Progressive gray matter reduction in schizophrenia patients with persistent auditory hallucinations by causal structural covariance network analysis.

Neuroimaging studies have revealed that the mechanisms of auditory hallucinations are related to morphological changes in multiple cortical regions, but studies on brain network properties are lacking. This study aims to construct intra-individual structural covariance networks and reveal network changes related to auditory hallucinations. T1-weighted MRI images were acquired from 90 schizophrenia patients with persistent auditory hallucinations (pAH group), 55 schizophrenia patients without auditory hallucinations (non-pAH group), and 83 healthy controls (HC group). Networks were constructed using the voxel-based gray matter volume and the intra-individual structural covariance was based on the similarity between the morphological variations of any two regions. One-way ANCOVA was employed to compare global and local network metrics among the three groups, and edge analysis was conducted via network-based statistics. In the pAH group, Pearson correlation analysis between network metrics and clinical symptoms was conducted. Compared with the HC group, both the pAH group (p = 0.01) and the non-pAH group (p = 3.56 × 10−4) had lower nodal efficiency of the left medial superior frontal gyrus. Compared to the non-pAH group and HC group, the pAH group presented lower nodal efficiency of the temporal pole of the left superior temporal gyrus (p = 1.09 × 10−3; p = 7.67 × 10−4) and right insula (p = 0.02; p = 8.99 × 10−6), and lower degree centrality of the right insula (p = 0.04; p = 1.65 × 10−5). The pAH group had a subnetwork with reduced structural covariance centered by the left temporal pole of the superior temporal gyrus. In the pAH group, the normalized clustering coefficient (r = −0.36, p = 8.45 × 10−3) and small-worldness (r = −0.35, p = 9.89 × 10−3) were negatively correlated with the PANSS positive scale score. This study revealed network changes in schizophrenia patients with persistent auditory hallucinations, and provided new insights into the structural architecture related to auditory hallucinations at the network level.

Volumetric MRI correlates of persistent auditory verbal hallucinations and olfactory identification impairment in chronic schizophrenia: A cross-sectional study

Persistent Auditory Hallucinations in a Sample of Schizophrenic Outpatients

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

Background High worldwide estimates of depression and suicidality in patients diagnosed with schizophrenia highlight the importance of understanding their associated factors for designing targeted interventions that can both improve distress symptoms and reduce suicide risk in this vulnerable population. In this regard, our study aims to assess the link between beliefs about voices, self-esteem, depression and suicidality in a sample of Lebanese long-stay patients with auditory hallucinations. Methods This study followed a cross-sectional design. Data has been gathered at the psychiatric hospital of the Cross, Lebanon, during the month of April 2022. Patients diagnosed with schizophrenia, aged >18 years, hospitalized for >1 year, clinically stable, and experiencing persistent auditory verbal hallucinations were included. Results Sixty-one patients were experiencing auditory hallucinations and were therefore enrolled in the study. Their mean age was 56.05 ± 12.25 years (27.9% females); 42.6% of patients had suicidal ideation, 48.9% had depression. Multivariable analyses models showed that, after adjusting for confounders, higher omnipotence (Beta = .49) and emotional resistance (Beta = .92) remained strongly linked with more depression; while only higher depression (aOR = 1.17) remained significantly linked with increased likelihood of having suicidal ideation. Discussion Pending future longitudinal research, findings suggest that mental health professionals should not only assess the presence of auditory hallucinations but also pay attention to the patient’s beliefs about their voices, as they may be determinant in the development of depression. Therapeutic approaches targeting resistant and malevolent beliefs about voices may be highly beneficial as adjuvant to existing pharmacological and psychological interventions.

Auditory verbal hallucinations are a cardinal symptom of schizophrenia. Bleuler and Kraepelin distinguished 2 main classes of hallucinations: hallucinations heard outside the head (outer space, or external, hallucinations) and hallucinations heard inside the head (inner space, or internal, hallucinations). This distinction has been confirmed by recent phenomenological studies that identified 3 independent dimensions in auditory hallucinations: language complexity, self-other misattribution, and spatial location. Brain imaging studies in schizophrenia patients with auditory hallucinations have already investigated language complexity and self-other misattribution, but the neural substrate of hallucination spatial location remains unknown. Magnetic resonance images of 45 right-handed patients with schizophrenia and persistent auditory hallucinations and 20 healthy right-handed subjects were acquired. Two homogeneous subgroups of patients were defined based on the hallucination spatial location: patients with only outer space hallucinations (N=12) and patients with only inner space hallucinations (N=15). Between-group differences were then assessed using 2 complementary brain morphometry approaches: voxel-based morphometry and sulcus-based morphometry. Convergent anatomical differences were detected between the patient subgroups in the right temporoparietal junction (rTPJ). In comparison to healthy subjects, opposite deviations in white matter volumes and sulcus displacements were found in patients with inner space hallucination and patients with outer space hallucination. The current results indicate that spatial location of auditory hallucinations is associated with the rTPJ anatomy, a key region of the "where" auditory pathway. The detected tilt in the sulcal junction suggests deviations during early brain maturation, when the superior temporal sulcus and its anterior terminal branch appear and merge.

Alterations in the volume of thalamic nuclei in patients with schizophrenia and persistent auditory hallucinations

Theta burst stimulation of temporo-parietal cortex regions for the treatment of persistent auditory hallucinations: a multicentre, randomised, sham-controlled, triple-blind phase 3 trial in Germany.

