[Show abstract][Hide abstract] ABSTRACT: Background
Most studies on the factors involved in the functional outcome of patients with bipolar disorder have identified subsyndromal depressive symptoms and cognitive impairment as key players. However, most studies are cross-sectional and very few have analyzed the interaction between cognition and subclinical depression. The present study aimed to identify the role of cognition, and particularly verbal memory, and subthreshold depressive symptoms in the functional outcome of patients with bipolar I and II disorder at one year follow-up.
A confirmatory analysis was performed using the path analysis. A total of 111 euthymic patients were included to test the role of verbal memory as a mediator in the relationship of subthreshold depressive symptoms and functional outcome at one year follow-up. Measures of verbal memory, subthreshold depressive symptoms and functioning (at baseline, at 6 months and at one year follow-up) were gathered through the use of a neuropsychological assessment and validated clinical scales.
The hypothesized mediation model displayed a good fit to data (Chi=0.393, df=2, p=0.625; RMSEA<0.001 with CI: 0.001–0.125 and CFI=1.00). Functional outcome at one year follow-up was predicted by the functional outcome at baseline, which in turn, was related to subthreshold depressive symptoms at baseline and to the verbal composite memory scores as a mediator variable.
The results of this study prospectively confirm previous findings on the disabling role of subthreshold depressive symptoms and verbal memory impairment on psychosocial functioning. However, these results come from a sample with moderate to severe functional impairment; hence, as a limitation, this may hinder the generalization of these results.
Journal of Affective Disorders 01/2014; 160:50–54. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, Functional Remediation (FR) has proven to be effective in improving the functional outcome of euthymic bipolar patients. The aim of this study was to test the efficacy of the FR program in a subsample of euthymic bipolar II patients (BPII). A post-hoc analyses were undertaken using data of 53 BPII outpatients who had participated in a multicenter, rater-blind, randomized, controlled trial exploring the efficacy of FR (n=17) as compared with a Psychoeducation group (PSY) (n=19) and a treatment as usual control group (TAU n=17). The primary outcome variable was the functional improvement defined as the mean change in the Functioning Assessment Short Test (FAST) from baseline to endpoint after the intervention. Regarding the treatment effect, data reveal a significant functional improvement from baseline to endpoint, suggestive for an interaction between program pertinence and time (pre-post). Nevertheless, Tukey's post-hoc test only revealed a trend in favour of a better outcome for FR when compared to the other two groups. We also found an interaction between program pertinence and time when analysing the subdepressive symptoms, with BPII patients in FR showing a significant reduction when compared to the PSY group. Our results suggest that the FR appears to be effective in improving the overall functional outcome in BPII, as well as in reducing subdepressive symptoms.
[Show abstract][Hide abstract] ABSTRACT: Processing of emotions has been an enduring topic of interest in neuroimaging research, but studies have mostly used facial emotional stimuli. The aim of this study was to determine neural networks involved in emotion processing using scenic emotional visual stimuli. One hundred and twenty photographs from the International Affective Picture System (IAPS), including ecological scenes of disgust, fear, happiness, and sadness, were presented to 40 healthy participants while they underwent functional magnetic imaging resonance (fMRI). Afterwards they evaluated the emotional content of the pictures in an offline task. The occipito-temporal cortex and the amygdala-hippocampal complex showed a non-specific emotion-related activation, which was more marked in response to negative emotions than to happiness. The temporo-parietal cortex and the ventral anterior cingulate gyrus showed deactivation, with the former being marked for all emotions except fear and the latter being most marked for disgust. The fusiform gyrus showed activation in response to disgust and deactivation in response to happiness or sadness. Brain regions involved in processing of scenic emotion therefore resemble those reported for facial expressions of emotion in that they respond to a range of different emotions, although there appears to be specificity in the intensity and direction of the response.
Brain Structure and Function 05/2013; · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukey's post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.
