Glutamate levels of the right and left anterior cingulate cortex in autistics adults.

BACKGROUND: The neurobiology of Autism Spectrum Disorder (ASD) is still unknown. Alteration in glutamate metabolism might translate into an imbalance of the excitation/inhibition equilibrium of cortical networks that in turn are related to autistic symptoms, but previous studies using voxel located in bilateral anterior cingulate cortex (ACC) failed to show abnormalities in total glutamate level. Due to the functional differences in the right and left ACC, we sought to determine whether a difference between right and left ACC glutamate levels could be found when comparing ASD patients and control subjects. METHODS: Using single-voxel proton magnetic resonance spectroscopy (1H-MRS), we analyzed the glutamate + glutamine (Glx) concentrations in the left and right ACC of 19 ASD patients with normal IQs and 25 matched control subjects. RESULTS: No overall group differences in Glx were shown, in the left ACC (p = 0.24) or in the right ACC (p = 0.11). CONCLUSIONS: No significant alterations in Glx levels were detected in the left and right ACC in high-functioning autistic adults. In the excitatory/inhibitory imbalance framework, our data reinforce the critical need to analyze the GABAergic pathway, for better understanding of basic neuropathology in autism.

Glutamatergic synapse in autism: a complex story for a complex disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathophysiological mechanisms are still unclear. Hypotheses suggest a role for glutamate dysfunctions in ASD development, but clinical studies investigating brain and peripheral glutamate levels showed heterogenous results leading to hypo- and hyper-glutamatergic hypotheses of ASD. Recently, studies proposed the implication of elevated mGluR5 densities in brain areas in the pathophysiology of ASD. Thus, our objective was to characterize glutamate dysfunctions in adult subjects with ASD by quantifying (1) glutamate levels in the cingulate cortex and periphery using proton magnetic resonance spectroscopy and metabolomics, and (2) mGluR5 brain density in this population and in a validated animal model of ASD (prenatal exposure to valproate) at developmental stages corresponding to childhood and adolescence in humans using positron emission tomography. No modifications in cingulate Glu levels were observed between individuals with ASD and controls further supporting the difficulty to evaluate modifications in excitatory transmission using spectroscopy in this population, and the complexity of its glutamate-related changes. Our imaging results showed an overall increased density in mGluR5 in adults with ASD, that was only observed mostly subcortically in adolescent male rats prenatally exposed to valproic acid, and not detected in the stage corresponding to childhood in the same animals. This suggest that clinical changes in mGluR5 density could reflect the adaptation of the glutamatergic dysfunctions occurring earlier rather than being key to the pathophysiology of ASD.

Emotional expression visual mismatch negativity in children.

Detection of changes in facial emotions is crucial to communicate and to rapidly process threats in the environment. This function develops throughout childhood via modulations of the earliest brain responses, such as the P100 and the N170 recorded using electroencephalography. Automatic brain signatures can be measured through expression-related visual mismatch negativity (vMMN), which reflects the processing of unattended changes. While increasing research has investigated vMMN processing in adults, few studies have been conducted on children. Here, a controlled paradigm previously validated was used to disentangle specific responses to emotional deviants (angry face) from that of neutral deviants. Latencies and amplitudes of P100 and N170 both decrease with age, confirming that sensory and face-specific activity is not yet mature in school-aged children. Automatic change detection-related activity is present in children, with a similar vMMN pattern in response to both emotional and neutral deviant stimuli to what previously observed in adults. However, vMMN processing is delayed in children compared to adults and no emotion-specific response is yet observed, suggesting nonmature automatic detection of salient emotional cues. To our knowledge, this is the first study investigating expression-related vMMN in school-aged children, and further investigations are needed to confirm these results.

When Alterations in Social Cognition Meet Subjective Complaints in Autism Spectrum Disorder: Evaluation With the "ClaCoS" Battery.

