From swing to cane: Sex differences of EEG resting-state temporal patterns during maturation and aging.

While many insights on brain development and aging have been gained by studying resting-state networks with fMRI, relating these changes to cognitive functions is limited by the temporal resolution of fMRI. In order to better grasp short-lasting and dynamically changing mental activities, an increasing number of studies utilize EEG to define resting-state networks, thereby often using the concept of EEG microstates. These are brief (around 100 ms) periods of stable scalp potential fields that are influenced by cognitive states and are sensitive to neuropsychiatric diseases. Despite the rising popularity of the EEG microstate approach, information about age changes is sparse and nothing is known about sex differences. Here we investigated age and sex related changes of the temporal dynamics of EEG microstates in 179 healthy individuals (6-87 years old, 90 females, 204-channel EEG). We show strong sex-specific changes in microstate dynamics during adolescence as well as at older age. In addition, males and females differ in the duration and occurrence of specific microstates. These results are of relevance for the comparison of studies in populations of different age and sex and for the understanding of the changes in neuropsychiatric diseases.

Does differential visual exploration contribute to visual memory impairments in 22q11.2 microdeletion syndrome?

BACKGROUND: Chromosome 22q11.2 microdeletion syndrome (22q11.2DS) is a genetic syndrome characterised by a unique cognitive profile. Individuals with the syndrome present several non-verbal deficits, including visual memory impairments and atypical exploration of visual information. In this study, we seek to understand how visual attention may contribute to memory difficulties in 22q11.2DS by tracking eye movements during the encoding phase of a visual short-term memory task. METHOD: Eye movements were recorded during a computerised version of the multiple-choice Benton Visual Retention Test, which consisted of exploring and then recognising complex visual stimuli. Seventy-four participants affected by 22q11.2DS were compared with 70 typically developing participants. RESULTS: Participants with 22q11.2DS performed less well than healthy controls on the task and spent more time and fixations on the principal (larger central) figures and less time and fixations on the smaller peripheral figures within the stimuli. CONCLUSIONS: This study is the first to investigate visual attention in 22q11.2DS during a memory task. The results delineate impaired processes during encoding that affect visual memory performance. The findings may be especially useful for informing interventions intended to boost visual learning in patients with 22q11.2DS.

Understanding others: a pilot investigation of cognitive and affective facets of social cognition in patients with 22q11.2 deletion syndrome (22q11DS).

BACKGROUND: Although significant impairments in the affective and cognitive facets of social cognition have been highlighted in patients with 22q11.2 deletion syndrome (22q11DS) in previous studies, these domains have never been investigated simultaneously within the same group of participants. Furthermore, despite theoretical evidence, associations between these two processes and schizotypal symptoms or social difficulties in this population have been scarcely examined. METHODS: Twenty-nine participants with 22q11DS and 27 typically developing controls (N = 5 siblings; N = 22 unrelated controls) aged between 11 and 21 years participated in the study. Both groups were matched for age and gender distribution. Two computerized social cognition tasks evaluating perspective and emotion recognition abilities were administered to all participants. The levels of schizotypal trait expression and social functioning were further investigated in both groups, based on a validated self-report questionnaire (Schizotypal Personality Questionnaire) and parental interview (Vineland Adaptive Behavior Scales). RESULTS: Participants with 22q11DS exhibited lower perspective-taking and emotion recognition capacities than typically developing controls. The two socio-cognitive dimensions investigated here were further correlated in healthy controls. The efficiency of perspective-taking processes (response time) was marginally related to the degree of schizotypal trait expression in patients with 22q11DS. CONCLUSIONS: This study first provides support for significant deficits in two core facets of social cognition in 22q11DS. The associations observed between the experimental tasks and measures of social functioning or schizotypal symptoms in 22q11DS open promising research avenue, which should be more deeply investigated in future studies.

Adolescence is the starting point of sex-dichotomous COMT genetic effects.

