Severity Of Auditory Verbal Hallucinations Research Articles

The Effects of Add-on Fronto-Temporal Transcranial Direct Current Stimulation (tDCS) on Auditory Verbal Hallucinations, Other Psychopathological Symptoms, and Insight in Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Trial.

BackgroundThe efficacy of fronto-temporal transcranial direct current stimulation in treating auditory verbal hallucinations and other psychopathological symptoms of schizophrenia patients has been examined in a small number of clinical trials with limited sample sizes, but the results are mixed. Fronto-temporal transcranial direct current stimulation has also been demonstrated to enhance patients’ insight into their mental illness in an open-label pilot study. The current investigation aimed to investigate the therapeutic effects of fronto-temporal transcranial direct current stimulation on the severity of auditory verbal hallucinations, other schizophrenia symptoms, and insight in a large double blind, randomized, sham-controlled trial.MethodsSixty patients with medication-refractory auditory verbal hallucinations were randomized over 2 conditions: transcranial direct current stimulation with 2-mA, twice-daily sessions for 5 consecutive days, with anodal stimulation to the left prefrontal cortex and cathodal stimulation to the left temporo-parietal junction, and sham treatment.ResultsFronto-temporal transcranial direct current stimulation failed to cause significant changes in the severity of auditory verbal hallucinations and other schizophrenia symptoms. The levels of insight into illness (effect size=0.511, P<.001) and positive symptoms (effect size=0.781, P<.001) were largely promoted by 5 days of transcranial direct current stimulation relative to sham treatment. The beneficial effects on the 2 insight dimensions remained 1 month after transcranial direct current stimulation.ConclusionsFronto-temporal transcranial direct current stimulation is not more effective for auditory verbal hallucinations and other schizophrenia symptoms than sham treatment. But the results of transcranial direct current stimulation-associated improvement in awareness of illness and positive symptoms show promise and provide a new direction for future research into insight promotion interventions in schizophrenia.

S58. A RANDOMIZED CONTROLLED TRIAL COMPARING VIRTUAL REALITY THERAPY TO COGNITIVE BEHAVIORAL THERAPY IN SCHIZOPHRENIA WITH TREATMENT REFRACTORY HALLUCINATIONS: PRELIMINARY RESULTS

BackgroundWhile many pharmacological and psychosocial interventions are available, many treatment-resistant schizophrenia patients continue to suffer from persistent psychotic symptoms, mainly auditory verbal hallucinations (AVH). Recently, a psychological therapy using computerized technology has shown large therapeutic effects on AVH severity by enabling patients to engage in a dialogue with a representation of their distressing voices. These very hopeful results have been extended by our team using immersive 3D virtual reality. The results of VR therapy (VRT) in our pilot trial involving 15 schizophrenia patients with refractory AVH were clinically promising for the severity and distress related to hallucinations, illness symptomatology, depressive symptoms and quality of life. Notably, clinical improvements of our pilot remained significant at our 3-month follow-up. Such findings suggest that VRT seems to be a highly promising intervention for refractory AVH.MethodsTo further research in this field, the primary goal of this randomized-controlled trial is to show that VRT is superior to a widely utilized psychotherapy, that is Cognitive behavioral therapy (CBT), for the treatment of persistent auditory verbal hallucinations in schizophrenia. Our secondary goal is to examine the effects of these interventions on beliefs about voices, illness symptomatology, mood symptoms (anxiety and depression), self-esteem, level of functioning and quality of life.This is a single-blinded randomized-controlled, single-site parallel study of VRT versus CBT. Each treatment group will include 52 randomized participants (assuming 20% attrition) of over 18 years of age hearing persecutory voices and suffering from treatment resistant schizophrenia or schizoaffective disorder. Diagnoses will be established with the Structured Interview for DSM-V. Patients will be included if they have been hearing persecutor voices that did not respond to ≥2 antipsychotic trials.VRT comprises of 9 weekly sessions: 1 avatar creation session and 8 therapeutic sessions, where the patients are confronted to their reproduced hallucinatory experience and are encouraged to enter in a dialogue with their virtual persecutor. CBT includes 9 weekly sessions consisting of learning modules and task assignments. Subjects will be evaluated at baseline and post-treatment to assess primary (auditory verbal hallucinations as measured with the Psychotic Symptoms Rating Scale) and secondary outcomes. Mixed Anova analyses will be performed to measure and compare the effects of both interventions.ResultsPresently, 37 patients have been recruited and 9 have abandoned the study. Our preliminary results on 28 patients show that there is no significant difference between the treatment conditions for all our measures. As expected, more participants will be required to show the superiority of VRT over CBT. However, when performing separate ANOVA analyses for each condition, VRT shows significant improvements of auditory verbal hallucinations severity after the treatment (on our primary outcome) contrarily to CBT. VRT also produced significant decreases on the beliefs that voices are omnipotent and malevolent, on psychotic symptomatology, depressive symptoms and an increase on quality of life. CBT obtained no significant improvements.DiscussionWhile limited by the small number of patients, such findings are nonetheless already supporting the hypothesis of the superiority of VRT on auditory verbal hallucinations. As expected, a moderate effect is found for our adapted short CBT for psychosis, though not significant at this point. The current trial will contribute to the validation of a novel innovative approach answering a fundamental clinical need.

