Alterations in the volume and shape of the basal ganglia and thalamus in schizophrenia with auditory hallucinations.

Different lines of evidence indicate that the structure and physiology of the basal ganglia and the thalamus is disturbed in schizophrenia. However, it is unknown whether the volume and shape of these subcortical structures are affected in schizophrenia with auditory hallucinations (AH), a core positive symptom of the disorder. We took structural MRI from 63 patients with schizophrenia, including 36 patients with AH and 27 patients who had never experienced AH (NAH), and 51 matched healthy controls. We extracted volumes for the left and right thalamus, globus pallidus, putamen, caudate and nucleus accumbens. Shape analysis was also carried out. When comparing to controls, the volume of the right globus pallidus, thalamus, and putamen, was only affected in AH patients. The volume of the left putamen was also increased in individuals with AH, whereas the left globus pallidus was affected in both groups of patients. The shapes of right and left putamen and thalamus were also affected in both groups. The shape of the left globus pallidus was only altered in patients lacking AH, both in comparison to controls and to cases with AH. Lastly, the general PANSS subscale was correlated with the volume of the right thalamus, and the right and left putamen, in patients with AH. We have found volume and shape alterations of many basal ganglia and thalamus in patients with and without AH, suggesting in some cases a possible relationship between this positive symptom and these morphometric alterations.

Progressive loss of cortical gray matter in first episode psychosis patients with auditory hallucinations.

BACKGROUND: Previous longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample. METHODS: A Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up. RESULTS: At baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up. CONCLUSIONS: Brain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients.

Volume alterations of the hippocampus and amygdala in patients with schizophrenia and persistent auditory hallucinations.

INTRODUCTION: Auditory hallucinations (AH) are one of the most prevalent symptoms of schizophrenia. They might cause several brain alterations, especially changes in the volumes of hippocampus and amygdala, regions related to the relay and processing of auditory cues and emotional memories. MATERIAL AND METHODS: We have recruited 41 patients with schizophrenia and persistent AH, 35 patients without AH, and 55 healthy controls. Using their MRIs, we have performed semiautomatic segmentations of the hippocampus and amygdala using Freesurfer. We have also performed bilateral correlations between the total PSYRATS score and the volumes of affected subregions and nuclei. RESULTS: In the hippocampus, we found bilateral increases in the volume of its hippocampal fissure and decreases in the right fimbria in patients with and without AH. The volume of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus were decreased in patients with AH. In the amygdala, we found its left total volume was shrunk, and there was a decrease of its left accessory basal nucleus in patients with AH. CONCLUSIONS: We have detected volume alterations of different limbic structures likely due to the presence of AH. The volumes of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus, and total volume of the amygdala and its accessory basal nucleus, were only affected in patients with AH. Bilateral volume alterations in the hippocampal fissure and right fimbria seem inherent of schizophrenia and due to traits not contemplated in our research.

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

The thalamus is a subcortical structure formed by different nuclei that relay information to the neocortex. Several reports have already described alterations of this structure in patients of schizophrenia that experience auditory hallucinations. However, to date no study has addressed whether the volumes of specific thalamic nuclei are altered in chronic patients experiencing persistent auditory hallucinations. We have processed structural MRI images using Freesurfer, and have segmented them into 25 nuclei using the probabilistic atlas developed by Iglesias and collaborators (Iglesias et al., 2018). To homogenize the sample, we have matched patients of schizophrenia, with and without persistent auditory hallucinations, with control subjects, considering sex, age and their estimated intracranial volume. This rendered a group number of 41 patients experiencing persistent auditory hallucinations, 35 patients without auditory hallucinations, and 55 healthy controls. In addition, we have also correlated the volume of the altered thalamic nuclei with the total score of the PSYRATS, a clinical scale used to evaluate the positive symptoms of this disorder. We have found alterations in the volume of 8 thalamic nuclei in both cohorts of patients with schizophrenia: The medial and lateral geniculate nuclei, the anterior, inferior, and lateral pulvinar nuclei, the lateral complex and the lateral and medial mediodorsal nuclei. We have also found some significant correlations between the volume of these nuclei in patients experiencing auditory hallucinations, and the total score of the PSYRATS scale. Altogether our results indicate that volumetric alterations of thalamic nuclei involved in audition may be related to persistent auditory hallucinations in chronic schizophrenia patients, whereas alterations in nuclei related to association cortices are evident in all patients. Future studies should explore whether the structural alterations are cause or consequence of these positive symptoms and whether they are already present in first episodes of psychosis.

