Esteve Gudayol-Ferré

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.

Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on attention and executive functions in patients with major depressive disorder

Several reports suggest that antidepressants may improve cognitive functioning in patients with major depressive disorder (MDD). The present work aims to study the effects of selective serotonin reuptake inhibitors (SSRIs) and serotonergic-noradrenergic reuptake inhibitors (SNRIs) treatments on the performance of working memory, attention and executive functions in patients with MDD. A total of 73 subjects meeting the Diagnostic and Statistical Manual of Mental Disorders version IV (DSM-IV) criteria for MDD, and 37 control subjects 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 tests. The depressed subjects showed alterations in attention and cognitive functions when compared to the control group. The administration of both treatments improved working memory, as well as attention and all the executive functions, but the cognitive functions of depressed patients do not improve enough to reach the levels of performance of the control subjects. Our results suggest that both SSRI and SNRI treatments presented the same efficacy in improving attention and the remaining executive functions.

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.

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.

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.

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.

Semantic memory as assessed by the Pyramids and Palm Trees Test: The impact of sociodemographic factors in a Spanish-speaking population

The objective of this study is to obtain preliminary normative data on the performance the Pyramids and Palm Trees Test (PPT) for a Spanish-speaking population. The effects of age, gender, and educational level on the PPT test were also analyzed. A total of 234 healthy participants, with a broad range of age (18-80 years) and education (1-20 years) performed the three-picture version of the PPT. The mean performance was 51.1 out of 52 possible points (SD=1.3). PPT performance did not vary with age or gender. However, subjects with less than 6 years of formal education scored significantly lower than those with more than 6 years of education though this effect was confounded with age because the group with lower education was also older. Given the ceiling effects of the PPT, further investigation is needed to determine if the visual PPT is sensitive to mild semantic memory impairment.

Comorbidity of anxiety disorders in major depressive disorder: A clinical trial to evaluate neuropsychological deficit

Background and objectives: Various clinical aspects of Major Depressive Disorder (MDD) are related to the neuropsychological impairments characteristic of this illness. The aim of this study was to determine the relation between certain clinical variables of MDD – in particular the presence of comorbid anxiety disorders – and the neuropsychological performance of patients with MDD selected for a clinical trial. Methods: Using cluster analyses, we generated two groups of patients: one group with Major Depressive Disorder and a Comorbid Anxiety Disorder (MDDAD), and the other 6 IXCHEL HERRERA-GUZMÁN ET AL.

Effect of verbal task complexity in a working memory paradigm in patients with type 1 diabetes. A fMRI study

Type 1 diabetes (T1D) is commonly diagnosed in childhood and adolescence, and the developing brain has to cope with its deleterious effects. Although brain adaptation to the disease may not result in evident cognitive dysfunction, the effects of T1D on neurodevelopment could alter the pattern of BOLD fMRI activation. The aim of this study was to explore the neural BOLD activation pattern in patients with T1D versus that of healthy matched controls while performing two visuospatial working memory tasks, which included a pair of assignments administered through a block design. In the first task (condition A), the subjects were shown a trial sequence of 3 or 4 white squares positioned pseudorandomly around a fixation point on a black background. After a fixed delay, a second corresponding sequence of 3 or 4 red squares was shown that either resembled (direct, 50%) or differed from (50%) the previous stimulation order. The subjects were required to press one button if the two spatial sequences were identical or a second button if they were not. In condition B, the participants had to determine whether the second sequence of red squares appeared in inverse order (inverse, 50%) or not (50%) and respond by pressing a button. If the latter sequence followed an order distinct from the inverse sequence, the subjects were instructed to press a different button. Sixteen patients with normal IQ and without diabetes complications and 16 healthy control subjects participated in the study. In the behavioral analysis, there were no significant differences between the groups in the pure visuo-spatial task, but the patients with diabetes exhibited poorer performance in the task with verbal stimuli (p < .001). However, fMRI analyses revealed that the patients with T1D showed significantly increased activation in the prefrontal inferior cortex, subcortical regions and the cerebellum (in general p < .001). These different activation patterns could be due to adaptive compensation mechanisms that are devoted to improving efficiency while solving more complex cognitive tasks.

Longitudinal Estimation of the Clinically Significant Change in the Treatment of Major Depression Disorder

Background: Although major depressive disorder is usually treated with antidepressants, only 50–70% of the patients respond to this treatment. This study applied Jacobson and Truax’s (1991) methodology (reliable change index, RCI) to a sample of depressive patients being treated with one of two antidepressants to evaluate their functioning and the effect of certain variables such as severity and age. Method: Seventy-three depressive patients medicated with Escitalopram (n = 37) or Duloxetine (n = 36) were assessed using the Hamilton depression rating scale over a 24-week period. Results: They indicate that the RCI stabilizes in an absolute way starting in week 16, and it is not until week 24 that all of the patients become part of the functional population. We found limited statistical significance with respect to the RCI and the external variables. Conclusion: Our study suggests the need to accompany the traditional statistical methodology with some other clinical estimation systems capable of going beyond a simple subtraction between pre and posttreatment values. Hence, it is concluded that RCI estimations could be stronger and more stable than the classical statistical techniques.