditory Hallucinations Rating Scale (AHRS), with a remarkable recovery in right temporal TBR of dMMN (p = 0.042) and a trending change in frontal TBR of fMMN (p = 0.090). The β band was decreased in dMMN (p = 0.035) by time. Additionally, P3 scores of Positive and Negative Syndrome Scale (PANSS) were negatively correlated with θ band of fMMN at baseline. Baseline scores of AHRS negatively predicted changes of dMMN amplitude after treatment, and changes of β band in left temporal dMMN predicted the reduction in scores of PANSS negative scale. These findings supported that deficits in θ oscillation and TBR during auditory attention process were crucial to clinical progression of schizophrenia with AVH.

The objective of this scoping review is to identify and describe a synthesis of psychological interventions to reduce auditory hallucinations in persons with psychosis in Low- and Middle-Income Countries (LMIC), and examine the effectiveness of these intervention.

This scoping review followed Arksey and O'Malley's framework. We searched MEDLINE (Pubmed), Embase, Cochrane Library, CINAHL, PsycINFO, and Psyndex databases for sources published in English between 2015 and 2025 related to interventions on auditory hallucinations in Low- and Middle-Income Countries.

Three psychological interventions were identified; Cognitive-behaviour Therapy for Psychosis, Acceptance and Commitment Therapy, and Music interventions. The intervention was delivered by psychologist. The outcome of these interventions was noted to reduce voice-related distress levels and this sustained during follow-up assessments. Adapting these interventions to the native language and culturally specific examples resulted in lower attrition rates.

To better understand the effectiveness of psychological interventions for mental health issues in LMICs, targeted research and multi-side studies are crucial. Engaging additional mental health professionals, such as nurses and occupational therapists, can enhance the effectiveness of these interventions.

Suicide is a major concern in individuals with psychotic disorders, with suicidality often emerging during the early stages of psychosis, when insight into psychosis-related changes in perception and thought is intact. Examining the association between suicidality and positive symptoms at an early phase of the illness can shed light on factors associated with the emergence of suicidality and inform prevention efforts. This study utilized data from the North American Prodrome Longitudinal Study Phase 3 to investigate whether positive symptoms and suicidality covaried over time in individuals at Clinical High Risk for Psychosis (CHR-P). Measures of suicidal ideation and positive symptoms, including hallucinations and delusions, were obtained at two-month intervals over an 8-month period among 464 CHR-P participants. Individuals who reported suicidal ideation at baseline and at later assessment timepoints (n = 92) in addition to those who reported suicidal ideation only at follow up assessment timepoints (n = 101) were found to exhibit sustained higher levels of positive symptom severity, specifically hallucinations and delusions, compared with individuals with remitted (n = 48) or absent (n = 223) suicidality, in whom positive symptoms declined significantly over the follow-up interval. This association remained significant after controlling for severity of depression symptoms (other than suicidality) at baseline and as a time-varying covariate. These findings highlight that hallucinations and delusions may be key factors in the emergence and persistence of suicidal ideation in CHR-P populations. This study underlines the potential to add targeted suicide prevention strategies in addressing specific positive symptoms (i.e., hallucinations and delusions) in early psychosis.

Both a shortage and an excess of dopamine (DA) in the prefrontal cortex and striatum result in their decreased functions, and the relationship between the DA levels and their functions exhibits an inverted-U shape. Increased DA transmission via dose reduction in the currently used antipsychotics may improve the activation of DA-related symptoms in schizophrenia; these include delusions and auditory hallucinations caused by increased DA release. In this case, reducing the dose of the antipsychotic may be a treatment option for relapse in patients with schizophrenia who are already on high doses of antipsychotics and find it difficult to further increase the dose. A total of 54 inpatients with schizophrenia receiving high-dose antipsychotic therapy were randomly assigned to either the halved-dose group or the high-dose group (symptomatic treatment). The study compared the time from relapse to improvement between the two groups. In the halved-dose group, the period until relapse improvement ranged from 1 to 3 weeks, while the high-dose group experienced improvement in 4 to 9 weeks, and a significant difference was observed between the two groups using Kaplan-Meier survival analysis (p < 0.001).

Auditory verbal hallucinations (AVHs) are experienced by the majority of patients with schizophrenia and are often resistant to treatment with antipsychotic agents. White matter (WM) tract abnormalities are associated with AVH treatment efficacy. Using a retrospective design, 115 patients with schizophrenia with AVHs, 48 with medication-resistant AVHs and 67 with treatable AVHs, and 70 healthy controls (HCs) were selected from the database of our cohort study for 5-year follow-up assessment. WM tract integrity was measured using tract-based spatial statistics (TBSS) at baseline and after 5 years of antipsychotic agent treatment. The fractional anisotropy (FA) value was used to demonstrate WM tract alterations in patients with schizophrenia with medication-resistant AVHs, in patients with schizophrenia with treatable AVHs, and in HCs. Our data demonstrated that medication-resistant patients showed significantly greater FA values in the corpus callosum (CC) fasciculus at baseline and in the corticospinal tract post-treatment compared to HCs, but the baseline difference in the CC fasciculus was no longer significant after 5 years of antipsychotic agent treatment. The medication-resistant AVH group exhibited greater FA values in the superior longitudinal fasciculus after 5 years of antipsychotic agent treatment. Compared to the HC group, the treatable AVH group exhibited significantly greater FA values in the visual radiation and CC after 5 years of antipsychotic agent treatment. In the medication-resistant and treatable groups, common WM tract abnormalities were noted, as greater FA values were observed in the CC group at baseline compared to the HC group. At the same time, distinct abnormalities were noted, as greater FA values were observed in the superior longitudinal fasciculus, which may contribute to medication-resistant AVHs, whereas abnormalities in the CC fasciculus may contribute to both treatable and medication-resistant AVHs. In the HCs, a decrease in FA values in the posterior CC was observed after 5 years of observation compared to baseline. In summary, patients with treatment-resistant AVHs with schizophrenia and patients with treatable AVHs with schizophrenia have common and distinct abnormalities in the WM tract.