American Journal of Psychiatry 03/2013; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Formal thought disorder (FTD) in schizophrenia has been found to be associated with volume reductions in the left superior temporal cortex. However, there have been negative findings and some studies have also found associations in other cortical regions. METHOD: Fifty-one schizophrenic patients were evaluated for presence of FTD with the Thought, Language and Communication (TLC) scale and underwent whole-brain structural MRI using optimized voxel-based morphometry (VBM). Fifty-nine matched healthy controls were also scanned. RESULTS: Compared to 31 patients without FTD (global TLC rating 0 or 1), 20 patients with FTD (global TLC rating 2-5) showed clusters of volume reduction in the medial frontal and orbitofrontal cortex bilaterally, and in two left-sided areas approximating to Broca's and Wernicke's areas. The pattern of FTD-associated volume reductions was largely different from that found in a comparison between the healthy controls and the patients without FTD. Analysis of correlations within regions-of-interest based on the above clusters indicated that the 'fluent disorganization' component of FTD was correlated with volume reductions in both Broca's and Wernicke's areas, whereas poverty of content of speech was correlated with reductions in the medial frontal/orbitofrontal cortex. CONCLUSIONS: The findings point to a relationship between FTD in schizophrenia and structural brain pathology in brain areas involved in language and executive function.
Schizophrenia Research 03/2013; · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reading music and playing a musical instrument is a complex activity that comprises motor and multisensory (auditory, visual, and somatosensory) integration in a unique way. Music has also a well-known impact on the emotional state, while it can be a motivating activity. For those reasons, musical training has become a useful framework to study brain plasticity. Our aim was to study the specific effects of musical training vs. the effects of other leisure activities in elderly people. With that purpose we evaluated the impact of piano training on cognitive function, mood and quality of life (QOL) in older adults. A group of participants that received piano lessons and did daily training for 4-month (n = 13) was compared to an age-matched control group (n = 16) that participated in other types of leisure activities (physical exercise, computer lessons, painting lessons, among other). An exhaustive assessment that included neuropsychological tests as well as mood and QOL questionnaires was carried out before starting the piano program and immediately after finishing (4 months later) in the two groups. We found a significant improvement on the piano training group on the Stroop test that measures executive function, inhibitory control and divided attention. Furthermore, a trend indicating an enhancement of visual scanning and motor ability was also found (Trial Making Test part A). Finally, in our study piano lessons decreased depression, induced positive mood states, and improved the psychological and physical QOL of the elderly. Our results suggest that playing piano and learning to read music can be a useful intervention in older adults to promote cognitive reserve (CR) and improve subjective well-being.
Frontiers in Psychology 01/2013; 4:810. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The pathological basis of tardive dyskinesia is unknown. Although its clinical features implicate the basal ganglia, imaging studies have not found clear evidence that it is associated with volume changes in these or other brain structures. AIMS: To determine, using voxel-based structural imaging, whether there are regions of grey matter volume change in people with schizophrenia who also have tardive dyskinesia compared with those without tardive dyskinesia. METHOD: A total of 81 people with chronic schizophrenia, 32 with tardive dyskinesia and 49 without, were examined using magnetic resonance imaging (MRI) and whole-brain, optimised voxel-based morphometry. A comparison group of 61 healthy controls was also examined. RESULTS: Compared with those without tardive dyskinesia, patients with tardive dyskinesia showed a pattern of volume reductions in predominantly subcortical regions, including the basal ganglia and the thalamus. Within the basal ganglia, volume reductions were seen in the caudate nucleus, to a lesser extent in the putamen, and only marginally in the globus pallidus. The patients with tardive dyskinesia, but not those without, showed significant volume reductions in the basal ganglia compared with the healthy controls but both groups had smaller volumes than controls in other affected areas. CONCLUSIONS: The pathological process or processes that underlie the development of tardive dyskinesia are not just neurochemical in nature, but affect brain structure.