The catechol-o-methyltransferase (COMT) genetic variations produce pleiotropic behavioral/neuroanatomical effects. Some of these effects may vary among sexes. However, the developmental trajectories of COMT-by-sex interactions are unclear. Here we found that extreme COMT reduction, in both humans (22q11.2 deletion syndrome COMT Met) and mice (COMT-/-), was associated to cortical thinning only after puberty and only in females. Molecular biomarkers, such as tyrosine hydroxylase, Akt and neuronal/cellular counting, confirmed that COMT-by-sex divergent effects started to appear at the cortical level during puberty. These biochemical differences were absent in infancy. Finally, developmental cognitive assessment in 22q11DS and COMT knockout mice established that COMT-by-sex-dichotomous effects in executive functions were already apparent in adolescence. These findings uncover that genetic variations severely reducing COMT result in detrimental cortical and cognitive development selectively in females after their sexual maturity. This highlights the importance of taking into account the combined effect of genetics, sex and developmental stage.

[Detection and early treatment of subjects at high risk of clinical psychosis: Definitions and recommendations]. / Détection et traitement précoce des sujets à haut risque clinique de psychose : définitions et recommandations.

In children and adolescents, psychotic disorders already represent one of the leading causes of disability-adjusted life years. During the past two decades, early detection of risk for psychosis has been intensively investigated, and in particular, predictive power for early signs of risk has been initiated and translated into clinical practice. In particular, the attenuated and transient positive symptoms of the ultra-high risk criteria, and the basic symptom criterion "cognitive disturbances", open promising routes to an indicated prevention and have recently been considered by the European Psychiatric Association (EPA) as diagnostic criteria of a psychosis-risk syndrome. The EPA recently provided evidence-based recommendations on the early detection of clinical high risk (CHR) for psychosis in patients with mental distress. In 2015, experts in the field of early detection conducted a meta-analysis reporting on studies examining conversion rates to psychosis in non-overlapping samples meeting at least one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria, examining the effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates. In the 42 identified samples, comprising more than 4000 CHR patients who had been mainly identified by means of UHR criteria and/or the basic symptom criterion 'cognitive disturbances' (COGDIS), conversion rates showed considerable heterogeneity. While UHR and COGDIS criteria were related to comparable conversion rates until a 2-year follow-up, rates for COGDIS were significantly higher for follow-up periods beyond 2 years. Differences in onset and frequency requirements of symptomatic UHR criteria, or in their different consideration of functional decline, substance use and co-morbidity, did not seem to have an impact on conversion rates. The 'genetic risk and functional decline' UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for the early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states. The EPA guidance on early intervention aimed to provide evidence-based recommendations on early intervention in CHR states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were also made by experts in the field of early intervention in psychoses and derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. In addition to analyses of treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n=1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status. Overall, age-related specificities and developmental transitions in the early detection and intervention in psychoses should be better accounted for in future research.

No evidence for the presence of genetic variants predisposing to psychotic disorders on the non-deleted 22q11.2 allele of VCFS patients.

The velo-cardio-facial syndrome (VCFS) is caused by hemizygous deletions on chromosome 22q11.2. The VCFS phenotype is complex and characterized by frequent occurrence of neuropsychiatric symptoms with up to 25-30% of cases suffering from psychotic disorders compared with only ~1% in the general population (odds ratio≈20-25). This makes the 22q11.2 deletion one of the most prominent risk factors for schizophrenia. However, its penetrance for neuropsychiatric phenotypes is incomplete suggesting that additional risk factors are required for disease development. These additional risk factors could lie anywhere on the genome, but by reducing the normal diploid to a haploid state, the 22q11.2 deletion could result in the unmasking of otherwise recessive alleles or functional variants on the non-deleted 22q11.2 allele. To test this hypothesis, we captured and sequenced the whole 22q11.2 non-deleted region in 88 VCFS patients with (n=40) and without (n=48) psychotic disorders to identify genetic variation that could increase the risk for schizophrenia. Single nucleotide variants (SNVs), small insertions/deletions (indels) and copy number variants were called and their distributions were compared between the two diagnostic groups using variant-, gene- and region-based association tests. None of these tests resulted in statistical evidence for the existence of a genetic variation in the non-deleted allele that would increase schizophrenia risk in VCFS patients. Power analysis showed that our study was able to achieve >80% statistical power to detect association of a risk variant with an odd ratio of ⩾22. However, it is certainly under-powered to detect risk variant of smaller effect sizes. Our study did not provide evidence that genetic variants of very large effect size located on the non-deleted 22q1.2 allele in VCFS patients increase the risk for developing psychotic disorders. Variants with smaller effects may be located in the remaining 22q11.2 allele and elsewhere in the genome. Therefore, whole exome or even genome sequencing for larger sample size would appear to be the next logical steps in the search for the genetic modifiers of the 22q11.2-deletion neuropsychiatric phenotype.

