Verbal Hallucinations Research Articles

S168. AUDITORY TRANSCALLOSAL FIBERS AND AUDITORY HALLUCINATIONS

BackgroundAuditory verbal hallucinations (AVH) are one of the most common symptoms in schizophrenia. Connectivity between left and right auditory cortex may be related to AVH. The aim of this study was to examine transcallosal auditory cortex connectivity in first-episode schizophrenia patients (FESz) who experience AVH.MethodsDiffusion spectrum imaging (DSI) data were obtained from 29 FESz and 23 healthy controls (HCs). Of the 29 FESz participants, 15 were AVH-, with a score of 0 for auditory hallucinations, voices commenting, and voices conversing measured with the Scale for the Assessment of Positive Symptoms (SAPS), and 14 were AVH+, with a score of 2 or greater on at least one of these questions. The three groups (AVH+, AVH-, and healthy controls) were matched for age, parental socioeconomic status, years of education, IQ, gender, and handedness. A deterministic fiber tracking algorithm was used to identify the transcallosal auditory white matter tract, which was identified as the 1000 fibers passing through the posterior third of the corpus callosum and ending bilaterally in Brodmann’s area 22, Heschl’s gyrus, or planum temporale. Transcallosal auditory cortex connectivity was compared between groups for tract volume, generalized Fractional Anisotropy (gFA), and isotropy.ResultsMANOVA revealed a significant difference in connectivity between groups (F(6, 94) = 2.34, p = .038) that was driven by group differences in tract volume (F(2, 49) = 3.46, p =.039) and gFA (F(2, 49) = 4.77, p = .013)). Within FESz, AVH severity significantly correlated with auditory cortex transcallosal gFA (r =-.44, p =.013). Pairwise t-tests indicated lower gFA and greater tract volume for AVH+ vs AVH- (p’s < .05). HCs had a trend towards greater gFA (p = .068) vs AVH+ and tract volume (p = .063) vs AVH-. All other comparisons were nonsignificant (p >.1).DiscussionThese findings suggest that structural connectivity differences may underlie AVH in schizophrenia, even early in disease course. FESz participants with AVH have less efficient transcallosal auditory connectivity compared to those without AVH. The reduced gFA in FESz correlated with hallucination severity, suggesting that inefficient coordination of left and right hemisphere auditory processing, crucial for language, was impaired in the disorder. The transcallosal structural integrity and connectivity may indicate a subtype characterized by AVH. Current work is determining the extent to which this fiber deficit is common across Kraepelinian diagnostic categories of psychosis (e.g., bipolar disorder and depression with psychotic features).

T150. REAL-TIME FMRI NEUROFEEDBACK TO DOWN-REGULATE SUPERIOR TEMPORAL GYRUS ACTIVITY IN PATIENTS WITH SCHIZOPHRENIA AND AUDITORY HALLUCINATIONS: A PROOF-OF-CONCEPT STUDY

BackgroundNeurocognitive models and previous neuroimaging work posit that auditory verbal hallucinations (AVH) arise due to increased auditory cortex (AC) activity and altered connectivity between the AC and other speech and language regions [e.g. 1]. In the present study we examined if patients with schizophrenia (SCZ) and AVH could be trained to down-regulate AC activity using real time functional Magnetic Resonance Imaging neurofeedback (rtfMRI-NF) [2]. We also examined the effects of rtfMRI-NF training on functional connectivity between the AC and other speech and language regions.MethodsEleven patients with SCZ (Table 1) and treatment refractory AVH were recruited to participate in the study and were trained to down-regulate auditory cortex (AC) activity over an average of fourteen rtfMRI-NF runs conducted during a two-week training period (Fig 1). We used a functional localiser to identify the speech sensitive superior temporal cortex (STG) (Figure 2A). At the end of the training period, AC activity, functional connectivity and AVH symptom levels were compared pre and post training.ResultsPatients successfully learnt to down-regulate activity in their AC over the rtfMRI-NF training period. Post training, patients showed increased connectivity between the AC, the inferior prefrontal gyrus and the inferior parietal lobe Figure. There was also a modest reduction in AVH symptom levels post compared to pre training (Table 2).DiscussionThe AC is as suitable target region for rtfMRI-NF in patients with SCZ and treatment refractory AVH. Successful down-regulation of AC activity can increase functional connectivity between speech motor and perception regions. These findings raise the possibility that rtfMRI-NF training could be used as a novel therapeutic intervention in this clinical population.

