Biomedical subjects

Vicente Molina

Publications and source records attributed to Vicente Molina.

At least 19 recordsLinked to original sources

PubMed2007

No association between dorsolateral prefrontal gray matter deficit and N-acetyl aspartate ratios in schizophrenia.

The cellular substrates of cortical volume deficit in schizophrenia are unclear. We may hypothesize that, if that deficit was related to a decrease in the amount in neuronal tissue, it should correlate with N-acetyl aspartate levels. We studied a group of 34 schizophrenia patients (of them, 17 first episodes) with both structural and spectroscopic magnetic resonance (MR). Using the data of 50 controls, we were able to calculate for each case residuals of gray matter and cortical cerebrospinal fluid (CSF) in the dorsolateral prefrontal (DLPF) region, representing the deviation from the expected values in normals, given individual intracranial volume and age. Although our patients showed a significant deficit in gray matter and excess in cortical CSF in the DLPF region, that deficit was unrelated to N-acetyl aspartate levels. This was also true for the chronic and first episode groups analyzed separately. These results do not support a neuronal tissue deficit as contributing to the cortical volume deficit in schizophrenia, at least in the DLPF region.

Adult↗

PubMed2006

Antibody persistence after primary vaccination with a hexavalent DTPa-HBV-IPV/HiB vaccine coadministered with a meningococcal C-CRM197 vaccine and response to a DTPa-IPV/HiB booster at 18 months of age.

Children 17-20 months of age (N = 344) received a diphtheria-tetanus toxoids-acellular pertussis (DTPa)-inactivated poliovirus vaccine (IPV)/Haemophilus influenzae (Hib) booster after a 3-dose primary vaccination course with DTPa-hepatitis B vaccine-IPV/Hib plus conjugate meningococcal C vaccine-CRM. Seroprotection rates were >80% (diphtheria, tetanus, hepatitis B, polio and polyribosylribitol phosphate) before and > or =96.6% (diphtheria, tetanus, polio and polyribosylribitol phosphate) after booster vaccination. The booster was well-tolerated (fever >39.5 degrees C after <2% of doses; large swelling reactions after 6.3% of doses).

Adjuvants, Immunologic↗

PubMed2005

Dorsolateral prefrontal cortex contribution to abnormalities of the P300 component of the event-related potential in schizophrenia.

Abnormalities of the P300 component of the event-related potential are a common finding in schizophrenia. It seems possible that the dysfunction in the dorsolateral prefrontal (DLPF) region that has been reported in schizophrenia contributes to this finding. To explore this possibility, we calculated the relationship between, on the one hand, P300 latency and amplitude and, on the other hand, the degree of DLPF atrophy (as measured by magnetic resonance imaging) and metabolic activity during an attentional task (as measured by positron emission tomography). Seventeen schizophrenia patients with a brief duration of illness and minimal exposition to treatment and 25 healthy controls were studied. Patients exhibited significantly lower metabolic activity in the DLPF region, but they did not show cortical atrophy. P300 amplitude was also significantly reduced in the schizophrenia patients compared with the controls. Right DLPF region metabolic activity correlated significantly with P300 amplitude. This pattern remained after partialling out the influence of activity in the hippocampus, superior temporal gyrus and parietal lobe. It is therefore suggested that the prefrontal cortex could be implicated in the P300 amplitude reduction in schizophrenia.

Adult↗

PubMed2005

Ventricular enlargement in schizophrenia is associated with a genetic polymorphism at the interleukin-1 receptor antagonist gene.

Magnetic resonance imaging (MRI) studies have shown some morphological and volumetric peculiarities in brains of schizophrenic patients. The authors explored the influence of genetic polymorphisms at interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) genes on these abnormalities. Hippocampus, lateral ventricles, and dorsolateral prefrontal cortex gray matter volumes were measured in a sample of 23 DSM-IV diagnosed schizophrenic patients of Spanish origin using MRI scans; MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n = 45). IL-1B and IL-1RN genes, involved in neurodevelopment and neurodegenerative processes, were analyzed in the patient sample. Patients carrying VNTR-allele*2 of IL-1RN gene showed a significant enlargement of both left (P = 0.002) and right (P = 0.01) ventricles. Sex and illness duration were controlled for in the analyses. Our results, though preliminary, suggest that IL-1RN gene might contribute to the ventricular volumetric changes observed in schizophrenic patients.