Implication of reward alterations in the expression of negative symptoms in 22q11.2 deletion syndrome: a behavioural and DTI study.

BACKGROUND: Alterations of the reward system have been proposed as one of the core mechanisms underlying the expression of negative symptoms in schizophrenia. Specifically, deficits in specific reward components and white matter (WM) integrity of the reward system have been highlighted. The putative link between negative symptoms and the hedonic experience, or structural connectivity of the reward system has never been examined in the 22q11.2 deletion syndrome (22q11DS), a condition with increased risk for psychosis. METHOD: Anticipatory and consummatory dimensions of pleasure were assessed in participants with 22q11DS (N = 54) and healthy controls (N = 55). In patients with 22q11DS, the association between pleasure scores and positive or negative symptoms was investigated. Furthermore, WM integrity of the accumbofrontal tract was quantified using diffusion tensor imaging (DTI). Associations between DTI measures, pleasure dimensions and negative symptoms were examined. RESULTS: Patients with 22q11DS showed reduced anticipatory and consummatory pleasure compared to controls. Furthermore, anticipatory pleasure scores were negatively correlated to negative and positive symptoms in 22q11DS. WM microstructural changes of the accumbofrontal tract in terms of increased fractional anisotropy and reduced radial anisotropy were also identified in patients. However, no significant correlation between the DTI measures and pleasure dimensions or psychotic symptoms was observed. CONCLUSIONS: This study revealed that participants with 22q11DS differed in their experience of pleasure compared to controls. The anticipatory pleasure component appears to be related to negative and positive symptom severity in patients. Alterations of WM integrity of the accumbofrontal tract seem to be related to myelination abnormalities in 22q11DS patients.

Long-range dysconnectivity in frontal and midline structures is associated to psychosis in 22q11.2 deletion syndrome.

Patients affected by 22q11.2 deletion syndrome (22q11DS) present a characteristic cognitive and psychiatric profile and have a genetic predisposition to develop schizophrenia. Although brain morphological alterations have been shown in the syndrome, they do not entirely account for the complex clinical picture of the patients with 22q11DS and for their high risk of psychotic symptoms. Since Friston proposed the "disconnection hypothesis" in 1998, schizophrenia is commonly considered as a disorder of brain connectivity. In this study, we review existing evidence pointing to altered brain structural and functional connectivity in 22q11DS, with a specific focus on the role of dysconnectivity in the emergence of psychotic symptoms. We show that widespread alterations of structural and functional connectivity have been described in association with 22q11DS. Moreover, alterations involving long-range association tracts as well as midline structures, such as the corpus callosum and the cingulate gyrus, have been associated with psychotic symptoms in this population. These results suggest common mechanisms for schizophrenia in syndromic and non-syndromic populations. Future directions for investigations are also discussed.

Visual processing of emotional dynamic faces in 22q11.2 deletion syndrome.

INTRODUCTION: The 22q11.2 deletion syndrome (22q11DS) is a neurogenetic syndrome. Individuals affected by this syndrome present poor social functioning and a high risk for the development of psychiatric disorders. Accurate emotion recognition and visual exploration of faces represent important skills for appropriate development of social cognition in individuals with 22q11DS. For these reasons, there is elevated interest in establishing relevant ways to test the mechanisms associated with emotion recognition in patients with 22q11DS. METHODS: This study investigated emotional recognition and visual exploration of emotional faces in persons with 22q11DS, with a dynamic emotion task using an eye-tracking device. To our knowledge, no previous studies have used emotional dynamic stimuli with 22q11DS, despite improved ecological validity of dynamic stimuli compared with static images. Furthermore, these stimuli provide the opportunity to collect reaction times, as indicators of the emotional intensity necessary for identifying each emotion. RESULTS: In our task, we observed comparable accuracy in emotion recognition in the 22q11DS and healthy control groups. However, individuals with 22q11DS were slower to recognise the emotions. They also spent less time looking at the nose during happy and fearful faces. CONCLUSIONS: These results suggest that individuals with 22q11DS may need either more time or more pronounced emotional cues to correctly label facial expressions.