F187. TBSS ANALYSIS OF WHITE MATTER ALTERATIONS IN SCHIZOPHRENIA PATIENTS VS. HEALTHY CONTROLS – RELATION TO AUDITORY VERBAL HALLUCINATIONS

BackgroundRecent Magnetic Resonance Imaging (MRI) studies on schizophrenia suggest that auditory verbal hallucinations (AVH) might be caused by alterations in connectivity of frontal and temporoparietal language-related areas.3 as well as in connectivity of the default mode network (DMN).1 Therefore, diffusion tensor imaging (DTI) of white matter fiber tracts, subserving anatomical connections between distant and proximal brain regions, could offer complementary information for understanding the anatomical underpinnings of AVH.MethodsTract-based spatial statistics (TBSS) allows voxel-wise analysis of multi-subject diffusion data based on fractional anisotropy (FA), assessing microstructural properties of white matter tracts. This study investigates brain white matter tracts in 85 schizophrenia patients and 111 healthy, matched controls using TBSS analysis. Patients were grouped into sub-groups (hallucinating and non-hallucinating) based on the Positive and Negative Syndrome Scale (PANSS), with a cut-off PANSS P3 >= 3 in a 12 months period. Additionally, a comparison between the whole patient sample and controls was performed. The whole-brain analysis was performed with permutation analysis of linear models (PALM).2 Two-tailed t-test was used for group comparison of the patients and controls and a 2 x 2 factorial design was used for hemispheric comparison between patients and controls.ResultsTBSS results shows significantly lower fractional anisotropy in the right inferior longitudinal fasciculus in schizophrenia patients in comparison to healthy controls (FDR correction p < 0.05). However, after subtracting non-hallucinating patients from the group this effect was no longer present. Hemispheric comparison between patients and healthy controls revealed wide- spread FA reduction in several white matter pathways such as: the corpus callosum (genu and body), cingulum cortex, inferior longitudinal fasciculus, superior corona radiata, anterior thalamic radiation (FDR correction p < 0.05). This effect was also present after excluding the non-hallucinating patients from the sample.DiscussionThe present findings indicate reduced white matter integrity in schizophrenia patients compared with controls in the inferior longitudinal fasciculus. However, this observation is most likely not related to hallucination proneness since it was not present when comparing the hallucinating patient subgroup with the control group. Hemispheric comparison between patients and controls in both the whole data sample as well as hallucinating group showed significant differences in several white matter pathways. This could indicate that schizophrenia patients (with or without AVH) have altered FA differences between the hemispheres. More research is needed to further understand the implications of these findings.

