[A mentalization-based perspective on childhood autism treatment]. / Perspective de prise en charge d'enfants atteints de troubles du spectre autistique par psychothérapie inspirée des thérapies basées sur la mentalisation.

Mentalization is a process by which a subject makes sense of both his own mental representations and of those around him. Disturbances in the mentalization process are found in several psychiatric disorders, notably borderline personality disorders for which mentalization-based treatments (MBT) have been developed and evaluated. Children with Autism Spectrum Disorder (ASD) display a theory of mind impairments, which corresponds to disturbances in the mentalization process. Although no MBT protocol for patients with ASD has been described in the literature, such treatment appears promising to improve theory of mind and functional outcome of these children. In this paper, we propose to discuss the theoretical ground of MBT therapeutic effect in children with ASD without intellectual disabilities and to describe a clinical protocol to test this perspective.

Are circadian rhythms new pathways to understand Autism Spectrum Disorder?

Autism Spectrum Disorder (ASD) is a frequent neurodevelopmental disorder. ASD is probably the result of intricate interactions between genes and environment altering progressively the development of brain structures and functions. Circadian rhythms are a complex intrinsic timing system composed of almost as many clocks as there are body cells. They regulate a variety of physiological and behavioral processes such as the sleep-wake rhythm. ASD is often associated with sleep disorders and low levels of melatonin. This first point raises the hypothesis that circadian rhythms could have an implication in ASD etiology. Moreover, circadian rhythms are generated by auto-regulatory genetic feedback loops, driven by transcription factors CLOCK and BMAL1, who drive transcription daily patterns of a wide number of clock-controlled genes (CCGs) in different cellular contexts across tissues. Among these, are some CCGs coding for synapses molecules associated to ASD susceptibility. Furthermore, evidence emerges about circadian rhythms control of time brain development processes.

[Childhood onset schizophrenia: current data and therapeutic approach]. / La schizophrénie infantile : données actuelles et principes de prise en charge thérapeutique.

Childhood schizophrenia is a rare but serious developmental disorder affecting most of the fields involved in the child's adaptive functioning: motor, emotional, cognitive, and social. The clinical expression of the disorder mainly depends on the child's age and the IQ level at the time the first clinical symptoms appear. The progression of childhood schizophrenia is generally poor, with different outcome studies suggesting a continuity of the process between childhood and adulthood. This stresses the importance of diagnosing the disorder early and initiating the adapted therapeutic measures as quickly as possible, including cognitive remediation (a new therapeutic tool to correct or anticipate cognitive disorders), which can prevent pejorative development.

[Emotional processes in schizophrenia: investigation of the evaluative component]. / Processus émotionnel dans la schizophrénie: étude de la composante d'évaluation.