Auditory hallucinations are linked to elevated striatal dopamine, but their underlying computational mechanisms have been obscured by regional heterogeneity in striatal dopamine signaling. To address this, we developed a normative circuit model in which corticostriatal plasticity in the ventral striatum is modulated by reward prediction errors to drive reinforcement learning while that in the sensory-dorsal striatum is modulated by sensory prediction errors derived from internal belief to drive self-supervised learning. We then validate the key predictions of this model using dopamine recordings across striatal regions in mice, as well as human behavior in a hybrid learning task. Finally, we find that changes in learning resulting from optogenetic stimulation of the sensory striatum in mice and individual variability in hallucination proneness in humans are best explained by selectively enhancing dopamine levels in the model sensory striatum. These findings identify plasticity mechanisms underlying biased learning of sensory expectations as a biologically plausible link between excess dopamine and hallucinations.

Transcranial alternating current stimulation (tACS) has been reported to treat refractory auditory hallucinations in schizophrenia. Despite diligent efforts, it is imperative to underscore that tACS does not uniformly demonstrate efficacy across all patients as with all treatments currently employed in clinical practice. The study aims to find biomarkers predicting individual responses to tACS, guiding treatment decisions, and preventing healthcare resource wastage. We divided 17 schizophrenic patients with refractory auditory hallucinations into responsive(RE) and non-responsive(NR) groups based on their auditory hallucination symptom reduction rates after one month of tACS treatment. The pre-treatment resting-state electroencephalogram(rsEEG) was recorded and then computed absolute power spectral density (PSD), Hjorth parameters (HPs, Hjorth activity (HA), Hjorth mobility (HM), and Hjorth complexity (HC) included) from different frequency bands to portray the brain oscillations. The results demonstrated that statistically significant differences localized within the high gamma frequency bands of the right brain hemisphere. Immediately, we input the significant dissociable features into popular machine learning algorithms, the Cascade Forward Neural Network achieved the best recognition accuracy of 93.87%. These findings preliminarily imply that high gamma oscillations in the right brain hemisphere may be the main influencing factor leading to different responses to tACS treatment, and incorporating rsEEG signatures could improve personalized decisions for integrating tACS in clinical treatment.

The polymorphism of dopamine receptor (DRD) and oxytocin (OXT) may be associated with schizophrenia. A case-control study of 248 schizophrenia patients and 236 controls was conducted using the Sequenom MassARRAY platform. The results showed that DRD2 rs1800497 was a heterozygote (AG vs. GG: adjusted odds ratio [OR] = 1.88; 95% confidence interval [CI]: 1.09-3.25) and DRD3 rs7631540 (TC vs. CC: adjusted OR = 0.60; 95% CI: 0.36-1.02) may be associated with an increased risk of developing schizophrenia. In addition, the DRD2 rs1800497 genotype GA showed a reduced risk of schizophrenia in the male subgroup and the late-onset subgroup (>27 years of age). For DRD3 polymorphisms, the rs7631540 TC genotype was associated with schizophrenia in the female subgroup. In OXT polymorphism analysis, rs2740210 codominant CA/AA was a risk factor for schizophrenia in the male and early-onset subgroup (≤27 years old). This study also concluded that OXT rs2740210 codominant CA/AA is associated with schizophrenia.

Alterations in the temporal characteristics of EEG microstates in patients with schizophrenia (SCZ) have been repeatedly found in previous studies. Nevertheless, altered temporal characteristics of EEG microstates in auditory verbal hallucinations (AVHs) SCZ are still unknown. This study aimed to investigate whether SCZ patients with sAVHs exhibit abnormal EEG microstates. We analyzed high-density electroencephalography data that from 79 SCZ patients, including 38 severe AVHs patients (sAVH group), 17 moderate auditory verbal hallucinations patients (mid-AVH group), and 24 without auditory verbal hallucinations patients (non-AVH group). Microstates were compared between three groups. Microstate C exhibited significant differences in duration and coverage and microstate B exhibited significant differences in occurrence between patients with sAVHs and without AVHs. There was a significant negative correlation between the coverage in microstate C and the severity of sAVH. Microstate C in duration, microstate B in occurrence were efficient in detecting sAVH patients. The decreased class C microstates in duration and coverage and increased class B microstates in occurrence may contribute to the severity of symptoms in AVH patients. Furthermore, we have identified that microstates C could serve as potential neurophysiological markers for detecting AVHs in SCZ patients. These results can provide potential avenues for therapeutic intervention of AVHs.

The lifetime prevalence of suicide is around 5% in patients with schizophrenia. Non-adherence to antipsychotic medication is an important risk factor, but prospective studies investigating joint effects of antipsychotic drugs, antidepressants, and benzodiazepines on suicidality are scarce. We aimed to investigate how use and non-use of psychotropic medications are associated with suicidality in schizophrenia.