T161. HEARING VOICES AMONG INDIGENOUS MAASAI WOMEN IN TANZANIA: IMPLICATIONS FOR GLOBAL MENTAL HEALTH

BackgroundStudies of the health of indigenous and tribal people can shed light on health inequalities with implications for global mental health. Almost no previous studies of mental health among the Maasai in Kenya or Tanzania or even pastoralist groups in general are available, with the exception of one mentioning the stress of rural-to-urban migration. While engaged in ethnographic research in 2013, Myers interviewed 13 Maasai women in northern Tanzania about their everyday lives. Interested in the phenomenology of voice-hearing, she also asked them if they heard voices. Eleven of the women (85%) reported regularly hearing voices that they found to be distressing. Myers returned in 2015 to collect data from a larger sample, which has resulted in this report.MethodsFor this study, we used a convenience sample (n=73) of females taken from a broader study whose eligibility criteria included being a Maasai person living in the Arusha Region of Tanzania and over the age of 18. We excluded people who reported being psychiatric patients or family members of patients being seen by the local mental health coordinator to create a nonclinical community sample. This project conducted an initial survey to: 1) estimate the community prevalence of voice-hearing, or auditory verbal hallucinations (AVHs) in this specific population; and, 2) examine any demographic correlates and two specific hypothesized correlates based on previous literature about voice-hearing (e.g., psychological stress and potentially traumatic events).ResultsThe prevalence of AVHs in this community sample was quite high compared to other studies in sub-Saharan Africa, at 34.3%. There were no differences between participants who did and did not experience AVHs in terms of demographics, but those experiencing AVHs had a statistically significantly higher level of psychological distress (30.1, SD=6.0, compared to 25.1, SD=6.0), with a Cohen’s d effect size of .87. Even though a numerical difference was observed in terms of potentially traumatic events (4.6, SD=2.1, compared to 3.8, SD=2.3), this difference was not statistically significant (d=.38).DiscussionHearing distressing voices may be an indicator of mental ill health that is easily recognizable to community health workers and brings much-needed attention to communities in need. Maasai women face tremendous social adversity in this time of rapid social, economic, and climate change in the region. Evidence for a link between stressful life events, social disadvantage, and the development of psychotic symptoms is strong in Europe, but not as well-developed in this region. The high level of psychosocial stress and AVHs in our sample may also be indicative of extreme social adversity. Maasai women have been historically disenfranchised since the advent of colonial and postcolonial policies favoring men. Women in this region also experiences extreme states of deprivation, including a 21.5 year gap in life expectancy at birth compared to the local population (for all Maasai), 81% severe food insecurity, and a rate of 59% for the stunted growth of children (as compared to their neighbors, the Meru, with 21% of children with stunted growth). Due to local livelihood insecurity, the age of first marriage has been decreasing, resulting in increased pressure on women. This analysis contextualizes these findings and calls for further research on the epidemiology of voice-hearing in this region, as well as further work on the phenomenology of these AVHs so that we can best understand how to address them and improve mental health outcomes for this marginalized group.

F173. PITCH AND DURATION MISMATCH NEGATIVITY, AUDITORY CORTEX GRAY MATTER, AND PRODROMAL ROLE FUNCTIONING IN THE FIRST EPISODE SCHIZOPHRENIA SPECTRUM

