Marie Raffin

Anterior Cingulate Glutamate Levels Related to Clinical Status Following Treatment in First-Episode Schizophrenia

Many patients with schizophrenia show a limited symptomatic response to treatment with dopaminergic antipsychotics. This may reflect the additional involvement of non-dopaminergic neurochemical dysfunction in the pathophysiology of the disorder. We tested the hypothesis that brain glutamate levels would differ between patients with first-episode psychosis who were symptomatic compared with those with minimal symptoms following antipsychotic treatment. Proton magnetic resonance spectroscopy (1H-MRS) spectra were acquired at 3u2009Tesla in the anterior cingulate cortex and left thalamus in 15 patients with first-episode psychosis in symptomatic remission, and 17 patients with first-episode psychosis who were still symptomatic following at least one course of antipsychotic treatment. Metabolite levels were estimated in ratio to creatine (Cr) using LCModel. Levels of glutamate/Cr in the anterior cingulate cortex were significantly higher in patients who were still symptomatic than in those in remission (T(30)=3.02; P=0.005). Across the entire sample, higher levels of glutamate/Cr in the anterior cingulate cortex were associated with a greater severity of negative symptoms (r=0.42; P=0.017) and a lower level of global functioning (r=−0.47; P=0.007). These findings suggest that clinical status following antipsychotic treatment in schizophrenia is linked to glutamate dysfunction. Treatment with compounds acting on the glutamatergic system might therefore be beneficial in patients who respond poorly to dopaminergic antipsychotics.

Altered medial temporal activation related to local glutamate levels in subjects with prodromal signs of psychosis.

BACKGROUNDnBoth medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated.nnnMETHODSnWe used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers.nnnRESULTSnWe observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent.nnnCONCLUSIONSnIn individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis.

Review: The biological basis of antipsychotic response in schizophrenia.

Schizophrenia is a severe mental illness affecting approximately 1% of the population worldwide. Antipsychotic drugs are effective in symptom control in up to two-thirds of patients, but in at least one-third of patients the response is poor. The reason for this is not clear, but one possibility is that good and poor responders have different neurochemical pathologies, and may therefore benefit from different treatment approaches. In this selective review we summarise research findings investigating the biological differences between patients with schizophrenia who show a good or a poor response to treatment with antipsychotic drugs.

Identifying Individuals at High Risk of Psychosis: Predictive Utility of Support Vector Machine using Structural and Functional MRI Data

The identification of individuals at high risk of developing psychosis is entirely based on clinical assessment, associated with limited predictive potential. There is, therefore, increasing interest in the development of biological markers that could be used in clinical practice for this purpose. We studied 25 individuals with an at-risk mental state for psychosis and 25 healthy controls using structural MRI, and functional MRI in conjunction with a verbal memory task. Data were analyzed using a standard univariate analysis, and with support vector machine (SVM), a multivariate pattern recognition technique that enables statistical inferences to be made at the level of the individual, yielding results with high translational potential. The application of SVM to structural MRI data permitted the identification of individuals at high risk of psychosis with a sensitivity of 68% and a specificity of 76%, resulting in an accuracy of 72% (pu2009<u20090.001). Univariate volumetric between-group differences did not reach statistical significance. By contrast, the univariate fMRI analysis identified between-group differences (pu2009<u20090.05 corrected), while the application of SVM to the same data did not. Since SVM is well suited at identifying the pattern of abnormality that distinguishes two groups, whereas univariate methods are more likely to identify regions that individually are most different between two groups, our results suggest the presence of focal functional abnormalities in the context of a diffuse pattern of structural abnormalities in individuals at high clinical risk of psychosis.

Validation of the Pediatric Catatonia Rating Scale (PCRS)

INTRODUCTIONnDespite the increased recognition of catatonia in children and adolescents, no specific assessment instrument has been validated in this population.nnnMETHODnWithin the context of a prospective study on catatonia, we developed the Pediatric Catatonia Rating Scale (PCRS, maximum score=60), adapted from the Bush and Francis Catatonia Rating Scale for its use in child and adolescent inpatients. We assessed the psychometric properties of the PCRS by measuring its internal consistency, construct validity, and factor structure. Bivariate analyses were performed to compare the different diagnostic patient groups across the extracted factors.nnnRESULTSnInternal consistency was moderate (Cronbachs α for total score=0.67) suggesting multidimensionality. Multiple factors underlie the PCRS items, as revealed by factor analysis. Four distinct dimensions of catatonic symptoms were identified and accounted for 44% of total variance: a negative withdrawal factor (with mutism, negativism, and social withdrawal), a catalepsy factor (with posturing and waxy flexibility), an abnormal movements factor (with mannerisms and stereotypes) and an echo phenomenon factor (with echolalia and echopraxia). Receiver operating characteristic (ROC) analysis showed that the PCRS performance in discriminating individuals with catatonia vs. those without catatonia was excellent for a threshold≥9 (Area Under the Curve=0.983) in this sample.nnnDISCUSSIONnThese results support the validity of the PCRS among children and adolescent inpatients. With regard to such analyses, the internal structure of catatonic syndrome in children and adolescents is roughly comparable with the adult form, except the lack of a hyperactive/excitement dimension.

