Miquel Bernardo

Standardized remission criteria in schizophrenia.

Objective:  Recent work has focussed on schizophrenia as a ‘deficit’ state but little attention has been paid to defining illness plasticity in terms of symptomatic remission.

Sustained attention impairment correlates to gray matter decreases in first episode neuroleptic-naive schizophrenic patients

Impaired sustained attention seems to be a specific neuropsychological deficit that is closely linked to schizophrenia. Voxel based morphometry has emerged as a useful tool for the detection of subtle gray matter (GM) abnormalities. The aim of our study was to identify the cerebral regions related to the Identical-Pair version of the Continuous Performance Test (CPT-IP) performance in schizophrenic patients. The study included 13 right-handed, male, first-episode, paranoic, neuroleptic-naive schizophrenic patients and 13 matched controls. High-resolution whole-brain MR images were segmented and analyzed for the whole brain and for regions of interest (ROI) using SPM99. Furthermore, the correlation between CPT-IP performance and GM density was examined. Volumetric analysis of the thalami was also carried out. GM density analysis shown decreases in patients in anterior cingulate gyrus, left inferior frontal, right claustrum, left pulvinar, and dorsomedial bilateral thalamic nuclei, and caudate nuclei as well as left hippocampus and parahippocampal gyrus. Thalamic ROIs revealed a strong correlation between groups differences. The thalamic GM density allowed a good individual classification. GM increases were detected in left insula, superior temporal gyrus, and putamen nucleus, and right supramarginal gyrus. Schizophrenic patients showed smaller left and right thalamic volumes. We found that GM density of the left thalamic nucleus, left angular, and supramarginal gyrus, and left inferior frontal and postcentral gyri correlated significantly with CPT-IP performance in patients but not in controls. Moreover, the restricted ROIs regression was strongly significant for both left and right thalamus. In summary, we provide evidence for the involvement of thalamic, inferior-parietal, and frontal regions in the attentional deficits observed in schizophrenic patients.

Decreased cerebral activation during CPT performance: structural and functional deficits in schizophrenic patients

Voxel-based morphometry (VBM) allows the output of structural data in a Statistical Parametric Map of the brain in the same way that the SPM can do with functional data. Using functional magnetic resonance (fMR), we studied brain activation in 14 patients with schizophrenia and 14 matched normal controls. We found significant hypoactivation in patients in several regions, especially in the right hemisphere, in the dorsolateral frontal and temporal regions and in the inferior parietal. Subcortically, we found strong hypoactivity in the thalamus. The optimized VBM method revealed gray matter (GM) abnormalities in the bilateral supramarginal gyrus and cingulate cortex, and in the right inferior temporal regions. Three regions involved in attentional processes showed both structural and functional deficits: the thalamus, the anterior cingulate and the inferior parietal. The results suggest that these regions may be involved in the attentional deficit in schizophrenia.

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.

Prefrontal dysfunction in young acute neuroleptic-naive schizophrenic patients: A resting and activation SPECT study

Regional cerebral blood flow (rCBF) was measured with single photon emission computed tomography (SPECT) in six neuroleptic-naive, young, acute schizophrenic patients and six normal control subjects. We evaluated rCBF changes in prefrontal areas at rest and during a prefrontal activation task, the Wisconsin Card Sorting Test (WCST). Schizophrenic patients had significantly higher prefrontal blood flow than did control subjects during the resting conditions. During activation, the control group showed significant increases in prefrontal blood flow, whereas the schizophrenic group did not. These results suggest that at rest there is no evidence of hypofrontality, whereas hyperfrontality seems to be the most frequent pattern in our selected sample of young acute neuroleptic-naive schizophrenic patients. Furthermore, schizophrenic patients seem to be unable to increase prefrontal blood flow under conditions that challenge the prefrontal cortex.