BackgroundPrimary auditory cortex, contained within Heschl’s gyrus, is implicated auditory processing deficits and auditory verbal hallucinations in schizophrenia. Previously we showed a pathological correlation between the magnitude of the pitch-deviant mismatch negativity (pMMN) response during a passive auditory task and reductions in gray matter volume in Heschl’s gyrus in subjects with first hospitalized for schizophrenia. The aim of this study was to replicate this finding, examine duration-deviant mismatch negativity (dMMN) and gray matter correlations, and to examine pre-psychosis role functioning, in a first episode psychosis sample within the schizophrenia-spectrum.MethodsParticipants included 40 first episode schizophrenia subjects (FESz) and 40 healthy controls (HC) matched for age, parental socioeconomic status, IQ, sex, and handedness. For MMN extracted from the EEG, standard tones were presented repeatedly (1 kHz, 75 dB, 50 ms pips, 5 ms rise/fall times, 330 ms SOA) with an occasional pitch deviant (1.2 kHz, 10% of trials) or duration deviant (100 ms, 10% of trials) interspersed. pMMN and dMMN were measured from subtraction waveforms as the average voltage within a 100-ms group averaged peak window at Fz. Role functioning was measured with the Cornblatt Global Functioning: Role scale. A subset of 28 FESz and 28 matched HC underwent structural MRI. High-resolution T1-weighted structural MRI data (3T) were acquired for each subject. Freesurfer was used to segment white matter, gray matter, and pial surfaces. Left and right Heschl’s gyri were manually edited regions of interest, and gray matter volumes determined.ResultsDespite a lack of pMMN or dMMN reduction at the group level in FESz, both measures were pathologically correlated with role functioning in the year prior to hospitalization. In FESz, smaller pMMN at Fz was associated with poorer role functioning in the year prior to psychosis (rho= -.35, p =.03). Similar associations were observed for dMMN (rho= -.41, p <.01). Furthermore, in the subset of FESz with sMRI, smaller pMMN at Fz was associated with less total gray matter volume in left Heschl’s gyrus (TGMV) (rho= -.40, p =.03) but not right. Similar associations were observed for dMMN (rho= -.47, p .01). As well, role functioning and auditory cortex gray matter volumes were not correlated in FESz. There were no significant correlations within HC.DiscussionAlthough pMMN and dMMN are not reduced at the group level, the size of both are associated with impaired functioning prior to psychosis and reduced gray matter volume of left hemisphere Heschl’s gyrus, containing primary and secondary auditory cortices. Thus, pMMN and dMMN although not sufficient as biomarkers of disease presence, are suitable as reliable biomarkers of disease progression. Presumably, poorer role functioning and less gray matter reflect more of the pre-psychosis progressive pathological process thought to occur in the prodromal phase of psychosis. Hence, pMMN and dMMN are likely to serve as sensitive and robust outcome measures for therapeutic interventions and to guide treatment strategies in the prodrome and during early psychosis.

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)

O2.7. CAN THEY HEAR IT? DO PATIENTS WITH AUDITORY VERBAL HALLUCINATIONS HAVE AUDITORY PROCESSING DEFICITS?

BackgroundIt has been well established for over half a century that patients with a diagnosis of schizophrenia have auditory processing deficits. More recently, there has been a small body of work that has suggested patients with a history of auditory hallucinations have particularly pertinent auditory processing deficits, with the importance of pitch perception being noted in a single study. This current body of work has systematically investigated whether auditory perception, using a tone detection task, are related to auditory verbal hallucinations (AVH).MethodsFour studies will be presented each of which used a tone detection task that manipulated pitch, with the study 1 also have a tone duration manipulation.ResultsStudy 1 compared 15 AVH with 15 non-AVH patients with schizophrenia with 34 healthy controls, AVH patients demonstrated the greatest impairments on pitch and tone duration deficits compared to the other two groups. Study 2 compared 99 patients with schizophrenia (65 with a history of AVH and 34 without) with 95 healthy controls and confirmed pitch deficits in schizophrenia, specifically those with AVH. Study 3 established in 100 healthy controls that unusual experiences or auditory hallucination proneness were significantly correlated to pitch perception performance. Lastly, study 4 demonstrated that relatives of patients with schizophrenia also showed a significant correlation between usual experiences and pitch perception.DiscussionThis research indicates auditory processing deficits are a core feature of AVH in schizophrenia, and potentially represent an endophenotype for AVH. The authors will discuss a potential cognitive model which explains the relationship between AVH and pitch perception. There are clear translational elements to this research, and we suggest there might be some utility in using auditory training as an intervention to reduce the impact of AVH.

T2. DO ADVERSE LIFE EVENTS AT FIRST ONSET OF AUDITORY VERBAL HALLUCINATIONS INFLUENCE SUBSEQUENT VOICE-CHARACTERISTICS? RESULTS FROM AN EPIDEMIOLOGICAL STUDY

