Eduardo J. Aguilar

Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible?

Accumulating evidence suggests alterations in brain structure, especially in the prefrontal and temporal cortex, in schizophrenia. Previous studies examining the progression of brain structural alterations in schizophrenia have led to conflicting results. Morphometric studies of the superior temporal gyrus (STG) volumes were conducted in a series of neuroleptic-naive first-episode schizophrenic patients, non-schizophrenic first-episode psychotic patients, and matched healthy controls. Three-dimensional MRI scans were carried out in these subjects before and after one year of treatment. Volume reductions were seen at baseline in the left superior temporal gyrus (adjusted for intracranial volume) in both of the patient groups. Pretreatment illness duration was inversely related to the volume of the left superior temporal gyrus; this relation was confined to males. One-year follow-up MRI investigations in a smaller subset of patients suggested that the STG volume reductions may be reversible. No significant changes were noted in the STG volumes in matched healthy controls who were also scanned at baseline as well as at one-year follow-up. These findings have implications for understanding the nature of the neuropathological processes in early schizophrenia, as well as the potential impact of early treatment.

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.

Left orbitofrontal and superior temporal gyrus structural changes associated to suicidal behavior in patients with schizophrenia

Suicidal attempts are relatively frequent and clinically relevant in patients with schizophrenia. Recent studies have found gray matter differences in suicidal and non-suicidal depressive patients. However, no previous neuroimaging study has investigated possible structural abnormalities associated to suicidal behaviors in patients with schizophrenia. A whole-brain magnetic resonance voxel-based morphometric examination was performed on 37 male patients meeting the DSM-IV criteria for schizophrenia. Thirteen (35.14%) patients had attempted suicide. A non-parametric permutation test was computed to perform the comparability between groups. An analysis of covariance (AnCova) model was constructed with a statistical threshold of p<0.05 corrected for multiple comparisons. After controlling for age and severity of illness, results showed significant gray matter density reduction in left superior temporal lobe (p=0.03) and left orbitofrontal cortex (p=0.04) in patients who had attempted suicide when comparing with non-suicidal patients. Although sample size limitations and potential clinical heterogeneity preclude definitive conclusions, these data point to structural differences in key cerebral areas. Neuroimaging studies are necessary to expand our knowledge of biological mechanisms underlying suicide in schizophrenia.

Emotional words induce enhanced brain activity in schizophrenic patients with auditory hallucinations

Neuroimaging studies of emotional response in schizophrenia have mainly used visual (faces) paradigms and shown globally reduced brain activity. None of these studies have used an auditory paradigm. Our principal aim is to evaluate the emotional response of patients with schizophrenia to neutral and emotional words. An auditory emotional paradigm based on the most frequent words heard by psychotic patients with auditory hallucinations was designed. This paradigm was applied to evaluate cerebral activation with functional magnetic resonance imaging (fMRI) in 11 patients with schizophrenia with persistent hallucinations and 10 healthy subjects. We found a clear enhanced activity of the frontal lobe, temporal cortex, insula, cingulate, and amygdala (mainly right side) in patients when hearing emotional words in comparison with controls. Our findings are consistent with other studies suggesting a relevant role for emotional response in the pathogenesis and treatment of auditory hallucinations.

Pleasurable auditory hallucinations

Objective:  The focus in auditory hallucination (AH) research is usually on the negative impact of the experience itself. There are practically no studies on whether voices can be perceived as pleasurable. The aim of the present study was to assess the frequency of voices as a pleasurable experience in a psychotic patient population.

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.

Hopelessness and first-episode psychosis: a longitudinal study.

Hopelessness has not been adequately studied in first‐episode psychotic patients, although it is already present at the early stages, especially in schizophrenic patients. We have studied 96 neuroleptic‐naive psychotic patients (49 schizophrenic patients and 47 other non‐affective psychotic patients) over a period of 12 months after their first admission. The total score on the Hopelessness Scale (HS) at first admission was higher in the schizophrenic patients, and correlated with younger age and with negative symptoms. High HS scores at baseline predicted poor short‐term outcome in schizophrenic patients, as evidenced by worse global functioning at the 12‐month follow‐up. These correlations were not observed in the other psychoses group. Our results suggest that young, severely affected schizophrenic patients who experience hopelessness might be at higher risk of poor outcome.

