Anna Mané

Progressive gray matter changes in first episode schizophrenia: A 4-year longitudinal magnetic resonance study using VBM

UNLABELLED Schizophrenia is a disabling illness, characterized by a heterogeneous course including clinical deterioration and poor outcome. Accumulating findings in schizophrenia suggest that it might involve two pathophysiologic processes, one early in life (neurodevelopmental), and one after onset of the illness (neurodegenerative). Longitudinal imaging studies after onset of the illness may help to clarify these pathophysiological aspects of schizophrenia, but so far, probably due to methodological differences, there have been no conclusive results. The present study sets out to investigate longitudinal gray matter changes in patients with first-episode schizophrenia relative to healthy subjects over the first 4 years of the illness and the relation of gray matter changes in patients with functional outcome, using an objective automatic method not biased to one particular structure to analyze gray matter changes. METHODS We included 28 first-episode neuroleptic-naïve patients with DSM-IV diagnosis of schizophreniform disorder or schizophrenia, and 17 controls. 15 patients and 11 controls completed the longitudinal study and were reevaluated after four years. Gray matter changes over time were measured with voxel-based morphometry (VBM) using SPM5. Functional outcome was measured with the global assessment functioning scale (GAF). RESULTS Excessive decrease in gray matter was found in patients as compared to healthy individuals in the left superior temporal gyrus and right orbitofrontal gyrus, and excessive increase in the bilateral lingual gyrus and right cuneus. Additionally, gray matter changes in patients in the left lingual gyrus, right insula and right cerebellum, were inversely related to functional outcome (p<0.001 uncorrected at voxel level, p<0.05 family-wise-error corrected at cluster level). CONCLUSIONS There are differing longitudinal gray matter changes in patients with schizophrenia during the first years of the illness as compared to healthy individuals. Some progressive gray matter changes in patients are related to functional outcome.

Polymorphism of dopamine D2 receptor (TaqIA, TaqIB, and-141C Ins/Del) and dopamine degradation enzyme (COMT G158A, A-278G) genes and extrapyramidal symptoms in patients with schizophrenia and bipolar disorders

OBJECTIVE The relationship is examined of the dopamine D2 receptor (DRD2) polymorphism (TaqIA, TaqIB, -141 C Ins/Del) and the catechol-O-methyltransferase (COMT) polymorphism (A-278G, G158A) to the risk of antipsychotic-induced extrapyramidal symptoms (EPS) in schizophrenia and bipolar disorders. Participants comprised 80 cases presenting with EPS (Simpson-Angus Scale score >3) and 188 controls presenting without EPS (Simpson-Angus Scale score <or=3) participated in this study. The COMT(L) allele conferred a reduction of EPS risk of 60% to heterozygotes, but the finding did not survive correction for multiple comparisons. In the bipolar subgroup, with a COMT(L) allele protection of 70%, the reduction remained significant after Bonferroni correction. The analysis of the COMT haplotypes revealed an association of the A-G haplotype with EPS risk in the overall group and the bipolar disorder subgroup, and an association of the A-A haplotype with EPS protection in the bipolar subgroup. No significant associations were found for DRD2 or COMT A-278G polymorphisms. This is the first report of an association between the COMT polymorphism and EPS susceptibility. These results are of interest in view of the increased use of antipsychotic drugs in bipolar patients in both the acute manic and the depressive phase.

Spanish adaptation and validation of the Brief Negative Symptoms Scale

Negative symptoms prevalent in schizophrenia are associated with poor outcome. Developing new instruments to identify new treatments was highlighted at the NIMH-MATRICS Consensus Development Conference on Negative Symptoms. The new Brief Negative Symptoms scale (BNSS) demonstrated strong psychometric properties, but there is a need for validating it in non-English languages. A multi-center study was conducted to validate the Spanish version of the BNSS (BNSS-Sp) in 20 schizophrenia patients, following the original BNSS validation methodology. We found strong inter-rater, test-retest and internal consistency properties (for the total BNSS-Sp, intraclass correlation coefficient=0.97, Pearsons correlation coefficient r=0.95 (p<0.001), Cronbachs alpha=0.98).

Predictors of Relapse and Functioning in First-Episode Psychosis: A Two-Year Follow-Up Study

OBJECTIVE First-episode psychosis has an annual incidence rate of 24.6 to 40.9 per 100,000 population, and most individuals develop chronic disorders, such as schizophrenia or affective psychosis. The first two to five years are thought to be key determinants of long-term functional and clinical prognosis. This study aimed to determine the two-year course of illness in first-episode psychosis, including diagnosis, relapse, and functioning and factors related to these variables. METHODS A total of 140 patients who experienced a first episode of psychosis were recruited and evaluated between 2008 and 2012 in a first-episode psychosis program in Barcelona, Spain. Regression models were used to determine factors predicting relapse and functioning. RESULTS A general trend was noted toward improved functioning and less severe psychotic symptoms. However, after two years, one-third of the patients had a diagnosis of schizophrenia and more than 40% had a diagnosis of affective psychosis. Rates of relapse were 31% after one year and 43% at two years. Cannabis use after illness onset and poor insight were the best predictors of relapse. Being male and severity of negative symptoms at baseline predicted worse functioning at two years. CONCLUSIONS Patients with first-episode psychosis were found to have high relapse rates during the first years after illness onset. Further studies evaluating treatment strategies focused on reducing cannabis use and improving insight in first-episode psychosis should be encouraged.

Differential brain glucose metabolic patterns in antipsychotic-naïve first-episode schizophrenia with and without auditory verbal hallucinations.