BackgroundUnderstanding what happens at first onset of auditory verbal hallucinations (AVHs) is important at both a clinical and theoretical level. Previous studies have focused on age with regard to first onset of AVHs. In the current epidemiological study, we investigated the role of adverse life events (e.g. accidents, divorce, bullying, unemployment) at the time of first onset of AVHs regarding symptom severity and general mental health later in life.MethodsUsing data from the Launay-Slade Hallucination Scale (LSHS), we compared participants who reported having experienced at least one adverse life events at first onset of AHVs (Trigger group; N = 76) to those who did not report any specific events at first onset of AVHs (No-trigger group; N = 59) on a large array of variables using Fisher’s exact test.ResultsResults revealed that the Trigger group experienced the AVHs as more emotional and they were also more troubled by the AVHs compared to the No-trigger group (all p < 0.01). Also, the Trigger group more often reported hallucinations in other (non-auditory) sensory modalities (e.g. visual, p = 0.012) compared to the No-trigger group. Furthermore, the Trigger group reported poorer mental health in general, and having had more frequent contact with mental health professionals, and also reported more frequently taking medication for mental problems in general (all p < 0.01).DiscussionAdverse life events at first onset of AVHs appear to have a negative influence on subsequent voice-characteristics and general mental health, suggesting their presence to be an important factor to take into account when determining the risk for psychosis or other mental disorders. However, future longitudinal studies are needed in order to corroborate these findings.

F123. BELIEFS ABOUT THEIR VOICES AND DEGREE OF RESILIENCE IN PERSONS WITH AUDITORY VERBAL HALLUCINATIONS WITH AND WITHOUT NEED FOR CARE

BackgroundAuditory Verbal Hallucinations (AVH) are prevalent in many psychopathologies but are also experienced by a minority of the healthy general population. There is cumulative evidence that the beliefs people hold about their voices (e.g., power) are strongly related to the impact of the voices (e.g., depression, anxiety) and to the coping strategies that they adopt (e.g., resistance, engagement). To date, research on resilience has identified many factors that promote wellbeing and that protect people from developing psychopathologies despite exposure to health or psychological adversities. However, no previous studies have examined resilience in people who experience AVH with and without need for care, and neither have the relations between resilience and beliefs about the voices been examined.MethodsFifty persons who report hearing voices frequently were recruited online. Based on the presence of a psychiatric diagnosis, the use of antipsychotic medication, and on the consultation of a psychiatrist, they were then classified as being Healthy Voice-Hearers (HVH) or Patients (P). One hundred and nineteen healthy participants who have never experienced hearing voices were also recruited as a control group (CTRL). All participants completed the Resilience Scale for Adults. In addition, the HVH and P groups completed questionnaires that assess the beliefs they hold about their voices (the revised Beliefs About Voices Questionnaire) and voice characteristics (frequency and emotional content).ResultsThe data collection is currently underway, and thus the following results are preliminary. Kruskal-Wallis ANOVAs revealed significant differences between the three groups (HVH, P, CTRL) on several resilience factors. In particular, post-hoc analyses demonstrated that the CTRL and HVH groups were more resilient than the P group for the perception of self and of future. In addition, the HVH group was found to be more resilient than the P group in terms of social competence. Finally, for social factors (social resources and family cohesion), results showed that the CTRL group was more resilient than the P group. However, the HVH group was not significantly different from the P and the CTRL groups. Concerning voice characteristics, Mann-Whitney tests revealed that, compared to the P, the HVH perceived their voices as being less omnipotent and malevolent, less negative and more positive, and showed less resistance against the voices. Finally, correlational analyses (Spearman) demonstrated that better resilience (and in particular the individual factors such as the perception of self and of the future, and social competence) was related to fewer negative beliefs about the voices, less resistance, lower voice frequency, and less negative and more positive emotional content.DiscussionThe present study showed that people who experience AVH without need for care have a different pattern of resilience compared to patients with AVH, and to healthy controls without AVH. In particular, the HVHs did not differ from the CTRL on the personal factors of resilience and did not differ from the patients in terms of social factors. In addition, better resilience (and especially the personal factors) was found to be related to fewer negative beliefs about the voices, better coping strategies, lower voice frequency, and less negative and more positive emotional content. Taken together, these results show that resilience – and in particular, the personal factors – may be an important variable influencing the need for care in people experiencing AVH. The present study has important theoretical and clinical implications, in particular, suggesting that the personal factors of resilience may be a treatment target in order to diminish the impact of voices.

