Down syndrome regression disorder, a case series: Clinical characterization and therapeutic approaches.

Down syndrome (DS) is one of the most frequent genetic disorders and represents the first cause of intellectual disability of genetic origin. While the majority of patients with DS follow a harmonious evolution, an unusual neurodevelopmental regression may occur, distinct from that described in the context of autism spectrum disorders, called down syndrome regression disorder (DSRD). Based on four patients, two males and two females, with age range between 20 and 24, treated at the Reference Center for Rare Psychiatric Disorders of the GHU Paris Psychiatry and Neurosciences [Pôle hospitalo-universitaire d'Évaluation Prévention et Innovation Thérapeutique (PEPIT)], we describe this syndrome, discuss its etiologies and propose therapeutic strategies. DSRD often occurs in late adolescence. There is a sudden onset of language disorders, loss of autonomy and daily living skills, as well as behavioral symptoms such as depression, psychosis, or catatonia. These symptoms are non-specific and lead to an overlap with other diagnostic categories, thus complicating diagnosis. The etiologies of the syndrome are not clearly identified but certain predispositions of patients with trisomy 21 have suggested an underlying immune-mediated mechanism. Symptomatic therapeutic approaches (serotonergic antidepressants, atypical antipsychotics, benzodiazepines) were not effective, and generally associated with poor tolerance. Etiological treatments, including anti-inflammatory drugs and corticosteroids, led to partial or good recovery in the four cases. Early recognition of regressive symptoms and rapid implementation of adapted treatments are required to improve the quality of life of patients and their families.

Influence of polygenic risk scores for schizophrenia and resilience on the cognition of individuals at-risk for psychosis.

Cognitive impairment is a core feature of schizophrenia which precedes the onset of full psychotic symptoms, even in the ultra-high-risk stage (UHR). Polygenic risk scores (PRS) can be computed for many psychiatric disorders and phenotyping traits, including scores for resilience. We explored the correlations between several PRS and neurocognition in UHR individuals. We included 107 UHR individuals; 29.9% of them converted to psychosis (UHR-C) while 57.0% did not (UHR-NC) during the 1-year follow-up. Cognitive performances were assessed with the Wechsler Adult Intelligence Scale estimating the Intelligence Quotient (IQ), the Trail Making Test, the verbal fluency, the Stroop test, and the Wisconsin card sorting test. Linear regression models were used to test their association with the PRS for schizophrenia, bipolar disorder, major depression, ADHD, cross-disorders, cognitive performance, intelligence, education attainment, and resilience to schizophrenia. UHR-C had a lower IQ than UHR-NC. The PRS for schizophrenia negatively correlated with IQ, while the PRS for cognitive performance and for resilience positively correlated with IQ. PRS for schizophrenia showed a significant correlation with working memory and processing speed indices. PRS for schizophrenia showed a higher effect on IQ in UHR-NC, and UHR-NC with high PRS for schizophrenia had a similar IQ as UHR-C. Conversely, UHR-C with a high PRS for resilience performed as well as UHR-NC. Our findings suggest that cognitive deficits may predate the onset of psychosis. The genetic architecture of schizophrenia seems to impacts the cognition in UHR-NC. Cognition is also mediated by PRS for resilience.

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.

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.

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.

Phenotypic continuum between autism and schizophrenia: Evidence from the Movie for the Assessment of Social Cognition (MASC).

Schizophrenic (SCZ) and autism (ASD) spectrum disorders share several features including social cognition impairments. In SCZ, the link between symptomatic dimensions and social cognition deficits remains unclear. The Movie for the Assessment of Social Cognition (MASC) test, available in several languages including English, investigates mental state attribution capabilities in complex interpersonal situations. After its translation into French, we used MASC to direct compare social cognition in 36 young participants with SCZ to 19 with ASD and 20 healthy controls (HC) matched for gender, age (18-25y.o.) and level of education. The MASC discriminated each group from the others, patients with SCZ exhibiting difficulties compared to ASD (MASC total score 28.1 (4) and 24.2 (6.6), respectively; p<.001). In the whole sample, MASC scores were inversely correlated with autistic traits, evaluated by autism quotient, and with disorganization symptoms. Finally, in SCZ, over-mentalizing difficulties were correlated with age at disease onset. Our results demonstrate the validity of the French version of the MASC and bring direct evidence supporting the hypothesis of a phenotypic continuum between autism and schizophrenia.