IntroductionSchizophrenia patients often experience auditory hallucinations (AHs) and visual hallucinations (VHs). However, the degree and type of brain and retinal alterations associated with combined AHs and VHs in schizophrenia patients remain unknown. There is an urgent need for a study that investigates the trajectory of brain and retinal alterations in patients with first‐episode untreated schizophrenia accompanied by combined AHs and VHs (FUSCHAV).MethodsFUSCHAV patients (n = 120), divided into four groups according to AH and VH symptom severity (severe AHs combined with severe VHs [FUSCHSASV, 20 patients]; middle‐to‐moderate AHs combined with severe VHs [FUSCHMASV, 23 patients]; severe AHs combined with middle‐to‐moderate VHs [FUSCHSAMV, 28 patients]; and middle‐to‐moderate AHs combined with middle‐to‐moderate VHs [FUSCHMAMV, 26 patients]), were compared to healthy controls (n = 30). Gray matter volume (GMV) was adopted for brain structural alteration assessment. Total retinal thickness was adopted as a measure of retinal thickness impairment.ResultsIn the pilot study, the rate of GMV reduction showed an inverted U‐shaped pattern across the different FUSCHAV patient groups according to AH and VH severity. The degree of retinal impairment remained stable across the groups. More notably, in the secondary follow‐up study, we observed that, after 6 months of treatment with antipsychotic agents, all the GMV reduction‐related differences across the different patient groups disappeared, and both GMV and retinal thickness demonstrated a tendency to deteriorate.ConclusionsThese findings indicate the need for heightened alertness on brain and retinal impairments in patients with FUSCHAV. Further deteriorations induced by antipsychotic agent treatment should be monitored in clinical practice.

A possible association between the CCK-AR gene and persistent auditory hallucinations in schizophrenia

BackgroundRepetitive transcranial magnetic stimulation of the left temporo-parietal junction area has been studied as a treatment option for auditory verbal hallucinations. Although the right temporo-parietal junction area has also shown involvement in the genesis of auditory verbal hallucinations, no studies have used bilateral stimulation. Moreover, little is known about durability effects. We studied the short and long term effects of 1 Hz treatment of the left temporo-parietal junction area in schizophrenia patients with persistent auditory verbal hallucinations, compared to sham stimulation, and added an extra treatment arm of bilateral TPJ area stimulation.MethodsIn this randomized controlled trial, 51 patients diagnosed with schizophrenia and persistent auditory verbal hallucinations were randomly allocated to treatment of the left or bilateral temporo-parietal junction area or sham treatment. Patients were treated for six days, twice daily for 20 minutes. Short term efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucinations Rating Scale (AHRS), and the Positive and Negative Affect Scale (PANAS). We included follow-up measures with the AHRS and PANAS at four weeks and three months.ResultsThe interaction between time and treatment for Hallucination item P3 of the PANSS showed a trend for significance, caused by a small reduction of scores in the left group. Although self-reported hallucination scores, as measured with the AHRS and PANAS, decreased significantly during the trial period, there were no differences between the three treatment groups.ConclusionWe did not find convincing evidence for the efficacy of left-sided rTMS, compared to sham rTMS. Moreover, bilateral rTMS was not superior over left rTMS or sham in improving AVH. Optimizing treatment parameters may result in stronger evidence for the efficacy of rTMS treatment of AVH. Moreover, future research should consider investigating factors predicting individual response.Trial RegistrationDutch Trial Register NTR1813

Insight facilitation with add-on tDCS in schizophrenia

Schizophrenic patients often experience auditory hallucinations (AHs) and visual hallucinations (VHs). However, brain and retinal alterations associated with combined AHs and VHs in schizophrenic patients are unknown. This study aimed o investigate brain and retinal alterations in first episode un-treated schizophrenic patients with combined AHs and VHs (FUSCHAV). FUSCHAV patients (n = 120), divided into four groups according to severity of AH and VH symptoms, were compared to healthy controls (n = 30). Gray matter volume (GMV) and global functional connectivity density (gFCD) were recorded to reflect brain structure and functional alterations. Total retinal thickness was acquired by optical coherence tomography to assess retinal impairment. The majority of FUSCHAV patients (85.8%) demonstrated both GMV reduction and gFCD increases along with retinal thinning compared to healthy controls. The severity of GMV reduction and gFCD increase differed between patient groups, ranked from highest to lowest severity as follows: severe AHs combined with severe VHs (FUSCHSASV, 20 patients), moderate AHs combined with severe VHs (FUSCHMASV, 23 patients), severe AHs combined with moderate VHs (FUSCHSAMV, 28 patients), and moderate AHs combined with moderate VHs (FUSCHMAMV, 26). Retinal impairment was similar among the four FUSCHAV groups. GMV reduction and gFCD increases in the frontal-parietal lobule show an inverted U-shaped pattern among FUSCHAV patients according to AH and VH severity, while retinal impairment remains stable among FUSCHAV groups. These findings indicate a reciprocal deterioration in auditory and visual disturbances among FUSCHAV patients.

A controlled study of temporal lobe structure volumes and P300 responses in schizophrenic patients with persistent auditory hallucinations

Reciprocal deterioration of visual and auditory hallucinations in schizophrenia presents V-shaped cognition impairment and widespread reduction in brain gray matter-A pilot study