The relationship between maternal-fetus attachment and perceived parental bonds in pregnant women: Considering a possible mediating role of psychological distress.

Maternal-Fetal Attachment (MFA) delineates the emotional, cognitive, and behavioral aspects that mothers develop toward the unborn baby during pregnancy. The literature indicates that optimal attachment in pregnancy represents a protective factor for the mother-child attachment bond after birth and child development outcomes. To date, there are few studies that have investigated associated factors of MFA. This study sets out to explore the association between perceived parental bonds and maternal-fetal bonding in pregnant women, accounting for factors such as psychological distress, socio-demographic and obstetric characteristics. Methods: In this cross-sectional study, 1,177 pregnant women answered the Parental Bonding Instrument, the Maternal-Fetal Attachment Scale, State-Trait Anxiety Inventory (STAI-Y), and Beck-Depression Inventory (BDI-II). Results: We found out that perceived maternal and paternal care had significant direct effects on maternal-infant bonding during the pregnancy period when controlling for some confounders, including gestational age and mother age among others. Such maternal and paternal perceived care effects were not mediated by levels of psychological distress, which in turn resulted to be a "borderline" significant predictor of prenatal attachment. Interestingly, the gestational age and the mother age emerged to have a significant and synergic nonlinear effect, suggesting the influence on the MFAS of the gestational age depends on the values of the mother age, and likewise, the effect of mother age on MFAS depends on the gestational week. Conclusion: This study expands our knowledge of the intergenerational transmission of attachment pointing out the effects of a woman's perceived bond in relation to her parental figures during the development of the prenatal attachment process. Findings also suggests that parenting support interventions may have benefits that are realized across generations.

Dysbindin C-A-T haplotype is associated with thicker medial orbitofrontal cortex in healthy population.

The dysbindin (dystrobrevin-binding protein 1) gene has been indicated as one of the most important schizophrenia susceptibility genes. Several genetic variations of this gene have been investigated by using an "intermediate phenotype" approach showing a particular detrimental effect on the prefrontal function in schizophrenic patients. However, the nature of dysbindin function within the brains of healthy individuals is poorly understood, in particular as concerns brain anatomy. We examine relationships between a previously implicated three marker C-A-T dysbindin haplotype and regional cortical thickness in a wide population genotyped for risk carriers (n=14) and non-risk carriers (n=93). Surface-based analysis of the cortical mantle showed that the dysbindin haplotype was associated with structural differences in the medial orbitofrontal cortex, where the risk carriers showed the highest cortical thickness values and the non-risk carriers the lowest. Our study extends previous evidence found on schizophrenic patients to the healthy population, demonstrating the influence of dysbindin risk variants on the neuronal architecture of a specific brain region relevant to the neuropathology of schizophrenia.

MAO A VNTR polymorphism and amygdala volume in healthy subjects.

The X-linked Monoamine Oxidase A (MAO A) gene presents a well known functional polymorphism consisting of a variable number of tandem repeats (VNTR) (long and short variants) previously associated with altered neural function of the amygdala. Using automatic subcortical segmentation (Freesurfer), we investigated whether amygdala volume could be influenced by this genotype. We studied 109 healthy subjects (age range 18-80 years; 59 male and 50 female), 74 carrying the MAO A High-activity allele and 35 the MAO A Low-activity allele. No significant effect of the MAO A polymorphism or interaction effect between polymorphism × gender was found on amygdalar volume. Thus, our findings suggest that the reported impact of the MAO A polymorphism on amygdala function is not coupled with consistent volumetric changes in healthy subjects. Future studies are needed to investigate whether the association between volume of the amygdala and the MAO A VNTR polymorphism is influenced by social/psychological variables, such as impulsivity, trauma history and cigarette smoking behaviour, not taken into account in this work.

Neurofunctional correlates of personality traits in relapsing-remitting multiple sclerosis: an fMRI study.

Extraversion and Neuroticism are two fundamental dimensions of human personality that influence cognitive functioning in healthy subjects. Little is known about personality changes that may occur in patients with multiple sclerosis (MS) nor about, in particular, their neurofunctional basis. The aim of this study is to determine the impact of personality characteristics on brain activity in patients with MS. Eighteen patients with clinically definite relapsing-remitting MS without any evidence of psychiatric or cognitive disorders and thirteen healthy controls matched for age, gender and education were investigated using functional magnetic resonance imaging (fMRI) during the execution of an "n-back" task. No differences were detected on the behavioral tests between the two groups, although the MS patients had lower total IQ and showed a trend towards higher Extraversion and Neuroticism scores than did the controls. fMRI analyses demonstrated that Extraversion scores were positively associated with brain activity in the fronto-parietal network including the superior parietal lobule and dorsolateral prefrontal cortex in both groups during the high load condition of the n-back task. Given the overlapping neural systems found in the two groups, we suggest that the neural activity associated with specific personality dimension is a neurophysiological characteristic preserved in patients with MS at an early stage in the course of their disease.