Schizophrenia is a disease that constitutes a particularly relevant way to investigate emotional processing. Indeed, major clinical signs of emotional disturbance (eg, anhedonia) suggest that some emotional mechanisms are defective in patients with schizophrenia. Evaluation can be considered as a fundamental component of the emotional system (28) and the first aim of the present study was to test the polarity hypothesis according to which different mechanisms are involved in the evaluation of positive vs negative emotional events. The second aim was to disentangle a -paradox emerging from the schizophrenia literature. On one hand, the tendency that schizophrenic patients have to under-evaluate the level of unpleasantness of negative stimuli suggests a deficit in the evaluation of negative events. For instance, it was proposed that patients with schizophrenia show a major deficit in the recognition of negative emotions, but a preserved recognition of positive emotions. On the other hand, the fact that anhedonia constitutes a critical cli-nical feature of schizophrenia suggests a deficit in the eva-luation of positive events. For instance, Crespo-Facorro et al. showed that patients with schizophrenia had a tendency to under-evaluate the level of pleasantness of positive stimuli but correctly evaluated the level of unpleasantness of negative stimuli. Given the importance of the social component in the analysis of deficits in patients with schizophrenia, we hypothesized that the variation of this component in stimuli used in the literature could explain the apparently inconsistent results described above. For example, the Bell et al. study used social stimuli whereas the Crespo-Facorro et al. study used non-social stimuli. Therefore, in our study, we have decided to manipulate the social component of stimuli. Another research issue of the present experiment was to study the explicit and/or implicit mode of processing of eva-luation in schizophrenic patients. In general, the experimental logic was to expect interaction effects between the factors polarity (negative vs positive) and participants (schizophrenic patients vs controls). Moreover, given the potential importance of the social component, a three-way interaction of the factors polarity, participants, and social component was expected. Finally, the experimental paradigm allowed us to search for dissociations in the context of both explicit and implicit evaluation. Stimuli used were negative and positive emotional pictures from the International Affective Picture System. Stimuli were chosen so that the mean valence -ratings of negative and positive pictures were at the same distance from neutrality. The factor arousal was controlled so that negative and positive pictures had equivalent mean arousal ratings. The social component factor was operatio-nalized by selecting pictures that either depicted or not a social scene. A fundamental criterion was that all social pictures were depicting at least one human being (eg, a wedding or a funeral), whereas non-social pictures never depicted any human being (eg, animals and landscapes). An upper and a lower border, that were either identical or different, were added to each picture. In a first experiment (the "implicit-task experiment"), patients with schizophrenia and matched controls were requested to decide whether the two borders surrounding the pictures were identical or different. Asking participants to process the borders was an experimental ruse to test if emotional processing takes place even when it is not task-relevant, and therefore if it is implicit. In a second experiment (the "explicit-task experiment"), the same participants were requested to evaluate whether the pictures were pleasant or unpleasant. Analyses of variance (ANOVA) were computed on response time and number of correct responses for both tasks. An important result was the observation of the expected three-way interaction effect of the factors polarity, participants, and social component on response time in the explicit task F(1, 19)=4.8, p<0.05. Critically, we observed that, for non-social stimuli, the interaction effect of the factors participants and polarity on response time was significant in the explicit task, F(1, 8)=4.9, p<0.05. These results are consistent with the polarity hypothesis and suggest a deficit in the processing of non-social positive stimuli in patients with schizophrenia. The expected three-way interaction effect was also observed on the number of correct responses in the explicit task F(1, 19)=5, p<0.04. For this task, we critically observed that, for social stimuli, the interaction effect of the factors participants and polarity on the number of correct responses was significant F(1, 19)=8.4, p<0.04. These results are also consistent with the polarity hypothesis and suggest a deficit in the processing of social negative stimuli in patients with schizophrenia. Moreover, let us notice that a comparison of the performances of the two groups revealed that patients made significantly more errors than controls for the evaluation of non-social positive stimuli, F(1, 19)=10,5, p<0.001, but not for the evaluation of non-social negative stimuli, F<1. In the implicit-task experiment, the analysis revealed that patients had a tendency to make more errors in the judgment of borders configuration for negative than for positive stimuli, whereas control participants showed the opposite tendency F(1, 19)=5.7, p<0.03, for the interaction of the factors polarity and participants. This result is consistent with the idea that distinct cognitive mechanisms are involved in the evaluation of positive vs negative emotional events even in the context of implicit processing. In conclusion, results obtained support the hypothesis according to which different cognitive mechanisms are involved in the evaluation of positive vs negative emotional events. Moreover, results suggest that patients with schizophrenia show a deficit in hedonic judgment of social negative and non-social positive stimuli. The later result indicates that the paradox described above becomes clearer whenever the social component of emotional stimuli happens to be taken into account. Results suggest that the polarity and the social component of events evaluated by patients with schizophrenia are critical parameters that should be considered in forthcoming studies that investigate affect disorders in schizophrenia.

Modulating the experience of agency: a positron emission tomography study.

