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Biomedical subjects

Miquel Bernardo

Publications and source records attributed to Miquel Bernardo.

16 recordsLinked to original sources

Human development, inequality, and their associations with brain structure across 29 countries.

BACKGROUND: The macro-social and environmental conditions in which people live, such as the level of a country's development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults. METHODS: We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country's level of development and inequality. RESULTS: Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain. CONCLUSIONS: Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants' brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.

Humans↗

Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics.

INTRODUCTION: Impaired dopamine transporter (DAT) function may be involved in antipsychotic (AP)-induced extrapyramidal symptoms (EPS). A polymorphism involving a variable number of tandem repeats (VNTR) has been described in the DAT gene (SLC6A3). OBJECTIVE: We studied whether the SLC6A3 VNTR polymorphism is a risk or protection factor for AP-induced EPS. We also investigated the relationship between the polymorphism and DAT availability in the schizophrenic patient's brain. METHODS: Sixty-one patients receiving AP therapy participated in the EPS study. Of these, thirty-two cases presented EPS (Simpson-Angus >3) and twenty-nine without EPS (Simpson-Angus < or =3). The DAT expression was studied in fifteen AP-naive patients by [(123)I] FP-CIT SPECT. RESULTS: No significant differences were observed for the more common alleles ((*)9R and (*)10R) or for genotype frequencies between patients with EPS and those without EPS. The frequency of the (*)9R and (*)10R alleles was similar to that described in other European populations. There were no significant differences in striatal DAT binding among the three major VNTR genotype groups. CONCLUSIONS: Our results suggest that the VNTR polymorphism did not influence AP-induced EPS and did not affect DAT gene expression or protein function.

Adult↗

Psychopathological and nutritional correlates of plasma homovanillic acid in adolescents with anorexia nervosa.

Dopaminergic abnormalities have been described in anorexia nervosa but studies about plasma level of homovanillic acid (pHVA) have yielded conflicting results probably due to the small number and the heterogeneity of patients. Plasma HVA, nutritional and hormonal parameters and several scales - the Eating Attitudes Test (EAT), the Beck Depression Inventory (BDI), the Leyton Obsessional Inventory-child version (LOI-C) and the State and Trait Anxiety Inventory (STAI) - were assessed in 44 adolescent anorexia nervosa patients (mean age 14.7 years, SD 1.7) consecutively admitted to an Eating Disorder Unit. They were evaluated at admission, at discharge and, in 34 cases, after 9 months of follow-up. pHVA was also assessed in 16 control adolescents. Patients had significantly higher pHVA than controls (p = .002). About 31% of patients had a very high level of pHVA, a significantly higher (p = .006) mean score in the BDI and a non significantly higher mean score in the EAT. After weight recovery some laboratory parameters improved as well as the EAT (p = .019), the BDI (p = 001) and the Interference score of the LOI-C (p = .004). Moreover, pHVA decreased significantly (p=.036). At follow-up, patients with normal weight had lower (p = .037) pHVA than patients with low weight. The conclusion would be that there is a dopaminergic dysfunction in anorexic patients, specially in a subgroup with high depressive and anorexic symptomatology. With weight recovery and psychopathological improvement, pHVA tends to normalization.

Adolescent↗

Lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic patients is not related to antipsychotic treatment but it suggests an illness trait.

INTRODUCTION: Drug induced parkinsonism (DIP) is directly related to dopamine D2 receptor blockade. However, there are many references describing parkinsonian signs (PS) in naive-patients. In our previous study, we observed lower DAT binding in a group of first-episode schizophrenic patients after short-term treatment with risperidone, compared with age-matched healthy controls. AIM: To clarify if DAT decrease could be an illness trait, excluding the effect of antipsychotics on DAT availability, and to determine whether DAT availability before treatment with antipsychotics may predict subsequent development of PS. MATERIALS AND METHODS: A new series of 20 neuroleptic-naive schizophrenic patients and 15 healthy subjects was recruited. SPECT with [(123)I] FP-CIT (DaTSCAN(R)) was performed before starting antipsychotics and after 4 weeks of treatment. PS and psychopathological status were assessed by the Simpson-Angus (SAS), CGI and PANSS scales. Quantitative analyses of SPECTs were performed using ROIs placed in the caudate, putamen and occipital cortex. RESULTS: Schizophrenic patients showed lower DAT binding compared with the healthy subjects at baseline (p<0.001) and after a 4-week-treatment period (p=0.001). Six out of eight schizophrenic patients of the DIP group were symptomatic for PS at baseline, in comparison to two out of 12 in the NoDIP group. Nonetheless, no differences were observed on DAT between DIP and NoDIP, neither at baseline (p=0.360) nor at endpoint (p=0.984). Finally, no differences between baseline-endpoint DAT binding were observed, neither in the DIP group (p=0.767) nor in the NoDIP group (p=0.093). CONCLUSION: Our new series of first-episode naive-schizophrenic patients (1) points out DAT dysfunction as an illness trait due to the significantly lower DAT binding in schizophrenic patients in comparison to healthy subjects; (2) supports the results of other authors who describe PS in never-treated patients; (3) confirms that [(123)I] FP-CIT does not allow us to predict which patients will develop parkinsonism due to the lack of differences between DIP and NoDIP patients; and (4) confirms a null effect of antipsychotics on DAT due to the lack of differences in [(123)I] FP-CIT before and after a 4-week-treatment period.