The British journal of psychiatry: the journal of mental science 12/2012; · 6.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Retrieval of proper names is a cause of concern and complaint among elderly adults and it is an early symptom of patients suffering from neurodegenerative diseases such as Alzheimer's disease (AD). While it is well established that AD patients have deficits of proper name retrieval, the nature of such impairment is not yet fully understood. Specifically, it is unknown whether this deficit is due to a degradation of the links between faces and proper names, or due to deficits in intentionally accessing and retrieving proper names from faces. Here, we aim to investigate the integrity of the links between famous faces and proper names in AD while minimizing the impact of the explicit retrieval. We compare the performances of AD patients and elderly controls in a face-name priming task. We assess the integrity of the link between faces and names at two different levels: identity level - the name and face belong to the same person; and semantic level - the name and face belong to the same category (e.g., politicians). Our results reveal that AD patients compared with controls show intact semantic priming but reduced priming for person identity. This suggests that the deficits in intentionally retrieving proper names in AD are the result of a partial disruption of the network at the identity level, i.e., the links between known faces and proper names.
Brain and Cognition 08/2012; 80(2):250-6. · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Bipolar depression has been found to be associated with changes in prefrontal cortex activity during performance of cognitive tasks. However, the role of task-related de-activations has been little investigated. METHOD: Forty-one bipolar depressed patients and 41 matched normal controls underwent fMRI scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups. RESULTS: The bipolar depressed patients showed reduced activation in the dorsolateral prefrontal cortex (DLPFC) bilaterally and several other regions. After controlling for differences in task performance only differences in the DLPFC and cerebellum remained. Left DLPFC activation was inversely correlated with Hamilton and MADRS scores. The patients showed failure to de-activate in the medial prefrontal cortex, an area corresponding to the anterior medial node of the default mode network. LIMITATIONS: To confirm default mode network dysfunction demonstration of resting-state connectivity abnormalities would also be required. The study was carried out on treated patients, and did not assess for presence of depressive symptoms in the healthy controls. CONCLUSIONS: Both prefrontal cortical and default mode network dysfunction appear to characterise bipolar depression. The former, but not the latter, is associated with symptom severity.
Journal of Affective Disorders 07/2012; · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Genetic studies have found that the interleukin-1β gene (IL1B, 2q13) influences the risk for schizophrenia, but the underlying biological mechanisms of the association are still unclear. Investigation of the effects of genetic variability in this gene on brain function could provide more information about its role in the disorder.
The present study examined the effects of a functional polymorphism at IL1B gene promoter (-511C/T; rs16944) on brain correlates of working memory performance in schizophrenia. Forty-eight schizophrenia patients and 46 control subjects underwent functional magnetic resonance imaging while performing the n-back task.
In the pooled sample, genetic variability at this locus was associated with differential brain activation in a bilateral frontal region including the dorsolateral prefrontal cortex. There was also a significant diagnosis × genotype interaction effect in an overlapping frontal region: the IL1B polymorphism did not affect activation in the control subjects in this area, but the schizophrenia patients who were T carriers showed significantly higher activation than the CC homozygotes.
The findings support a role for IL1B variability in the dorsolateral prefrontal cortex dysfunction classically associated with schizophrenia.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder.Method
Thirty-two patients meeting Research Diagnostic Criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.
Psychological Medicine 05/2012; · 5.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Beyond their traditional role in the immune system, interleukins have been found to be involved in a variety of neural processes such as regulation of neuronal excitability, synaptic transmission, maturation and plasticity, glial migration and differentiation and other processes of brain development (Nawa et al 2006). Recent meta-analyses have confirmed that the interleukin-1 beta gene (IL1B, 2q13) influences the risk for schizophrenia (Allen et al 2008, Xu et al 2010), but the underlying biological mechanisms of this association are still unclear. Investigation of the effects of genetic variability in this gene on brain function could provide more information about its role in the disorder.