Background: Deficit in social communication is a core feature in Autism Spectrum Disorder but remains poorly assessed in classical clinical practice, especially in adult populations. This gap between needs and practice is partly due to a lack of standardized evaluation tools. The multicentric Research group in psychiatry GDR3557 (Institut de Psychiatrie) developed a new battery for social cognitive evaluation named "ClaCoS," which allows testing the main components of social cognition: Emotion Recognition, Theory of Mind, Attributional Style, and Social Perception and Knowledge. It further provides an assessment of subjective complaints in social cognition. Methods: We compared the social cognition abilities of 45 adults with Autism Spectrum Disorder without intellectual disability and 45 neurotypically developed volunteers using the "ClaCoS" battery, in order to determine its relevance in the evaluation of social cognition impairments in autism. A correlational approach allowed us to test the links between subjective complaints and objectively measured impairments for the different components of social cognition. Results: As expected, the Autism Spectrum Disorder group showed deficits in all four components of social cognition. Moreover, they reported greater subjective complaints than controls regarding their social abilities, correlated to the neuropsychological assessments. Conclusion: The "ClaCoS" battery is an interesting tool allowing to assess social impairments in autism and to specify the altered components, for a better adjustment of tailored social cognition training programs. Our results further suggest that people with Autism Spectrum Disorder have a good social cognitive insight, i.e., awareness into social cognitive functioning, and may thus benefit from social cognitive training tools.

Emotional visual mismatch negativity: a joint investigation of social and non-social dimensions in adults with autism.

Unusual behaviors and brain activity to socio-emotional stimuli have been reported in Autism Spectrum Disorder (ASD). Atypical reactivity to change and intolerance of uncertainty are also present, but little is known on their possible impact on facial expression processing in autism. The visual mismatch negativity (vMMN) is an electrophysiological response automatically elicited by changing events such as deviant emotional faces presented among regular neutral faces. While vMMN has been found altered in ASD in response to low-level changes in simple stimuli, no study has investigated this response to visual social stimuli. Here two deviant expressions were presented, neutral and angry, embedded in a sequence of repetitive neutral stimuli. vMMN peak analyses were performed for latency and amplitude in early and late time windows. The ASD group presented smaller amplitude of the late vMMN to both neutral and emotional deviants compared to the typically developed adults (TD) group, and only the TD group presented a sustained activity related to emotional change (i.e., angry deviant). Source reconstruction of the vMMNs further revealed that any change processing elicited a reduced activity in ASD group compared to TD in the saliency network, while the specific processing emotional change elicited activity in the temporal region and in the insula. This study confirms atypical change processing in ASD and points to a specific difficulty in the processing of emotional changes, potentially playing a crucial role in social interaction deficits. Nevertheless, these results require to be further replicated with a greater sample size and generalized to other emotional expressions.

Brain correlates of emotional prosodic change detection in autism spectrum disorder.

Autism Spectrum Disorder (ASD) is currently diagnosed by the joint presence of social impairments and restrictive, repetitive patterns of behaviors. While the co-occurrence of these two categories of symptoms is at the core of the pathology, most studies investigated only one dimension to understand underlying physiopathology. In this study, we analyzed brain hemodynamic responses in neurotypical adults (CTRL) and adults with autism spectrum disorder during an oddball paradigm allowing to explore brain responses to vocal changes with different levels of saliency (deviancy or novelty) and different emotional content (neutral, angry). Change detection relies on activation of the supratemporal gyrus and insula and on deactivation of the lingual area. The activity of these brain areas involved in the processing of deviancy with vocal stimuli was modulated by saliency and emotion. No group difference between CTRL and ASD was reported for vocal stimuli processing or for deviancy/novelty processing, regardless of emotional content. Findings highlight that brain processing of voices and of neutral/ emotional vocal changes is typical in adults with ASD. Yet, at the behavioral level, persons with ASD still experience difficulties with those cues. This might indicate impairments at latter processing stages or simply show that alterations present in childhood might have repercussions at adult age.

A Transnosographic Self-Assessment of Social Cognitive Impairments (ACSO): First Data.