Adult↗

Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first-episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism.

RATIONALE: Drug-induced parkinsonism (DIP) is one of the main causes of treatment drop-out in schizophrenic patients causing a high incidence of relapse that leads patients to a bad clinical prognosis. The dopaminergic nigrostriatal pathway is involved in the movement control, so the study of the dopamine transporter (DAT) could be of great value to determine its implication in the appearance of DIP. OBJECTIVE: The goal of the study is to determine the striatal DAT binding assessed with [(123)I] FP-CIT SPECT in first-episode neuroleptic-naive schizophrenic in-patients with DIP after short-term antipsychotic treatment. METHOD: The [(123)I] FP-CIT binding ratios of ten schizophrenic in-patients who developed DIP during the first 4-week period of risperidone treatment (6+/-2 mg/day) were compared with ten schizophrenic in-patients treated with the same doses of risperidone and who do not developed DIP and with ten age-matched healthy subjects. Quantitative analyses of SPECTs were performed using regions of interest located in caudate, putamen and occipital cortex. Parkinsonism was assessed by the Simpson-Angus Scale and the psychopathological status by the Clinical General Impression and Positive and Negative Syndrome Scales. RESULTS: Whole striatal [(123)I] FP-CIT binding ratios were significantly lower in patients with and without DIP than in healthy subjects (p<0.001). This was also observed in whole putamen (p<0.001) and caudate nucleus (p<0.001). Females showed higher whole striatal [(123)I] FP-CIT binding ratios than males (p<0.05). No differences in psychopathological scales were observed between patients with and without DIP. CONCLUSION: Our first-episode schizophrenic patients with and without DIP after short-term risperidone treatment have a decreased striatal DAT binding assessed with [(123)I] FP-CIT. This alteration could be related to the schizophrenic disease or may be secondary to the antipsychotic treatment.

Adult↗

Volume changes in gray matter in first-episode neuroleptic-naive schizophrenic patients treated with risperidone.

Structural neuroimaging techniques have consistently shown that treatment of schizophrenic patients with conventional antipsychotics causes an increase in basal ganglia volume. However, findings in schizophrenic patients treated with the newer atypical antipsychotic drugs are less consistently reported. To explore this issue, the authors used a whole-brain, unbiased, and automated technique for comparing brain structural features across scans in schizophrenic patients before and after a treatment with the atypical antipsychotic risperidone. T1-weighted images from 11 first-episode neuroleptic-naive schizophrenic patients were processed and analyzed for regions of interest (basal ganglia) by using optimized voxel-based morphometry. Scans were repeated after 3 months of continuous treatment with risperidone. Region of interest-based voxel-based morphometry analyses revealed increases in gray matter volume for the right and left caudate nuclei and for the left accumbens after the treatment with risperidone. Hence, in our sample of schizophrenic patients, treatment with risperidone was associated, in contrast to the findings for other atypical antipsychotics, with an increase in basal ganglia volume. Such discrepancy could be related to the pharmacodynamics of risperidone (the atypical antipsychotic showing the higher affinity for D2 receptors) and the rather high mean doses used in our study (ie, 6.05 mg/d).

Adolescent↗

Lack of sex differences in striatal dopamine D2 receptor binding in drug-naive schizophrenic patients: an IBZM-SPECT study.

