Complexity Analysis of the Default Mode Network Using Resting-State fMRI in Down Syndrome: Relationships Highlighted by a Neuropsychological Assessment.

BACKGROUND: Studies on complexity indicators in the field of functional connectivity derived from resting-state fMRI (rs-fMRI) in Down syndrome (DS) samples and their possible relationship with cognitive functioning variables are rare. We analyze how some complexity indicators estimated in the subareas that constitute the default mode network (DMN) might be predictors of the neuropsychological outcomes evaluating Intelligence Quotient (IQ) and cognitive performance in persons with DS. METHODS: Twenty-two DS people were assessed with the Kaufman Brief Test of Intelligence (KBIT) and Frontal Assessment Battery (FAB) tests, and fMRI signals were recorded in a resting state over a six-minute period. In addition, 22 controls, matched by age and sex, were evaluated with the same rs-fMRI procedure. RESULTS: There was a significant difference in complexity indicators between groups: the control group showed less complexity than the DS group. Moreover, the DS group showed more variance in the complexity indicator distributions than the control group. In the DS group, significant and negative relationships were found between some of the complexity indicators in some of the DMN networks and the cognitive performance scores. CONCLUSIONS: The DS group is characterized by more complex DMN networks and exhibits an inverse relationship between complexity and cognitive performance based on the negative parameter estimates.

Structural equation models to estimate dynamic effective connectivity networks in resting fMRI. A comparison between individuals with Down syndrome and controls.

Emerging evidence suggests that an effective or functional connectivity network does not use a static process over time but incorporates dynamic connectivity that shows changes in neuronal activity patterns. Using structural equation models (SEMs), we estimated a dynamic component of the effective network through the effects (recursive and nonrecursive) between regions of interest (ROIs), taking into account the lag 1 effect. The aim of the paper was to find the best structural equation model (SEM) to represent dynamic effective connectivity in people with Down syndrome (DS) in comparison with healthy controls. Twenty-two people with DS were registered in a functional magnetic resonance imaging (fMRI) resting-state paradigm for a period of six minutes. In addition, 22 controls, matched by age and sex, were analyzed with the same statistical approach. In both groups, we found the best global model, which included 6 ROIs within the default mode network (DMN). Connectivity patterns appeared to be different in both groups, and networks in people with DS showed more complexity and had more significant effects than networks in control participants. However, both groups had synchronous and dynamic effects associated with ROIs 3 and 4 related to the upper parietal areas in both brain hemispheres as axes of association and functional integration. It is evident that the correct classification of these groups, especially in cognitive competence, is a good initial step to propose a biomarker in network complexity studies.

Resting-state default mode network connectivity in young individuals with Down syndrome.

BACKGROUND: Down syndrome (DS) is a chromosomal disorder that causes intellectual disability. Few studies have been conducted on functional connectivity using resting-state fMRI (functional magnetic resonance imaging) signals or more specifically, on the relevant structure and density of the default mode network (DMN). Although data on this issue have been reported in adult DS individuals (age: >45 years), the DMN properties in young DS individuals have not been studied. The aim of this study was to describe the density and structure of the DMN network from fMRI signals in young DS (age: <36 years). METHOD: A sample of 22 young people with DS between the ages of 16 and 35 (M = 25.5 and SD = 5.1) was recruited in various centers for people with intellectual disability (ID). In addition to sociodemographic data, a six-minute fMRI session was recorded with a 3. T Philips Ingenia scanner. A control group of 22 young people, matched by age and gender, was obtained from the Human Connectome Project (to compare the networks properties between groups). RESULTS: The values of the 48 ROIs that configured the DMN were obtained, and the connectivity graphs for each subject, the average connectivity graph for each group, the clustering and degree values for each ROI, and the average functional connectivity network were estimated. CONCLUSIONS: A higher density of overactivation was identified in DS group in the ventral, sensorimotor, and visual DMN networks, although within a framework of a wide variability of connectivity patterns in comparison with the control group network. These results extend our understanding of the functional connectivity networks pattern and intrasubject variability in DS.

The Effect of Second-Generation Antidepressant Treatment on the Memory of Patients With Major Depressive Disorder: A Meta-analysis Study With Structural Equation Models.