S55. MECHANISTIC BASIS OF FRONTO-TEMPORAL TRANSCRANIAL DIRECT CURRENT STIMULATION ON AUDITORY VERBAL HALLUCINATION IN SCHIZOPHRENIA: A MEDIATION ANALYSIS OF COROLLARY DISCHARGE

BackgroundCorollary discharge (CD), ubiquitous throughout the animal kingdom, refers to suppression of sensory consequences arising from self-generated actions. Complex motor acts like covert/overt speech are associated with corollary discharge that helps in ascertaining agency. Auditory verbal hallucinations (AVH) are hypothesized to originate due to failure of corollary discharge in auditory processing system. Transcranial Direct Current Stimulation (tDCS), as an add-on treatment, has been reported to significantly reduce severity of persistent AVH in schizophrenia patients. In this study, we describe mediation analysis findings that strongly support a role for amelioration of corollary discharge deficits as a mechanistic basis for tDCS effects on AVH in schizophrenia.Methods27 DSM-IV-TR Schizophrenia patients (SCZ) with persistent AVH despite adequate antipsychotic treatment and 27 healthy controls (HC) underwent neurophysiological assessment for CD. In an event-related potential task, N1 component that reflects cortical responsiveness of auditory cortex to sounds, was elicited and examined in two conditions – i) Talk (with online auricular feedback of self-spoken speech sounds) and ii) Listen (passive playback of recorded self-spoken speech sounds). Corollary discharge index (CDI) was calculated by subtracting Listen condition N1 amplitude from Talk condition N1 amplitude (at FCz). Among these 27 patients, 13 patients participated in a randomized, double-blind, sham-controlled study examining the effect of add-on tDCS on AVH and CDI [5 consecutive days, twice-daily, 20-minute sessions; 2mA; anode: left dorsolateral prefrontal cortex; cathode: left temporo-parietal junction]. Mediation analysis was modelled with tDCS type (Verum vs. Sham) as independent variable, percent change in auditory hallucination rating scale score (AHRS) as dependent variable and percent change in CDI as the mediator. As recommended for small samples, bootstrap estimation approach with 5000 samples was used to examine the indirect effect of independent variable on dependent variable through proposed mediator for significance.ResultsSCZ (Mean±SD: -0.67 ± 1.93) had significantly deficient CDI than HC (1.36 ± 2.18) (t=3.62; p=0.001). Verum tDCS (32.24 ± 16.48) resulted in greater percentage reduction in AHRS than sham (4.79 ± 8.84) (t=3.64, p=0.004). There was a significant increase in CDI (t=2.48; p=0.03) with verum (0.85 ± 1.08) but not sham (-0.55 ± 0.98) tDCS. Percent change in CDI positively correlated with percent change in AHRS from pre-RCT to post-RCT time-point for the entire sample (N=13; ρ=0.55, p=0.05). Regression analysis showed that tDCS type (verum/sham) was a significant predictor of percent change in AHRS (β=-27.46, p=0.003) as well as percent change in CDI (β=-1.40, p=0.033). Percent change in CDI was a significant predictor of percent change in AHRS (β=8.87, p=0.014). When controlled for percent change in CDI, tDCS type ceased to be a significant predictor of percent change in AHRS (β=-15.0, p=0.063). The predictors accounted for approximately 75% of the variance (R2=0.756, p<0.001). Bootstrap estimation results indicate the coefficient of indirect effect to be significant, β=-12.46, SE=6.92, 95% CI=-31.20, -2.79, and significantly different from zero at p<0.05 (two tailed).DiscussionFronto-temporal tDCS reduces severity of auditory verbal hallucination in schizophrenia possibly through correction of the deficient corollary discharge. Fronto-temporal network is crucial to self-tagging component of auditory processing and has conspicuous implications for auditory verbal hallucination pathophysiology.Trial No. CTRI/2014/12/005307 (Clinical Trials Registry–India)