Impact of catechol-O-methyltransferase Val(108/158) Met genotype on hippocampal and prefrontal gray matter volume.

A variation in catechol-O-methyltransferase (COMT) gene (Val(108/158)Met) affects the physiological response of hippocampal-prefrontal circuits, predicts variation in human memory and is associated with increased risk for psychiatric disorders. Using optimized voxel-based morphometry we studied the effect of this functional polymorphism on the anatomy of the hippocampus, and the prefrontal cortex. Fifty-seven healthy participants were investigated (nine had Met/Met, 30 Val/Met, and 14 Val/Val). Voxel-based morphometry showed that individuals who are homozygous for the Val-COMT allele had greater gray matter volume of the prefrontal cortex bilaterally, whereas Met-COMT carriers were associated with increased tissue volume of the hippocampus bilaterally. This study provides evidence that the Val(108/158)Met polymorphism of the COMT gene might be responsible for individual variation in the human brain morphology.

MAO A VNTR polymorphism and variation in human morphology: a VBM study.

The X-linked monoamine oxidase A (MAO A) gene, coding for an enzyme especially involved in the serotonin catabolism, presents a well-characterized functional polymorphism (long and short variants) in the promoter region that alters the transcriptional activity of the gene and hence the function of the corresponding proteins. Using optimized voxel-based morphometry, we studied the effect of this functional polymorphism on brain morphology in normal individuals. Fifty-nine male healthy individuals (33 MAO A-high and 26 MAO A-low) were investigated. Voxel-based morphometry showed that the carriers of the long variant were significantly associated with loss of grey matter in orbitofrontal cortex, bilaterally. This study reveals pronounced genotype-related structural changes in a specific prefrontal region previously observed to mediate neurofunctional responses in behavioral tasks.

Ventro-lateral prefrontal activity during working memory is modulated by MAO A genetic variation.

Several lines of evidence have highlighted the role of the serotonergic system in working memory (WM) processes. The X-linked Mono-Amine Oxidase A (MAO A) gene, coding for an enzyme especially involved in the serotonin (5-HT) catabolism, presents a well-characterized functional polymorphism consisting in a variable number of tandem repeats (VNTR) in the promoter region with high activity and low activity variants. The high activity allele carriers have been associated with higher enzyme expression, lower amine concentration and altered prefrontal cortex (PFC) function during motor inhibition, but a direct effect of MAO A genotype on WM-related brain activity has not been demonstrated. We have studied the relationship of this polymorphism to brain activity elicited by a spatial working memory task (n-back) using blood oxygenation level-dependent functional magnetic resonance imaging in 30 healthy male individuals matched for a series of demographic and genetic variables (COMT Val108/158Met). We show that the high activity allele was significantly (p-level<0,001) associated with increased activity of the right ventro-lateral PFC (VLPFC, BA 47) during the high load condition of the n-back task. Our data reveal pronounced genotype-related functional changes in specific prefrontal region (VLPFC) subserving spatial working memory. Moreover, given the well-known role of this area in inhibitory control, our finding also provides new evidence for the involvement of 5-HT in PFC-mediated WM function.

Dopaminergic modulation of cognitive interference after pharmacological washout in Parkinson's disease.

The dopaminergic modulation of prefrontal function in Parkinson's disease (PD) has been consistently demonstrated. There is evidence that the effects of pharmacological manipulations on cognitive performances are described by an "Inverted-U" shaped curve. Neuroimaging studies performed before and after an overnight withdrawal from therapy showed significant differences between drug states, but did not control for the relative impact of the long duration response to levodopa. Here we evaluate the brain response after a complete pharmacological washout by correlating dopaminergic-related changes of this response to changes in performance during cognitive interference. Twelve idiopathic PD patients were studied with functional MRI while performing a modified version of the Stroop task. Patients were scanned twice: (1) following a prolonged washout procedure ("OFF" state) and (2) 90-120 min after the administration of levodopa ("ON" state). Task-related changes of PD patients were compared to those of matched healthy controls. Healthy controls displayed prefrontal and parietal responses that were positively correlated with task accuracy. In the "OFF" state, PD patients showed significant responses in anterior cingulate and pre-supplementary motor area, which are hypothesized to operate at a higher level of basal dopaminergic modulation. Levodopa administration attenuated such responses and enhanced the response of prefrontal cortex (PFC), which was correlated with improved accuracy. Results demonstrate that the behavioral effects of pharmacological manipulations of the dopamine system are highly dependent on the baseline status of PFC. When a true hypodopaminergic state is induced in PD patients, cognitive interference might significantly benefit from the administration of levodopa via an enhanced PFC response.

