The impact of sex on gene expression in the brain of schizophrenic patients: a systematic review and meta-analysis of transcriptomic studies.

BACKGROUND: Schizophrenia is a severe neuropsychiatric disorder characterized by altered perception, mood, and behavior that profoundly impacts patients and society despite its relatively low prevalence. Sex-based differences have been described in schizophrenia epidemiology, symptomatology and outcomes. Different studies explored the impact of schizophrenia in the brain transcriptome, however we lack a consensus transcriptomic profile that considers sex and differentiates specific cerebral regions. METHODS: We performed a systematic review on bulk RNA-sequencing studies of post-mortem brain samples. Then, we fulfilled differential expression analysis on each study and summarized their results with regions-specific meta-analyses (prefrontal cortex and hippocampus) and a global all-studies meta-analysis. Finally, we used the consensus transcriptomic profiles to functionally characterize the impact of schizophrenia in males and females by protein-protein interaction networks, enriched biological processes and dysregulated transcription factors. RESULTS: We discovered the sex-based dysregulation of 265 genes in the prefrontal cortex, 1.414 genes in the hippocampus and 66 genes in the all-studies meta-analyses. The functional characterization of these gene sets unveiled increased processes related to immune response functions in the prefrontal cortex in male and the hippocampus in female schizophrenia patients and the overexpression of genes related to neurotransmission and synapses in the prefrontal cortex of female schizophrenia patients. Considering a meta-analysis of all brain regions available, we encountered the relative overexpression of genes related to synaptic plasticity and transmission in females and the overexpression of genes involved in organizing genetic information and protein folding in male schizophrenia patients. The protein-protein interaction networks and transcription factors activity analyses supported these sex-based profiles. CONCLUSIONS: Our results report multiple sex-based transcriptomic alterations in specific brain regions of schizophrenia patients, which provides new insight into the role of sex in schizophrenia. Moreover, we unveil a partial overlapping of inflammatory processes in the prefrontal cortex of males and the hippocampus of females.

Schizophrenia is a serious illness characterised by changes in perception, mood and behaviour that profoundly affect patients and society. The frequency, symptoms and progression of schizophrenia are different in women and men, but the biological reason for this is not understood. The identification of disease mechanisms specific in men and women, is relevant because it would allow a better understanding of this pathology, as well as improving the personalisation of diagnoses and treatments for patients. To achieve this goal, in this work we reviewed all available RNA sequencing studies of post-mortem brain samples from women and men affected by schizophrenia. Then, we compared gene expression in each study by sex, and integrated all study results in different brain regions: prefrontal cortex, hippocampus and all-studies. We discovered significant changes between men and women: 265 genes differentially expressed in the prefrontal cortex, 1414 genes in the hippocampus and 66 genes in meta-analyses of all-studies. The study of these genes revealed increased immune response functions in the prefrontal cortex of men and in the hippocampus of women with schizophrenia, as well as increased neurotransmission and synapses in the prefrontal cortex of women with schizophrenia. Our results report multiple gene expression changes in specific brain regions of patients with schizophrenia, providing new insights into the role of sex in schizophrenia.

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.

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.

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.

Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

BACKGROUND: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls. METHODS: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group. RESULTS: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings. CONCLUSIONS: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum.

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.

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.

[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.

Auditory hallucinations in first-episode psychosis: A voxel-based morphometry study.

BACKGROUND: Auditory hallucinations (AH) are a core symptom of psychosis. The brain abnormalities responsible for AH remain controversial due to inconsistent and conflicting findings across studies, with substantial confounding factors, such as chronicity. Few studies have examined the pathological changes that occur in the gray matter (GM) of patients with first-episode psychosis (FEP) and AH. The present study aims to validate the presence and characteristics of these structural abnormalities in relation to the intensity of psychotic symptoms and AH in a larger homogeneous sample than those of previous studies. METHODS: A magnetic resonance voxel-based morphometric analysis was applied to a group of 215 patients with FEP (93 patients with AH and 122 patients without AH) and 177 healthy controls. The patients were evaluated using the PANSS scale. RESULTS: Patients with FEP exhibited greater reductions in GM concentrations in the temporal, frontal, cingulate and insular areas than the healthy controls did. No specific differences were found between the patients with FEP and AH and the patients without AH. In addition, total scores on the PANSS were negatively correlated with GM reductions in the FEP group. No correlations were found between the severity of the AH and the GM volumes. CONCLUSIONS: As in previous studies, reductions in the GM concentrations in patients with FEP suggest that alterations are present in the early stages of psychosis, and these alterations are correlated with the severity of the illness. The GM reductions were not found to be related to the presence or severity of AH.