An open cohort study followed all patients consecutively admitted to a psychiatric acute unit during a 10-year period with a diagnosis of schizophrenia (n = 696). Cox multiple regression analyses were conducted with use of antipsychotics, antidepressants, and benzodiazepines as time-dependent variables. Adjustments were made for age, gender, depressive mood, agitated behavior, and use of alcohol and illicit substances.

A total of 32 (4.6%) suicide events were registered during follow-up. Of these, 9 (28%) were completed suicides and 23 (72%) were attempted suicides. A total of 59 (8.5%) patients were readmitted with suicidal plans during the follow-up. Compared to non-use, use of antipsychotics was associated with 70% lower risk of attempted or completed suicide (adjusted hazard ratio [AHR] = 0.30, p < 0.01, CI 0.14-0.65) and 69% reduced risk of readmission with suicidal plans (AHR = 0.31, p < 0.01, CI 0.18-0.55). Use of prescribed benzodiazepines was associated with 126% increased risk of readmission with suicidal plans (AHR = 2.26, p = 0.01, CI 1.24-4.13).

Adherence to antipsychotic medication is strongly associated with reduced suicidal risk in schizophrenia. The use of prescribed benzodiazepines was identified as a significant risk factor for being readmitted with suicidal plans.

Auditory verbal hallucinations (AVH) are a common symptom of schizophrenia, increasing the patient's risks of suicide and violence. Repetitive transcranial magnetic stimulation (rTMS) is a potential treatment for AVH.

To investigate the effect of imaging-navigated rTMS on AVH in patients with schizophrenia.

This 6-week, double-blind, sham-controlled, randomized clinical trial was performed at the Anhui Mental Health Center, Hefei, China, from September 1, 2016, to August 31, 2021. Participants included 66 patients with AVH and schizophrenia. Data were analyzed from May 1, 2022, to March 31, 2023.

Participants were randomly assigned 1:1 to either imaging-navigated active or sham rTMS over the left temporoparietal junction for 2 weeks.

The primary outcome measured improvements in AVH from baseline to week 2 and week 6 using the Auditory Hallucination Rating Scale (AHRS) scores. In addition, the TMS-induced electric field strength was used to estimate improvements in AVH as a secondary outcome.

A total of 62 participants (33 women [53%]; mean [SD] age, 27.4 [9.2] years) completed the 2-week treatments. Of these, 32 were randomized to the active rTMS group (18 women [56%]; mean [SD] age, 26.9 [9.2] years) and 30 to the sham treatment group (15 women [50%]; mean [SD] age, 27.8 [9.4] years). In the intention-to-treat analyses, patients receiving active rTMS showed a significantly greater reduction in AHRS scores compared with those receiving sham treatment at week 2 (difference, 5.96 [95% CI, 3.42-8.50]; t = 4.61; P < .001; Cohen d, 1.17 [95% CI, 0.62-1.71]). These clinical effects were sustained at week 6. Additionally, a stronger TMS-induced electric field within a predefined AVH brain network was associated with greater reductions in AHRS scores (B = 3.12; t = 3.58; P = .002). No serious adverse event was observed.

The findings of this randomized clinical trial suggest that imaging-navigated rTMS may effectively and safely alleviate AVH in patients with schizophrenia. Findings also suggest that the electric field strength in the individualized AVH network is a vital parameter for optimizing the efficacy of the rTMS protocol.

ClinicalTrials.gov Identifier: NCT02863094.

Auditory verbal hallucinations (AVHs) are one of the signature positive symptoms of schizophrenia, affecting a substantial portion of patients with schizophrenia. These hallucinations seriously impact the lives of patients, resulting in a substantial social burden. Recent studies have shown a significant correlation between abnormal local brain activity and the neurobiological mechanisms of AVHs. However, it is not fully clear whether altered intrinsic brain activity in schizophrenia patients with AVHs is correlated with specific neurotransmitter systems.

We included 50 first-episode, drug-naïve schizophrenia patients with AVHs, 50 patients without AVHs (NAVHs), and 50 age- and sex-matched healthy controls (HCs). The amplitude of low-frequency fluctuation (ALFF) was utilized to explore the altered intrinsic brain activity in the AVH group. Subsequently, we spatially correlated the altered ALFF with neurotransmitter maps using JuSpace.

In our study, compared to HCs, the AVH group exhibited significantly reduced ALFF in multiple brain regions, mainly including the left precuneus, bilateral supplementary motor areas, bilateral paracentral lobules, bilateral precentral gyri, and bilateral postcentral gyri. The NAVH group showed significantly reduced ALFF in the left inferior occipital gyrus, left calcarine gyrus, and left lingual gyrus compared to HCs. Furthermore, the AVH group showed higher ALFF in the right inferior frontal gyrus compared to the NAVH group. Additionally, these ALFF alterations in the AVH group were closely related to three neurotransmitters, including dopamine, serotonin and norepinephrine.

We link neurotransmitters to abnormal intrinsic brain activity in first-episode, drug-naïve schizophrenia patients with AVHs, contributing to a comprehensive understanding of the pathophysiological processes and treatment pathways underlying AVHs.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness.

In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined.

Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction).

Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients.