Are there subtypes of suicidal schizophrenia? A prospective study

BACKGROUND Tragically, suicide is not uncommon in schizophrenia. The principal objective of this study was to examine possible subtypes of suicidal schizophrenic patients and identify their clinical and psychopathological profiles at long-term follow-up. METHOD The study involved 62 patients diagnosed with schizophrenia according to ICD-10 criteria, who were consecutively admitted following a suicide attempt. Of these subjects, 47 (75.8%) could be re-evaluated after 1 year. Sociodemographic, general clinical, and psychopathological variables were evaluated. RESULTS Two predominant subgroups were identified according to suicidal motivation: psychotic motivation and depressive motivation. At re-evaluation after 1 year, the depressive motivation subgroup showed higher depression and hopelessness scores. This subgroup also had greater educational level, age, and duration of illness, and more frequent existence of previous suicide attempts compared to the psychotic motivation subgroup. Of note in the psychotic motivation subgroup was the presence of hopelessness. The variables of educational level, duration of illness, and previous suicide attempts were the ones that best distinguished these subgroups. CONCLUSION These findings reinforce the notion that meaningful subgroups occur among suicidal schizophrenic patients. The different psychopathological profiles of the two prominent subgroups suggest the need for a different management approach in each case. The identification of these profiles in both subtypes at long-term follow-up may facilitate their detection by clinicians and, therefore, foster the adoption of appropriate preventive measures against subsequent suicidal behavior.

FOXP2 polymorphisms in patients with schizophrenia

BACKGROUND FOXP2 was described as the first gene involved in our ability to acquire spoken language. The main objective of this study was to compare the distribution of FOXP2 gene polymorphisms between patients with schizophrenia and healthy controls. METHODS Two FOXP2 polymorphisms, Intron3a and SNP 923875, and the G-->A transition in exon 14 were analysed in 149 patients with schizophrenia and schizoaffective disorders according to DSM-IV, as well as in 137 controls. All the patients showed a history of auditory hallucinations. RESULTS The transition G-->A at exon 14, detected in all the affected members in KE family, was not found in any of the analyzed samples from patients or controls. No significant differences were found between individual controls and patients for the two analysed polymorphisms. CONCLUSIONS This study would not support a possible role of the two FOXP2 analyzed polymorphisms in the vulnerability to schizophrenia.

Spectroscopic metabolomic abnormalities in the thalamus related to auditory hallucinations in patients with schizophrenia.

OBJECTIVE Previous studies have found neurochemical abnormalities in thalamic nuclei in patients with schizophrenia. These abnormalities have been associated with information processing deficiencies and symptom formation. There are no metabolic spectroscopy studies in patients with schizophrenia attending to auditory hallucinations. The aim of the present study is to explore metabolic Magnetic Resonance Spectroscopy (MRS) ratio differences in the thalamus between schizophrenic patients with and without auditory hallucinations and control subjects. METHODS MRS studies (MRI 1.5 T unit) were performed in 49 patients with schizophrenia (30 with auditory hallucinations and 19 without auditory hallucinations) and 37 controls. (1)H MRS imaging was used to acquire 2 transverse slices (TR/TE 2700/272 ms, region of interest 110 x 100 x 23 mm). In the quantitative analysis four elements of volume (9.2 x 9.2 x 23 x 4 mm), added into one spectrum representative of each thalamus, were chosen in the slice passing through the main body of the thalamus. The areas of metabolites were integrated with the jMRUI program. RESULTS The patients with schizophrenia had significantly lower bilateral NAA/Cho ratios when compared with healthy subjects. There was also a lower NAA/Cho ratio in the right thalamus in patients with auditory hallucinations compared to patients without auditory hallucinations and control subjects. Significant correlations were found between metabolic ratios and BPRS, PANSS and PSYRATS scores, age of onset of auditory hallucinations, and age of subjects. CONCLUSIONS Choline and NAA ratio abnormalities determined by thalamic spectroscopy may be related to the pathogenesis of auditory hallucinations in patients with schizophrenia.