Rafael Penadés

Executive Function in Patients with Remitted Bipolar Disorder and Schizophrenia and Its Relationship with Functional Outcome

Background: Recent studies have reported that differences in cognitive performance between schizophrenic and bipolar patients seem to be smaller than expected. Patients with schizophrenia have consistently shown frontal executive dysfunctions, but studies regarding executive abilities in bipolar patients are scarce and discrepant. As executive function has been associated with psychosocial functioning in schizophrenia, we wanted to investigate if such a relationship is also present in bipolar disorder and the differences between the two groups. Methods: Executive function was assessed in 49 euthymic (at least 6 months in remission, Hamilton Depression Rating Scale ≤8 and Young Mania Rating Scale ≤6) bipolar and in 49 schizophrenic, residual-type (with at least 1 year without acute exacerbation and predominant negative symptomatology) patients, by the Wisconsin Card Sorting Test (WCST), FAS Test (COWAT) and Trail Making Test. Baseline clinical and psychosocial variables were controlled and psychopathology evaluated by means of the Positive and Negative Syndrome Scale (PANSS). Results: The two groups showed a similar pattern of cognitive deficits in tests of executive function, except for the number of categories achieved in the WCST, which was significantly lower in the schizophrenic group (F = 7.26; p = 0.009). Functional outcome was predicted by the negative syndrome (PANSSN) and perseverative errors (WCST) in schizophrenic patients, and general psychopathology (PANSSG) was the best predictor of functional outcome in the bipolar group. Conclusion: Executive function was a good predictor of functional outcome in the schizophrenic group, whereas clinical variables were more predictive of the bipolar one. Patterns of cognitive disturbances in tasks of executive function are similar in both groups but quantitatively more marked in schizophrenia.

Executive function and nonverbal memory in obsessive-compulsive disorder

It has been suggested that memory impairments found in obsessive-compulsive disorder (OCD) are mediated by organizational problems in encoding that are caused by primary executive dysfunction. Performance on different nonverbal memory and executive skills was tested in 68 subjects (35 non-depressed OCD sufferers and 33 healthy controls). Multiple regression models were performed to analyze the role of different cognitive variables, especially organizational encoding strategies in nonverbal memory. OCD patients performed significantly worse than controls in immediate nonverbal memory [Rey-Osterrieth Complex Figure Test (RCFT)] and on all the executive functions such as interference control (Stroop test), mental set shifting (Trail-Making Test), and organizational strategies (copy organization). As no differences were found in the memory of faces, where organizational strategies are minimal, it is possible to speculate that immediate nonverbal memory problems in OCD appear only when organizational strategies mediate the recalling process. Thus, memory deficits appear to have less to do with memory, per se, and more to do with the degree of organization necessary to effectively complete the task. Statistical analyses of mediation models showed the highest explanatory power for the organizational approach and demonstrated the mediation effect of organizational strategies in nonverbal impairment.

Cognitive Remediation Therapy for outpatients with chronic schizophrenia: A controlled and randomized study

Cognitive Remediation Therapy (CRT) is a novel rehabilitation approach designed to improve neurocognitive abilities such as attention, memory and executive functioning. The aim of the present study is to evaluate the effect of CRT on neurocognition, and secondarily on symptomatology and psychosocial functioning. Cognitive Behavioural Therapy (CBT) was used as a control condition because it aims to improve emotional problems and positive symptoms, focusing on modification of maladaptive beliefs and schemas, but neurocognition is not targeted. A total of 40 chronic patients with DSM-IV schizophrenia disorder were randomly assigned for 4 months to one of two treatment groups: CRT or CBT. Repeated assessments were conducted before and after the treatments and at the end of a follow-up period of 6 months. Additionally, a method to establish reliable change was calculated from a separate sample of 20 schizophrenic patients who were under standard medication without any kind of psychological treatment. Results showed that CRT produced an overall improvement on neurocognition (Mean effect size=0.5), particularly in verbal and nonverbal memory, and executive function. CBT showed the expected treatment effect on general psychopathology (anxiety and depression) but produced only a slight non-specific improvement in neurocognition (Working Memory). Furthermore, patients receiving CRT showed improvement in social functioning, demonstrating that cognitive improvements are clinically meaningful. These gains were still present at the 6 month follow-up.

Brain Effects of Cognitive Remediation Therapy in Schizophrenia: A Structural and Functional Neuroimaging Study

BACKGROUND Cognitive remediation therapy positively affects cognition and daily functioning in patients with schizophrenia. However, studies on the underlying neurobiological mechanisms of this treatment are scarce. The aim of the current study was to investigate functional and structural connectivity brain changes in schizophrenia patients after cognitive remediation therapy using a whole-brain approach that combined functional magnetic resonance imaging and diffusion tensor imaging. METHODS A randomized controlled trial with 30 schizophrenia outpatients and 15 healthy volunteers. A strategy-learning-based treatment was used as a cognitive remediation therapy. A social skills training that provides useful information about illness management was used as an active control. We investigated changes in the pattern of functional connectivity assessed during an n-back task by tensorial independent component analysis as implemented in the multivariate exploratory linear decomposition into independent components and in the fractional anisotropy index of white matter integrity using tract-based spatial statistics. RESULTS Brain networks activation pattern significantly changed in patients exposed to the cognitive treatment in the sense of normalizing toward the patterns observed in healthy control subjects. Additionally, in white matter, they showed an increase in fractional anisotropy index in the anterior part of the genu of the corpus callosum. Cognitive improvement, functional, and also structural changes showed statistically significant correlations. CONCLUSIONS Improvement in brain functioning detected after cognitive remediation therapy in schizophrenia patients might be based on an increase of the interhemispheric information transfer between the bilateral prefrontal cortexes via the corpus callosum.