BACKGROUND: Major depressive disorder (MDD) has been linked to episodic memory deficits that may be improved after pharmacological treatment, but it is unclear whether there is a class of antidepressants that is more effective than others to ameliorate these deficits in MDD. In addition, the possible effects of clinical and sociodemographic variables on the improvement of MDD memory deficits after pharmacological treatment are currently unknown. Our aims are to study the possible neuropsychological effects of second-generation antidepressant classes on the episodic memory of MDD patients and to study the potential effects of clinical and demographic variables as moderators of the effects of antidepressants on the memory of depressed patients through a meta-analysis approach. PROCEDURES: Nine articles were included in our study. A structural equation model meta-analysis was performed. RESULTS: Our results suggest that selective serotonin reuptake inhibitors and serotonine-noradrenaline reuptake inhibitors would bring about a substantial improvement in the memory of depressed patients, whereas other antidepressant classes would cause rather modest effects. Our results also suggest that clinical and demographic variables play a very important role as mediators of memory improvement after MDD treatment. Thus, a relatively low level of symptom severity, a high degree of clinical improvement, a younger age, and more years of education were positively related to memory improvement after MDD treatment. CONCLUSIONS: Although antidepressant class is an important variable linked to memory improvement in MDD, overall, the degree of memory amelioration in depression is very closely related to clinical and demographic variables of patients with depression.

Analysis of Pseudohomophone Orthographic Errors through Functional Magnetic Resonance Imaging (fMRI).

The study of orthographic errors in a transparent language such as Spanish is an important topic in relation to writing acquisition because in Spanish it is common to write pseudohomophones as valid words. The main objective of the present study was to explore the possible differences in activation patterns in brain areas while processing pseudohomophone orthographic errors between participants with high (High Spelling Skills (HSS)) and low (Low Spelling Skills (LSS)) spelling orthographic abilities. We hypothesize that (a) the detection of orthographic errors will activate bilateral inferior frontal gyri, and that (b) this effect will be greater in the HSS group. Two groups of 12 Mexican participants, each matched by age, were formed based on their results in a group of spelling-related ad hoc tests: HSS and LSS groups. During the fMRI session, two experimental tasks were applied involving correct and pseudohomophone substitution of Spanish words. First, a spelling recognition task and second a letter searching task. The LSS group showed, as expected, a lower number of correct responses (F(1, 21) = 52.72, p <.001, η2 = .715) and higher reaction times compared to the HSS group for the spelling task (F(1, 21) = 60.03, p <.001, η2 = .741). However, this pattern was reversed when the participants were asked to decide on the presence of a vowel in the words, regardless of spelling. The fMRI data showed an engagement of the right inferior frontal gyrus in HSS group during the spelling task. However, temporal, frontal, and subcortical brain regions of the LSS group were activated during the same task.

Changes in brain connectivity related to the treatment of depression measured through fMRI: a systematic review.

Depression is a mental illness that presents alterations in brain connectivity in the Default Mode Network (DMN), the Affective Network (AN) and other cortical-limbic networks, and the Cognitive Control Network (CCN), among others. In recent years the interest in the possible effect of the different antidepressant treatments on functional connectivity has increased substantially. The goal of this paper is to conduct a systematic review of the studies on the relationship between the treatment of depression and brain connectivity. Nineteen studies were found in a systematic review on this topic. In all of them, there was improvement of the clinical symptoms after antidepressant treatment. In 18 out of the 19 studies, clinical improvement was associated to changes in brain connectivity. It seems that both DMN and the connectivity between cortical and limbic structures consistently changes after antidepressant treatment. However, the current evidence does not allow us to assure that the treatment of depression leads to changes in the CCN. In this regard, some papers report a positive correlation between changes in brain connectivity and improvement of depressive symptomatology, particularly when they measure cortical-limbic connectivity, whereas the changes in DMN do not significantly correlate with clinical improvement. Finally, some papers suggest that changes in connectivity after antidepressant treatment might be partly related to the mechanisms of action of the treatment administered. This effect has been observed in two studies with stimulation treatment (one with rTMS and one with ECT), and in two papers that administered three different pharmacological treatments. Our review allows us to make a series of recommendations that might guide future researchers exploring the effect of anti-depression treatments on brain connectivity.

Type 1 Diabetes Modifies Brain Activation in Young Patients While Performing Visuospatial Working Memory Tasks.