This study investigated agency, the feeling of being causally involved in an action. This is the feeling that leads us to attribute an action to ourselves rather than to another person. We were interested in the effects of experimentally modulating this experience on brain areas known to be involved in action recognition and self-recognition. We used a device that allowed us to modify the subject's degree of control of the movements of a virtual hand presented on a screen. Four main conditions were used: (1) a condition where the subject had a full control of the movements of the virtual hand, (2) a condition where the movements of the virtual hand appeared rotated by 25 degrees with respect to the movements made by the subject, (3) a condition where the movements of the virtual hand appeared rotated by 50 degrees, and (4) a condition where the movements of the virtual hand were produced by another person and did not correspond to the subject's movements. The activity of two main brain areas appeared to be modulated by the degree of discrepancy between the movement executed and the movement seen on the screen. In the inferior part of the parietal lobe, specifically on the right side, the less the subject felt in control of the movements of the virtual hand, the higher the level of activation. A reverse covariation was observed in the insula. These results demonstrate that the level of activity of specific brain areas maps onto the experience of causing or controlling an action. The implication of these results for understanding pathological conditions is discussed.

Anticipating incoming events: an impaired cognitive process in schizophrenia.

Intentions are central to guiding actions to their completion because they generate expectations which precede the realization of a task. This ability to manage time was investigated by using a cognitive task which involves several highly integrated processes: sequential learning, explicit processing, and working memory. In this task, participants are required to explicitly learn a repeating color sequence before receiving an instruction to give an anticipatory motor response concerning the next element. Two types of sequences (temporal and spatial) and three experimental conditions were tested in both a group of normal participants and a group of schizophrenic patients. Schizophrenics were included because their condition is known to alter conscious executive function. Our results showed that schizophrenic patients have a strong deficit in performing anticipation tasks. Although they learned the sequences almost normally, their anticipatory ability was reduced in comparison to normal participants in all the tested conditions. These results expand the notion of a working memory deficit in schizophrenia and bear strong implications for understanding executive disorders observed in such patients.

Defective recognition of one's own actions in patients with schizophrenia.

OBJECTIVE: The possibility that delusions of influence could be related to abnormal recognition of one's own actions was investigated in persons with schizophrenia. METHOD: Schizophrenic patients with (N=6) and without (N=18) delusions of influence were compared with normal subjects (N=29) on an action recognition task. The image of a virtual right hand holding a joystick was presented to the subjects through a mirror so that the image was superimposed on their real hand holding a real joystick. Subjects executed discrete movements in different directions. Angular biases and temporal delays were randomly introduced in some trials, such that the movement of the virtual hand departed from the movement executed by the subjects. After each trial, subjects were asked whether the movement they saw was their own. RESULTS: Compared with normal subjects, both patient groups made significantly more recognition errors in trials with temporal delays. In trials with angular biases, the error rate of patients with delusions of influence significantly differed from that of comparison subjects and from that of patients without delusions of influence. CONCLUSIONS: The findings support the hypothesis that delusions of influence are associated with a quantifiable difficulty in correct self-attribution of actions. This difficulty may be related to a specific impairment of a neural action attribution system.

Peripheral auditory asymmetry in infantile autism.

Difficulty in filtering relevant auditory information in background noise is one of the features of autism. Auditory filtering processes can be investigated at the peripheral level as they are hypothesized to involve active cochlear mechanisms which are regulated by the efferent activity of the medial olivocochlear (MOC) system. The aim of the present work was therefore to assess these peripheral auditory processes in 22 children and adolescents with autism compared with age- and gender-matched normal controls. Active cochlear mechanisms were evaluated with transiently evoked otoacoustic emissions (TEOAEs) and MOC system efficiency was assessed via TEOAEs which are decreased when stimulating the contralateral ear with noise. The MOC system evaluation was performed on 18 of the 22 children. In both studies, results were analysed according to age (from 4 to 10 years and from 11 to 20 years). The main result concerns the asymmetry of the efferent system which differs in individuals with autism. Several neural processes might be hypothesized as involved in the results obtained as the MOC system which originates in the brainstem received regulating controls from upper brain structures including auditory cortex. Lateralization abnormalities at the auditory periphery may reflect indirectly a problem at a higher level of auditory processing. A second important result shows a decrease in TEOAE amplitude with age, in patients, that may correspond to a decrease in hearing sensitivity.