Cognitive mechanisms, psychosocial functioning, and neurocognitive rehabilitation in schizophrenia

The aim of the present study is to test Brenners model of cognitive functioning in schizophrenia. It is assumed that elementary cognitive disorders (attention and encoding) and complex cognitive disorders (recall, concept formation) reinforce each other. Cognitive disorders are supposed to cause detrimental effects on functional outcome. We used cognitive rehabilitation as a strategy to induce cognitive changes in 27 patients assigned to treatment groups following the cognitive modules of the Integrated Psychological Treatment (IPT). Ten schizophrenic patients without cognitive impairments worked as a control group. With only one minor conceptual change (replacing concept formation with executive function, a more comprehensive construct), we found that our data fitted with Brenners model. A relationship has been found between neuropsychological improvements and higher levels of autonomy and social functioning. These findings have important implications not only for cognitive assessment but also for selecting targets in cognitive rehabilitation.

Executive function needs to be targeted to improve social functioning with Cognitive Remediation Therapy (CRT) in schizophrenia.

While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established, the relationship between cognitive and functional change in the context of treatments is far from clear. The current paper tries to identify which cognitive changes lead to improvements in daily functioning among persons with chronic schizophrenia who had current negative symptoms and evidenced neuropsychological impairments. In a previous work, Cognitive Remediation Therapy (CRT) was compared with a control therapy, involving similar length of therapist contact but different targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and functioning [Schizophrenia Research, 87 (2006) 323-331]. Subsequently, analyses of covariance (ANCOVA) were conducted with baseline and cognitive change scores as covariates to test whether cognitive change predicted change in functioning. Additionally, statistical tests to establish the mediation path with significant variables were performed. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present.

Neuropsychological Performance in Children and Adolescents with Obsessive-Compulsive Disorder and Influence of Clinical Variables

BACKGROUND Several studies have found impairment in visual memory and visual organization in adults with obsessive-compulsive disorder (OCD), but little is known about the neuropsychological profile of children and adolescents with this disorder. The influence of clinical variables such as age, severity of obsessive-compulsive symptomatology, depressive symptomatology, and pharmacological treatment on cognitive performance in these patients has not been thoroughly studied. METHODS A neuropsychological battery designed for this study was administered to 35 patients with DSM-IV-TR diagnosis of OCD without psychiatric comorbidity aged between 7 and 18 years and 35 gender- and age-matched healthy subjects. RESULTS Children and adolescents with OCD performed significantly worse on verbal and visual memory and velocity. When depressive symptomatology was controlled, impairment in visual memory, visual organization, and velocity again was found, but impairment in verbal memory was not. Neuropsychological impairment was not related to age, obsessive-compulsive severity, and pharmacological treatment. CONCLUSIONS Children and adolescents with OCD without psychiatric comorbidity with acute illness show impairment in visual memory, visual organization, and velocity, similar to adults. The influence of depressive symptomatology is important in cognitive performance. No relation was found between neuropsychology and age, severity of obsessive-compulsive symptomatology, or pharmacological treatment in this study.

Continuation/Maintenance Treatment with Nortriptyline Versus Combined Nortriptyline and ECT in Late-Life Psychotic Depression : A Two-Year Randomized Study

OBJECTIVE The identification of effective continuation and maintenance strategies for elderly patients with psychotic depression is a critical issue that has not been fully explored. The aim of this study was to assess the tolerability and efficacy of continuation/maintenance electroconvulsive therapy (ECT) in elderly patients with psychotic depression after acute ECT remission. METHODS The authors used a longitudinal, randomized, single-blind design to compare by survival analysis the 2-year outcome of two subgroups of elderly patients with psychotic unipolar depression who were ECT (plus nortriptyline) remitters. One group was treated with a continuation/maintenance nortriptyline regimen (N = 17) and the other with combined continuation/maintenance ECT plus nortriptyline (N = 16). RESULTS Over 2 years of treatment in elderly, psychotic, unipolar depressed ECT (plus nortriptyline) remitters, the mean survival time was significantly longer in the combined ECT plus nortriptyline subgroup than in the nortriptyline subgroup. No differences were observed between treatments with regard to tolerability. CONCLUSIONS This study supports the judicious use of combined continuation/maintenance ECT and antidepressant treatment in elderly patients with psychotic unipolar depression who are ECT remitters.

Could the hypofrontality pattern in schizophrenia be modified through neuropsychological rehabilitation

Objective: The effects of neuropsychological treatment on cognitive hypofrontality were examined in schizophrenic patients through the score activation.

Verbal memory, negative symptomatology and prediction of psychosocial functioning in schizophrenia

Negative symptomatology and neurocognitive variables have been considered good predictors of functional outcome in schizophrenia. Specifically, secondary verbal memory has been proposed to be one of the main predictors of psychosocial functioning. In this study, negative symptoms and memory performance were analyzed for associations with psychosocial function. Linear regression methods were used to analyze the value of verbal memory and negative symptomatology as predictors of everyday life skills in a sample of 29 DSM-IV schizophrenia outpatients with predominant negative symptoms. We also took into account the role of gender in the analyses. Secondary verbal memory was found to explain 40% of the variance in psychosocial functioning, independently of gender, whereas the negative symptoms predicted 26%. When both variables were combined, the explained variance was about 49%. These results support the hypothesis that cognitive variables are better predictors than symptomatology. Finally, secondary verbal memory is a good predictor of psychosocial functioning in chronic schizophrenia with predominant negative symptomatology.