This randomised, crossover, sham-controlled study explored the neural basis of source-monitoring, a crucial cognitive process implicated in schizophrenia. Left superior temporal gyrus (STG) and dorsolateral prefrontal cortex (DLPFC) were the key focus areas. Thirty participants without neurological or psychological disorders underwent offline sham and active tDCS sessions with specific electrode montage targeting the left STG and DLPFC. Source-monitoring tasks, reality monitoring (Hear-Imagine), internal source-monitoring (Say-Imagine), and external source monitoring (Virtual-Real) were administered. Paired t-test and estimation statistics was performed with Graphpad version 10.1.0. The Benjamini-Hochberg procedure was employed to control the false discovery rate in multiple hypothesis testing. A significant improvement in internal source monitoring tasks (p = 0.001, Cohen's d = 0.97) was observed, but reality monitoring tasks demonstrated moderate improvement (p = 0.02, Cohen's d = 0.44). The study provides insights into the neural mechanisms of source monitoring in healthy individuals and proposes tDCS as a therapeutic intervention, laying the foundation for future studies to refine tDCS protocols and develop individualized approaches to address source monitoring deficits in schizophrenia.

Hallucinations are a core feature of psychosis, and their severity during the acute phase of illness is associated with a range of poor outcomes. Various clinical and sociodemographic factors may predict hallucinations and other positive psychotic symptoms in first episode psychosis (FEP). Despite this, the precise factors associated with hallucinations at first presentation to an early intervention service have not been extensively researched. Through detailed interviews and chart reviews, we investigated sociodemographic and clinical predictors in 636 minimally-medicated patients who entered PEPP-Montréal, an early intervention service for FEP, between 2003 and 2018. Hallucinations were measured using the Scale for the Assessment of Positive Symptoms (SAPS), while negative symptoms were assessed using the Scale for the Assessment of Negative symptoms (SANS). Depressive symptoms were evaluated through the Calgary Depression Scale for Schizophrenia (CDSS), and anxiety symptoms via the Hamilton Rating Scale for Anxiety (HAS). A majority (n = 381, 59.9 %) of the sample presented with clinically significant hallucinations (SAPS global hallucinations score ≥ 3) at program entry. These patients had an earlier age at onset, fewer years of education, and a higher severity of delusions, depression and negative symptoms than those without clinical-level hallucinations. These results suggest that individuals with clinically significant hallucinations at admission tend to be younger and have a greater overall symptom burden. This makes it especially important to monitor hallucinations alongside delusions, depression and negative symptoms in order to identify who might benefit from targeted interventions. The implications of these findings for early intervention and person-centered care are discussed.

Our object is to examine the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on the symptoms, cognitive functions and subjective experiences in patients with chronic schizophrenia and to enhance the overall understanding of the TMS method.

Thirty three patients who had chronic schizophrenia were included in the study. Seventeen patients received rTMS and 16 received sham. The Positive and Negative Syndrome Scale, Repeatable Battery for the Assessment of Neuropsychological Status Scale, Insight and Treatment Attitudes Questionnaire and a self-experience checklist developed by the researchers to evaluate post-TMS experiences were applied to all patients.

There were no statistical differences between the groups with regard to symptoms, cognitive functions and insight. However rTMS group reported overall better treatment experience and more positive subjective experiences.

rTMS treatment did not cause any improvement in symptoms, cognitive functions and insight but provided a better self-experience, which might improve treatment compliance.

A large group of psychiatric patients suffer from auditory hallucinations (AH) despite relevant treatment regimens. In mental health populations, AH tend to be verbal (AVH) and the content critical or abusive. Trials employing immersive virtual reality (VR) to treat mental health disorders are emerging.

The aim of this scoping review is to provide an overview of clinical trials utilizing VR in the treatment of AH and to document knowledge gaps in the literature.

PubMed, Cochrane Library, and Embase were searched for studies reporting on the use of VR to target AH.

16 papers were included in this PRISMA scoping review (ScR). In most studies VR therapy (VRT) was employed to ameliorate treatment resistant AVH in schizophrenia spectrum disorders. Only two studies included patients with a diagnosis of affective disorders. The VRT was carried out with the use of an avatar to represent the patient's most dominant voice.

The research field employing VR to treat AH is promising but still in its infancy. Results from larger randomized clinical trials are needed to establish substantial evidence of therapy effectiveness. Additionally, the knowledge base would benefit from more profound qualitative data exploring views of patients and therapists.

Paranoia is a common symptom of psychotic disorders but is also present on a spectrum of severity in the general population. Although paranoia is associated with an increased tendency to perceive cohesion and conspiracy within groups, the mechanistic basis of this variation remains unclear. One potential avenue involves the brain's dopaminergic system, which is known to be altered in psychosis. In this study, we used large-N online samples to establish the association between trait paranoia and perceptions of cohesion and conspiracy. We further evaluated the role of dopamine on perceptions of cohesion and conspiracy using a double-blind, placebo-controlled laboratory experiment where participants received levodopa or a placebo control. Our results were mixed: group perceptions and perceptions of cohesion were higher among more paranoid individuals but were not altered under dopamine administration. We outline the potential reasons for these discrepancies and the broader implications for understanding paranoia in terms of dopamine dysregulation.

Understanding how antipsychotic medication ameliorates auditory verbal hallucinations (AVHs) through modulation of brain circuitry is pivotal for understanding the pathophysiology of psychosis and for predicting treatment response.

