Nuria Pujol

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.

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.

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.

Inferior frontal and insular cortical thinning is related to dysfunctional brain activation/deactivation during working memory task in schizophrenic patients

Although working memory is known to be impaired in schizophrenia the anatomical and functional relationships underlying this deficit remain to be elucidated. A combined imaging approach involving functional and structural magnetic resonance techniques was used, applying independent component analysis and surface-based morphometry to 14 patients with schizophrenia and 14 healthy controls. Neurocognitive functioning was assessed by a neuropsychological test battery that measured executive function. It was hypothesized that working memory dysfunctional connectivity in schizophrenia is related to underlying anatomical abnormalities. Patients with schizophrenia showed cortical thinning in the left inferior frontal gyrus and insula, which explained 57% of blood oxygenation level-dependent signal magnitude in functional magnetic resonance imaging in the central executive network (lateral prefrontal and parietal cortex) over-activation and default mode network (anterior and posterior cingulate) deactivation. No structure-function relationship emerged in the healthy control group. The study provides evidence to suggest that dysfunctional activation/deactivation patterns in schizophrenia may be explained in terms of underlying gray matter deficits.

Is memory impairment a rate limiter in cognitive behavioural therapy for chronic schizophrenia

129 17 Laumann AE, Derick AJ: Tattoos and body piercings in the United States: a national data set. J Am Acad Dermatol 2006; 55: 413–421. 18 Nathanson C, Paulhus DL, Williams KM: Personality and misconduct correlates of body modification and other cultural deviance markers. J Res Pers 2006; 40: 779–802. 19 Oliveira MD, Matos MA, Martins RM, Teles SA: Tattooing and body piercing as lifestyle indicator of risk behaviors in Brazilian adolescents. Eur J Epidemiol 2006; 21: 559–560. 20 Preti A, Pinna C, Nocco S, Mulliri E, Pilia S, Petretto DR, Masala C: Body of evidence: tattoos, body piercing, and eating disorder symptoms among adolescents. J Psychosom Res 2006; 61: 561–566. 21 Roberti J, Storch E, Bravata E: Sensation seeking, exposure to psychosocial stressors, and body modifications in a college population. Pers Individ Differ 2004; 37: 1167–1177. 22 Roberts TA, Auinger P, Ryan SA: Body piercing and high-risk behavior in adolescents. J Adolesc Health 2004; 34: 224–229. 23 Skegg K, Nada-Raja S, Paul C, Skegg DCG: Body piercing, personality, and sexual behavior. Arch Sex Behav 2007; 36: 47–54. 24 Wohlrab S, Stahl J, Rammsayer T, Kappler PM: Differences in personality characteristics between body-modified and non-modified individuals: associations with individual personality traits and their possible evolutionary implications. Eur J Pers 2007; 21: 931–951. 25 Mayers LB, Chiffriller SH: Body art (body piercing and tattooing) among undergraduate university students: ‘then and now’. J Adolesc Health 2008; 42: 201–203. 26 Meltzer DI: Complications of body piercing. Am Fam Physician 2005; 72: 2029–2034. 27 Chabrol H, Montovany A, Chouicha K, Callahan S, Mullet E: Frequency of borderline personality disorder in a sample of French high school students. Can J Psychiatry 2001; 46: 847–849.

Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan

BACKGROUND Hippocampal abnormalities have been demonstrated in schizophrenia. It is unclear whether these abnormalities worsen with age, and whether they affect cognition and function. AIMS To determine whether hippocampal abnormalities in chronic schizophrenia are associated with age, cognition and socio-occupational function. METHOD Using 3 T magnetic resonance imaging we scanned 100 persons aged 19-82 years: 51 were out-patients with stable schizophrenia at least 2 years after diagnosis and 49 were healthy volunteers matched for age and gender. Automated analysis was used to determine hippocampal volume and shape. RESULTS There were differential effects of age in the schizophrenia and control samples on total hippocampal volume (group × age interaction: F(1,95) = 6.57, P = 0.012), with steeper age-related reduction in the schizophrenia group. Three-dimensional shape analysis located the age-related deformations predominantly in the mid-body of the hippocampus. In the schizophrenia group similar patterns of morphometric abnormalities were correlated with impaired cognition and poorer socio-occupational function. CONCLUSIONS Hippocampal abnormalities are associated with age in people with chronic schizophrenia, with a steeper decline than in healthy individuals. These abnormalities are associated with cognitive and functional deficits, suggesting that hippocampal morphometry may be a biomarker for cognitive decline in older patients with schizophrenia.