Schizotypal traits in adolescents with 22q11.2 deletion syndrome: validity, reliability and risk for psychosis.

BACKGROUND: Very little is known about the phenotypic expression of schizotypal traits in individuals with 22q11.2 deletion syndrome (22q11DS). The main purpose was to analyse the factorial structure, internal consistency and temporal stability of schizotypal traits, as well as their associations with prodromal states and clinical psychotic symptoms in adolescents with 22q11DS. METHOD: The sample comprised 61 adolescents with 22q11DS (mean = 14.95 years, s.d. = 2.13; n = 24 at follow-up). An age-matched comparison group (n = 61, mean = 15.44 years, s.d. = 1.76) was also included. The Schizotypal Personality Questionnaire (SPQ), the Structured Interview for Prodromal Syndromes, the Positive and Negative Syndrome Scale, and the Brief Psychiatric Rating Scale were used. RESULTS: Adolescents with 22q11DS scored higher than the control group on the interpersonal dimension and suspiciousness subscale of the SPQ. The analysis of the internal structure of the SPQ in the sample of 22q11DS participants yielded a three-component solution (cognitive-perceptual, interpersonal, and disorganized). In addition, internal consistency coefficients ranged between 0.63 and 0.91. The schizotypal traits were highly stable across a 3.6-year interval, and ranged from 0.50 to 0.63. Self-reported schizotypal traits correlated with interview-based ratings of prodromal states and psychotic symptoms. CONCLUSIONS: These results indicate that the SPQ may be a valid tool to assess schizotypal traits in adolescents with 22q11DS. The identification of a reliable self-report instrument for use in individuals with learning disabilities and at genetic high risk for psychosis could be useful in clinical and research settings. Assessment of schizotypal traits may be used as a distal risk marker and in a close-in strategy in high-risk genetic samples to enhance the possibility of early detection of psychosis.

[Neurocognitive and psychiatric management of the 22q11.2 deletion syndrome]. / Perspectives actuelles dans la microdélétion 22q11.2 : prise en charge du phénotype neurocomportemental.

INTRODUCTION: The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22. 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). The inheritance of the syndrome (10%) is autosomal dominant. Most people with 22q11.2DS are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. A small percentage of affected individuals have shorter deletions in the same region (contiguous gene deletion syndrome). The general features of 22q11.2DS vary widely (more than 180 phenotypic presentations) and the syndrome is under diagnosed. Characteristic symptoms may include congenital heart disease, defects in the palate, neuromuscular problems, velo-pharyngeal insufficiency, hypoparathyroidism, craniofacial features and problems with the immune system T-cell mediated response (caused by hypoplasia of the thymus). COGNITIVE PHENOTYPE: The neurocognitive phenotype of the 22q11.2DS is complex. Cognitive deficits are seen in the majority (80-100%) of individuals with 22q11DS with impairments in sustained attention, executive function, memory and visual-spatial perception. Borderline intellectual function (IQ: 70-75) is most common, mild intellectual disability (IQ: 55-75) is slightly less frequent and a small percentage of children fall into the low average intelligence range. Most children with 22q11.2DS achieve higher scores in verbal tasks than in non-verbal tasks, although this pattern of dysfunction being not universal. Brain MRI studies have shown volumetric changes in multiple cortical and subcortical regions in individuals with 22q11DS that could be related to both cognition and psychoses. PSYCHIATRIC PHENOTYPE: General psychiatric features included anxiety disorders, attention deficit disorder and poor social skills (40-50%). An elevated risk of bipolar disorder and major depression occurs in adolescence and young adulthood. A strong and specific relationship exists between the presence of the 22q11.2 microdeletion and schizophrenia (30-40%). This risk is not associated with any other neurogenetic syndrome. Social cognition is impaired in 22q11.2 DS and this observation is correlated with psychotic features. So, long-term medical care is increasingly being directed towards the treatment and recognition of these symptoms. TREATMENT: Required pharmacological treatment strategies have to be adapted to the syndrome. Moreover, cognitive remediation is a promising tool for treating neuro- and social cognitive deficits in 22q11.2DS. However, these new therapeutic strategies have to be developed to improve quality of life.