Aberrant salience network functional connectivity in auditory verbal hallucinations: a first episode psychosis sample

Auditory verbal hallucinations (AVH) often lead to distress and functional disability, and are frequently associated with psychotic illness. Previously both state and trait magnetic resonance imaging (MRI) studies of AVH have identified activity in brain regions involving auditory processing, language, memory and areas of default mode network (DMN) and salience network (SN). Current evidence is clouded by research mainly in participants on long-term medication, with chronic illness and by choice of seed regions made ‘a priori’. Thus, the aim of this study was to elucidate the intrinsic functional connectivity in patients presenting with first episode psychosis (FEP). Resting state functional MRI data were available from 18 FEP patients, 9 of whom also experienced AVH of sufficient duration in the scanner and had symptom capture functional MRI (sc fMRI), together with 18 healthy controls. Symptom capture results were used to accurately identify specific brain regions active during AVH; including the superior temporal cortex, insula, precuneus, posterior cingulate and parahippocampal complex. Using these as seed regions, patients with FEP and AVH showed increased resting sb-FC between parts of the SN and the DMN and between the SN and the cerebellum, but reduced sb-FC between the claustrum and the insula, compared to healthy controls.It is possible that aberrant activity within the DMN and SN complex may be directly linked to impaired salience appraisal of internal activity and AVH generation. Furthermore, decreased intrinsic functional connectivity between the claustrum and the insula may lead to compensatory over activity in parts of the auditory network including areas involved in DMN, auditory processing, language and memory, potentially related to the complex and individual content of AVH when they occur.

Are there clinical differences between inner, outer or dual spatial locations of auditory verbal hallucinations?

The aim of the present exploratory study was to examine the clinical differences of Auditory Verbal Hallucinations (AVHs) according to their spatial localization. Sixty-six outpatients were divided into three separate groups: inner, external and dual AVHs. The three groups were compared on sociodemographic variables (age, gender, education, marital status, living situation, employment, social disability), on clinical psychiatric characteristics (diagnosis, medication, comorbidities, illness onset, illness duration and hospitalizations) and on the measure yielded by the clinical assessments (Brief Psychiatric Rating Scale-Expanded, version 4.0; Maastricht Voices Interview for Adults; Belief About Voices Questionnaire Revised, the Clinical Global Impression, the Global Assessment Functioning Self-Esteem Rating Short Form, the World Health Organisation Quality of Life-Bref). Gender, living situation, social quality of life and some items regarding beliefs about AVHs raised significant difference, however most of the other comparisons failed to reach significance. Taken together, our findings suggest that all AVHs subtypes have equal clinical significance in patients presenting a chronic mental illness. However, the power of the study limits the generalization of the findings. Clinical implications of the findings are proposed.

Neurofeedback-Based Enhancement of Single-Trial Auditory Evoked Potentials: Treatment of Auditory Verbal Hallucinations in Schizophrenia.

Auditory verbal hallucinations depend on a broad neurobiological network ranging from the auditory system to language as well as memory-related processes. As part of this, the auditory N100 event-related potential (ERP) component is attenuated in patients with schizophrenia, with stronger attenuation occurring during auditory verbal hallucinations. Changes in the N100 component assumingly reflect disturbed responsiveness of the auditory system toward external stimuli in schizophrenia. With this premise, we investigated the therapeutic utility of neurofeedback training to modulate the auditory-evoked N100 component in patients with schizophrenia and associated auditory verbal hallucinations. Ten patients completed electroencephalography neurofeedback training for modulation of N100 (treatment condition) or another unrelated component, P200 (control condition). On a behavioral level, only the control group showed a tendency for symptom improvement in the Positive and Negative Syndrome Scale total score in a pre-/postcomparison ( t(4) = 2.71, P = .054); however, no significant differences were found in specific hallucination related symptoms ( t(7) = -0.53, P = .62). There was no significant overall effect of neurofeedback training on ERP components in our paradigm; however, we were able to identify different learning patterns, and found a correlation between learning and improvement in auditory verbal hallucination symptoms across training sessions ( r = 0.664, n = 9, P = .05). This effect results, with cautious interpretation due to the small sample size, primarily from the treatment group ( r = 0.97, n = 4, P = .03). In particular, a within-session learning parameter showed utility for predicting symptom improvement with neurofeedback training. In conclusion, patients with schizophrenia and associated auditory verbal hallucinations who exhibit a learning pattern more characterized by within-session aptitude may benefit from electroencephalography neurofeedback. Furthermore, independent of the training group, a significant spatial pre-post difference was found in the event-related component P200 ( P = .04).