Sensorimotor transduction of time information is preserved in subjects with cerebellar damage.

The cerebellar contribution to motor entrainment through rhythmic auditory stimuli was analyzed by comparing rhythmic motor responses in subjects with cerebellar pathologies and in healthy controls. Eleven patients with cerebellar lesions and eight healthy subjects tapped in synchrony with an auditory rhythmic stimulus using a hand-held pencil-shaped electrode connected to a PC. A 60-stimulus sequence was delivered with an ISI of 500 ms and changed at random to a new ISI value with either consciously perceived (+/-50 ms) or unperceived tempo changes (+/-10 ms). Synchronization patterns for both groups were computed based on the timing of inter-response intervals (IRIs) and synchronization errors (SE). Variability of IRI as well as the timing of adaptation patterns after the tempo changes were modeled and analyzed mathematically using a logistic/sigmoid function. Healthy subjects performed with significantly lower IRI variability than cerebellar patients. Patients with focal lesions performed with significantly lower IRI variability than patients with atrophic lesions. Asymptote parameters during isochronous synchronization as well as slope angles and symmetry points of the adaptation curves after tempo perturbation showed no significant differences between groups. Present data indicate that temporal variability of rhythmic motor responses is differentially affected by distinct cerebellar pathologies but that motor entrainment to auditory rhythms is not affected by lesion of the cerebellar circuits.

The neuroanatomical correlates of anxiety in a healthy population: differences between the State-Trait Anxiety Inventory and the Hamilton Anxiety Rating Scale.

OBJECTIVES: The State-Trait Anxiety Inventory (STAI) and the Hamilton scale for anxiety (HARS) are two of the most important scales employed in clinical and psychological realms for the evaluation of anxiety. Although the reliability and sensibility of these scales are widely demonstrated there is an open debate on what exactly their scores reflect. Neuroimaging provides the potential to validate the quality and reliability of clinical scales through the identification of specific biomarkers. For this reason, we evaluated the neural correlates of these two scales in a large cohort of healthy individuals using structural neuroimaging methods. CASE REPORT: Neuroimaging analysis included thickness/volume estimation of cortical and subcortical limbic structures, which were regressed on anxiety inventory scores with age and gender used for assessing discriminant validity. A total of 121 healthy subjects were evaluated. Despite the two anxiety scales, at a behavioral level, displaying significant correlations among them (HARS with STAI-state (r = 0.24; P = 0.006) and HARS with STAI-trait (r = 0.42; P < 0.001)), multivariate neuroimaging analyses demonstrated that anatomical variability in the anterior cingulate cortex was the best predictor of the HARS scores (all ß's ≥ 0.31 and P's ≤ 0.01), whereas STAI-related measures did not show any significant relationship with regions of limbic circuits, but their scores were predicted by gender (all ß's ≥ 0.23 and P's ≤ 0.02). CONCLUSION: Although the purpose of HARS and STAI is to quantify the degree and characteristics of anxiety-like behaviors, our neuroimaging data indicated that these scales are neurobiologically different, confirming that their scores might reflect different aspects of anxiety: the HARS is more related to subclinical expression of anxiety disorders, whereas the STAI captures sub-dimensions of personality linked to anxiety.

A Cellular Neural Network methodology for the automated segmentation of multiple sclerosis lesions.

We present a new application based on genetic algorithms (GAs) that evolves a Cellular Neural Network (CNN) capable of automatically determining the lesion load in multiple sclerosis (MS) patients from magnetic resonance imaging (MRI). In particular, it seeks to identify brain areas affected by lesions, whose presence is revealed by areas of higher intensity if compared to healthy tissue. The performance of the CNN algorithm has been quantitatively evaluated by comparing the CNN output with the expert's manual delineation of MS lesions. The CNN algorithm was run on a data set of 11 MS patients; for each one a single dataset of MRI images (matrix resolution of 256×256 pixels) was acquired. Our automated approach gives satisfactory results showing that after the learning process the CNN is capable of detecting MS lesions with different shapes and intensities (mean DICE coefficient=0.64). The system could provide a useful support tool for the evaluation of lesions in MS patients, although it needs to be evolved and developed in the future.