Simplified gyral pattern in severe developmental microcephalies? New insights from allometric modeling for spatial and spectral analysis of gyrification.

The strong positive-allometric relationship between brain size, cortical extension and gyrification complexity, recently highlighted in the general population, could be modified by brain developmental disorders. Indeed, in case of brain growth insufficiency, the pathophysiological relevance of the "simplified gyral pattern" phenotype is strongly disputed since almost no genotype-phenotype correlations have been found in primary microcephalies. Using surface scaling analysis and newly-developed spectral analysis of gyrification (Spangy), we tested whether the gyral simplification in groups of severe microcephalies related to ASPM, PQBP1 or fetal-alcohol-syndrome could be fully explained by brain size reduction according to the allometric scaling law established in typically-developing control groups, or whether an additional disease effect was to be suspected. We found the surface area reductions to be fully explained by scaling effect, leading to predictable folding intensities measured by gyrification indices. As for folding pattern assessed by spectral analysis, scaling effect also accounted for the majority of the variations, but an additional negative or positive disease effect was found in the case of ASPM and PQBP1-linked microcephalies, respectively. Our results point out the necessity of taking allometric scaling into account when studying the gyrification variability in pathological conditions. They also show that the quantitative analysis of gyrification complexity through spectral analysis can enable distinguishing between even (predictable, non-specific) and uneven (unpredictable, maybe disease-specific) gyral simplifications.

Cortical folding in Broca's area relates to obstetric complications in schizophrenia patients and healthy controls.

BACKGROUND: The increased occurrence of obstetric complications (OCs) in patients with schizophrenia suggests that alterations in neurodevelopment may be of importance to the aetiology of the illness. Abnormal cortical folding may reflect subtle deviation from normal neurodevelopment during the foetal or neonatal period. In the present study, we hypothesized that OCs would be related to cortical folding abnormalities in schizophrenia patients corresponding to areas where patients with schizophrenia display altered cortical folding when compared with healthy controls. METHOD: In total, 54 schizophrenia patients and 54 healthy control subjects underwent clinical examination and magnetic resonance image scanning on a 1.5 T scanner. Information on OCs was collected from original birth records. An automated algorithm was used to calculate a three-dimensional local gyrification index (lGI) at numerous points across the cortical mantle. RESULTS: In both schizophrenia patients and healthy controls, an increasing number of OCs was significantly related to lower lGI in the left pars triangularis (p<0.0005) in Broca's area. For five other anatomical cortical parcellations in the left hemisphere, a similar trend was demonstrated. No significant relationships between OCs and lGI were found in the right hemisphere and there were no significant case-control differences in lGI. CONCLUSIONS: The reduced cortical folding in the left pars triangularis, associated with OCs in both patients and control subjects suggests that the cortical effect of OCs is caused by factors shared by schizophrenia patients and healthy controls rather than factors related to schizophrenia alone.

[Validation study of the French schizotypal personality questionnaire in a sample of adolescents: a confirmatory factor analysis]. / Validation de la version française du questionnaire de personnalité schizotypique de Raine dans la population adolescente : étude de la structure factorielle.