Adult↗

PubMed2005

Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia.

The effects of atypical antipsychotic treatment on the brain volume deficits associated with schizophrenia are poorly understood. We assessed the brain volumes of eleven healthy controls and 29 patients with schizophrenia, using magnetic resonance imaging at baseline and at follow-up after two years of treatment with atypical neuroleptics. Two groups of patients were analyzed: treatment-naïve patients (n = 17) and chronic treatment-resistant patients (n = 12). Treatment-naïve patients received risperidone during the follow-up period, whereas chronic patients received clozapine. Gray matter (GM) and white matter (WM) volumes in the frontal, parietal, occipital, and temporal lobes were measured. Contrary to the controls, both groups of patients presented GM increases and WM decreases in the parietal and occipital lobes (p < .005). Frontal GM also increased in the chronic group with clozapine. There was a significant (p < .001) inverse relationship between the baseline volumes (GM deficit/WM excess) and the longitudinal change. These GM and WM changes were not related to changes in weight. Thus, treatment with risperidone and clozapine in schizophrenia may have an effect on gray and white matter volume and needs further exploration.

Adult↗

PubMed2005

Dorsolateral prefrontal and superior temporal volume deficits in first-episode psychoses that evolve into schizophrenia.

Regions with a likely involvement in schizophrenia may differ between patients with first-episodes of psychosis respectively with and without evolution into schizophrenia following the initial episode. We have used magnetic resonance imaging (MRI) to assess the volumes of dorsolateral prefrontal (DLPF) and superior temporal gyrus (STG) in a group of 37 first-episode psychotic patients. After an initial MRI study performed by the time of the first episode, the subjects were followed for two years. After this period 22 cases were diagnosed with schizophrenia, while the other 15 did not show clinical evidence for this illness. A Talairach-based tool was used for segmentation and volumetry of the MRI scans. A group of 44 healthy controls was used for comparison and, using lineal regression, to control for the normal effects of age and intracranial volume on the regional parameters of the patients. By the time of their first episode, patients with schizophrenia had significantly less grey matter in the right DLPF and STG regions as compared to both controls and FE without schizophrenia. Nevertheless, these parameters could not predict final diagnosis in a discriminant analysis model. Our findings indicate that subtle structural defects are already found by the time of the first psychotic break in schizophrenia, although clinical implications for these differences seem unclear.

Adult↗

PubMed2005

N-acetyl-aspartate levels in the dorsolateral prefrontal cortex in the early years of schizophrenia are inversely related to disease duration.

Magnetic resonance spectroscopy studies in schizophrenia have revealed consistently reduced N-acetyl aspartate (NAA) levels in chronic patients, but not in recent-onset patients. Studies on the relationship between this marker and disease duration have commonly been negative, although it is also true that they have been conducted in patients with long-standing disease. We compared NAA levels in the dorsolateral prefrontal cortex in 16 recent-onset patients (duration: 1.8+/-0.6 years), 19 chronic patients (duration: 9.7+/-6.1 years), and 20 healthy controls. We studied the NAA/creatine and choline/creatine ratios in the dorsolateral prefrontal cortex in both hemispheres, controlling for the effect of age. Chronic patients had significantly lower NAA/Cr ratios in the left hemisphere compared to recent-onset patients and healthy controls, with no difference in Cho/Cr ratio. There were no differences between controls and recent-onset patients. There was a significant inverse relationship between left-side NAA/Cr and disease duration, suggesting that prefrontal NAA levels may progressively decrease in schizophrenia. Taken within the context of the existing literature, these results indicate that this process may be limited to the early years following the onset of the disease. Therefore, reduced prefrontal levels of NAA may be limited to chronic schizophrenia patients.