Negative voice-content as a full mediator of a relation between childhood adversity and distress ensuing from hearing voices

A key predictor of whether or not an individual who hears voices (auditory verbal hallucinations; AVH) meets criteria for a psychiatric diagnosis is the level of negative content of the voices (e.g., threats, criticism, abuse). Yet the factors that contribute to negative voice-content are still not well understood. This study aimed to test the hypotheses that levels of childhood adversity would predict levels of negative voice-content, and that negative voice-content would partially mediate a relation between childhood adversity and voice-related distress. These hypotheses were tested in a clinical sample of 61 patients with formally diagnosed psychotic disorders (48 schizophrenia, 13 bipolar). We found evidence consistent with negative voice-content fully (not partially) mediating the relation between childhood adversity and voice-related distress. Although bivariate analyses found depression to be associated with both negative voice-content and voice-related distress, we found no evidence of an indirect effect of childhood adversity on either negative voice-content or voice-related distress via depression. Alternative study designs are now needed to test if our findings are replicable and causal. Should they be, it will be necessary for psychological therapies to devise ways to reduce negative voice-content itself, rather than just changing beliefs about voices. A number of techniques are discussed (Avatar Therapy, Compassion Focused Therapy, voice-dialogue) that already show promise for this.

Gene polymorphisms and response to transcranial direct current stimulation for auditory verbal hallucinations in schizophrenia.

Recent observations demonstrate a significant ameliorative effect of add-on transcranial direct current stimulation (tDCS) on auditory verbal hallucinations (AVHs) in schizophrenia. Of the many SNPs, NRG1 rs35753505 and catechol-o-methyl transferase (COMT) rs4680 polymorphisms have shown to have a strong association with neuroplasticity effect in schizophrenia. Schizophrenia patients (n=32) with treatment resistant auditory hallucinations were administered with an add-on tDCS. The COMT (rs4680) and NRG1 (rs35753505) genotypes were determined. The COMT genotypes were categorised into Val group (GG; n=15) and Met group (GG/AG; n=17) and NRG1 genotypes were categorised into AA group (n=12) and AG/GG group (n=20). The reduction in auditory hallucination sub-scale score was significantly affected by COMT-GG genotype [Time×COMT interaction: F(1,28)=10.55, p=0.003, ɳ2=0.27]. Further, COMT-GG effect was epistatically influenced by the co-occurrence of NRG1-AA genotype [Time×COMT×NRG1 interaction: F(1,28)=8.09, p=0.008, ɳ2=0.22]. Irrespective of genotype, females showed better tDCS response than males [Time×Sex interaction: F(1,21)=4.67, p=0.04, ɳ2=0.18]. COMT-GG and NRG1-AA genotypes aid the tDCS-induced improvement in AVHs in schizophrenia patients. Our preliminary observations need replication and further systematic research to understand the neuroplastic gene determinants that modulate the effect of tDCS.

Aberrant Functional Connectivity Patterns of Default Mode Network May Play a Key Role in the Interaction between Auditory Verbal Hallucinations and Insight.

Aberrant Functional Connectivity Patterns of Default Mode Network May Play a Key Role in the Interaction between Auditory Verbal Hallucinations and Insight.