N-Acetyl-Aspartate in the dorsolateral prefrontal cortex in men with schizophrenia and auditory verbal hallucinations: A 1.5\u2009T Magnetic Resonance Spectroscopy Study

Auditory verbal hallucinations (AVH) in patients with schizophrenia are linked to abnormalities within a large cerebral network including frontal and temporal regions. Whilst abnormalities of frontal speech production and temporal speech perception regions have been extensively studied, alterations of the dorsolateral prefrontal cortex (DLPFC), a region critically involved in the pathophysiology of schizophrenia, have rarely been studied in relation to AVH. Using 1.5 T proton magnetic resonance spectroscopy, this study examined the relationship between right and left DLPFCs N-AcetylAspartate (NAA) levels and the severity of AVH in patients with schizophrenia. Twenty-seven male patients with schizophrenia were enrolled in this study, 15 presented daily treatment-resistant AVH (AVH+) and 12 reported no AVH (no-AVH). AVH+ patients displayed higher NAA levels in the right DLPFC than no-AVH patients (p = 0.033). In AVH+ patients, NAA levels were higher in the right DLPFC than in the left (p = 0.024). No difference between the right and left DLPFC was observed in no-AVH patients. There was a positive correlation between NAA levels in the right DLPFC and the severity of AVH (r = 0.404, p = 0.037). Despite limited by magnetic field strength, these results suggest that AVH may be associated with increased NAA levels in the right DLPFC in schizophrenia.

Virtual reality therapy for refractory auditory verbal hallucinations in schizophrenia: A pilot clinical trial

Schizophrenia is a chronic and severe mental illness that poses significant challenges. While many pharmacological and psychosocial interventions are available, many treatment-resistant schizophrenia patients continue to suffer from persistent psychotic symptoms, notably auditory verbal hallucinations (AVH), which are highly disabling. This unmet clinical need requires new innovative treatment options. Recently, a psychological therapy using computerized technology has shown large therapeutic effects on AVH severity by enabling patients to engage in a dialogue with a computerized representation of their voices. These very promising results have been extended by our team using immersive virtual reality (VR). Our study was a 7-week phase-II, randomized, partial cross-over trial. Nineteen schizophrenia patients with refractory AVH were recruited and randomly allocated to either VR-assisted therapy (VRT) or treatment-as-usual (TAU). The group allocated to TAU consisted of antipsychotic treatment and usual meetings with clinicians. The TAU group then received a delayed 7weeks of VRT. A follow-up was ensured 3months after the last VRT therapy session. Changes in psychiatric symptoms, before and after TAU or VRT, were assessed using a linear mixed-effects model. Our findings showed that VRT produced significant improvements in AVH severity, depressive symptoms and quality of life that lasted at the 3-month follow-up period. Consistent with previous research, our results suggest that VRT might be efficacious in reducing AVH related distress. The therapeutic effects of VRT on the distress associated with the voices were particularly prominent (d=1.2). VRT is a highly novel and promising intervention for refractory AVH in schizophrenia.

Understanding AVATAR therapy: who, or what, is changing?

Understanding AVATAR therapy: who, or what, is changing?