Adult↗

PubMed2005

Association between excessive frontal cerebrospinal fluid and illness duration in males but not in females with schizophrenia.

OBJECTIVE: Excessive cortical cerebrospinal fluid (CSF) has been acknowledged as a possible marker of a gray matter loss. This excess in schizophrenia is found predominantly in the prefrontal and temporal regions. We hypothesized that the poorer global outcome and treatment response in males with schizophrenia are related to a greater cortical volume loss as compared to females. SUBJECTS AND METHODS: In order to test this hypothesis we have used magnetic resonance imaging (MRI) to study the cortical (prefrontal, temporal, and hemispheric) CSF values in a group of 85 patients with schizophrenia, of whom 56 were males and 29, females. We calculated the residual values of CSF in the patients based on the data pertaining to 45 control subjects and linear regression, from which the normal effects of age and intracranial volume were discounted. These residual scores constitute a quantitative measurement of the excess of CSF due to the disease. RESULTS: Males, but not females, presented a trend-level significant excess of left prefrontal CSF. The prefrontal and temporal residual values were significantly associated with illness duration in males, but not in females. DISCUSSION: These results conform to the worse outcome and the higher severity of structural abnormalities generally found in schizophrenia in male subjects. CONCLUSION: Our data support the hypothesis of accelerated prefrontal cortical loss in males, but not in females with schizophrenia.

Adult↗

PubMed2005

Prefrontal atrophy in first episodes of schizophrenia associated with limbic metabolic hyperactivity.

Reduced volume and activity of the prefrontal (PF) cortical gray matter (GM) and hippocampal hypermetabolism are repeated findings in schizophrenia. There is still an information deficit about the significance of reduction of PF GM in schizophrenia, and a simultaneous study of PF anatomy and activity and limbic metabolism can contribute to fill that deficit. In order to do so, we used positron emission tomography (PET) with 18-fluoro-deoxy-glucose (FDG) during an attention task and magnetic resonance imaging (MRI) to study a sample of first episodes of psychosis. We included 21 first episodes (FE) of psychosis and 16 healthy controls. A diagnosis of schizophrenia was confirmed in the follow-up in eleven of these patients and ruled out in the remaining 10 cases. Volumes of PF GM were determined and also activity in the same region and in the hippocampus. Residual GM was estimated in the PF region as a quantitative measurement of the degree of atrophy in each individual, using age and intracranial volume data from a set of 45 healthy controls and linear regression. Patients with schizophrenia had lower PF metabolic activation and greater hippocampal activity than controls. FE patients without schizophrenia were no different in any parameter as compared to controls. Patients with schizophrenia presented an inverse and significant association between GM deficit and hippocampal activity that was not observed in controls or in patients without schizophrenia. The same association was previously described by our group using PET in the resting state in recent-onset and chronic patients with schizophrenia. These findings support a loss in PF inhibitory capacity as a possible link between anatomical and functional alterations in schizophrenia.

Adult↗

PubMed2005

Olanzapine-induced cerebral metabolic changes related to symptom improvement in schizophrenia.

The pattern of brain metabolic changes produced by olanzapine has yet to be described, despite the theoretical and clinical interest of this new antipsychotic. We studied a group of 17 schizophrenic patients who underwent two fluoro-deoxyglucose-positron emission tomography (FDG-PET) studies under two different conditions: a baseline scan during treatment with either conventional antipsychotics (n=15) or risperidone (n=2) and a second scan performed 17-24 weeks after switching to olanzapine. PET scans were obtained while performing a standard cognitive paradigm (Continuous Performance Test) and analysed by means of Statistical Parametric Mapping. No significant metabolic changes were found in the comparison between pre- and post-olanzapine conditions. A brain map of the statistical power of our design showed that changes up to 3% in the frontal and up to 8% in the occipital region were not likely to exist (1-beta=0.8). The degree of improvement in positive symptoms was related to the amount of activity decrease in the right orbital region and to the amount of activity increase in the primary visual area. Improvement in negative symptoms was associated with an activity increase in the dorsal prefrontal cortex, and a higher baseline activity in both temporal poles. These correlation patterns suggest that the functional mechanism of action of olanzapine may share traits from both typical and atypical neuroleptics.