Abnormal peripheral auditory asymmetry in schizophrenia.

OBJECTIVE: Auditory processing difficulties have been reported in schizophrenia. This study explores peripheral auditory function in patients with schizophrenia in whom certain early disturbances of auditory message filtering have been found and may be associated with certain abnormalities which are particularly localised in the left temporal lobe. METHODS: Otoacoustic emissions, including click evoked and spontaneous emissions and measurements of functioning of the medial olivocochlear efferent system were obtained from 12 chronic schizophrenic patients and compared with normative data recorded from 12 normal controls. RESULTS: Otoacoustic emission amplitudes and medial olivocochlear functioning were similar between the normal controls and schizophrenic patients; the schizophrenic patients did, however, differ from the normal controls in otoacoustic emission intensity and in medial olivocochlear asymmetry. A tendency to a higher number of spontaneous peaks, and a significantly higher click evoked otoacoustic emission response amplitude were found in the right ear compared with the left ear of schizophrenic patients. For the medial olivocochlear system, whereas normal controls showed greater attenuation in the right than in the left ear, schizophrenic patients lacked such an asymmetry. CONCLUSION: In the absence of any attention task, the findings show disturbed peripheral lateralisation in schizophrenia of mechanisms involved in auditory information filtering. Such a lack of right ear advantage in medial olivocochlear functioning may thus be a peripheral reflection of central lateralisation anomalies.

Cognitive sequence processing and syntactic comprehension in schizophrenia.

It has been repeatedly demonstrated that schizophrenic patients are impaired in the comprehension of sentences with complex syntax. We investigated the hypothesis that this syntactic comprehension impairment in schizophrenia is not a purely linguistic dysfunction, but rather the reflection of a cognitive sequence processing impairment that is revealed as task complexity increases. We tested 10 schizophrenic patients using a standard measure of syntactic comprehension, and a non-linguistic sequence processing task, both of which required simple and complex transformation processing. Patients' performance impairment on the two tasks was highly correlated (r2 = 0.84), and there was a significant effect for complexity, independent of the task. These results are quite similar to those of aphasic patients with left hemisphere lesions. This suggests that syntactic comprehension deficits in schizophrenia reveal the dysfunction of cognitive sequence processing mechanisms that can be expressed both in linguistic and non-linguistic sequence tasks.

Confusion between silent and overt reading in schizophrenia.

The present study was aimed at investigating whether schizophrenic patients are impaired in monitoring their own speech. In particular, we attempted to assess their ability to discriminate between overt and covert speech in a reading task, in order to verify whether they can correctly recollect the modality in which an internally generated action is produced. Subjects were asked to read either silently or aloud, items from a list of words. After a delay of 5 min, they were required to indicate in a new list which words had been read previously (either silently or overtly), or had never been presented during the reading task. With respect to normal controls, schizophrenic patients showed a significant bias to report that they had read aloud words which they had actually read silently, or which were absent during the reading task. The results are discussed in relation to recent neuroimaging studies on inner and overt speech in hallucinating schizophrenic patients. Our data favour the hypothesis that the inability to correctly discriminate between inner and overt speech may play a role in the onset of schizophrenic hallucinations.

Gaze discrimination is unimpaired in schizophrenia.