3rd Biennial Schizophrenia International Research Conference; 04/2012
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and the findings are conflicting.MethodWe used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill. RESULTS: All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms. CONCLUSIONS: Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.
Psychological Medicine 02/2012; · 5.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this article we aimed to assess how Alzheimer's disease (AD), which is neurodegenerative, affects the linguistic performance of early, high-proficient bilinguals in their two languages. To this end, we compared the Picture Naming and Word Translation performances of two groups of AD patients varying in disease progression (Mild and Moderate) with that of bilingual individuals diagnosed with mild cognitive impairment (MCI). The results revealed that the linguistic deterioration caused by AD affected the two languages similarly. We also found that cognate status and word frequency were two major determinants of language performance in all three groups of participants. These results are consistent with the notion of a common neural substrate recruited to represent and process the two languages of high-proficient bilinguals.
[Show abstract][Hide abstract] ABSTRACT: Patients with schizophrenia have been found to show unawareness of cognitive impairment. However, its frequency and its relationship to lack of insight into illness are uncertain.
Forty-two patients with chronic schizophrenia were given tests of executive function and memory. Awareness of cognitive impairment was measured by means of discrepancy scores--differences between patient and psychologist ratings of memory and frontal/executive failures in daily life. Insight into illness was assessed using the Scale to Assess Unawareness of Mental Disorder (SUMD).
A majority of the patients were found to underestimate their cognitive impairment; however, some overestimated it. Unawareness of cognitive impairment and lack of clinical insight loaded on different factors in a factor analysis, but these two factors were themselves correlated.
The findings suggest that both unawareness and overestimation of cognitive impairment characterise patients with schizophrenia, although the former is more common. Awareness of cognitive impairment occurs independently of insight into illness at the clinical level, although the two phenomena may be linked at a deeper level.
Schizophrenia Research 09/2011; 133(1-3):187-92. · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cognitive impairment is an established feature of schizophrenia. However, little is known about its relationship to the structural and functional brain abnormalities that characterise the disorder. Aims To identify structural and/or functional brain abnormalities associated with schizophrenic cognitive impairment.
We carried out structural magnetic resonance imaging (MRI) and voxel-based morphometry in 26 participants who were cognitively impaired and 23 who were cognitively preserved, all with schizophrenia, plus 39 matched controls. Nineteen of those who were cognitively impaired and 18 of those who were cognitively preserved plus 34 controls also underwent functional MRI during performance of a working memory task.
No differences were found between the participants who were cognitively intact and those who were cognitively impaired in lateral ventricular volume or whole brain volume. Voxel-based morphometry also failed to reveal clusters of significant difference in grey and white matter volume between these two groups. However, during performance of the n-back task, the participants who were cognitively impaired showed hypoactivation compared with those who were cognitively intact in the dorsolateral prefrontal cortex among other brain regions.
Cognitive impairment in schizophrenia is not a function of the structural brain abnormality that accompanies the disorder but has correlates in altered brain function.
The British journal of psychiatry: the journal of mental science 07/2011; 199(3):202-10. · 6.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Val158Met polymorphism in the COMT gene has been found to be associated with differences in brain activation in both healthy subjects and patients with schizophrenia. The predominant finding has been increased prefrontal activation associated with the Val allele; however, genotype-related de-activations have not been studied. In this study 42 schizophrenia patients and 31 controls underwent fMRI while performing the n-back task. Brain differences related to presence/absence of disease and presence/absence of the Val/Val genotype were examined. Both disease and Val/Val genotype were associated with failure of de-activation in a cluster centred in the medial prefrontal cortex. There was no interaction between disease and genotype at this location, but clusters where there were significant interactions emerged in the right prefrontal cortex and left temporal/parietal cortex. These findings suggest that Val158Met polymorphism influences task-related de-activations in the default mode network in both healthy subjects and schizophrenia patients to an equivalent extent. However the Val158Met polymorphism also has disease-specific effects on DLPFC activation in schizophrenia.