Adult↗

PubMed2004

An electrophysiological (ERP) component, the recognition potential, in the assessment of brain semantic networks in patients with schizophrenia.

Abnormal activation of semantic networks may be the underlying basis for thought disorder (ThD) in patients with schizophrenia. However, whether this abnormality consists of increased or decreased activation is unclear. Previous behavioral and electrophysiological (N400) data have failed to yield consistent evidence for clarifying this hypothesis. One of the event-related potentials (ERP) components (the recognition potential, RP), presumably reflecting activation of specific semantic networks involved in ThD, has not been used to studies of schizophrenia, and may add additional information to support or refute this hypothesis. In an initial experiment, RP amplitude was reduced in schizophrenic patients, but particularly in those with ThD. In a second experiment, in addition to reduced overall RP amplitude, concrete words were shown to have higher amplitudes than abstract words in both patients and controls, supporting a relative integrity of the lexicon in ThD patients. RP reduction suggests that a fewer number of networks' elements are activated when an incoming word is processed, thus supporting hypoactivation of the semantic networks as the basis for ThD.

Adult↗

PubMed2004

Cerebral metabolic changes induced by clozapine in schizophrenia and related to clinical improvement.

RATIONALE: The study of the different effects on brain metabolism between typical and atypical antipsychotics would aid in understanding their mechanisms of action. Clozapine is of special interest, since it is one of the most effective antipsychotic drugs and demonstrates a distinctive mechanism of action in pre-clinical studies with respect to typical neuroleptics. OBJECTIVE: To study the differences in cerebral activity induced by clozapine as compared to those produced by haloperidol. METHODS: [18F]Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) scans were obtained in the resting condition before and after 6 months of treatment with clozapine in 22 treatment-resistant patients with schizophrenia. Before inclusion, patients had been chronically treated with classical drugs, and all of them received haloperidol during the last month. Data were analyzed with statistical parametric mapping (SPM'99) methods, comparing pre-treatment and post-treatment conditions. The association between the changes in symptom scores and metabolism was also assessed to corroborate the functional relevance of possible metabolic changes. RESULTS: Clozapine decreased prefrontal and basal ganglia activity, and increased occipital metabolism, including primary and association visual areas. The change in negative symptoms was related with the decrease of basal ganglia activity; the improvement in disorganization related to the metabolic decrease in the motor area, and the change in positive symptoms was associated to the increase of activity in the visual area. CONCLUSIONS: These results show that haloperidol and clozapine produce different patterns of metabolic changes in schizophrenia. Compared to the haloperidol baseline, clozapine inhibited the metabolic activity of the prefrontal and motor cortical regions and basal ganglia and induced a higher activation of the visual cortex. The improvement in disorganization, negative and positive syndromes with clozapine may be respectively associated with metabolic changes in the motor area, basal ganglia, and visual cortex.

Adult↗

PubMed2004

Lower prefrontal gray matter volume in schizophrenia in chronic but not in first episode schizophrenia patients.