This case-control study included examinations at baseline and at follow-up after 6 weeks. Initially, antipsychotic-naïve patients with first-episode schizophrenia who were experiencing AVHs were recruited together with healthy control participants. Antipsychotic treatment with the relatively selective D2 receptor antagonist amisulpride was administered as monotherapy. Functional connectivity measured by resting-state functional magnetic resonance imaging between networks of interest was used to study the effects of D2 blockade on brain circuitry and predict clinical treatment response. Hallucinations were rated with the Positive and Negative Syndrome Scale.

Thirty-two patients experiencing AVHs and 34 healthy control participants were scanned at baseline. Twenty-two patients and 34 healthy control participants were rescanned at follow-up. Connectivity between the auditory network and the medial temporal lobe network was increased in patients at baseline (p = .002) and normalized within 6 weeks of D2 blockade (p = .018). At baseline, the connectivity between these networks was positively correlated with ratings of hallucinations (t = 2.67, p = .013). Moreover, baseline connectivity between the auditory network and the medial temporal lobe network predicted reduction in hallucinations (t = 2.34, p = .032).

Functional connectivity between the auditory network and the medial temporal lobe predicted response to initial antipsychotic treatment. These findings demonstrate that connectivity between networks involved in auditory processing, internal monitoring, and memory is associated with the clinical effect of dopamine antagonism.

Abnormal 40 Hz auditory steady-state response (ASSR) has been observed in some psychiatric disorders. Nevertheless, the role of 40 Hz ASSR in persistent auditory verbal hallucinations (pAVHs) schizophrenia (SCZ) is still unknown. This study aims to investigate whether the 40 Hz ASSR impairment is related to pAVHs and can detect pAVHs severity.

We analyzed high-density electroencephalography data that from 43 pAVHs patients (pAVH group), 20 moderate auditory verbal hallucinations patients (mid-AVH group), and 24 without auditory verbal hallucinations patients (non-AVH group). Event-related spectral perturbation and inter-trial phase coherence (ITPC) were calculated to quantify dynamic changes of the 40 Hz ASSR power and ITPC, respectively.

Frontal-central, the 40 Hz ASSR power, and ITPC were significantly lower in the pAVH group than in the non-AVH group; There was no significant difference between the pAVH and mid-AVH group. The 40 Hz ASSR was significantly negatively correlated with the severity of pAVHs. The 40 Hz ASSR power, and ITPC could be used as a combinational marker to detect SCZ patients with and without pAVHs.

Our findings have shed light on the pathological mechanism of pAVHs in SCZ patients. These results can provide potential avenues for therapeutic intervention of pAVHs.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique that could improve cognitive function. It is being developed as a non-pharmacological intervention to alleviate symptoms of cognitive deterioration. We assessed the efficacy of rTMS in improving cognitive functioning among people with Mild Cognitive Impairment (MCI) in a partially-blinded, sham-controlled randomized trial. Out of 91 subjects screened, 31 participants with MCI (mean age 70.73; SD = 4.47), were randomly assigned to one of three groups: (A) Active rTMS; (B) Active rTMS with Computerized Cognitive Training RehaCom; and (C) Sham control. The study evaluated cognitive function using the DemTect, FAS, and CANTAB tests before and after the stimulation. The following treatment protocol was applied: 2000 pulses at 10 Hz, 5-s train duration, and 25-s intervals at 110% of resting MT delivered over the left Dorsolateral Prefrontal Cortex (DLPFC) five times a week for 2 weeks. After 10 sessions of high-frequency rTMS, there was an improvement in overall cognitive function and memory, assessed by the DemTect evaluation, with no serious adverse effects. Analysis of differences in time (after 10 sessions) between studied groups showed statistically significant improvement in DemTect total score (time by group interaction p = 0.026) in favor of rTMS+RehaCom. The linear regression of CANTAB Paired Associates Learning revealed significant differences in favor of rTMS+RehaCom in three subtests. Our study shows that 10 sessions of rTMS over the left DLPFC (alone as well as combined with Computerized Cognitive Training) can have a positive impact on cognitive function in people with MCI. Further research should investigate the underlying mechanism and determine the optimal parameters for rTMS, which will be important for its efficacy in clinical settings.

It is unknown to what extent mental imagery and auditory verbal hallucinations (AVHs) are related. Trials evaluating this issue used both emotional and non-emotional mental imagery tools, thereby complicating outcomes comparisons. Therefore, the present study aimed to systematically review the literature on mental imagery in individuals with AVHs to (1) inventory imagery assessment tools used in this population, (2) to collect information on the relation between emotional and non-emotional mental imagery in all sensory domains and AVHs and (3) to integrate the outcomes of this systematic review in a model of different mental imagery domains and related assessment tools. We conducted a systematic literature search in the PubMed Database. After full-text screening, 17 papers were included. Findings showed that a variety of assessment methods have been used to assess various aspects of mental imagery in people with AVHs, suggesting that there is a lack of agreed theoretical conceptualization of mental imagery and AVHs. In addition, the studies confirmed as was expected that non-emotional mental imagery seemed unrelated to AVHs whereas emotional mental imagery was related to AVHs. Lastly, we proposed a model of mental imagery domains and corresponding assessment methods distinguishing between emotional and non-emotional mental imagery.