Social cognition refers to the mental operations underlying social interactions. Given the major role of social cognitive deficits in the disability associated with severe psychiatric disorders, they therefore constitute a crucial therapeutic target. However, no easily understandable and transnosographic self-assessment scale evaluating the perceived difficulties is available. This study aimed to analyze the psychometric qualities of a new self-administered questionnaire (ACSo) assessing subjective complaints in different domains of social cognition from 89 patients with schizophrenia, schizoaffective disorders, bipolar disorders or autism. The results revealed satisfactory internal validity and test-retest properties allowing the computation of a total score along with four sub scores (attributional biases, social perception and knowledge, emotional perception and theory of mind). Moreover, the ACSo total score was correlated with other subjective assessments traditionally used in cognitive remediation practice but not with objective neuropsychological assessments of social cognition. In summary, the ACSo is of interest to complete the objective evaluation of social cognition processes with a subjective assessment adapted to people with serious mental illness or autism spectrum disorder.

[Autism: a lifelong condition]. / L'autisme, un trouble de la vie entière.

Autism: a lifelong condition. Outcome in adults with autism is generally considered as poor. Autistic symptoms and behaviors improve throughout life whereas somatic or psychiatric conditions, largely ignored or misdiagnosed because of atypical sensory profile or langage deficit, result in decreased quality of life and in discomfort. Poor outcomes are mainly observed but recovery or optimal outcomes have been described in the last decade studies. Despite autism heterogeneity, it is essential to recognize physical comorbidities and mental health conditions to treat them and to plan health education and healthcare for this specific population. It is particularly important to provide and develop specific educational, health, social and cognitive remediation supports not only for autistic children but also during transition to adulthood.

L'autisme, un trouble de la vie entière. Bien que la symptomatologie des troubles du spectre de l'autisme évolue positivement avec l'âge, la qualité de vie des autistes à l'âge adulte est régulièrement qualifiée de « pauvre ¼. Ce paradoxe s'explique probablement par l'association comorbide fréquente de ces troubles à de nombreuses affections somatiques ou psychiatriques plus complexes à diagnostiquer chez ces personnes du fait de leurs profils cognitif, sensoriel, langagier atypiques. Ces comorbidités émergentes à partir de l'adolescence ou de l'âge adulte viennent souvent ternir un tableau évolutif qui pourrait être optimal, sous réserve du possible repérage diagnostique chez les acteurs de santé de première ligne, d'actes de prévention adaptés aux personnes souffrant de handicaps psychiques et du développement de soins et accompagnement spécifiques aux adultes avec des troubles du spectre de l'autisme visant le rétablissement, voire la rémission pour une inclusion sociale optimale.

From "under" to "over" social cognition in schizophrenia: Is there distinct profiles of impairments according to negative and positive symptoms?

Interactions between social cognition and symptoms of schizophrenia have been investigated, but mostly component by component. Here we tested the assumption that two categories of deficits exist depending on clinical profiles, one corresponding to a defect in social cognition - "under-social cognition" - and one corresponding to excessive attributions leading to social cognitive impairments - "over-social cognition". To conduct the investigation, we performed a Hierarchical Clustering Analysis using positive and negative symptoms in seventy patients with schizophrenia and we compared the clusters obtained to a group of healthy controls on social cognitive measures. We distinguished two social cognitive profiles based on prevailing symptoms for emotion processes and Theory of Mind. Actually, patients with negative symptoms showed lower performances in emotion recognition task than both those with positive symptoms and controls. Concerning Theory of Mind, patients with positive symptoms had a significant tendency to make over interpretative errors than both patients with negative symptoms and controls. For other processes assessed, further explorations are needed. Actually, concerning social perception and knowledge both patients' groups presented significant impairments compared to controls. Assessment of attribution bias showed that patients in the positive group presented a significant hostility bias and a higher intentionality score compared to healthy controls. These results favor the existence of different categories of impairments depending more on the clinical characteristics of patients than on nosographical categories, but further investigations are now necessary to specify these profiles. It nevertheless showed the importance of assessing symptoms in relationship with cognitive functioning.