Efficacy of fronto-temporal transcranial direct current stimulation for refractory auditory verbal hallucinations in schizophrenia: A randomized, double-blind, sham-controlled study

Persistent auditory verbal hallucinations (AVH) that are refractory to antipsychotic medications are reported in about 20–30% of schizophrenia patients. Transcranial Direct Current Stimulation (tDCS), a non-invasive and safe neuromodulatory technique, has attracted significant interest as an add-on treatment for refractory AVH in schizophrenia. Studies examining the efficacy of tDCS for refractory AVH in schizophrenia have reported inconsistent findings. In this study, using a randomized, double-blind, sham-controlled design (RCT), we sought to examine the effect of add-on tDCS [anode corresponding to left dorsolateral prefrontal cortex and cathode to left temporo-parietal junction; 2-mA, twice-daily sessions for 5-days] to treat refractory AVH in schizophrenia patients (N=25); following this RCT phase, patients that had <30% reduction in AVH severity were offered an open-label extension (OLE) active stimulation to evaluate the effect of cross-over to verum tDCS. In the RCT phase, repeated measures ANOVA with tDCS type [verum (N=12) vs. sham (N=13)] as between subjects factor demonstrated a significant tDCS-type X time-point interaction [F=21.5, p<0.001, partial-η2=0.48] with significantly greater reduction of AVH score in verum tDCS group as compared to sham group. In the OLE phase, sham-to-verum crossed over patients (N=13) showed significantly greater reduction in AVH severity than their corresponding change during RCT phase (t=2.9; p=0.01). Together, these observations add further support to the beneficial effects of add-on tDCS to treat refractory AVH schizophrenia.

Working memory predicts presence of auditory verbal hallucinations in schizophrenia and bipolar disorder with psychosis

ABSTRACTObjective: The recent dramatic increase in research investigating auditory verbal hallucinations (AVHs) has broadened the former narrow focus on schizophrenia to incorporate additional populations that experience these symptoms. However, an understanding of potential shared mechanisms remains elusive. Based on theories suggesting a failure of top-down cognitive control, we aimed to compare the relationship between AVHs and cognition in two categorical diagnoses of psychosis, schizophrenia and psychotic bipolar disorder. Method: A total of 124 adults aged 21–60 participated, of whom 76 had present-state psychosis (schizophrenia, n = 53; bipolar disorder with psychosis, n = 23), and 48 were non-clinical controls. Diagnosis and hallucination presence was determined using the Structured Clinical Diagnostic Interview for DSM-IV TR. AVHs severity was assessed using the Positive and Negative Syndrome Scale. Participants also completed the MATRICS cognitive battery. Results: The bipolar disorder with psychosis group performed better than the schizophrenia group for cognitive domains of Processing speed, Attention, Working memory (WM), and Visual memory. Hierarchical binary logistic regression found that WM significantly predicted presence of AVHs in both psychotic groups, but diagnosis did not significantly increase the predictive value of the model. A hierarchical multiple linear regression found that schizophrenia diagnosis was the only significant predictor of hallucination severity. Conclusions: The findings of this study—the first, to our knowledge, to compare the relationship between AVHs and MATRICS domains across schizophrenia and bipolar disorder with psychosis—support theories that deficits in WM underly the genesis of AVHs. WM potentially represents a shared mechanism of AVHs across diagnoses, supporting dimensional classifications of these psychotic disorders. However, non-cognitive factors predictive of hallucination severity may be specific to schizophrenia.

Abnormal Effective Connectivity in the Brain is Involved in Auditory Verbal Hallucinations in Schizophrenia.

Information flow among auditory and language processing-related regions implicated in the pathophysiology of auditory verbal hallucinations (AVHs) in schizophrenia (SZ) remains unclear. In this study, we used stochastic dynamic causal modeling (sDCM) to quantify connections among the left dorsolateral prefrontal cortex (inner speech monitoring), auditory cortex (auditory processing), hippocampus (memory retrieval), thalamus (information filtering), and Broca's area (language production) in 17 first-episode drug-naïve SZ patients with AVHs, 15 without AVHs, and 19 healthy controls using resting-state functional magnetic resonance imaging. Finally, we performed receiver operating characteristic (ROC) analysis and correlation analysis between image measures and symptoms. sDCM revealed an increased sensitivity of auditory cortex to its thalamic afferents and a decrease in hippocampal sensitivity to auditory inputs in SZ patients with AVHs. The area under the ROC curve showed the diagnostic value of these two connections to distinguish SZ patients with AVHs from those without AVHs. Furthermore, we found a positive correlation between the strength of the connectivity from Broca's area to the auditory cortex and the severity of AVHs. These findings demonstrate, for the first time, augmented AVH-specific excitatory afferents from the thalamus to the auditory cortex in SZ patients, resulting in auditory perception without external auditory stimuli. Our results provide insights into the neural mechanisms underlying AVHs in SZ. This thalamic-auditory cortical-hippocampal dysconnectivity may also serve as a diagnostic biomarker of AVHs in SZ and a therapeutic target based on direct in vivo evidence.