The aim of this review is to explore the clinical nursing application of cognitive behavioral therapy (CBT) in patients with schizophrenia. A literature search was conducted using the CINAHL and MEDLINE databases. The database search occurred during the month of December 2022. This article comprehensively summarizes the theoretical basis of CBT in improving schizophrenia in clinical nursing, its application in managing symptoms and improving social function, as well as research progress in this field. There are still inconsistencies in the research results on CBT, but overall, psychological intervention combined with drug treatment is more effective than conventional treatment alone. If social function training can be added at the same time, it is believed that it will have better effects on clinical treatment and can maintain long-lasting effectiveness. Only in this way can patients truly understand and recognize the disease, improve treatment compliance, and ultimately achieve the goal of improving prognosis and quality of life.

Repetitive transcranial magnetic stimulation is a noninvasive intervention, can significantly reduce behavioral and psychological symptoms and cognitive impairment in AD patients. Only few cases have been reported the adverse reactions after the treatment. This report described the different adverse reactions after repetitive transcranial magnetic stimulation with different parameters.

This article reports a patient with dementia complicated with mental behavior disorder who was treated with repetitive transcranial magnetic stimulation (rTMS) in spite of poor drug response. First, 1 Hz rTMS was initiated. After 1 month, the patient showed improved symptoms of mental behavior, decreased cognitive function and prolonged sleep duration. After switched to 10 Hz rTMS, the patient's cognitive function and mental behavior abnormalities improved, and the sleep time returned to normal. However, epilepsy occurred after one session and was changed to 0.8 Hz rTMS treatment. The patient's symptoms improved and did not have seizure.

Repetitive transcranial magnetic stimulation has a positive effect on cognitive function and Behavioral And Psychological Symptoms Of Dementia, and adverse reactions are inevitable. Playing personalized treatment according to the patients can reduce occurrence of adverse reactions.

Previous sleep electroencephalography studies have detected abnormalities in sleep architecture and sleep spindle deficits in schizophrenia (SCZ), but the consistency of these results was not robust, which might be due to the small sample size and the influence of clinical factors such as the various medication therapies and symptom heterogeneity. This study aimed to regard auditory verbal hallucinations (AVHs) as a pointcut to downscale the heterogeneity of SCZ and explore whether some sleep architecture and spindle parameters were more severely impaired in SCZ patients with AVHs compared with those without AVHs.

A total of 90 SCZ patients with AVHs, 92 SCZ patients without AVHs, and 91 healthy control subjects were recruited, and parameters of sleep architecture and spindle activities were compared between groups. The correlation between significant sleep parameters and clinical indicators was analyzed.

Deficits of sleep spindle activities at prefrontal electrodes and intrahemispheric spindle coherence were observed in both AVH and non-AVH groups, several of which were more serious in the AVH group. In addition, deficits of spindle activities at central and occipital electrodes and interhemispheric spindle coherence mainly manifested accompanying AVH symptoms, most of which were retained in the medication-naive first-episode patients, and were associated with Auditory Hallucination Rating Scale scores.

Our results suggest that the underlying mechanism of spindle deficits might be different between SCZ patients with and without AVHs. In the future, the sleep feature of SCZ patients with different symptoms and the influence of clinical factors, such as medication therapy, should be further illustrated.

Approximately one-third of patients with a psychotic disorder experience visual hallucinations (VH). While new, more targeted treatment options are warranted, the pathophysiology of VH remains largely unknown. Previous studies hypothesized that VH result from impaired functioning of the vision-related networks and impaired interaction between those networks, including a possible functional disconnection between the primary visual cortex (V1) and higher-order visual processing regions. Testing these hypotheses requires sufficient data on brain activation during actual VH, but such data are extremely scarce.

We therefore recruited seven participants with a psychotic disorder who were scanned in a 3 T fMRI scanner while indicating the occurrence of VH by pressing a button. Following the scan session, we interviewed participants about the VH experienced during scanning. We then used the fMRI scans to identify regions with increased or decreased activity during VH periods versus baseline (no VH).

In six participants, V1 was not activated during VH, and in one participant V1 showed decreased activation. All participants reported complex VH such as human-like beings, objects and/or animals, during which higher-order visual areas and regions belonging to the vision-related networks on attention and memory were activated.

These results indicate that VH are associated with diffuse involvement of the vision-related networks, with the exception of V1. We therefore propose a model for the pathophysiology of psychotic VH in which a dissociation of higher-order visual processing areas from V1 biases conscious perception away from reality and towards internally generated percepts.

The aim of this study was to investigate the relationship between persistent auditory verbal hallucinations (pAVHs) and N-acetyl-aspartate (NAA) levels in posterior cingulate cortex (PCC). 117 schizophrenia (SCZ) patients (61 pAVHs and 56 non-AVHs) and 66 healthy controls were included. The P3 item of the Positive and Negative Syndrome Scale and the Auditory Hallucinations subscale of the Psychotic Symptom Rating Scale were used to assess the severity of pAVHs. NAA levels were significantly lower in the AVHs group, and were negatively correlated with pAVHs. Therefore, increasing the NAA levels in PCC may be helpful in treating pAVHs.