The effects of BDNF Val66Met polymorphism on brain function in controls and patients with multiple sclerosis: an imaging genetic study.

Relatively little is known about genetic determinants of cognitive dysfunction in multiple sclerosis (MS). A growing body of evidence demonstrates that a functional variant of the brain-derived neurotrophic factor (BDNF) gene, the Val(66)Met polymorphism, contributes to poor hippocampal and prefrontal functions, particularly memory processes, in healthy controls. In contrast, findings from previous association studies examining this polymorphism and memory performance in MS patients yielded conflicting results. However, the way in which this BDNF polymorphism affects brain function in MS patients has not been examined. In line with the "intermediate phenotype" approach, we assessed effects of the BDNF Val(66)Met polymorphism on brain activity during a spatial working memory task. We used functional magnetic resonance imaging (fMRI) to measure brain responses in a total of 61 subjects comprising 29 relapsing-remitting MS patients and 32 healthy controls. The fMRI results demonstrated association of the BDNF polymorphism with brain activity during working memory, with opposite effects in MS patients and controls. Healthy carriers of the Met(66) allele showed increased activation of the parieto-prefrontal network and altered disengagement of the ventro-medial prefrontal cortex and hippocampus in comparison with their respective Val(66) counterparts. Analysis within the group demonstrated that this working memory-related activation pattern was absent in MS patients. Our imaging genetic study demonstrates that the Val(66)Met polymorphism of the BDNF gene contributes to some of the individual variability in the functional response to a working memory challenge in healthy controls but it does not provide evidence for an MS-specific pattern of gene action.

Morphological correlates of MAO A VNTR polymorphism: new evidence from cortical thickness measurement.

A functional variant in the mono-amine oxidase A (MAO A) gene has been shown to impact neural function related to cognitive and affective processing and increase risk for conduct disorders. However, whether MAO A could be a candidate gene for structural variation in the human brain remains to be clarified. This study is the first to investigate the effect of this genotype on brain morphology by measuring cortical thickness. We genotyped 59 healthy male subjects (36 carrying the MAO A High-activity allele and 23 the MAO A Low-activity allele) who underwent structural MRI at 3T. Models of the grey-white and pial surfaces were generated for each individual's cortices, and the distance between these two surfaces was used to compute cortical thickness within a priori regions of interest of the orbitofrontal and cingulate cortices. Surface-based analysis of the cortical mantle showed that the MAO A genotype was associated with structural differences in the orbitofrontal cortex bilaterally, where the MAO A High-activity group showed the highest cortical thickness value and the MAO A Low-activity group the lowest. Otherwise, no significant difference was detected within the cingulate cortex. Thus, we confirm the hypothesis that the MAO A genotype has a specific impact on human brain morphology. In particular, thickness measurement of the orbitofrontal cortex provides new evidence about the biological impact of the MAO A genotype on neural systems relevant to the pathophysiology of behavioural disorders.

Síndrome del primer uso: presentación de un caso y revisión de la literatura / First-use syndrome: report a patient who present and literature of review

Las reacciones graves de hipersensibilidad que se observan durante el primer uso de los materiales de hemodiálisis son relativamente infrecuentes. No obstante, cuando éstas se presentan pueden comprometer la vida del enfermo. El motivo de nuestra comunicación es describir el caso de un paciente con el denominado "síndrome del primer uso" y analizar los mecanismos fisiopatológicos involucrados en este tipo de reacciones

Síndrome del primer uso: presentación de un caso y revisión de la literatura / First-use syndrome: report a patient who present and literature of review

Las reacciones graves de hipersensibilidad que se observan durante el primer uso de los materiales de hemodiálisis son relativamente infrecuentes. No obstante, cuando éstas se presentan pueden comprometer la vida del enfermo. El motivo de nuestra comunicación es describir el caso de un paciente con el denominado "síndrome del primer uso" y analizar los mecanismos fisiopatológicos involucrados en este tipo de reacciones

Síndrome del primer uso: presentación de un caso y revisión de la literatura / First-use syndrome: report a patient who present and literature of review

Las reacciones graves de hipersensibilidad que se observan durante el primer uso de los materiales de hemodiálisis son relativamente infrecuentes. No obstante, cuando éstas se presentan pueden comprometer la vida del enfermo. El motivo de nuestra comunicación es describir el caso de un paciente con el denominado "síndrome del primer uso" y analizar los mecanismos fisiopatológicos involucrados en este tipo de reacciones