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.

Differences in the Use and Opinions About New eHealth Technologies Among Patients With Psychosis: Structured Questionnaire.

BACKGROUND: Despite a growing interest in the use of technology in order to support the treatment of psychotic disorders, limited knowledge exists about the viability and acceptability of these eHealth interventions in relation to the clinical characteristics of patients. OBJECTIVE: The objective of this study was to assess the access and use of, as well as experiences and interest in, new technologies using a survey of patients diagnosed with early psychosis compared with a survey of patients diagnosed with chronic psychotic disorders. METHODS: We designed a structured questionnaire. This questionnaire was divided into five parts: (1) clinical and demographic information, (2) access and use of the internet, (3) use of the internet in relation to mental health, (4) experiences with technology, and (5) patients' interest in eHealth services. In total, 105 patients were recruited from early psychosis units (n=65) and recovery units (n=40). RESULTS: In this study, 84.8% (89/105) of the patients had access to the internet and 88.6% (93/105) owned an electronic internet device. In total, 71.3% (57/80) of patients who owned a mobile phone were interested in eHealth systems and 38.2% (37/97) reported negative experiences related to the internet usage. We observed differences between the groups in terms of device ownership (P=.02), the frequency of internet access (P<.001), the use of social media (P=.01), and seeking health information (P=.04); the differences were found to be higher in the early psychosis group. No differences were found between the groups in terms of the use of internet in relation to mental health, experiences and opinions about the internet, or interest in eHealth interventions (P=.43). CONCLUSIONS: The availability and use of technology for the participants in our survey were equivalent to those for the general population. The differences found between the groups in relation to the access or use of technology seemed to due to age-related factors. The use of technology involving mental health and the interest in eHealth interventions were mainly positive and equivalent between the groups. Accordingly, this group of patients is a potential target for the emerging eHealth interventions, regardless of their clinical status. However, 28.7% (23/80) of the studied patients rejected the use of internet interventions and 38.2% (37/97) had unpleasant experiences related to its usage; thus, more in-depth studies are needed to better define the profile of patients with psychosis who may benefit from eHealth treatments.

Use of mobile technologies in patients with psychosis: A systematic review. / Utilización de tecnologías móviles en pacientes con psicosis: una revisión sistemática.

There is a growing interest in mobile Health interventions (m-Health) in patients with psychosis. The aim of this study is to conduct a systematic review in order to analysethe current state of research in this area. The search of articles was carried out following the PRISMA criteria, focusing on those studies that used mobile technologies in patients with psychosis during the period from 1990 to 2016. A total of 20 articles were selected from the 431 studies found. Three types of studies are distinguished: 1) Analysis of quality and usability, 2) Improving treatment adherence and reducing hospital admissions, and 3) Analysisof patient symptoms. CONCLUSIONS: m-Health interventions are feasible, and are easy to use for patients with psychosis. They evaluate the evolution of psychotic symptoms more efficiently, and improve adherence to treatment, as well as symptoms and hospital admissions. However, a particular strategy does not stand out over the rest, because differences in methodology make them difficult to compare.

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.

Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations.

Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital-cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH.