Regional cerebral blood flow pattern in normal young and aged volunteers: a99mTc-HMPAO SPET study

The aim of this study was to investigate the normal pattern of regional cerebral blood flow (rCBF) distribution in normal young and aged volunteers using technetium-99m hexamethylpropylene amine oxime (99m-Te-HMPAO) as a tracer. The region brain perfusion of young and aged subjects was compared, especially regarding rCBF differences due to age and gender, and interhemispheric rCBF asymmetries. Sixty-eight right-handed normal volunteers — 40 young (mean age 29.5±6.3 years) and 28 aged (mean age 71.2±4.3 years) — were included in the study. rCBF was estimated on the basis of a semiquantitative approach by means of a left/right index and two region/reference ratios, using the cerebellum and the whole brain activity as references. A good correlation between these two region/reference ratios was found (P<0.005 in all cerebral regions). The highest rCBF ratios corresponded to the cerebellum, followed by the occipital lobe. The remaining cortical regions (temporal, parietal, frontal and basal ganglia) showed slightly lower values. The white matter showed rCBF ratios substantially lower than the grey matter. In neither young nor aged subjects were significant rCBF differences between the genders found in any of the two region/reference indices employed. Aged subjects showed significantly lower rCBF ratios than young subjects in the left frontal lobe and in the posterior region of the left temporal lobe. In both young and aged subjects, lower perfusion was found in the left hemisphere, except for the white matter region in both age groups and the frontal lobe in the young subjects. Aged subjects presented a slightly higher interhemispheric asymmetry in the frontal lobe. However, interhemispheric asymmetry was minimal (−1.01% to 3.14%). Consequently, a symmetrical rCBF distribution can be assumed between homologous regions, independent of age.

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.

Volume changes in gray matter in first-episode neuroleptic-naive schizophrenic patients treated with risperidone.

Abstract: Structural neuroimaging techniques have consistently shown that treatment of schizophrenic patients with conventional antipsychotics causes an increase in basal ganglia volume. However, findings in schizophrenic patients treated with the newer atypical antipsychotic drugs are less consistently reported. To explore this issue, the authors used a whole-brain, unbiased, and automated technique for comparing brain structural features across scans in schizophrenic patients before and after a treatment with the atypical antipsychotic risperidone. T1-weighted images from 11 first-episode neuroleptic-naive schizophrenic patients were processed and analyzed for regions of interest (basal ganglia) by using optimized voxel-based morphometry. Scans were repeated after 3 months of continuous treatment with risperidone. Region of interest-based voxel-based morphometry analyses revealed increases in gray matter volume for the right and left caudate nuclei and for the left accumbens after the treatment with risperidone. Hence, in our sample of schizophrenic patients, treatment with risperidone was associated, in contrast to the findings for other atypical antipsychotics, with an increase in basal ganglia volume. Such discrepancy could be related to the pharmacodynamics of risperidone (the atypical antipsychotic showing the higher affinity for D2 receptors) and the rather high mean doses used in our study (ie, 6.05 mg/d).

Subtypes of memory dysfunction associated with ECT: characteristics and neurobiological bases.

Electroconvulsive therapy (ECT) is an effective treatment for a variety of psychiatric syndromes. However, one of its adverse secondary effects is neurocognitive dysfunction. The aim of this paper is to review different subtypes of memory dysfunction associated with ECT from a neuropsychological perspective. Declarative memory is clearly impaired after ECT. Immediate memory, however, is broadly preserved. Few studies have addressed procedural and incidental memory. Selective memory is impaired, probably due to the disruption of specific brain regions. Some of the possible neurobiological bases of ECT memory dysfunction are discussed in this paper. Synaptic plasticity, the cerebral neurotransmission system, and cerebral metabolism are examined in relation to the dysfunction and subsequent recovery of each memory subtype.

Assessment and management of agitation in psychiatry: Expert consensus

Abstract Background Psychomotor agitation is associated with different psychiatric conditions and represents an important issue in psychiatry. Current recommendations on agitation in psychiatry are not univocal. Actually, an improper assessment and management may result in unnecessary coercive or sedative treatments. A thorough and balanced review plus an expert consensus can guide assessment and treatment decisions. Methods An expert task force iteratively developed consensus using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new, re-worded or re-rated items. Results Out of 2175 papers assessing psychomotor agitation, 124 were included in the review. Each component was assigned a level of evidence. Integrating the evidence and the experience of the task force members, a consensus was reached on 22 statements on this topic. Conclusions Recommendations on the assessment of agitation emphasise the importance of identifying any possible medical cause. For its management, experts agreed in considering verbal de-escalation and environmental modification techniques as first choice, considering physical restraint as a last resort strategy. Regarding pharmacological treatment, the “ideal” medication should calm without over-sedate. Generally, oral or inhaled formulations should be preferred over i.m. routes in mildly agitated patients. Intravenous treatments should be avoided.