T005 Transcranial Direct Current stimulation (tDCS) for schizophrenia

Transcranial Direct Current stimulation (tDCS) has been proposed as a treatment for treatment-resistant auditory verbal hallucinations and negative symptoms in patients with schizophrenia. Despite first clinical studies hold promises, little is known regarding predictive marker of response as well as brain and on cognitive modulation that can underlie beneficial clinical effects in patients with schizophrenia. It was recently observed that tDCS placed with the cathode over of the left temporo-parietal junction (TPJ) coupled with the anode over the left dorsolateral prefrontal cortex (DLPFC) led to decrease the severity of auditory verbal hallucinations, to modulate the functional connectivity of the left TPJ and to improve self recognition in patients with schizophrenia. In these studies, 10 sessions of tDCS (20 min, 2 mA) were delivered twice a day during 5 consecutive days. There was a correlation between the decrease in the severity of hallucinations and the decrease of functional connectivity between the left TPJ and the left insula. There was also a correlation between the decrease in the severity of hallucinations and the increase in source-monitoring performance. These results suggested that tDCS may led to clinical improvement by modulating functional connectivity within a large network involving brain region implicated in language and self-recognition processing. However, evidence also suggested that some patients with schizophrenia failed to respond to this tDCS regimen. Several factors may explain the discrepancies observed between responders and non-responders. Among them, COMT val/met polymorphism or drug intake (including nicotine) were observed to modulate clinical response to tDCS in patients with schizophrenia. Strategies of combination (with medication and or cognitive remediation therapy) and optimization of stimulation parameters (e.g., transcranial alternating current stimulation – tACS) should allow enhancing clinical beneficial effect.

Is this my voice or yours? The role of emotion and acoustic quality in self-other voice discrimination in schizophrenia

ABSTRACTIntroduction: Impairments in self-other voice discrimination have been consistently reported in schizophrenia, and associated with the severity of auditory verbal hallucinations (AVHs). This study probed the interactions between voice identity, voice acoustic quality, and semantic valence in a self-other voice discrimination task in schizophrenia patients compared with healthy subjects. The relationship between voice identity discrimination and AVH severity was also explored.Methods: Seventeen chronic schizophrenia patients and 19 healthy controls were asked to read aloud a list of adjectives characterised by emotional or neutral content. Participants’ voice was recorded in the first session. In the behavioural task, 840 spoken words differing in identity (self/non-self), acoustic quality (undistorted/distorted), and semantic valence (negative/positive/neutral) were presented. Participants indicated if the words were spoken in their own voice, another person’s voice, or were unsure.Results: Patients were less accurate than controls in the recognition of self-generated speech with negative content only. Impaired recognition of negative self-generated speech was associated with AVH severity (“voices conversing”).Conclusions: These results suggest that abnormalities in higher order processes (evaluation of the salience of a speech stimulus) modulate impaired self-other voice discrimination in schizophrenia. Abnormal processing of negative self-generated speech may play a role in the experience of AVH.

Integrity of the arcuate fasciculus in patients with schizophrenia with auditory verbal hallucinations: A DTI-tractography study.