The course of negative symptoms in first-episode schizophrenia and its predictors: A prospective two-year follow-up study.

AIMS: This study aimed to investigate the course of negative symptoms and its stability over a two-year period following a first-episode schizophrenia (FES) and the possible predictors of higher severity in this symptomatology after this period. METHODS: In this longitudinal two-year prospective follow-up study we included 268 patients with a FES, according to DSM-IV. Analysis of variance was conducted in patients who completed the full follow-up to study changes in negative symptoms over three visits. Regression analyses were conducted to show correlates and potential predictors of negative symptoms at two-year follow-up. RESULTS: There was a significant effect for time in negative symptomatology, which was less severe at one-year follow-up after a FES and remained stable up to two years (Time 1>Time 2>Time 3); F(2,151)=20.45, p<0.001. Poorer premorbid adjustment (p=0.01) and higher negative symptoms at baseline (p<0.001) made a significant contribution to the changes in the negative symptoms severity at two-years after a FES (R2=0.21, p<0.001). CONCLUSIONS: We found a reduction in the negative symptomatology at one-year after a FES. This change remained stable at two-year. Our results suggested that the presence of this symptomatology early in the course of the illness, together with a poorer premorbid adjustment, predict more severe negative symptoms at mid-term outcome.

The role of striatal dopamine D2 receptors in the occurrence of extrapyramidal side effects: iodine-123-iodobenzamide single photon emission computed tomography study.

Levels above 75% of striatal dopamine 2 receptor occupancy (D2RO) have been associated with extrapyramidal symptoms (EPS). The aim of the present study is to investigate the relationship between D2RO and EPS in a sample of psychotic patients in current treatment with both typical and atypical antipsychotics. Brain iodine-123-iodobenzamide single photon emission computed tomography ((123)I-IBZM SPECT) was performed in 81 patients taking stable doses of haloperidol, risperidone, olanzapine, quetiapine, clozapine or ziprasidone. First, the degree of D2RO and Positive and Negative Syndrome Scale (PANSS) scores was compared between the group of patients who presented EPS and the group free of EPS. Afterwards, these variables were compared among the different antipsychotic medications. The group with EPS presented means of D2RO significantly higher than the group free of EPS. Significant differences in D2RO were found in clozapine, quetiapine and ziprasidone groups compared with the haloperidol group. No differences were observed between either olanzapine or risperidone and haloperidol. No quetiapine- or clozapine-treated patients developed EPS. Haloperidol and risperidone demonstrated a relationship between striatal D2RO and EPS. The findings suggest that higher D2RO is related to appearance of EPS. Occupancy in the group with EPS was in agreement with previous studies that suggested a high degree of D2RO is necessary for the occurrence of EPS.

Cannabis use and striatal D2 receptor density in untreated first-episode psychosis: an in vivo SPECT study.

The biological basis of the association between cannabis-induced dopamine dysregulation and psychosis remains poorly understood. This (123)I-IBZM SPECT study assessed striatal dopamine D2 receptor (D2R) binding in 37 untreated first-episode psychosis (FEP) subjects, and 18 healthy controls. The aim was to examine if there were differences between FEP subjects with (n=14) and without (n=23) cannabis use in uptake ratios in the D2R. Striatal/Frontal cortex (S/F) uptake ratios were obtained. Healthy controls showed the lowest D2R binding ratios. No differences were found in S/F ratios between users and non-users, suggesting similar dopaminergic mechanisms underlying psychotic symptoms in both groups.