Neonatal Abstinence Syndrome Following Tianeptine Dependence During Pregnancy.

Tianeptine, an atypical antidepressant, has been found to exhibit a potential for abuse. The use of therapeutic doses of tianeptine during pregnancy has never raised safety concerns. However, the impact of tianeptine abuse on the mother-child dyad has never been assessed. We report herein the case of a female patient who presented with dependence on tianeptine, with the use of >650 mg of the drug per day. She had 2 successive pregnancies with similar doses. The state of dependence remained unidentified throughout the first pregnancy, but just after delivery, her full-term newborn exhibited unexpected neonatal abstinence syndrome (NAS). The NAS was successfully treated with morphine, although both the mother's and newborn's urine drug screen was negative. The causality of tianeptine in inducing NAS was retrospectively assessed as "probable" by using a validated causality algorithm. During the second pregnancy, this patient sought addiction treatment and was admitted for residential detoxification treatment in her seventh month of pregnancy. Delivery occurred at full term with a low birth weight neonate. No further developmental insults or medical problems were subsequently identified in the 2 children. Maternal tianeptine dependence during pregnancy may induce a type of NAS that mimics opiate NAS. This finding appears to be consistent with a recent finding of the agonist action of tianeptine on the opiate µ-receptor.

Cognitive and affective theory of mind abilities in alcohol-dependent patients: the role of autobiographical memory.

BACKGROUND: Many studies of patients with alcohol dependence (AD) have highlighted their difficulty in identifying both their own emotional state and those of a social partner. We examined (1) the cognitive and affective theory of mind (ToM) abilities of AD patients and (2) how the efficiency of their autobiographical memory (AM) can affect the effectiveness of ToM ability. METHOD: In a cross-sectional design, AD patients (N=50) and healthy controls (N=30) completed a ToM movie paradigm (Versailles-Situational Intention Reading, V-SIR) in which they inferred the intentions of characters in movies depicting social interactions, and the "Reading the Mind in the Eyes" Test (RMET), which assessed the emotional dimension of the ToM. AM was investigated using the "Autobiographical Memory Interview" (AMI) to assess both episodic and semantic components of AM. RESULTS: Concerning ToM, patients with AD showed lower performance in the RMET than control participants, whereas no difference was observed on the V-SIR test. AD patients had lower scores than controls on the AMI, for both episodic and semantic components and for different periods of life. A multiple linear regression analysis also showed that AM deficits might predict lower ToM performance, especially for the RMET task. CONCLUSIONS: Patients with AD have a specific affective ToM deficit. They used episodic memories to perceive the emotions of others, whereas controls used preferentially semantic memories to perform the task. Both these deficits could constitute a risk of relapse and should be a target for psychotherapeutic interventions.

Subjects at Ultra High Risk for psychosis have 'heterogeneous' intellectual functioning profile: a multiple-case study.

In Ultra High Risk (UHR) studies, intellectual functioning is commonly assessed using premorbid IQ tools as a covariate. The aim of this study was to show that the use of the Wechsler Adult Intelligence Scale (WAIS) could yield accurate neuropsychological profiling and that an alternative approach such as a multiple-case study could be a more interesting way to isolate discrete cognitive processes in the early stage of illness. The studied population consisted of 198 adolescents and young adults (16-30 y.o.) referred to our outpatient clinic. After the CAARMS' interview, we defined 3 subgroups: UHR (N=104), First Episode (FE; N=30), and Help-Seekers (HS; N=64) who were neither UHR nor psychotic. Intellectual functioning was assessed by the WAIS-III (9 subtests version) and 'heterogeneous' intellectual profiles were defined based on the existence of a 3-point difference in scoring at subtests constitutive of the same WAIS index. While UHR did not differ from FE or HS on WAIS' scores and sub-scores, the multiple-case study indicated a higher proportion of 'heterogeneous' profiles in the Verbal Comprehension Index in the UHR sample than in FE and HS (p=0.04). The disease progression could heterogeneously impact on specific domains, in patterns depending on the stage of the illness. This approach exploring intra-subject WAIS performances might be more relevant than the use of global scores in detecting the subtle cognitive alteration of emerging psychosis.