Auditory verbal hallucinations (AVH) of schizophrenia are associated with a disrupted connectivity between frontal and temporoparietal language areas. We hypothesized that this dysconnectivity is underpinned by white matter abnormalities in the left arcuate fasciculus, the main fiber bundle connecting speech production and perception areas. We therefore investigated the relationship between AVH severity and the integrity of the arcuate fasciculus measured by diffusion tensor imaging (DTI) tractography in patients with schizophrenia.Thirty-eight patients with treatment-resistant schizophrenia were included: 26 presented with daily severe treatment-resistant AVH, 12 reported prominent negative symptoms and no AVH. Fractional anisotropy (FA) was measured along the length of the left and right anterior arcuate fasciculi and severity of AVH was assessed using P3 PANSS item.FA values were significantly higher in the left arcuate fasciculus in patients with AVH than in no AVH patients (F(1,35) = 3.86; p = 0.05). No difference was observed in the right arcuate fasciculus. There was a significant positive correlation between FA value in the left arcuate fasciculus and the severity of AVH (r = 0.36; p = 0.02). No correlation was observed between FA values and PANSS total score suggesting a specific relationship between AVH severity and the left arcuate fasciculus integrity.These results support the hypothesis of a relationship between left frontotemporal connectivity and AVH in patients with schizophrenia and suggest that whilst a disruption of frontotemporal connectivity might be present to ensure the emergence of AVH, more severe anatomical alterations may prevent the occurrence of AVH in patients with schizophrenia.

Effects of Fronto-Temporal Transcranial Direct Current Stimulation on Auditory Verbal Hallucinations and Resting-State Functional Connectivity of the Left Temporo-Parietal Junction in Patients With Schizophrenia.

Auditory verbal hallucinations (AVH) in patients with schizophrenia are associated with abnormal hyperactivity in the left temporo-parietal junction (TPJ) and abnormal connectivity between frontal and temporal areas. Recent findings suggest that fronto-temporal transcranial Direct Current stimulation (tDCS) with the cathode placed over the left TPJ and the anode over the left prefrontal cortex can alleviate treatment-resistant AVH in patients with schizophrenia. However, brain correlates of the AVH reduction are unclear. Here, we investigated the effect of tDCS on the resting-state functional connectivity (rs-FC) of the left TPJ. Twenty-three patients with schizophrenia and treatment-resistant AVH were randomly allocated to receive 10 sessions of active (2 mA, 20min) or sham tDCS (2 sessions/d for 5 d). We compared the rs-FC of the left TPJ between patients before and after they received active or sham tDCS. Relative to sham tDCS, active tDCS significantly reduced AVH as well as the negative symptoms. Active tDCS also reduced rs-FC of the left TPJ with the left anterior insula and the right inferior frontal gyrus and increased rs-FC of the left TPJ with the left angular gyrus, the left dorsolateral prefrontal cortex and the precuneus. The reduction of AVH severity was correlated with the reduction of the rs-FC between the left TPJ and the left anterior insula. These findings suggest that the reduction of AVH induced by tDCS is associated with a modulation of the rs-FC within an AVH-related brain network, including brain areas involved in inner speech production and monitoring.

The effects of an Audio Visual Assisted Therapy Aid for Refractory auditory hallucinations (AVATAR therapy): study protocol for a randomised controlled trial.

BackgroundPsychological interventions which adopt an explicitly interpersonal approach are a recent development in the treatment of distressing voices. AVATAR therapy is one such approach which creates a direct dialogue between a voice-hearer and a computerised representation of their persecutory voice (the avatar) through which the person may be supported to gain a sense of greater power and control. The main objective of the trial is to test the clinical efficacy of this therapy to reduce the frequency and severity of auditory verbal hallucinations (AVH). Secondary objectives of the study are to explore explanatory mechanisms of action and potential moderators, to carry out a qualitative evaluation of participants’ experience and to conduct an economic evaluation.Methods/DesignThe AVATAR randomised clinical trial will independently randomise 142 participants to receive either 7 sessions of AVATAR therapy or supportive counselling (SC). The study population will be individuals with schizophrenia spectrum and other psychotic disorders who report hearing persistent distressing voices, for more than 12 months, which are unresponsive or only partially responsive to antipsychotic medication. The main hypotheses are that, compared to SC, AVATAR therapy will reduce the frequency and severity of AVH and will also reduce the reported omnipotence and malevolence of these voices. Assessments will occur at 0 weeks (baseline), 12 weeks (post-intervention) and 24 weeks (follow-up), and will be carried out by blinded assessors. Both interventions will be delivered in a community-based mental health centre. Therapy competence and adherence will be monitored in both groups. Statistical analysis will follow the intention-to-treat principle and data will be analysed using a mixed (random) effects model at each post treatment time point separately. A formal mediation and moderator analysis using contemporary causal inference methods will be conducted as a secondary analysis. The trial is funded by the Welcome Trust (WT).DiscussionAVATAR therapy showed promising effects in a pilot study, but the efficacy of the approach needs to be examined in a larger randomised clinical trial before wider dissemination and implementation in mental health services.Trial registrationCurrent Controlled Trials ISRCTN: 65314790, registration date: 27 March 2013.