There is growing clinical interest in addressing relationship dynamics between service-users and their voices. The Talking With Voices (TwV) trial aimed to establish feasibility and acceptability of a novel dialogical intervention to reduce distress associated with voices amongst adults diagnosed with schizophrenia spectrum disorders. The single-site, single-blind (rater) randomised controlled trial recruited 50 participants who were allocated 1:1 to treatment as usual (TAU), or TAU plus up to 26 sessions of TwV therapy. Participants were assessed at baseline and again at end of treatment (six-months). The primary outcomes were quantitative and qualitative assessments of feasibility and acceptability. Secondary outcomes involved clinical measures, including targeted instruments for voice-hearing, dissociation, and emotional distress. The trial achieved 100 % of the target sample, 24 of whom were allocated to therapy and 26 to TAU. The trial had high retention (40/50 [80 %] participants at six-months) and high intervention adherence (21/24 [87.5 %] receiving ≥8 sessions). Signals of efficacy were shown in targeted measures of voice-hearing, dissociation, and perceptions of recovery. Analysis on the Positive and Negative Syndrome Scale indicated that there were no differences in means of general psychosis symptom scores in TwV compared to the control group. There were four serious adverse events in the therapy group and eight in TAU, none of which were related to study proceedings. The trial demonstrates the acceptability of the intervention and the feasibility of delivering it under controlled, randomised conditions. An adequately powered definitive trial is necessary to provide robust evidence regarding efficacy evaluation and cost-effectiveness. Trial registration: ISRCTN 45308981.

Although alterations of the default mode network (DMN) in schizophrenia (SZ) have been largely investigated, less research has been carried out on DMN alterations in different sub-phenotypes of this disorder. The aim of this pilot study was to compare DMN features among SZ patients with and without auditory verbal hallucinations (AVH). Three groups of 17 participants each were considered: patients with hallucinations (AVH-SZ), patients without hallucinations (nAVH-SZ) and age-matched healthy controls (HC). The DMN spatial pattern was similar between the nAVH-SZ and HC, but the comparison between these two groups and the AVH-SZ group revealed alterations in the left Angular Gyrus (lAG) node of the DMN. Using a novel approach based on normalized fractional Amplitude of Low-Frequency Fluctuations (fALFF), the AVH-SZ subgroup showed altered spectral activity in the DMN compared with the other two groups, especially in the lower-frequency bands (0.017-0.04 Hz). Significant positive correlations were found for both SZ groups collapsed, and for the nAVH-SZ group alone between delusional scores (PANSS-P1) and slow fALFF bands of the DMN. Narrowing the analysis to the ROI centered on the lAG, significant correlations were found in the AVH-SZ group for hallucination scores (PANSS-P3) and Slow-5 and Slow-4 (both positive), and Slow-3 (negative) fALFF bands. Our results reveal the central role of the lAG in relation to hallucinations, an important cortical area connecting auditory cortex with several hubs (including frontal linguistic centers) and involved in auditory process monitoring.

Temstem is a mobile application developed in cooperation with voice-hearing persons to help them cope with distressing voices. After psychoeducation about voice hearing, Temstem offers two functions: Silencing is a mode designed to inhibit voice activity through the processing of incompatible language; the Challenging mode introduces dual tasking (as used in eye movement desensitisation and reprocessing) designed to reduce the emotionality and vividness of a voice memory. Two different language games, Lingo Tapper and Word Link, are provided, containing both functions. This study aimed to explore the momentary effects of Temstem on voice-hearing distress, emotionality and vividness in a naturalistic sample of voice-hearing app users.

Temstem is freely available in the Netherlands. We collected data through the app from 1048 individual users who had given informed consent for the study. We assessed changes in pre- and post-session scores on distress, emotionality and vividness, and we evaluated differences in outcomes between the games and whether effects remained stable over multiple sessions.

Users had been hearing voices for an average of 4.95 years; 79 % had been informed about Temstem by a mental health therapist or coach. After a Silencing session, voice-hearing distress was reduced, t(958) = 27.12, p < .001, d = 0.49; the degree of reduction remained stable after repeated use, F(1, 7905.57) = 1.91, p = .167. After a Challenging session, emotionality, t(651) = 23.16, p < .001, d = 0.74, and the vividness of voice memories were reduced, t(651) = 22.20, p < .001, d = 0.71; both diminished slightly with frequent use, F(1, 2222.86) = 7.21, p < .05; F(1, 2289.92) = 4.25, p < .05. In comparison with Lingo Tapper, larger reductions were seen for a Word Link game: emotionality t(226) = 2.88, p < .005, d = 0.21; vividness t(226) = 2.29, p < .05, d = 0.17.

In this heterogeneous sample of voice-hearing individuals, Temstem appeared to be a promising coping tool; momentary voice-hearing distress and the emotionality and vividness of voice statements were reduced after a Temstem session. Despite important limitations and the need for more research, naturalistic studies of user app data may yield interesting and generalisable findings.

Schizophrenia is a major mental disorder with a wide range of psychiatric symptoms. This study explored the structure of psychiatric symptoms of schizophrenia using network analysis in a large representative Asian sample based on a survey of clinical features and treatment used in schizophrenia patients across 15 countries/territories in Asia.

Data on the demographic characteristics and psychiatric symptoms in schizophrenia patients were extracted from the dataset of the fourth Research on Asia Psychotropic Prescription for Antipsychotics (REAP-AP) project. The presence of the following psychiatric symptoms including delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms, social/occupational dysfunction, verbal aggression, physical aggression, and affective symptoms were analyzed.

A total of 3681 patients were included. The network analysis revealed that verbal aggression, hallucinations, and social/occupational dysfunction were the most central symptoms, while the connections between social/occupational dysfunction and verbal aggression, and between hallucinations and disorganized speech were the two strongest edges. There were significant gender differences in the network structure based on the network structure invariance test (M=0.74, P = 0.03) and invariant edge strength test. The positive correlation between verbal aggression and hallucinations was significantly stronger in the female network than that in the male network (P = 0.03), while a negative correlation between affective symptoms and negative symptoms was found in the female, but not the male network (P < 0.01).