The Integration of Cognitive Remediation Therapy into the Whole Psychosocial Rehabilitation Process: An Evidence-Based and Person-Centered Approach

Cognitive remediation therapies seem to ameliorate cognitive impairments in patients with schizophrenia. Interestingly, some improvement in daily functioning can also be expected as a result. However, to achieve these results it is necessary that cognitive remediation is carried out in the context of broader psychosocial rehabilitation involving the learning of other communication, social, and self-control skills. Unfortunately, little is known about how to integrate these different rehabilitation tools in broader rehabilitation programs. Based on both the neurocognitive behavioral approach and the action theory framework, a hierarchical flowchart is represented in this paper to integrate CRT with other evidence-based psychological therapies in outpatient settings. Finally, some evidence is provided in which cognitive abilities need to be targeted in remediation programs to improve functioning. In summary, to improve daily functioning, according to these studies, cognitive remediation needs to include the teaching of some cognitive strategies that target executive skills.

Cortical thickness in regions of frontal and temporal lobes is associated with responsiveness to cognitive remediation therapy in schizophrenia.

BACKGROUND Despite the evidence for the efficacy of cognitive remediation therapy (CRT) in patients with schizophrenia, comparatively little is known about the potential predictors of good treatment response. We tried to determine whether improvement in cognition following CRT is positively associated with baseline cortical thickness (CTh) or baseline clinical symptoms level or baseline cognitive performance. METHODS The current work uses data collected in a previous study (Penadés et al., 2013) in which a CRT program was investigated through a controlled randomized trial (NCT 01318850) with three groups: patients receiving cognitive treatment, patients receiving a different psychological intervention as an active and a healthy control groups (HC). CTh was estimated from the T1-weighted MRIs using the FreeSurfer software. RESULTS We found that CRT responsiveness was associated with baseline measures of cortical thickness in the frontal and temporal lobes. Positive changes in non-verbal memory were associated with greater initial thickness in cortical regions involving left superior frontal, left caudal middle frontal, left precuneus and paracentral; superior frontal, right caudal middle frontal gyrus and pars opercularis. Additionally, uncorrected data also suggested that verbal memory improvement could be associated with CTh in some areas of the frontal and temporal lobes. DISCUSSION Our findings are consistent with the hypothesis that greater CTh in specific brain areas could be associated with better response to CRT. Furthermore, brain areas associated with CRT responsiveness were located mainly in regions of frontal and temporal lobes.

F47. COGNITIVE REMEDIATION AND PHYSICAL EXERCISE IN MULTI-EPISODE SCHIZOPHRENIA: STUDY PROTOCOL FOR A RANDOMISED CONTROLLED TRIAL

Abstract Background Cognitive remediation (CR) and physical exercise have separately shown promising results in schizophrenia cognitive improvement, despite this, the impact on daily functionality is still limited. Physical exercise increases Brain Derived Neurotrophic Factor (BDNF) levels, promoting neuronal and cognitive plasticity, which can maximize the impact of CR. We are conducting a randomised controlled trial to determine the efficacy of an intensive program that combines CR and physical exercise on cognition and related outcomes for patients with schizophrenia. In addition, we investigate functional and structural brain effects of this intervention and its association to BDNF. Methods This study protocol describes a randomized controlled trial in which 74 patients are randomly assigned to either CR and physical exercise or CR and health promotion. The interventions are 12-week long and consist of three weekly sessions (90min of CR and 40min of either aerobic exercise or health promotion). To be included in the study, patients must be diagnosed with schizophrenia or schizoaffective disorder, aged 28–60 years, and do low physical activity, as measured by International Physical Activity Questionnaire, IPAQ. Exclusion Criteria for participation in the study are the presence of neurological or substance use disorders, IQ < 70 and somatic illnesses that contraindicate physical exercise. Healthy control participants (n=18) are screened for the presence of lifetime Axis I psychotic disorders and for the presence of a first-degree relative with schizophrenia. Primary outcome measures are cognitive performance, functional outcome, negative symptoms, BDNF levels and neuroimaging measures. Secondary outcome measures are quality of life and metabolic parameters. All measures are blindly assessed at baseline, at 3 months follow up and at 15 months follow up. This trial was approved by the Comité Ètic d’Investigació Clínica de l’Hospital del Mar (CEIC) 2015/6209/I Results This poster is a study protocol. We will correct data from now on. Discussion The results of this trial will provide valuable information about whether cognitive remediation efficacy for patients with schizophrenia can be enhanced by aerobic exercise-induced BDNF upregulation. TRIAL REGISTRATION The trial is registered at www.clinicaltrials.gov (NCT02864576)