Differences in antipsychotic treatment response, clinical course and outcome of schizophrenia could be related to gender-related cerebral differences in anatomy and function. The aim of the study was to assess sex differences in the striatal dopamine D2 receptor binding in 15 drug-naive schizophrenic patients (seven males, eight females) using (123)I-IBZM single photon emission computed tomography. Basal ganglia/frontal cortex (BG/FC) uptake ratios were obtained. No significant differences were found in global, left and right BG/FC ratios or laterality indices between males and females. No correlation was found between BG/FC ratios and age, duration of illness or scores on symptom rating scales. Our data indicate a lack of sex differences in striatal D2 receptor binding in drug-naive schizophrenic patients and do not support previous reports of left lateralized striatal asymmetry in male schizophrenic patients.

Adult↗

Decreased cerebral activation during CPT performance: structural and functional deficits in schizophrenic patients.

Voxel-based morphometry (VBM) allows the output of structural data in a Statistical Parametric Map of the brain in the same way that the SPM can do with functional data. Using functional magnetic resonance (fMR), we studied brain activation in 14 patients with schizophrenia and 14 matched normal controls. We found significant hypoactivation in patients in several regions, especially in the right hemisphere, in the dorsolateral frontal and temporal regions and in the inferior parietal. Subcortically, we found strong hypoactivity in the thalamus. The optimized VBM method revealed gray matter (GM) abnormalities in the bilateral supramarginal gyrus and cingulate cortex, and in the right inferior temporal regions. Three regions involved in attentional processes showed both structural and functional deficits: the thalamus, the anterior cingulate and the inferior parietal. The results suggest that these regions may be involved in the attentional deficit in schizophrenia.

Adolescent↗

Absence of additional cognitive impairment in schizophrenia patients during maintenance electroconvulsive therapy.

This study examines the cognitive impairment profile of schizophrenia patients during maintenance electroconvulsive therapy (M-ECT). Ten schizophrenia patients treated with M-ECT and ten control patients matched for diagnosis, sex, and age who had never been treated with ECT were assessed with a comprehensive neuropsychological battery. M-ECT patients did not show a higher level of memory, attention, or frontal function impairment than the control group. The absence of additional memory dysfunction may favor the functional adaptation of these patients during M-ECT.

Adult↗

Cognitive status of psychiatric patients under maintenance electroconvulsive therapy: a one-year longitudinal study.

In recent years, maintenance electroconvulsive therapy (M-ECT) has been a common treatment within psychiatric practice. Little information is available regarding the cognitive risks of this treatment, however. In this study, twenty psychiatric outpatients were assessed during M-ECT and 1 year later on treatment. A comprehensive cognitive battery was administered, and a separate comparison group was used to calculate the Reliable Change Index. Global cognitive measures showed no significant difference in scores over time. Our results concur with those described in case reports and suggest that there is no significant association between cognitive decline and M-ECT.

Adult↗

Striatal dopamine D2 receptor density in neuroleptic-naive and in neuroleptic-free schizophrenic patients: an 123I-IBZM-SPECT study.

Most post-mortem autoradiographic studies have described striatal dopamine D(2) receptor up-regulation due to chronic neuroleptic exposure. The aim of our study was to compare in-vivo striatal D(2) receptor density in neuroleptic-naive and neuroleptic-free schizophrenic patients. We included 28 young (mean age: 28+/-8 years) acute psychotic patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder. Enrolled patients were either first-episode neuroleptic-naive (n=12) or neuroleptic-free (n=16) after a minimum washout period of 7 days. All neuroleptic-free subjects had previously received neuroleptic treatment for a median period of 3.5 years. Both groups were evaluated using standard clinical scales. In-vivo striatal D(2) receptor binding was assessed by basal ganglia/frontal cortex ratios using (123)I-IBZM SPECT. No statistically significant differences were found in age or clinical assessment between neuroleptic-naive and neuroleptic-free schizophrenic patients. No differences were found in the basal ganglia/frontal cortex ratios of neuroleptic-naive (1.78+/-0.11) and neuroleptic-free (1.81+/-0.15) patients. No striatal uptake laterality was observed in either group. No correlation was demonstrated between BG/FC ratios and duration of illness, period of neuroleptic exposure or time of drug washout. We conclude that our neuroleptic-naive and neuroleptic-free schizophrenic patients did not show differences in striatal D(2) receptor binding, suggesting that IBZM-SPECT fails to detect D(2) receptor up-regulation induced by chronic exposure to neuroleptic drugs.

Adult↗

Cognitive mechanisms, psychosocial functioning, and neurocognitive rehabilitation in schizophrenia.