Utilización de tecnologías móviles en pacientes con psicosis: una revisión sistemática / Use of mobile technologies in patients with psychosis: a systematic review

Hay un creciente interés en las intervenciones mobile Health (m-Health) en pacientes con psicosis. El objetivo de este estudio es realizar una revisión sistemática para analizar el estado actual de la investigación en este ámbito. La búsqueda de publicaciones se llevó a cabo siguiendo los criterios PRISMA, centrándose en aquellos estudios que utilizan tecnologías móviles en pacientes con psicosis durante el periodo de 1990 a 2016. Se seleccionó un total de 20 artículos de los 431 estudios que se encontraron. Se diferencian 3 tipos de intervenciones: 1) análisis de calidad y usabilidad; 2) mejora de la adherencia, síntomas y reducción de hospitalizaciones, y 3) análisis de la sintomatología del paciente. Conclusión: Las intervenciones m-Health son viables y resultan fáciles de utilizar para los pacientes con psicosis. Evalúan de forma más eficiente la evolución de los síntomas psicóticos y mejoran la adherencia al tratamiento, los síntomas y las hospitalizaciones. No se puede destacar una estrategia sobre las demás debido a que las diferencias en la metodología las hace difícilmente comparables (AU)

There is a growing interest in mobile Health interventions (m-Health) in patients with psychosis. The aim of this study is to conduct a systematic review in order to analysethe current state of research in this area. The search of articles was carried out following the PRISMA criteria, focusing on those studies that used mobile technologies in patients with psychosis during the period from 1990 to 2016. A total of 20 articles were selected from the 431 studies found. Three types of studies are distinguished: 1) Analysis of quality and usability, 2) Improving treatment adherence and reducing hospital admissions, and 3) Analysisof patient symptoms. Conclusions: m-Health interventions are feasible, and are easy to use for patients with psychosis. They evaluate the evolution of psychotic symptoms more efficiently, and improve adherence to treatment, as well as symptoms and hospital admissions. However, a particular strategy does not stand out over the rest, because differences in methodology make them difficult to compare (AU)

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.

Increased amygdala and parahippocampal gyrus activation in schizophrenic patients with auditory hallucinations: an fMRI study using independent component analysis.

OBJECTIVE: Hallucinations in patients with schizophrenia have strong emotional connotations. Functional neuroimaging techniques have been widely used to study brain activity in patients with schizophrenia with hallucinations or emotional impairments. However, few of these studies have investigated the association between hallucinations and emotional dysfunctions using an emotional auditory paradigm. Independent component analysis (ICA) is an analysis method that is especially useful for decomposing activation during complex cognitive tasks in which multiple operations occur simultaneously. Our aim in this study is to analyze brain activation after the presentation of emotional auditory stimuli in patients with schizophrenia with and without chronic auditory hallucinations using ICA methodology. It was hypothesized that functional connectivity differences in limbic regions responsible for emotional processing would be demonstrated. METHODS: The present functional magnetic resonance imaging (fMRI) study compared neural activity in 41 patients with schizophrenia (27 with auditory hallucinations, 14 without auditory hallucinations) with 31 controls. Neural activity data was generated while participants were presented with an auditory paradigm containing emotional words. The comparison was performed using a multivariate approach, ICA. Differences in temporo-spatial aspects of limbic network were examined in three study groups. RESULTS: Limbic networks responded differently in patients with auditory hallucinations compared to healthy controls and patients without auditory hallucinations. Unlike control subjects and non-hallucinators, the group of hallucinatory patients showed an increase of activity in the parahippocampal gyrus and the amygdala during the emotional session. CONCLUSIONS: These findings may reflect an increase in parahippocampal gyrus and amygdala activity during passive listening of emotional words in patients with schizophrenia and auditory hallucinations.

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

La evolución ha dotado al ser humano de un sistema de detección de peligros cuyo adecuado funcionamiento facilita la adaptación al medio. Tanto en la psicosis como en los trastornos de ansiedad existe una disfunción de estos mecanismos de alarma. El objetivo de este estudio es comparar la respuesta ante estímulos visuales amenazantes entre estos grupos diagnósticos y sujetos sanos. Se estudiaron 24 pacientes con trastorno de ansiedad, 39 con psicosis y 39 controles, comparando las respuestas en percepción de amenaza y agradabilidad ante distintos tipos de estímulos visuales, humanos y no humanos, ya fueran amenazantes o no. Los resultados reflejan una diferente percepción de amenaza entre psicóticos y sanos, así como una valoración de las imágenes como más desagradables por parte del grupo ansioso. Todo ello sugeriría una diferente evaluación emocional de los distintos estímulos entre ambos trastornos (AU)

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 (AU)