In recent years, increasing attention has been paid to the effects of Type 1 Diabetes (T1D) on cognitive functions. T1D onset usually occurs during childhood, so it is possible that the brain could be affected during neurodevelopment. We selected young patients of normal intelligence with T1D onset during neurodevelopment, no complications from diabetes, and adequate glycemic control. The purpose of this study was to compare the neural BOLD activation pattern in a group of patients with T1D versus healthy control subjects while performing a visuospatial working memory task. Sixteen patients and 16 matched healthy control subjects participated. There was no significant statistical difference in behavioral performance between the groups, but, in accordance with our hypothesis, results showed distinct brain activation patterns. Control subjects presented the expected activations related to the task, whereas the patients had greater activation in the prefrontal inferior cortex, basal ganglia, posterior cerebellum, and substantia nigra. These different patterns could be due to compensation mechanisms that allow them to maintain a behavioral performance similar to that of control subjects.

Factorial structural analysis of the Spanish version of WHOQOL-BREF: an exploratory structural equation model study.

PURPOSE: The purpose of this study was to analyze the factor structure of the abbreviated Spanish version of the World Health Organization Quality of Life (WHOQOL-BREF; WHOQOL Group in Psychol Med 28(3): 551-558, 1998b) questionnaire in a sample of individuals from several Spanish-speaking countries. METHOD: The data were based on a sample of 1,972 undergraduates from nine Spanish-speaking countries. Within the framework of a somewhat wider research protocol, they were administered the WHOQOL-BREF. RESULTS: The data were initially analyzed using a confirmatory factor analysis, which yielded a poor fit to the four-factor theoretical model. Based on these results, the best solution was estimated assuming structural invariance across countries. The data showed a four-factor structure that differed slightly from the model proposed. This four-factor model was subsequently analyzed using exploratory structural equation modeling (ESEM; Asparouhov and Muthén in Struct Equ Model 16(3): 397-438, 2009) to obtain the invariant structure across countries and an estimation of the relation between the four latent factors. The results obtained allowed us to establish that the factor structure of WHOQOL-BREF maintains the four-factor solution hypothesized for a Spanish-speaking population, although the solution has a different and more complex configuration than the original one with a clear tendency toward non-orthogonality of the latent factors. CONCLUSIONS: As has been suggested by some studies on the application of ESEM, it is reasonable to think that the ESEM approximation is a useful approach for conducting the factor analysis of instruments measuring complex psychological phenomena.

Prediction of the time-course pattern of remission in depression by using clinical, neuropsychological, and genetic variables.

BACKGROUND: The prediction of remission in pharmacologically-treated MDD patients has been scarcely studied. The goal of our work is to study the possible effect of clinical variables, neuropsychological performance, and the 5HTTLPR, the rs25531 of the SLC6A4 gene, and the val108/58Met of the COMT gene polymorphisms on the prediction of the speed of remission in MDD patients. METHODS: Seventy-two depressed patients were genotyped according to the aforementioned polymorphisms and were clinically and neuropsychologically assessed before a 12-week fluoxetine treatment. RESULTS: From this original sample 51 patients were considered as remitters at the end of week 12. Thirteen out of those showed a rapid response pattern, 24 showed an oscillating response pattern, and 14 showed a slow response pattern. The following variable combination is capable of showing a statistically significant relationship with the pattern of remission of patients with MDD: initial Hamilton score, age at first depressive episode, AG and GG alleles of the val108/58Met COMT polymorphism, Stroop PC, and SWM Strategy. LIMITATIONS: We have a slightly small sample size, which came to prominence during the data analysis since we were working with 3 subgroups. In this study, the placebo effect has not been controlled. DISCUSSION: Our data suggest that the patients with MDD who remit after a 12-week treatment with fluoxetine show one of the following time-course patterns: a rapid symptomatic improvement, or a slow or oscillating pattern of remission. A combination of clinical, neuropsychological, and genetic variables allows us to predict these response patterns.

Data mining and mall users profile / Minería de datos y perfiles de usuarios en los centros comerciales

Marketing scholars have suggested a need for more empirical research on consumer response to malls, in order to have a better understanding of the variables that explain the behavior of the consumers. The segmentation methodology CHAID (Chi-square automatic interaction detection) was used in order to identify the profiles of consumers with regard to their activities at malls, on the basis of socio-demographic variables and behavioral variables (how and with whom they go to the malls). A sample of 790 subjects answered an online questionnaire. The CHAID analysis of the results was used to identify the profiles of consumers with regard to their activities at malls. In the set of variables analyzed the transport used in order to go shopping and the frequency of visits to centers are the main predictors of behavior in malls. The results provide guidelines for the development of effective strategies to attract consumers to malls and retain them there.

