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Biomedical subjects

Carles Soriano-Mas

Publications and source records attributed to Carles Soriano-Mas.

9 recordsLinked to original sources

Genetic and epigenetic changes to the glucocorticoid receptor gene (NR3C1) and cognition in major depressive disorder.

INTRODUCTION: Many studies have found that hypothalamic-pituitary-adrenal (HPA) axis abnormalities are related to the pathophysiology of major depressive disorder (MDD) and cognitive functioning. Our aim was to assess the influence of genetic polymorphisms and methylation levels in three different promoter regions throughout the glucocorticoid receptor (GR) gene NR3C1 on cognitive performance in MDD. Plausible interactions with childhood adversity and mediation relationships between genetic and epigenetic variables were explored. MATERIALS AND METHODS: The sample included a total of 64 MDD patients and 82 healthy controls. Child maltreatment and neurocognitive performance were assessed in all participants. HPA negative feedback was analyzed using the dexamethasone suppression test after the administration of 0.25mg of dexamethasone. A total of 23 single-nucleotide polymorphisms were genotyped, and methylation levels at several CpGs in exons 1D, 1F and 1H of the GR gene were measured. RESULTS: Results show that, beyond the influence of other covariables, NR3C1 single-nucleotide polymorphisms and methylation levels predicted performance in executive functioning and working memory tasks. No significant interactions or mediation relationships were detected. CONCLUSIONS: Results suggest that genetic variations and epigenetic regulation of the GR gene are relevant factors influencing cognitive performance in MDD and could emerge as significant biomarkers and therapeutic targets in mood disorders and other stress-related disorders.

Humans↗

Post-training intracranial self-stimulation facilitates a hippocampus-dependent task.

Previous research has shown that post-training intracranial self-stimulation facilitates implicit or procedural memory. To know whether it can also facilitate explicit memory, post-training intracranial self-stimulation was given to Wistar rats immediately after every daily session of a delayed spatial alternation task that seems to depend on the integrity of the hippocampal memory system. We tested the effects of intracranial self-stimulation in three consecutive learning phases which tried to make the task progressively more difficult: 10 s delay (D10 phase), 30 s delay (D30 phase), and inverting the starting position of the animals to make their response more dependent on allocentric cues (INV phase). Every phase finished when each rat achieved a fixed learning criterion. Intracranial self-stimulation facilitated the flexible expression of the learned response (INV phase). That is, when the starting position was randomly inverted, only the rats that received intracranial self-stimulation maintained the performance level acquired in the previous training phases. Changing the starting position reduced the correct performance of the non-treated subjects, which need more training sessions to achieve the learning criterion and made less correct responses than treated rats. These findings show that post-training intracranial self-stimulation can facilitate hippocampus-dependent memories.

Animals↗

Age-related metabolic changes in the upper brainstem tegmentum by MR spectroscopy.

Several neurodegenerative disorders have a profound metabolic and structural impact on the brainstem. MR spectroscopy provides metabolic information non-invasively and has the potential to characterize the changes associated with normal aging and differentiate them from neurodegenerative alterations. The present work was aimed at studying the upper brainstem tegmentum at the midbrain and pontine levels in 57 adult normal volunteers, aged 23-79 years, with long-echo time proton MR spectroscopy to evaluate possible regional differences and the effect of age. Higher ratios of N-acetyl aspartate (NAA)/total creatine (Cr) and choline-containing compounds (Cho)/Cr were observed in the pons compared to the midbrain, resulting from higher net NAA and Cho content. In the midbrain, there was a linear decline of NAA and Cho with age in subjects over 50, most probably related to neuronal tissue loss. In the pons, such an aging effect was not observed, with subjects over 50 showing higher Cr and Cho than the under-50 subjects. Our findings provided evidence of regional differences and suggest different effects of age on the two studied brainstem segments, hitherto undescribed.

Adult↗

Mapping structural brain alterations in obsessive-compulsive disorder.

BACKGROUND: Recent technical developments have made it feasible to comprehensively assess brain anatomy in psychiatric populations. OBJECTIVE: To describe the structural brain alterations detected in the magnetic resonance images of a large series of patients with obsessive-compulsive disorder (OCD) using imaging procedures that allow the evaluation of volume changes throughout the brain. DESIGN: Case-control study. SETTING: Referral OCD unit in a tertiary hospital. PARTICIPANTS: A consecutive sample of 72 outpatients with OCD and 72 age- and sex-matched control subjects. INTERVENTIONS: Three-dimensional sequences were obtained in all participants. A statistical parametric mapping approach was used to delineate possible anatomical alterations in the entire brain. To preserve volumetric information, voxel values were modulated by the Jacobian determinants (volume change measurement) derived from spatial normalization. MAIN OUTCOME MEASURES: Voxelwise brain volumes. RESULTS: The brains of patients with OCD showed reduced gray matter volume in the medial frontal gyrus, the medial orbitofrontal cortex, and the left insulo-opercular region. A relative increase in gray matter volume was observed bilaterally in the ventral part of the putamen and in the anterior cerebellum. All these brain alterations were abnormally correlated in patients with OCD, and age statistically significantly contributed to the relative enlargement observed in the striatal areas. Disease severity, the nature of symptoms, and comorbidities were not related to the changes described. Nevertheless, patients with prominent aggressive obsessions and checking compulsions showed reduced amygdala volume in the right hemisphere. CONCLUSIONS: The pattern of anatomical features depicted by this voxelwise approach is consistent with data from functional studies. The reported anatomical maps identified the specific parts of the frontostriatal system that were altered in patients with OCD and detected changes in anatomically connected distant regions. These data further define the structural brain alterations in OCD and may contribute to constraining the prevailing biological models of this psychiatric process.