Comorbid Diagnosis of Psychotic Disorders in Borderline Personality Disorder: Prevalence and Influence on Outcome.

A diagnosis of psychotic disorder is traditionally considered incompatible with borderline personality disorder (BPD), even though patients sometimes fulfill the diagnostic criteria for both disorders. How often this happens is barely known, as is the influence of comorbid psychotic disorders on the outcome of BPD. Since studies on isolated auditory verbal hallucinations in patients with BPD indicate that these perceptual symptoms have severe consequences and are associated with suicidal behavior and hospitalization, patients with comorbid psychotic disorders are unlikely to fare better. To examine the point prevalence of psychotic disorders in patients with BPD, their association with the outcome of BPD, and their predictive value for outcome. In a cross-sectional design, 84 female outpatients diagnosed with BPD were interviewed with the aid of the MINI-International Neuropsychiatric Interview to establish the point prevalence of comorbid psychotic and other comorbid disorders. After termination of their treatment at a specialized outpatient clinic, the type of referral was considered to be a "good" outcome when they were referred to their general practitioner or to basic psychiatric care for noncomplex patients, and a "poor" outcome when referred to a specialized psychiatric department or to a psychiatric district team for patients with severe psychiatric disorders. Psychotic disorders were present in 38% of the patients with BPD. With a prevalence of 20%, psychotic disorder not otherwise specified (NOS) was the most common subtype; the least common types were schizophrenia (2%), substance-induced psychotic disorder (2%), and brief psychotic disorder (1%). Among six types of comorbid disorders, only psychotic disorders were associated with a poor outcome; they were also predictors for a poor outcome, along with comorbid mood disorders, eating disorders, and somatoform disorders, as well as the severity of BPD, and, counterintuitively, more years of education. Psychotic disorders, notably of the psychotic disorder NOS subtype, are common among patients with BPD, and their presence is associated with a poor outcome. This implies that adequate diagnosis and treatment of both disorders is warranted in this subgroup with a dual diagnosis.

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.

Reducing distress and improving social functioning in daily life in people with auditory verbal hallucinations: study protocol for the ‘Temstem’ randomised controlled trial

IntroductionAuditory verbal hallucinations (AVH) are prevalent experiences that can induce distress and impede social functioning. While most voice hearers benefit from antipsychotic medication or cognitive–behavioural therapy, additional effective interventions are...

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.

A Computational Assessment of Target Engagement in the Treatment of Auditory Hallucinations with Transcranial Direct Current Stimulation.

We use auditory verbal hallucinations (AVH) to illustrate the challenges in defining and assessing target engagement in the context of transcranial direct current stimulation (tDCS) for psychiatric disorders. We defined the target network as the cluster of regions of interest (ROIs) that are consistently implicated in AVH based on the conjunction of multimodal meta-analytic neuroimaging data. These were prescribed in the New York Head (a population derived model) and head models of four single individuals. We appraised two potential measures of target engagement, tDCS-induced peak electric field strength and tDCS-modulated volume defined as the percentage of the volume of the AVH network exposed to electric field magnitude stronger than the postulated threshold for neuronal excitability. We examined a left unilateral (LUL) montage targeting the prefrontal cortex (PFC) and temporoparietal junction (TPJ), a bilateral (BL) prefrontal montage, and a 2 × 1 montage targeting the left PFC and the TPJ bilaterally. Using computational modeling, we estimated the peak electric field strength and modulated volume induced by each montage for current amplitudes ranging 1–4 mA. We found that the LUL montage was inferior to both other montages in terms of peak electric field strength in right-sided AVH-ROIs. The BL montage was inferior to both other montages in terms of modulated volume of the left-sided AVH-ROIs. As the modulated volume is non-linear, its variability between montages reduced for current amplitudes above 3 mA. These findings illustrate how computational target engagement for tDCS can be tailored to specific networks and provide a principled approach for future study design.