Recientes estudios del ámbito del marketing ponen de manifiesto la necesidad de incrementar la investigación empírica sobre las actividades desarrolladas por los consumidores en los centros comerciales, con el objeto de obtener una mejor comprensión de las variables que explican el comportamiento de estos. La metodología de segmentación CHAID (chi-square automatic interaction detection) se ha utilizado con el objeto de identificar los perfiles de los consumidores en relación con las actividades que desarrollan en los centros comerciales, con base en variables sociodemográficas y de comportamiento (cómo y con quién van a los centros comerciales). Una muestra de 790 sujetos contestaron un cuestionario on-line. El análisis CHAID de los resultados permite identificar los perfiles de los consumidores con respecto a sus actividades en dichos centros. Del conjunto de variables analizadas, el transporte utilizado y la frecuencia de las visitas son los principales pre-dictores de la conducta en los centros comerciales. Los resultados obtenidos proporcionan directrices para el desarrollo de estrategias que faciliten la atracción y fidelización de los consumidores a los centros comerciales.

Child homicide by parents in Chile: a gender-based study and analysis of post-filicide attempted suicide.

INTRODUCTION: The victimization of children has attracted considerable attention over the years. Some authors conceptualize child murder as an intra-familial phenomenon. Over the last 40 years, extensive literature has suggested that there are differences between neonaticide and infanticide, and differential characteristics between filicidal men and women. Although suicide attempts after these crimes have not been as widely studied, there are some distinctive features compared to non-suicidal filicide. STUDY PURPOSE: The main objective of the current study was to analyze the phenomenon of filicide in the Chilean population. METHODS: The sample consisted of 98 cases of filicide committed in Chile between 1998 and 2009 that were evaluated in the Area of Mental Health of the Legal Medical Service (LMS) of Santiago, Chile. Forensic reports including psychiatric and psychological evaluations of the perpetrators were reviewed and variables extracted. Bivariate analyses were used to determine differences between male and female filicide perpetrators and the possible differences between the presence and absence of a suicide attempt following filicide on selected demographic, situational, and psychopathological variables. Then, logistic regression was used to identify which of the variables may be relevant (significant predictors) to the presence of a suicide attempt following the commission of an infanticide. RESULTS AND DISCUSSION: Analysis of the data revealed differences between filicidal men and women with regard to demographic characteristics, but the differences in psychopathological factors and variables that were related to the crimes were minor. A comparative analysis of the filicide perpetrators based on post-crime suicide attempts did not find significant differences between groups. In addition, a predictive analysis of suicidal behavior concludes that individual variables (such as the level of education of the person committing infanticide and the method used for the homicide) are not sufficient to explain the entire phenomenon by themselves.

Prediction of remission of depression with clinical variables, neuropsychological performance, and serotonergic/dopaminergic gene polymorphisms.

OBJECTIVE: The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms on the prediction of depression remission after 12 weeks' treatment with fluoxetine. These variables have been studied as potential predictors of depression remission, but they present poor prognostic sensitivity and specificity by themselves. METHODS: Seventy-two depressed patients were genotyped according to the aforementioned polymorphisms and were clinically and neuropsychologically assessed before a 12-week fluxetine treatment. RESULTS: Only the La allele of rs25531 polymorphism and the GG and AA forms of the val 108/158 Met polymorphism predict major depressive disorder remission after 12 weeks' treatment with fluoxetine. None of the clinical and neuropsychological variables studied predicted remission. CONCLUSIONS: Our results suggest that clinical and neuropsychological variables can initially predict early response to fluoxetine and mask the predictive role of genetic variables; but in remission, where clinical and neuropsychological symptoms associated with depression tend to disappear thanks to the treatment administered, the polymorphisms studied are the only variables in our model capable of predicting remission. However, placebo effects that are difficult to control require cautious interpretation of the results.

Classical and Bayesian estimation in the logistic regression model applied to diagnosis of child attention deficit hyperactivity disorder.

The limitations inherent to classical estimation of the logistic regression models are known. The Bayesian approach in statistical analysis is an alternative to be considered, given that it makes it possible to introduce prior information about the phenomenon under study. The aim of the present work is to analyze binary and multinomial logistic regression simple models estimated by means of a Bayesian approach in comparison to classical estimation. To that effect, Child Attention Deficit Hyperactivity Disorder (ADHD) clinical data were analyzed. The sample included 286 participants of 6-12 years (78% boys, 22% girls) with ADHD positive diagnosis in 86.7% of the cases. The results show a reduction of standard errors associated to the coefficients obtained from the Bayesian analysis, thus bringing a greater stability to the coefficients. Complex models where parameter estimation may be easily compromised could benefit from this advantage.