Central symptoms including verbal aggression, hallucinations, and socio-occupational dysfunction should be addressed in developing targeted treatment strategy for schizophrenia patients.

This study compared voice characteristics and beliefs in participants diagnosed with post-traumatic stress disorder (PTSD) with dissociation, schizophrenia (SCZ) and both diagnoses of SCZ and PTSD. The relationship between dissociation and voice beliefs was also assessed.

We identified 56 participants meeting the diagnostic criteria for PTSD with dissociation, SCZ or both diagnoses (PTSD + SCZ) who also experienced auditory hallucinations. Measures included PTSD Symptoms Scales Interview (PSSI-5), Psychotic Symptoms Rating Scale (PSYRAT), Clinician Administered Dissociative States Scale (CADSS), Beliefs about Voices Questionnaire (BAVQ) and Positive and Negative Syndrome Scale (PANSS).

Beliefs about voices were similar across diagnostic groups. Participants with SCZ were more likely to attribute their voices to an external origin, and participants with dual diagnosis were less able to control their voices. The PTSD-only group scored higher in dissociation scores than either the SCZ-only or dual diagnosis group. Malevolent voice appraisals correlated with dissociation scores only in the dual diagnosis group.

This research supports the hypothesis that voice beliefs are similar across diagnoses of PTSD and SCZ. However, differences in voice characteristics, emotional responses and relationship to dissociation may need to be considered in the psychological management of voices.

Recent advances in computational psychiatry have provided unique insights into the neural and cognitive underpinnings of psychotic symptoms. In particular, a host of new data has demonstrated the utility of computational frameworks for understanding how hallucinations might arise from alterations in typical perceptual processing. Of particular promise are models based in Bayesian inference that link hallucinatory perceptual experiences to latent states that may drive them. In this piece, we move beyond these findings to ask: how and why do these latent states arise, and how might we take advantage of heterogeneity in that process to develop precision approaches to the treatment of hallucinations? We leverage specific models of Bayesian inference to discuss components that might lead to the development of hallucinations. Using the unifying power of our model, we attempt to place disparate findings in the study of psychotic symptoms within a common framework. Finally, we suggest directions for future elaboration of these models in the service of a more refined psychiatric nosology based on predictable, testable, and ultimately treatable information processing derangements.

Treatment-refractory auditory hallucinations (TRAH) in schizophrenia often do not improve with pharmacotherapy. We performed a meta-analysis of randomized, double-blind, sham-controlled clinical trials (RCTs) that systematically examined the therapeutic effects and tolerability of adjunctive active versus sham active transcranial direct current stimulation (tDCS) for auditory hallucinations as measured by the Auditory Hallucination Rating Scale (AHRS) in schizophrenia patients with TRAH.

Relevant data were extracted, checked and analyzed using the Review Manager, Version 5.3 by three independent investigators.

Eight double-blind RCTs covering 329 schizophrenia patients (168 in active tDCS group, 161 in sham tDCS group) were included. Although no advantage of active tDCS on auditory hallucinations [7 RCTs, n = 224; standardized mean difference (SMD): - 0.33 (95% confidence interval (CI): - 0.71, 0.05), P = 0.09; I² = 46%] was found compared to sham, subgroup analyses revealed that active tDCS with twice-daily stimulation [6 RCTs, n = 198; SMD: - 0.42 (95%CI: -0.82, -0.02), P = 0.04; I² = 44%] and active tDCS with ≥ 10 stimulation sessions [6 RCTs, n = 198; SMD: - 0.42 (95%CI: -0.82, -0.02), P = 0.04; I² = 44%] showed a significantly better therapeutic effect than sham in improving auditory hallucinations symptoms. Meta-analyses of total psychopathology and discontinuation due to any reason were not significantly different between the active and sham tDCS groups.

This meta-analysis demonstrated that the effects of tDCS for auditory hallucinations symptoms were influenced by the tDCS parameters. Twice-daily stimulation and ≥ 10 stimulation sessions may be needed to improve auditory hallucinations symptoms in schizophrenia with TRAH.

The family of epidermal growth factor (EGF) including neuregulin-1 are implicated in the neuropathology of schizophrenia. We established a rat model of schizophrenia by exposing perinatal rats to EGF and reported that the auditory pathophysiological traits of this model such as prepulse inhibition, auditory steady-state response, and mismatch negativity are relevant to those of schizophrenia. We assessed the activation status of the auditory cortex in this model, as well as that in patients with schizophrenia, by monitoring the three neural activity-induced proteins: EGR1 (zif268), c-fos, and Arc. Among the activity markers, protein levels of EGR1 were significantly higher at the adult stage in EGF model rats than those in control rats. The group difference was observed despite an EGF model rat and a control rat being housed together, ruling out the contribution of rat vocalization effects. These changes in EGR1 levels were seen to be specific to the auditory cortex of this model. The increase in EGR1 levels were detectable at the juvenile stage and continued until old ages but displayed a peak immediately after puberty, whereas c-fos and Arc levels were nearly indistinguishable between groups at all ages with an exception of Arc decrease at the juvenile stage. A similar increase in EGR1 levels was observed in the postmortem superior temporal cortex of patients with schizophrenia. The commonality of the EGR1 increase indicates that the EGR1 elevation in the auditory cortex might be one of the molecular signatures of this animal model and schizophrenia associating with hallucination.