Reduced cortical thickness in right Heschl's gyrus associated with auditory verbal hallucinations severity in first-episode schizophrenia.

BackgroundAuditory verbal hallucinations (AVHs) represent one of the most intriguing phenomena in schizophrenia, however, brain abnormalities underlying AVHs remain unclear. The present study examined the association between cortical thickness and AVHs in first-episode schizophrenia.MethodHigh-resolution MR images were obtained in 49 first-episode schizophrenia (FES) patients and 50 well-matched healthy controls (HCs). Among the FES patients, 18 suffered persistent AVHs (“auditory hallucination” AH group), and 31 never experienced AVHs (“no hallucination” NH group). The severity of AVHs was rated by the Auditory Hallucinations Rating Scale (AHRS). Cortical thickness differences among the three groups and their association with AVHs severity were examined.ResultsCompared to both HCs and NH patients, AH patients showed lower cortical thickness in the right Heschl’s gyrus. The degree of reduction in the cortical thickness was correlated with AVH severity in the AH patients.ConclusionsAbnormalities of cortical thickness in the Heschl’s gyrus may be a physiological factor underlying auditory verbal hallucinations in schizophrenia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0546-2) contains supplementary material, which is available to authorized users.

Adjuvant low-frequency rTMS in treating auditory hallucinations in recent-onset schizophrenia: a randomized controlled study investigating the effect of high-frequency priming stimulation.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been found to be effective in reducing frequency and duration of auditory verbal hallucinations (AVH). Priming stimulation, which involves high-frequency rTMS stimulation followed by low-frequency rTMS, has been shown to markedly enhance the neural response to the low-frequency stimulation train. However, this technique has not been investigated in recent onset schizophrenia patients. The aim of this randomized controlled study was to investigate whether the effects of rTMS on AVH can be enhanced with priming rTMS in recent onset schizophrenia patients.MethodsForty recent onset schizophrenia patients completed the study. Patients were randomized over two groups: one receiving low-frequency rTMS preceded by priming and another receiving low-frequency rTMS without priming. Both treatments were directed at the left temporo-parietal region. The severity of AVH and other psychotic symptoms were assessed with the auditory hallucination subscale (AHRS) of the Psychotic Symptom Rating Scales (PSYRATS), the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression (CGI).ResultsWe found that all the scores of these ratings significantly reduced over time (i.e. baseline through 1, 2, 4 and 6 weeks) in both the treatment groups. We found no difference between the two groups on all measures, except for significantly greater improvement on loudness of AVH in the group with priming stimulation during the follow-ups (F = 2.72; p < .05).ConclusionsWe conclude that low-frequency rTMS alone and high-frequency priming of low-frequency rTMS do not elicit significant differences in treatment of overall psychopathology, particularly AVH when given in recent onset schizophrenia patients. Add on priming however, seems to be particularly better in faster reduction in loudness of AVH.

High frequency rTMS; a more effective treatment for auditory verbal hallucinations?

The great majority of studies on repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool for auditory verbal hallucinations (AVH) have used 1-Hz stimulation with inconsistent results. Recently, it has been suggested that 20-Hz rTMS has strong therapeutic effects. It is conceivable that this 20-Hz stimulation is more effective than 1-Hz stimulation. The aim of this preliminary study is to investigate the efficacy of 20-Hz rTMS compared with 1-Hz rTMS as a treatment for AVH. Eighteen schizophrenia patients with medication-resistant AVH were randomized over two treatment groups. Each group received either 20min of 1-Hz rTMS or 13 trains of 20-Hz rTMS daily over 1 week. After week 1, patients received a follow-up treatment once a week for 3 weeks. Stimulation location was based on individual AVH-related activation patterns identified with functional magnetic resonance imaging. Severity of AVH was monitored with the Auditory Hallucination Rating Scale (AHRS). Both groups showed a decrease in AVH after week 1 of rTMS. This decrease was significant for the 20-Hz group and the 1-Hz group. When the two treatment types were compared, no treatment type was superior. Based on these results we cannot conclude whether high frequency rTMS is more effective against AVH than is traditional 1-Hz rTMS. More research is needed to optimize stimulation parameters and to investigate potential target locations for stimulation.