Interpersonal communication is largely dependent on interpretation of facial expression and emotion. Difficulties in face processing, and more specifically in gaze discrimination, have been described in schizophrenic patients. According to Baron-Cohen (Mindblindness. M.I.T. Press, Cambridge, MA, 1995), gaze discrimination relies on the functioning of a specific cognitive module, the Eye Direction Detector (EDD). It has been proposed [Rosse et al. (1994) Gaze discrimination in patients with schizophrenia: preliminary report. American Journal of Psychiatry 151, 919-921] that an impairment in gaze discrimination is present in schizophrenia, and plays a fundamental role in inducing the paranoid symptoms reported by many patients. However, in the previous studies, gaze direction detection and interpretation of gaze have never been completely dissociated. The present experiment attempts to test the schizophrenics' skill in a simple gaze direction detection task. A series of photographic portraits of models looking at different directions have been presented to 22 schizophrenic patients and 36 control subjects. For each portrait subjects were asked to determine whether gaze was directed to the right or to the left by pressing a keyboard key. A forced choice paradigm was used. No differences were reported between schizophrenic patients and control subjects. That is, in the present paradigm, schizophrenic patients did not show any specific impairment in detecting the direction of gaze of the portraits. The results are discussed according to the notion that a dissociation is present in schizophrenia between implicit and explicit processes. The present case illustrates how the more automatic elementary functions, such as the detection of gaze direction, may be spared in schizophrenic patients, whereas explicit cognitive functions are likely more affected.

Beyond consciousness of external reality: a "who" system for consciousness of action and self-consciousness.

This paper offers a framework for consciousness of internal reality. Recent PET experiments are reviewed, showing partial overlap of cortical activation during self-produced actions and actions observed from other people. This overlap suggests that representations for actions may be shared by several individuals, a situation which creates a potential problem for correctly attributing an action to its agent. The neural conditions for correct agency judgments are thus assigned a key role in self/other distinction and self-consciousness. A series of behavioral experiments that demonstrate, in normal subjects, the poor monitoring of action-related signals and the difficulty in recognizing self-produced actions are described. In patients presenting delusions, this difficulty dramatically increases and actions become systematically misattributed. These results point to schizophrenia and related disorders as a paradigmatic alteration of a "Who?" system for self-consciousness.

Anomia in major depressive state.

Anomia, or word finding difficulty, is a frequent clinical symptom of the depressive state. This study investigates naming and lexicalization processes (or word production processes) in 11 depressive patients (major depressive state), through a picture naming task of 53 images corresponding to low frequency words. Depressives showed significantly more anomia and made more naming errors (semantically related substitution words) than control subjects. Tip-of-the-tongue (TOT) states, which correspond to an impairment at a later stage of phonological encoding with partial activation of phonological shape, remained rare in depressives despite the increase of lexicalization difficulties observed. Anomia observed in depressives could thus be related to an impairment at the early stage of lexicalization or word production processes (pre-phonological item selection and access, or storage of the semantic lexical item in Working Memory for further phonological encoding), without lexical-semantic disorganization. We discuss the relationship between such an elementary speech production disorder and cognitive impairments demonstrated in the depressive state (deficit of effortful and attentional processes, impairment in activation or initiation of cognitive processes and responses).

Semantic priming in major depressive state.

We studied semantic priming in 20 major depressive subjects. The methodology used was a visual lexical decision task. Semantic priming is the facilitation of target word recognition (shortening of response time) by the prior presentation of a semantically related context (a prime word). It relies on semantic processing of words and context, facilitating early cognitive stages of response. Varying the temporal interval between prime and target words onset allows us to distinguish between two priming mechanisms, relying on more automatic (test 1) or more controlled (i.e. attention dependent) (test 2) information processing. We observe a significant retardation for words and pseudo-words in depressives (in relation to controls) in both tests. In spite of a general retardation and increase of response times in depressives, semantic priming is evident in both groups and both tests, and does not differ significantly between depressive and control groups in either automatic or controlled conditions. Theses results confirm that semantic processing is not impaired in depression, and are discussed with regard to the hypothesis of an effortful processing impairment in depression, and to depressive retardation.

[Basic cognitive-perceptive module in schizophrenics]. / Etude d'un module cognitif perceptif élémentaire chez les schizophrènes.