Adolescent↗

Delayed myelination in children with developmental delay detected by volumetric MRI.

Delayed acquisition of developmental motor and cognitive milestones is a common clinical expression of many etiological processes. Imaging exams of developmentally delayed children often show no structural brain alterations despite suspicion of brain maturation delay. MRI studies increasingly suggest that white matter myelination finely reflects the progression in functional brain maturation. In this volumetric MRI study, we sought to evaluate whether developmental delay in children with normal conventional MRI exams is associated with reduced myelinated white matter. A total of 100 children (mean age, 4.4 years) with developmental delay and 50 normally developing age-matched control children underwent 3-D MRI to measure the volume of myelinated white matter. Patients showed a significant reduction in the relative content of myelinated white matter (accounting for 19.8% of brain volume in patients and 21.4% in control subjects, P = 0.005). The observed difference was equivalent to a 3.2-year myelination delay. Although the whole hemispheres were invariably symmetrical, the volume of myelinated white matter was asymmetrical in 30% of patients and 10% of control subjects (P = 0.006). We conclude that volumetric assessment of white matter may reveal a reduction in brain myelination beyond early childhood in developmentally delayed children showing normal brain appearance. This finding further emphasizes the view of white matter myelination as an indicator of functional brain maturation.

Age Distribution↗

Posttraining intracranial self-stimulation ameliorates the detrimental effects of parafascicular thalamic lesions on active avoidance in young and aged rats.

To evaluate whether intracranial self-stimulation (SS) ameliorates conditioning deficits induced by parafascicular nucleus (PF) damage in young and aged rats, the authors gave rats a daily session of 2-way active avoidance until a fixed criterion was achieved. Four experimental groups were established in both young and aged rats: SS treatment after every conditioning session (SS groups), pretraining PF lesions (lesion groups), PF lesions and SS treatment (L + SS groups), and controls. SS treatment not only canceled the detrimental effects of PF lesions, but also improved conditioning in lesioned rats (L + SS groups). This effect was more powerful in aged rats. SS treatment compensated for memory deficits generated by hypofunctionality of arousal systems such as that involving the PF.

Age Factors↗

Beneficial effect of donepezil on sensorimotor function after stroke.

Pharmacotherapy of poststroke sensorimotor deficits is currently used alone or combined with physiotherapy to promote recovery of mobility problems. This case study examined the effectiveness of donepezil hydrochloride (HCl) administered to a stroke patient with chronic, dense, left sensorimotor deficit. The patient received donepezil HCl (5 mg daily for 4 wk, followed by 10 mg daily for 12 wk) but no physiotherapy. Baseline and posttreatment evaluations were performed with the Fugl-Meyer scale and the Rivermead Mobility Index. One month after starting donepezil HCl (10 mg/day), sensorimotor function improved dramatically in the hemiplegic lower limb and shoulder. It was concluded that donepezil HCl may be an effective treatment for improving sensorimotor function in chronic stroke patients. Randomized controlled trials are required to support these preliminary findings.

Cholinesterase Inhibitors↗

Intracranial self-stimulation facilitates memory consolidation, but not retrieval: its effects are more effective than increased training.

To evaluate possible differential effects of lateral hypothalamic intracranial self-stimulation (ICSS) on memory consolidation and retrieval, independent groups of Wistar rats were trained in a single session of two-way active avoidance task (acquisition session) and tested 24 h later (retention session). The post-ICSS groups received an ICSS treatment immediately after the acquisition session, and the pre-ICSS groups received the same treatment immediately before the retention session. Because the ICSS effects on memory seem to be dependent on the initial performance level shown by the subjects, the possible influence of initial training (number of trials) on ICSS effects was also studied. Therefore, we used different control and experimental groups, which received either 30 or 50 trials in the acquisition session. Post-training ICSS facilitated the 24-h retention in both training conditions (30 and 50 trials). In contrast, pre-retention ICSS treatment did not facilitate performance in the retention test. We also observed that post-training ICSS was more effective for improving the 24-h retention than increasing the initial training from 30 to 50 trials. This findings confirm that ICSS treatment improves memory consolidation and suggest that it might not affect memory retrieval mechanisms.

Animals↗

Alexithymia correlates with the size of the right anterior cingulate.

OBJECTIVE: The authors investigated a possible relationship between interindividual variability in anterior cingulate gyrus (ACG) morphology and alexithymia. MATERIALS AND METHODS: Magnetic resonance images were obtained in 100 healthy university graduates (51 female, 49 male; mean age 25.6 y). Surface area measurements of the ACG were performed on reformatted sagittal views in both hemispheres. The Toronto Alexithymia Scale (TAS-20) and the Temperament and Character Inventory (TCI) were administered. RESULTS: Right ACG surface area significantly correlated with TAS-20 total score in men (r = 0.37; p = 0.009) and in women (r = 0.30; p = 0.034). After controlling for three TCI subscales (harm avoidance, self-directedness, and self-transcendency), the correlation between TAS-20 total and right ACG became nonsignificant in women, but was only slightly reduced (r = 0.32; p = 0.032) in men. A linear regression model with right ACG as a dependent variable revealed brain volume, TCI-harm avoidance and TAS 20 total score as significant predictors in the total sample (explained proportion of total variation (EPTV) 37%). In men, beside brain volume, only TAS-20 total score showed a highly significant contribution (EPTV 41%), whereas in women only TCI-harm avoidance was a significant predictor (EPTV 36%). CONCLUSIONS: The authors' findings indicate that there is a significant positive relation between the size of the right ACG and alexithymia as measured with the TAS in healthy subjects. This applies especially for men whereas in women ACG size is more associated with the subscale harm avoidance of the TCI. Our findings also suggest a partial lateralization of human emotion processing, especially negative emotion.

Adult↗