The aim of the present study is to test Brenner's model of cognitive functioning in schizophrenia. It is assumed that elementary cognitive disorders (attention and encoding) and complex cognitive disorders (recall, concept formation) reinforce each other. Cognitive disorders are supposed to cause detrimental effects on functional outcome. We used cognitive rehabilitation as a strategy to induce cognitive changes in 27 patients assigned to treatment groups following the cognitive modules of the Integrated Psychological Treatment (IPT). Ten schizophrenic patients without cognitive impairments worked as a control group. With only one minor conceptual change (replacing concept formation with executive function, a more comprehensive construct), we found that our data fitted with Brenner's model. A relationship has been found between neuropsychological improvements and higher levels of autonomy and social functioning. These findings have important implications not only for cognitive assessment but also for selecting targets in cognitive rehabilitation.

Activities of Daily Living↗

Basal ganglia N-acetylaspartate correlates with the performance in the procedural task 'Tower of Hanoi' of neuroleptic-naive schizophrenic patients.

We tested the hypothesis that basal ganglia dysfunction may be related to procedural learning impairment in schizophrenia. We determined the N-acetylaspartate/choline (NAA/Cho) ratio in the left striatal area in 11 young first-episode antipsychotic-naive patients and matched controls. Procedural learning was assessed by the four-disk version of the Tower of Hanoi. Analysis of variance showed that the number of moves and the execution time had a significant group effect (P=0.02, P<0.0001, respectively). Correlation analysis between procedural learning and the NAA/Cho ratio showed a negative significant correlation only in patients, measured by both time (P=0.006) and by moves (P=0.001). In summary, we found that schizophrenic patients have impaired procedural learning, and that this impairment is related to basal ganglia metabolism.

Adult↗

Sustained attention impairment correlates to gray matter decreases in first episode neuroleptic-naive schizophrenic patients.

Impaired sustained attention seems to be a specific neuropsychological deficit that is closely linked to schizophrenia. Voxel based morphometry has emerged as a useful tool for the detection of subtle gray matter (GM) abnormalities. The aim of our study was to identify the cerebral regions related to the Identical-Pair version of the Continuous Performance Test (CPT-IP) performance in schizophrenic patients. The study included 13 right-handed, male, first-episode, paranoic, neuroleptic-naive schizophrenic patients and 13 matched controls. High-resolution whole-brain MR images were segmented and analyzed for the whole brain and for regions of interest (ROI) using SPM99. Furthermore, the correlation between CPT-IP performance and GM density was examined. Volumetric analysis of the thalami was also carried out. GM density analysis shown decreases in patients in anterior cingulate gyrus, left inferior frontal, right claustrum, left pulvinar, and dorsomedial bilateral thalamic nuclei, and caudate nuclei as well as left hippocampus and parahippocampal gyrus. Thalamic ROIs revealed a strong correlation between groups differences. The thalamic GM density allowed a good individual classification. GM increases were detected in left insula, superior temporal gyrus, and putamen nucleus, and right supramarginal gyrus. Schizophrenic patients showed smaller left and right thalamic volumes. We found that GM density of the left thalamic nucleus, left angular, and supramarginal gyrus, and left inferior frontal and postcentral gyri correlated significantly with CPT-IP performance in patients but not in controls. Moreover, the restricted ROIs regression was strongly significant for both left and right thalamus. In summary, we provide evidence for the involvement of thalamic, inferior-parietal, and frontal regions in the attentional deficits observed in schizophrenic patients.

Adult↗

Paracingulate sulcus morphology in men with early-onset schizophrenia.

BACKGROUND: Cingulate dysfunction has been reported in schizophrenia. Although the paracingulate sulcus (PCS) is known to be asymmetric in healthy people, little information is available about its morphology in schizophrenia. AIMS: To search for morphological anomalies of the PCS in men with early-onset schizophrenia. METHOD: The PCS was examined in magnetic resonance images of the brains of men with schizophrenia and 100 healthy men. RESULTS: A significant asymmetry was found in the brains of healthy volunteers, whose sulci were more frequent and more marked in the left hemisphere. In contrast, the sulcus was as frequent in the right as in the left hemisphere in the patient group. Moreover, patients displayed significantly more rightward asymmetry, and overall less-asymmetrical patterns than the comparison group. CONCLUSIONS: Since the PCS has developed at 36 weeks of gestation, these findings suggest an impaired maturation of the cingulate region during the third trimester.

Adult↗