A specific deficit in gaze discrimination has been hypothesized for schizophrenic patients (Rosse et al., 1994). Gaze discrimination is a basic ability for animals as well as for human beings. It plays an important role in mutual control of social interactions. According to Baron-Cohen (1995), sensitivity to eye gaze relies on a specific cognitive module, the Eye Direction Detector (EDD). The author distinguishes three basic functions of the EDD; first, the EDD is involved in eyes detection; second, the EDD is used in order to establish direction of gaze, and specially to compute whether the eyes one is looking at are directed to the subject or somewhere else; third, the EDD is implied in interpretation of gaze as seeing. Rosse et al. (1994) tested subjective impressions concerning gaze discrimination in a group of schizophrenic patients. Schizophrenics reported the subjective impression of being looked at by the portraits significantly more often than controls. The authors concluded that a specific impairment in gaze detection is present in the patients, and that it may be responsible for the paranoid symptoms often reported in schizophrenia. However, it seems difficult to assert that a response bias in schizophrenics toward perceiving faces as looking at them results from the deficit of an elementary perceptual module responsible for the detection of eye-direction. Rather we suspect such a bias to be the consequence of an impairment of the more complex level of mindreading, responsible for the interpretation of gaze as seeing in terms of mental states. The aim of the present experiment was to test in a more specific way the elementary gaze discrimination system. A series of portraits of models looking at five different directions (-30 degrees, -15 degrees, 0 degree, 15 degrees, 30 degrees), have been presented to 22 schizophrenic patients and 36 normal control subjects. In each trial one portrait was presented. Subjects were asked to determine the direction of its gaze by pressing the "z-key" (left side of the keyboard) if the portrait was looking to the left, and the "/-key" (right side of the keyboard) if the portrait was looking to the right. For each trial, we recorded both the side of the response (left key or right key) and the corresponding reaction time (RT). For the purpose of the analysis, the mean numbers of left responses were computed for each subject. The mean numbers of left responses recorded for each direction of gaze did not significantly differ between patients and controls. That is schizophrenic patients are not impaired in the gaze discrimination task used in the present study. In Rosse's experiment, subjects were required to decide whether the portrait on the screen was looking at them or not. On the contrary, in our task, subjects were simply required to state whether gaze was directed to the right or to the left. No explicit judgment was required as to whom or what gaze was directed. Therefore, we can assume that the present paradigm investigated the functioning of a more basic process than that tested by Rosse et al. Our data are consistent with those reporting that basic cognitive processes are unimpaired in schizophrenia, whereas explicit processes are extensively affected.

Schizophrenics learn surface but not abstract structure in a serial reaction time task.

We investigated the hypothesis that explicit cognitive processing is impaired in schizophrenia, while implicit processing is left largely intact, using a single sequence learning paradigm that simultaneously measures surface and abstract structure learning. Surface structure is the serial order of sequence elements. Abstract structure is defined in terms of the relationships between repeating elements. Sequences ABCBAC and DEFEDF thus share the same abstract structure, with different surface structures. Learning abstract structure requires explicit processing, while surface structure can be learned in implicit conditions. We predict however, that in explicit conditions, schizophrenics should learn surface structure but not abstract structure. Indeed, schizophrenic patients learned surface structure, but failed to learn abstract structure, demonstrating that implicit sequence processing is spared in schizophrenia while explicit sequence processing is impaired.

Looking for the agent: an investigation into consciousness of action and self-consciousness in schizophrenic patients.

The abilities to attribute an action to its proper agent and to understand its meaning when it is produced by someone else are basic aspects of human social communication. Several psychiatric syndromes, such as schizophrenia, seem to lead to a dysfunction of the awareness of one's own action as well as of recognition of actions performed by others. Such syndromes offer a framework for studying the determinants of agency, the ability to correctly attribute actions to their veridical source. Thirty normal subjects and 30 schizophrenic patients with and without hallucinations and/or delusional experiences were required to execute simple finger and wrist movements, without direct visual control of their hand. The image of either their own hand or an alien hand executing the same or a different movement was presented on a TV-screen in real time. The task for the subjects was to discriminate whether the hand presented on the screen was their own or not. Hallucinating and deluded schizophrenic patients were more impaired in discriminating their own hand from the alien one than the non-hallucinating ones, and tended to misattribute the alien hand to themselves. Results are discussed according to a model of action control. A tentative description of the mechanisms leading to action consciousness is proposed.