Density of striatal D2 receptors in untreated first-episode psychosis: an I123-IBZM SPECT study.

There is as yet no definite prognostic marker to determine whether a first-episode psychosis will become schizophrenia or not. The aim of the present study is to address whether the mechanism of sensitization of the subcortical dopaminergic pathway - yielding to an increase of the postsynaptic D2 receptors - may serve as a prognostic marker of clinical outcome in drug naïve patients with a first-episode psychosis, by means of a prospective and multicentric study with untreated first-episode psychosis patients (n=37). 123I-IBZM SPECT was performed at the time of the inclusion in the study, before antipsychotic medication was initiated. One year later, patients were assessed again so as to determine their diagnosis. There was a significant group effect at baseline in D2 Striatal/Frontal (S/F) ratios (F=10.2, p<0.001). Bonferroni posthoc comparisons attested significant differences between diagnosis (p=0.006), and between schizophrenia and control groups (p<0.001) but no differences between non-schizophrenia and control groups (p=0.9). The logistic regression model showed that D2R binding (p=0.02) and PAS (Premorbid Adjustment Scale) adulthood score (p=0.03) were predictive of the final diagnosis (schizophrenia/non-schizophrenia; Nagelkerke R(2)=0.59; X(2)=11.08, p=0.001). These findings replicate previous results on the usefulness of D2R binding as an objective prognostic parameter, together with the evaluation of premorbid adjustment, of the evolution of first-episode psychosis. In this regard, the results may provide a new view in the approach of early and personalized treatment in the debut of a psychosis.

[Emotional response to threatening stimuli in psychosis and anxiety disorders]. / Respuesta emocional ante estímulos amenazantes en psicosis y trastornos de ansiedad.

Emotional response to threatening stimuli in psychosis and anxiety disorders. Evolution has provided humans with an alarm system that may facilitate adaptation. Both psychosis and anxiety disorders involve danger detection difficulties. Our main goal is to compare threat responses of these diagnostic groups and with those of healthy subjects. We studied 24 subjects with an anxiety disorder diagnosis, 39 with psychosis, and 39 healthy control subjects. We compared threat and pleasantness perception using visual stimuli (human and nonhuman stimuli, either threatening or nonthreatening). Regarding threat perception, significant differences were found between psychosis and control groups. Subjects with anxiety disorder diagnosis evaluated any kind of stimuli more negatively. These results suggest differential emotional processing of diverse visual stimuli in these diagnostic groups.

Schizophrenia with auditory hallucinations: a voxel-based morphometry study.

Many studies have shown widespread but subtle pathological changes in gray matter in patients with schizophrenia. Some of these studies have related specific alterations to the genesis of auditory hallucinations, particularly in the left superior temporal gyrus, but none has analysed the relationship between morphometric data and a specific scale for auditory hallucinations. The present study aims to define the presence and characteristics of structural abnormalities in relation with the intensity and phenomenology of auditory hallucinations by means of magnetic resonance voxel-based morphometry (MR-VBM) method applied on a highly homogeneous group of 18 persistent hallucinatory patients meeting DSM-IV criteria for schizophrenia compared to 19 healthy matched controls. Patients were evaluated using the PSYRATS scale for auditory hallucinations. Reductions of gray matter concentration in patients to controls were observed in bilateral insula, bilateral superior temporal gyri and left amygdala. In addition, specific relationships between left inferior frontal and right postcentral gyri reductions and the severity of auditory hallucinations were observed. All these areas might be implicated in the genesis and/or persistence of auditory hallucinations through specific mechanisms. Precise morphological abnormalities may help to define reliable MR-VBM biomarkers for the genesis and persistence of auditory hallucinations.