Although a lower volume of prefrontal (PF) gray matter (GM) in patients with schizophrenia than in normal control subjects is a replicated finding, it is not yet clear whether this finding is present at the onset of illness. Clinical and imaging data suggest that the reduction in PF GM becomes apparent only some years following the onset of illness. To test this hypothesis, we used magnetic resonance imaging to study PF GM and sulcal cerebrospinal fluid (CSF) volumes in 81 schizophrenic patients. A Talairach-based tool was used for segmentation. Subjects included 44 healthy controls, 22 first-episode (FE), treatment-naïve patients with duration of illness of less than 1 year; 29 short-term chronic (SC) patients with durations of illness between 1.5 and 6 years; and 30 long-term chronic (LC) patients with duration of illness of more than 6 years. The data from healthy controls were used to calculate volume residuals in the patients, defined as deviations from the expected values given individual age and intracranial volume. The FE group did not show significant differences in GM or in CSF volumes compared with controls. However, both the SC and the LC patients showed the expected pattern of lower values for PF GM and an excess of PF sulcal CSF compared with controls. There were no significant differences between SC and LC patients in any of these measurements. There was a significant and inverse association between duration of illness and GM residuals. That association fit a nonlinear rather than a linear model, which was consistent with a decrease of GM volume during the first years following illness onset. No significant differences were found between those receiving atypical and typical antipsychotic drugs during the previous year.

Adult↗

PubMed2004

Direct association between orbitofrontal atrophy and the response of psychotic symptoms to olanzapine in schizophrenia.

The study of cerebral variables associated with response to neuroleptics holds interest from both theoretical and clinical points of view. To date, no studies have aimed to identify predictors of response to olanzapine based on cerebral measurements. Here, we used magnetic resonance to assess the relationship between volumes of the prefrontal (dorsolateral and orbitofrontal) and temporal (temporal lobe and hippocampus) cortical regions and ventricles and, on the other hand, the response to olanzapine in 16 schizophrenic patients. Data from 42 healthy controls were used to calculate volume residuals in the patients, defined as deviations from the expected values, given individual age and intracranial volume. Residuals thus represent the effect of illness on regional measurements. The association between clinical change and those residuals was calculated separately for the positive, negative and total scores from the Positive and Negative Syndrome Scale (PANSS). There was a significant direct association between the degree of orbitofrontal atrophy and the improvement of positive symptoms with olanzapine. No predictors were found for change in the negative dimension. A trend was found for patients with larger ventricles to show a greater global decrease in total PANSS scores. Neither age nor duration of illness explained a significant proportion of the symptom improvement. This result, together with others from the literature, supports the idea that atypical antipsychotics may offer some benefit to patients with significant regional atrophy, and this may have implications for the choice of antipsychotic in clinical practice.

Adult↗

PubMed2004

Long-term olanzapine treatment and p300 parameters in schizophrenia.

The well-known amplitude reduction of the P300 appears to be unaffected by the treatment with classical antipsychotics in schizophrenia, whereas the effects of atypical neuroleptics on this event-related potential are less understood. The study of these changes could help in deciding whether the P300 amplitude reduction in schizophrenia is a trait or state marker of that illness and in better describing the effect of atypical antipsychotics on altered cognitive functions. We present a prospective longitudinal study of P300 amplitude and latency before and after 6 months' treatment with olanzapine in 11 patients with schizophrenia. A healthy control group (n = 30) was also studied. Overall, no significant changes, either in amplitude or in latency as measured at Pz and Fz electrodes, were found when comparing the pre- and postolanzapine conditions, despite the overall improvement in positive and negative symptoms. Nevertheless a direct specific association was observed between a P300 amplitude increase with olanzapine and the improvement in negative symptoms. These data would suggest that P300 amplitude reduction in schizophrenia may be relatively independent from clinical state and treatment, thus constituting a trait marker of schizophrenia. Our data also suggest that, in addition to this, some further changes in P300 amplitude might depend on the clinical state of the patients.

Adult↗

PubMed2004

Immunogenicity and reactogenicity of a three-dose primary vaccination course with a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-haemophilus influenzae type b vaccine coadministered with a meningococcal C conjugate vaccine.