BACKGROUND Auditory verbal hallucinations (AVHs) are a core symptom of schizophrenia. Previous reports on neural activity patterns associated with AVHs are inconsistent, arguably owing to the lack of an adequate control group (i.e., patients with similar characteristics but without AVHs) and neglect of the potential confounding effects of medication. METHODS The current study was conducted in a homogeneous group of patients with schizophrenia to assess whether the presence or absence of AVHs was associated with differential regional cerebral glucose metabolic patterns. We investigated differences between patients with commenting AVHs and patients without AVHs among a group of dextral antipsychotic-naive inpatients with acute first-episode schizophrenia examined with [(18)F]fluoro-deoxyglucose positron emission tomography (FDG-PET) at rest. Univariate and multivariate approaches were used to establish between-group differences. RESULTS We included 9 patients with AVHs and 7 patients without AVHs in this study. Patients experiencing AVHs during FDG uptake had significantly higher metabolic rates in the left superior and middle temporal cortices, bilateral superior medial frontal cortex and left caudate nucleus (cluster level p < 0.005, family wise error-corrected, and bootstrap ratio > 3.3, respectively). Additionally, the multivariate method identified hippocampal-parahippocampal, cerebellar and parietal relative hypoactivity during AVHs in both hemispheres (bootstrap ratio < -3.3). LIMITATIONS The FDG-PET imaging technique does not provide information regarding the temporal course of neural activity. The limited sample size may have increased the risk of false-negative findings. CONCLUSION Our results indicate that AVHs in patients with schizophrenia may be mediated by an alteration of neural pathways responsible for normal language function. Our findings also point to the potential role of the dominant caudate nucleus and the parahippocampal gyri in the pathophysiology of AVHs. We discuss the relevance of phenomenology-based grouping in the study of AVHs.

Brain-derived neurotrophic factor levels in first episode of psychosis: A systematic review.

AIM To systematically review studies measuring peripheric brain-derived neurotrophic factor (BDNF) levels on first-episode psychosis patients and variables related to them. METHODS A systematic search was made of articles published in the Medline database from 2002 up to June 2014. Included are original studies that report enzyme-linked immunosorbent assay measurement of BDNF levels in serum or plasma in patients with a diagnosis of first episode psychosis (FEP) and age- and gender- matched healthy controls. RESULTS Of the initially identified 147 articles, only 18 satisfied the inclusion criteria. Of this, 15 found a significant reduction in patients with FEP compared with age- and gender - matched controls. CONCLUSION Peripheral BDNF levels are generally reduced in FEP patients. There are some factors that may influence BDNF levels that need to be further studied. Furthermore, a future meta-analysis in this topic is needed.

Brain Metabolism during Hallucination-Like Auditory Stimulation in Schizophrenia

Auditory verbal hallucinations (AVH) in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1) at rest and (2) during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophrenia.

The negative syndrome of schizophrenia: Three -underlying components are better than two

AIMS To analyse the underlying structure of the negative syndrome of schizophrenia as it is represented in the Brief Negative Symptom Scale. METHODS Cross-sectional, multicentre study, employing data from 190 evaluations. STATISTICS Exploratory factor analysis using the principal component analysis method. RESULTS The three-component solution explained 77.4% of the total variance. Pearson correlation coefficients between components were: 1-2=-0.494, 1-3=-0.117, and 2-3=0.179. CONCLUSION Our solution favours a three-component structure of the negative syndrome, consisting of: external world (anhedonia and asociality), inner world (avolition and blunted affect), and alogia, with the latter only marginally related to the two former components.

Relationship between cannabis and psychosis: Reasons for use and associated clinical variables

The mechanism underneath the relationship between cannabis and psychosis remains controversial, for which several hypotheses have been proposed, including cannabis as self-medication and cannabis as a risk for the development of psychosis. The aim of this work was to study the relationship between cannabis and psychosis in first-episode psychosis cannabis users and non-users, and non-psychotic cannabis users. The age at the first psychotic episode, duration of untreated psychosis, psychopathology and reasons for cannabis use were assessed. First-episode psychosis cannabis users showed an earlier age at psychosis onset than non-user patients. No significant differences in symptomatology were found. The distinguishing reasons to use cannabis for patients with first-episode psychosis with respect to non-psychotic users were to arrange their thoughts and deal with hallucinations and suspiciousness. These findings are in agreement with both hypotheses: self-medication and secondary psychosis hypothesis. However, longitudinal prospective cohort studies assessing reasons for cannabis use are needed to investigate both hypotheses and their complementarity.

The course of negative symptoms in first-episode schizophrenia and its predictors: A prospective two-year follow-up study

AIMS This study aimed to investigate the course of negative symptoms and its stability over a two-year period following a first-episode schizophrenia (FES) and the possible predictors of higher severity in this symptomatology after this period. METHODS In this longitudinal two-year prospective follow-up study we included 268 patients with a FES, according to DSM-IV. Analysis of variance was conducted in patients who completed the full follow-up to study changes in negative symptoms over three visits. Regression analyses were conducted to show correlates and potential predictors of negative symptoms at two-year follow-up. RESULTS There was a significant effect for time in negative symptomatology, which was less severe at one-year follow-up after a FES and remained stable up to two years (Time 1>Time 2>Time 3); F(2,151)=20.45, p<0.001. Poorer premorbid adjustment (p=0.01) and higher negative symptoms at baseline (p<0.001) made a significant contribution to the changes in the negative symptoms severity at two-years after a FES (R2=0.21, p<0.001). CONCLUSIONS We found a reduction in the negative symptomatology at one-year after a FES. This change remained stable at two-year. Our results suggested that the presence of this symptomatology early in the course of the illness, together with a poorer premorbid adjustment, predict more severe negative symptoms at mid-term outcome.