Effectiveness of a Brief Group Cognitive Behavioral Therapy for Auditory Verbal Hallucinations

The current study investigated the effectiveness of a group cognitive behavioral therapy for auditory verbal hallucinations (AVHs), the Voices Group. This consists of seven specific sessions. Forty-one participants with schizophrenic or schizoaffective disorders completed a battery of questionnaires. The severity of psychiatric symptoms, beliefs about voices, quality of life, self-esteem, clinical global impression, and functioning were assessed at baseline, before and after intervention, and at the 6-month follow-up. After intervention, there was a statistically significant reduction in the severity of AVHs. This result remained stable at follow-up. The dropout rate was high. Some differences were found in subjective experience of AVHs between the patients who completed the intervention and those who dropped out. Altogether, these findings suggest that a brief intervention has some positive benefits in patients struggling with voices, which remain stable over time.

EPA-0228 - Non invasive brain stimulation in the treatment of schizophrenia

Auditory verbal hallucinations (AVH) are a characteristic symptom of schizophrenia. Previous studies have investigated 1-Hz repetitive transcranial magnetic stimulation (rTMS) to the left temporoparietal region as a non-invasive treatment option for treatment-resistant patients, with several studies with large sample sizes not demonstrating efficacy of rTMS compared to sham stimulation. A new stimulation protocol using continuous theta-burst rTMS could provide a more effective therapeutic option. In a double-blind study, forty-one patients with AVH were randomly allocated to either continuous theta-burst rTMS or sham treatment. The theta-burst TMS group received 10 treatments over left temporoparietal cortex distributed over five consecutive days. The placebo group received 10 treatments of sham stimulation following the same procedures as the theta-burst group. Severity of AVH was assessed using the psychotic symptom rating scales (PSYRATS), the auditory hallucinations rating scale (AHRS) and item P3 of the positive and negative syndrome scale (PANSS) before treatment, after five days of treatment, and during follow-up one month later. Data were analyzed using repeated measures ANOVA. Significant main effects of treatment were observed for the PSYRATS (p=0.017) and a trend was observed for the AHRS (p=0.053), indicating lower hallucination severity scores after treatment. No significant interaction effects were observed for any of the hallucination severity scales, indicating that AVH did not significantly improve after theta-burst stimulation compared to sham stimulation. These results suggest a placebo effect of continuous theta-burst rTMS on the left temporoparietal region.

EPA-1392 – Transcranial direct-current stimulation (tDCS) in patients with schizophrenia

Introduction Some 25%–30% of patients with schizophrenia have auditory verbal hallucinations that are refractory to antipsychotic drugs. transcranial directcurrent stimulation (tDCS) is a novel somatic treatment proposed for hallucinations and negative symptoms (Brunelin et al. 2012). Objectives/Aims We aimed to assess the efficacy of tDCS in reducing the severity of auditory verbal hallucinations as well as negative symptoms in patients with schizophrenia. Methods Six patients (aged 41–66 year) with schizophrenia and medication-refractory auditory verbal hallucinations were enrolled. Positive and Negative Syndrome Scale (PANSS) and Cardiff Anomalous Perceptions Scale (CAPS) were administered as outcome measure, before (T0) and after tDCS (T1), to assess treatment response. tDCS delivered by a HDCstim (Newronika, Milano, Italy) (2mA, twenty minutes, twice a day for 5 consecutive days) with the anodal electrode over the left dorsolateral prefrontal cortex and cathodal electrode on the left temporo parietal cortex. Results The patients tolerated well the procedure and there was no side effect. After tDCS auditory verbal hallucinations improved by 33% in frequency (T0 vs T1 p=0.03) and by 40% in distress (T0 vs T1 p=0.02), for up to one month. Negative symptoms as measured by the PANSS also decreased by 24% (T0 vs T1, p=0.02). Conclusion The results of this small, open tDCS trial prompt the further studies with controlled, double blind design in a larger sample size of schizophrenic patients. Nonetheless, our findings are in line with available data reporting a beneficial effects of tDCS in schizophrenia (Brunelin et al. 2012).