The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. METHODS: 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. RESULTS: Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. LIMITATIONS: The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. CONCLUSIONS: Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment.

Major Depressive Disorder in recovery and neuropsychological functioning: effects of selective serotonin reuptake inhibitor and dual inhibitor depression treatments on residual cognitive deficits in patients with Major Depressive Disorder in recovery.

INTRODUCTION: Cognitive disturbances in Major Depressive Disorder (MDD) could persist beyond the symptomatic phase of the illness. However, the works addressing this topic did not usually account for the possible impact of medication on the cognitive functions of depressed patients. The present study aims to investigate whether MDD patients in remission treated with selective serotonin reuptake inhibitors (SSRI) or dual serotonergic-noradrenergic reuptake inhibitors (SNRI) show cognitive deficits, to study whether the same patients suffer neuropsychological disturbances when they are unmedicated and in recovery phase, and if the previous pharmacological treatment used to achieve the remission of MDD clinical symptoms had any effect in the profile of these patients' cognitive performance in the recovery phase. METHODS: Thirty-six subjects with MDD treated with escitalopram and 37 depressed patients with duloxetine were compared both in remission phase and 24 weeks later, when they were unmedicated and in recovery phase. They were also compared, in both moments, to 37 healthy subjects. RESULTS: The control subjects showed a broader better cognitive performance than MDD patients in both measurement moments, but several cognitive functions improved over time. Also, the patients treated with SNRI performed better in memory tests than the SNRI-treated patients in remission phase, and in recovery phase. LIMITATIONS: Our sample size is somewhat small, and we followed our patients only for 6months after treatment. CONCLUSIONS: Cognitive functions improve over time in patients with MDD beyond the remission phase, and the antidepressant treatment class used in acute depressive phase could influence his/her memory improvement.

Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on memory and mental processing speed in patients with major depressive disorder.

Patients with major depressive disorder (MDD) usually suffer from altered cognitive functions of episodic memory, working memory, mental processing speed and motor response. Diverse studies suggest that different antidepressant agents may improve cognitive functions in patients with MDD. The aim of this work is to study the effects of serotonergic reuptake inhibitors (SSRIs) and serotonergic-noradrenergic reuptake inhibitors (SNRIs) treatments to improve the performance on memory tasks and mental processing speed in MDD. Seventy-three subjects meeting criteria for major depressive disorder were assessed with the Hamilton depression rating scale and a neuropsychological battery. The subjects were medicated with escitalopram (n=36) or duloxetine (n=37) for 24 weeks. At the end of the trial, the subjects were assessed again with the same neuropsychological battery used prior to the treatment. Both treatments improved importantly the episodic memory and to a lesser extent, working memory, mental processing speed and motor performance. Our results suggest that cognition is partially independent from improvement in clinical symptoms. Both groups achieved remission rates in the HAM-D-17 after 24 weeks of treatment, but SNRI was superior to SSRI at improving episodic and working memory. Our work indicates that the superiority of SNRI over the SSRI at episodic memory improvement is clinically relevant.

Cognitive predictors of treatment response to bupropion and cognitive effects of bupropion in patients with major depressive disorder.

Cognitive effects of antidepressants and cognitive predictors of antidepressant treatment response are recent focuses of interest in the neuropsychology of depression. We studied the cognitive predictors of treatment response to bupropion and its neuropsychological effects in patients with major depressive disorder. Twenty subjects meeting the DSM-IV criteria for major depressive disorder were assessed with the Hamilton Depression Rating Scale and a neuropsychological battery. Subjects were medicated with 150 mg/day of bupropion sustained release for 8 weeks. At the end of the trial, 12 subjects were classified as responders to treatment and 8 were non-responders. Our findings suggest that low pretreatment measures of visual memory and low levels of mental processing speed are predictive of good response to bupropion. The cognitive effects of bupropion after the treatment showed that patients improved in visual memory measures and in mental processing speed. Our results suggest that cognitive predictors of treatment response to bupropion and cognitive effects of bupropion in patients with major depressive disorder could be closely related. These findings need to be replicated due to the exploratory nature of the present work.