AIM: To evaluate the immunogenicity and safety of 3 doses of the combined diphtheria-tetanus toxoids-acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine (Infanrix hexa) when coadministered with a CRM197-conjugated meningococcal C vaccine (Meningitec) at different injection sites during the same visit or during separate visits. METHODS: Healthy infants were randomized in an open randomized multicenter study to receive either the DTPa-HBV-IPV/Hib and meningococcal C conjugate vaccines during the same vaccination visit at 2, 4 and 6 months of age (coadministration group) or the DTPa-HBV-IPV/Hib vaccine at 2, 4 and 6 months of age and the meningococcal C conjugate vaccine at 3, 5 and 7 months of age (separate administration group). RESULTS: The immunogenicity analysis included 452 infants, 228 in the coadministration group and 224 in the separate administration group. One month after primary vaccination, 99.1% of subjects in both groups achieved anti-polyribosylribitol phosphate antibody concentrations >/=0.15 microg/mL. The vaccine response against pertussis antigens was at least 99.1% in both groups. For all other DTPa-HBV-IPV/Hib vaccine antigens, at least 97.8% of all subjects of both groups were seroprotected. In addition, 99.5% of all subjects had meningococcal C bactericidal antibody titers >/=1/8 and 99.1% >/=1/128. Coadministration of both vaccines did not result in an increased local or general reactogenicity compared with separate administration. CONCLUSION: Coadministration of the combined DTPa-HBV-IPV/Hib vaccine and the meningococcal C conjugate vaccine during the same vaccination visit was immunogenic and safe.

Antibodies, Bacterial↗

PubMed2003

Anatomical and functional cerebral variables associated with basal symptoms but not risperidone response in minimally treated schizophrenia.

In schizophrenia, structural and functional cerebral variables show an unclear association with clinical features and their value as predictors of response to a typical antipsychotic agents has yet to be determined. The goal of this study was to investigate the relationships between clinical variables (baseline syndromes and response to risperidone) and anatomo-functional brain variables. We studied 19 minimally treated patients with schizophrenia of recent onset using magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) under resting conditions. The following brain variables were studied: volume of the cerebrospinal fluid (CSF) and gray matter (GM) of the dorsolateral prefrontal cortex (DLPFC) and temporal lobe; hippocampal metabolic activity and volume; and metabolic activity of the DLPFC, temporal lobe, putamen and caudate. Anatomical volume measurements were corrected for age and intracranial size using regression parameters determined from a matched sample of control subjects. Using stepwise multiple regression, we assessed the relation between these brain measures and basal scores of symptom dimensions (positive, disorganization, negative and total), as well as their change in response to risperidone. We found that positive and disorganization symptoms improved with risperidone treatment and that hippocampal metabolism, DLPFC CSF volume, and temporal CSF volume predicted baseline symptoms. However, none of the brain measures predicted response to treatment. We conclude that there is evidence of a significant association between basal symptoms and DLPFC atrophy and limbic hyperactivity at rest in recent-onset schizophrenic patients.

Adult↗

PubMed2003

Anatomical and functional brain variables associated with clozapine response in treatment-resistant schizophrenia.

Clozapine alleviates the symptoms of a significant proportion of treatment-resistant schizophrenic patients. Previous studies suggest that the response to clozapine may be associated with prefrontal and temporal anatomy as well as with prefrontal, basal ganglia and thalamic metabolism. A sample of 25 treatment-resistant (TR) schizophrenic patients underwent magnetic resonance imaging (MRI) and 18F-deoxyglucose positron emission tomography (PET) before and after treatment with clozapine. We investigated the association between changes in positive, disorganized, and negative schizophrenic syndromes with clozapine treatment and a set of cerebral variables that included total intracranial volume (ICV); hippocampal, dorsolateral prefrontal (DLPF) and temporal gray-matter volume and metabolism; and metabolic activity of the thalamus, pallidum/putamen, and caudate head. Improvement in positive symptoms with clozapine was directly related to temporal gray-matter volume, whereas improvement of disorganization symptoms was inversely related to ICV and hippocampal volume. Patients with high baseline DLPF cortical volume and metabolic activity were more likely to experience improvement in their negative symptoms. We conclude that clinical improvement with clozapine may be related with the anatomy and metabolic activity of specific brain areas, with the structural integrity of the DLPF and temporal regions showing the maximum predictive capacity.

Adult↗