Brain mechanisms involved in angry prosody change detection in school-age children and adults, revealed by electrophysiology.

Voices transmit social signals through speech and/or prosody. Emotional prosody conveys key information about the emotional state of a speaker and is thus a crucial cue that one has to detect in order to develop efficient social communication. Previous studies in adults reported different brain responses to emotional than to neutral prosodic deviancy. The aim of this study was to characterize such specific emotional deviancy effects in school-age children. The mismatch negativity (MMN) and P3a evoked potentials, reflecting automatic change detection and automatic attention orienting, respectively, were obtained for neutral and emotional angry deviants in both school-age children (n = 26) and adults (n = 14). Shorter latencies were found for emotional than for neutral preattentional responses in both groups. However, whereas this effect was observed on the MMN in adults, it appeared in an early discriminative negativity preceding the MMN in children. A smaller P3a amplitude was observed for the emotional than for the neutral deviants at all ages. Overall, the brain responses involved in specific emotional change processing are already present during childhood, but responses have not yet reached an adult pattern. We suggest that these processing differences might contribute to the known improvement of emotional prosody perception between childhood and adulthood.

A strategic plan to identify key neurophysiological mechanisms and brain circuits in autism.

Autism and Autism Spectrum Disorder (ASD) cover a large variety of clinical profiles which share two main dimensions: social and communication impairment and repetitive behaviors or restricted interests, which are present during childhood. There is now no doubt that genetic factors are a major component in the etiology of autism but precise physiopathological pathways are still being investigated. Furthermore, developmental trajectories combined with compensatory mechanisms will lead to various clinical and neurophysiological profiles which together constitute this Autism Spectrum Disorder. To better understand the pathophysiology of autism, comprehension of key neurophysiological mechanisms and brain circuits underlying the different bioclinical profiles is thus crucial. To achieve this goal we propose a strategy which investigates different levels of information processing from sensory perception to complex cognitive processing, taking into account the complexity of the stimulus and whether it is social or non-social in nature. In order to identify different developmental trajectories and to take into account compensatory mechanisms, we further propose that such protocols should be carried out in individuals from childhood to adulthood representing a wide variety of clinical forms.

Facial Expression Related vMMN: Disentangling Emotional from Neutral Change Detection.

Detection of changes in facial emotional expressions is crucial to communicate and to rapidly and automatically process possible threats in the environment. Recent studies suggest that expression-related visual mismatch negativity (vMMN) reflects automatic processing of emotional changes. In the present study we used a controlled paradigm to investigate the specificity of emotional change-detection. In order to disentangle specific responses to emotional deviants from that of neutral deviants, we presented neutral expression as standard stimulus (p = 0.80) and both angry and neutral expressions as deviants (p = 0.10, each). In addition to an oddball sequence, an equiprobable sequence was presented, to control for refractoriness and low-level differences. Our results showed that in an early time window (100-200 ms), the controlled vMMN was greater than the oddball vMMN only for the angry deviant, suggesting the importance of controlling for refractoriness and stimulus physical features in emotion related studies. Within the controlled vMMN, angry and neutral deviants both elicited early and late peaks occurring at 140 and 310 ms, respectively, but only the emotional vMMN presented sustained amplitude after each peak. By directly comparing responses to emotional and neutral deviants, our study provides evidence of specific activity reflecting the automatic detection of emotional change. This differs from broader "visual" change processing, and suggests the involvement of two partially-distinct pre-attentional systems in the detection of changes in facial expressions.

Atypical Brain Mechanisms of Prediction According to Uncertainty in Autism.