Adverse childhood experiences among inpatient youths with severe and early-onset psychiatric disorders: prevalence and clinical correlates

This study aimed to determine the prevalence and the clinical correlates of Adverse Childhood Experiences (ACEs) among 158 inpatient youths with two types of severe psychiatric disorders. ACEs were retrospectively collected with the ACEs scale and the List of Threatening Experiences Questionnaire in 77 patients hospitalized for a catatonic syndrome (average age 15.2xa0years) and 81 for a manic or mixed episode (average age 15.7xa0years). ACEs were frequent in youths suffering from bipolar disorder type I (BD-I) (58xa0%) and from catatonia (57xa0%), with around one quarter exposed to severe abuse (i.e., physical/sexual/emotional abuse or physical/emotional neglect). Youths with BD-I were more likely to be exposed to family violence compared to those with catatonia. Youths who had been exposed to ACEs did not exhibit a more severe presentation or a poorer response to treatment compared to others, either in the bipolar group or in the catatonic group.

Clinical utility of magnetic resonance imaging in first-episode psychosis

BackgroundThere is no consensus as to whether magnetic resonance imaging (MRI) should be used as part of the initial clinical evaluation of patients with first-episode psychosis (FEP).Aims(a) To assess the logistical feasibility of routine MRI; (b) to define the clinical significance of radiological abnormalities in patients with FEP.MethodRadiological reports from MRI scans of two FEP samples were reviewed; one comprised 108 patients and 98 healthy controls recruited to a research study and the other comprised 241 patients scanned at initial clinical presentation plus 66 healthy controls.ResultsIn the great majority of patients, MRI was logistically feasible. Radiological abnormalities were reported in 6% of the research sample and in 15% of the clinical sample (odds ratio (OR)=3.1, 95% CI 1.26-7.57, χ2(1) = 6.63, P = 0.01). None of the findings necessitated a change in clinical management.ConclusionsRates of neuroradiological abnormalities in FEP are likely to be underestimated in research samples that often exclude patients with organic abnormalities. However, the majority of findings do not require intervention.

Catatonia in Children and Adolescents: A High Rate of Genetic Conditions

Pediatric catatonia is a rare and severe neuropsychiatric syndrome. We previously reported, in 58 children and adolescents with catatonia, a high prevalence (up to 20%) of medical conditions, some of which have specific treatments.1 Here we extend the cohort inclusion and report the first systematic molecular genetic data for this syndrome. Among the 89 patients consecutively admitted for catatonia (according to the pediatric catatonia rating scale)2 between 1993 and 2014, we identify 51 patients (57.3%) who had genetic laboratory testing, of whom 37 had single nucleotide polymorphism (SNP) microarray tests for CNVs and 14 had routine genetic explorations (karyotyping and searches for specific chromosomal abnormalities by fluorescence in situ hybridization [FISH]) or a specific diagnosis test based on clinical history. To assess the causality of observed genetic findings in each patient, we used a causality assessment score (CAUS)3 including 5 causality-support criteria on a 3-point scale (0xa0= absent; 1xa0= moderate; 2xa0= high): the existence of similar cases in the literature; the presence of a clinical contributing factor; the presence of a biological contributing factor; the presence of other paraclinical symptoms; and response to a specific treatment related to the suspected genetic or medical condition.

Pattern of activation during delayed matching to sample task predicts functional outcome in people at ultra high risk for psychosis

BACKGROUNDnClinical outcomes in people identified as at ultra-high risk (UHR) for psychosis are remarkably heterogeneous, and are difficult to predict on the basis of the presenting clinical features. Individuals at UHR are at risk of poor functional outcome regardless of development of psychotic disorder. The aim of the present study was to assess whether there is a relationship between functional neuroimaging measures at presentation and functional outcome as measured by the GAF three years after scanning.nnnMETHODSnFunctional magnetic resonance imaging (fMRI) data were collected during an object working memory task in 34 ultra-high risk (UHR) subjects and 20 healthy controls. On the basis of their GAF scores at follow up, the UHR participants were divided into subgroups with good and poor functional outcomes, respectively.nnnRESULTSnAt baseline, the UHR group differed from controls in showing altered frontal and cuneus/posterior cingulate activation. Significant group x task interactions were found in the left cuneus and posterior cingulate gyrus, reflecting differential responses to the task conditions. Within the UHR sample, the subgroup with a poor functional outcome exhibited altered activation in frontal, temporal and striatal regions, and reduced deactivation within default-mode network regions, relative to those with a good outcome. Within the whole UHR sample, in these regions the local task response was correlated with the GAF score at follow up.nnnCONCLUSIONSnThe findings suggest a potential role of functional neuroimaging in the prediction of outcomes in people at high clinical risk of psychosis.

OASIS (Outreach And Support in South London), évaluation et traitement des adolescents et jeunes adultes, « à haut risque » de développer un trouble psychotique

d’irritabilite. Sans traitement environ un tiers des sujets vont developper un premier episode psychotique dans les 12 mois suivant [4]. L’objectif du service OASIS est d’une part de prevenir ou de retarder le developpement de ces troubles psychotiques, et d’autre part de permettre une orientation rapide des patients developpant un etat psychotique vers des services specialises. Le service OASIS ne recoit que des patients en demande de soin.