Resistance to change is often reported in autism and may arise from an inability to predict events in uncertain contexts. Using EEG recorded in 12 adults with autism and age-matched controls performing a visual target detection task, we characterized the influence of a certain context (targets preceded by a predictive sequence of three distinct stimuli) or an uncertain context (random targets) on behavior and electrophysiological markers of predictive processing. During an uncertain context, adults with autism were faster than controls to detect targets. They also had an enhancement in CNV amplitude preceding all random stimuli-indexing enhanced preparatory mechanisms, and an earlier N2 to targets-reflecting faster information processing-compared to controls. During a certain context, both controls and adults with autism presented an increase in P3 amplitude to predictive stimuli-indexing information encoding of the predictive sequence, an enhancement in CNV amplitude preceding predictable targets-corresponding to the deployment of preparatory mechanisms, and an earlier P3 to predictable targets-reflecting efficient prediction building and implementation. These results suggest an efficient extraction of predictive information to generate predictions in both controls and adults with autism during a certain context. However, adults with autism displayed a failure to decrease mu power during motor preparation accompanied by a reduced benefit in reaction times to predictable targets. The data reveal that patients with autism over-anticipate stimuli occurring in an uncertain context, in accord with their sense of being overwhelmed by incoming information. These results suggest that adults with autism cannot flexibly modulate cortical activity according to changing levels of uncertainty.

Detection of eating disorders in patients: validity and reliability of the French version of the SCOFF questionnaire.

BACKGROUND & AIMS: Although eating disorders prevalence is increasing, they are often under diagnosed in cases of unspecific signs of malnutrition. Screening scales may allow earlier diagnosis and nutritional intervention. This study aimed to evaluate the validity of the French version (SCOFF-F) of the SCOFF questionnaire for the detection of eating disorders among a female patient population referred to a clinical nutrition unit. METHODS: After answering the 5 dichotomous questions of the paper version of SCOFF-F, patients were evaluated by one eating disorders specialist blinded to questionnaire results, using the MINI and Diagnosis and Statistical Manual for Mental diseases (DSM-IV) criteria as a gold standard. RESULTS: Patients with anorexia nervosa (n = 67) and with bulimia nervosa (n = 45) were assessed. Age-matched healthy female students (n = 114) served as control group. At a cut-off of two positive responses, the sensibility, specificity and the area under the curve of SCOFF-F were 94.6%, 94.7% and 97.9% respectively. Cohen's kappa coefficient between SCOFF-F and MINI results was 89%. CONCLUSIONS: The results of this study confirm the reliability of SCOFF-F as a screening and diagnostic-facilitating test for eating disorders in a French-speaking female patient population. SCOFF-F should help professionals in clinical nutrition to achieve earlier diagnosis and care of eating disorder patients.

Obsessive compulsive disorder as a cause of atypical eating disorder: a case report.

OBJECTIVE: To describe a case of an atypical eating disorder with a diagnosis of obsessive-compulsive disorder and discuss the phenomenological and neurobiological aspects links between the disorders. CASE: a 20-year-old Caucasian woman presented with obsessive-compulsive disorder followed by altered eating habits with major weight loss and amenorrhea. The medical workup, treatment and outcome are described. Using cognitive-behavioural therapy, clomipramine and enteral nutrition, weight gain and disappearance of restrictive and obsessive-compulsive behaviours were obtained. CONCLUSION: Available evidence in the literature suggests a continuum in eating disorder and obsessive compulsive disorder. Our case illustrates that an obsessive-compulsive disorder may precede or precipitate the development of an eating disorder and highlights the importance of a precise differential diagnosis in eating disorders clinics.

[Treatment of schizophrenia]. / Traitements des schizophrénies.

Efficacy of neuroleptic treatment is well recognized in the treatment of schizophrenia. Both "Practice Guideline of Paris" (1994) and "the Practice Guideline of the APA" (1997) could advise psychiatrists in the choice of therapeutic strategies. The early recognition and management of a first episode of schizophrenia and the maintenance of antipsychotic medication at lower doses (for at least one year after a first episode, and five years after two or more relapses) seem to influence positively the long-term outcome of the disease. Despite the advantages of atypical neuroleptics with regard to extrapyramidal symptoms and their clinical efficacy in the short term treatment of schizophrenia, these treatments induce other side effects (cardiovascular or metabolic) that need to be further investigated; in addition, their long-term efficacy has not been adequately studied.