AIMS: This article aims to validate the schizotypal personality questionnaire in a sample of French speaking adolescents. Because early schizotypal manifestations are predictive of psychosis-proneness, reliable self-report measures are crucial for early detection of vulnerability to schizophrenia during adolescence. Unlike most existing self-reports, the questionnaire de personnalité schizotypique (SPQ) assesses individual differences in all nine feature of DSM-IV schizotypal personality (i.e. ideas of reference, excessive social anxiety, odd beliefs, unusual perceptual experience, odd behaviour, no close friends, odd speech, constricted affect and suspiciousness). Furthermore, it yields dimensional scores concerning the main schizotypal factors, which represent valuable information for the clinician's case formulation and can be used as a screening instrument in the general population. METHOD: Our sample consisted of 174 adolescents (98 girls) between 12 and 17 years old. All completed the SPQ 74-item self-report. Participants were recruited in secondary schools in Switzerland, and through the child and adolescent community outpatient psychiatric service (office médico-pédagogique) affiliated to the University of Geneva's Psychiatry Department and to the Canton of Geneva Education Department. A confirmatory factorial analysis was conducted on our sample to test nine competing models of SPQ. The 3-factor model of Raine et al. was compared to concurrent 2, 3, and 4-factor models. Simple structure models of Raine et al. and Stefanis et al. were also tested. RESULTS: The following observations were highlighted in our results: (1) goodness-of-fit indices are better for structures allowing cross loadings than for simple structures; (2) amongst the simple structures, the best goodness-of-fit index was obtained for the Raine model and (3) the fit between our data and the Raine model is improved by a cross loading for suspiciousness subscale. The latter seems problematic for the global data fitting. This led us to test simple structures models of Siever and Gunderson, Raine et al., and Stefanis et al., based on eight subscales rather than nine. Without suspiciousness subscale, goodness-of-fit indices are enhanced in these three models. The 3-factor model yields the clearest and most reliable results in comparison with other competing models. In summary, the best goodness-of-fit indices were obtained for the 3-factor Raine model. Goodness-of-fit indices could be improved by the exclusion of the suspiciousness scale. CONCLUSIONS: Consistent with earlier analyses by Raine et al. and Dumas et al., our data confirm the 3-factor model of the SPQ (cognitive-perceptive; interpersonal; disorganized) in a sample of French speaking adolescents. Our analyses confirm that two dimensions are insufficient to explain the structure of schizotypy during adolescence. These results further suggest the stability of a 3-factor structure during lifespan. We note that the inclusion of the suspiciousness subscales engenders statistical issues. Most studies to date have dealt with these issues by performing a cross-loading with this subscale, or by the inclusion of a paranoid factor which is linked with the negative and the cognitive-perceptive factors. We found that the most statistically sound strategy was reached without the inclusion of the suspiciousness subscale. Future studies with larger samples could investigate the SPQ structure at an item-level, which carries the benefit of reduced restrictions on the factorial analysis. In conclusion, the current study shows that the French version SPQ constitutes a reliable self-report questionnaire for the assessment of schizotypal trait expression during adolescence that may assist in the evaluation of psychosis proneness in youths.

[Time processing in the velo-cardio-facial syndrome (22q11) and its link with the caudate nucleus]. / Noyau caudé et traitement temporel dans le syndrome vélocardiofacial (22q11).

INTRODUCTION: Velocardiofacial syndrome (VCFS) is a neurogenetic disorder caused by a microdeletion on chromosome 22q11. Among other cognitive impairments and learning difficulties, affected individuals show difficulties in estimating time intervals (Debbané et al., 2005). Interestingly, neuroimaging studies have found an increased volume of the basal ganglia of people with VCFS (Eliez et al., 2002; Kates et al., 2004; Campbell et al., 2006). Given that the caudate nucleus represents a central component of the cerebral network underlying temporal perception skills, the present report proposes to examine potential relationships between cerebral alteration to the caudate nucleus and time estimation in individuals with VCFS. METHODS: A group of 30 patients with VCFS and 38 age-matched healthy individuals participated in time perception and time reproduction tasks. In the time perception task, individuals listened to two sequential stimuli and had to choose the longer of both stimuli by pressing a button. In the time reproduction task, subjects listened to a succession of sounds and once this succession had stopped they had to reproduce the same rhythm with their dominant index. Cerebral MRI images were also obtained for each participant. A manual tracing procedure was performed to measure the basal ganglia volume. RESULTS: Participants with VCFS demonstrated significantly poorer performances during the time perception and time reproduction tasks in comparison to the control participants. Further, increased volume of the caudate nucleus was found in individuals with VCFS. Correlational analyses revealed a significant relationship between the caudate nucleus's volume and the performances obtained in the time perception task for control participants. This correlation was not found for individuals with VCFS. CONCLUSION: The present results suggest that cerebral alterations to the caudate nucleus in VCFS may alter the temporal perception function it sustains.

[22q11.2 microdeletion]. / La microdélétion 22q11.2.

22q11.2 deletion syndrome (22q11DS), most frequently caused by a de novo microdeletion on the long arm of chromosome 22, is one of the most common neurogenetic syndromes. The cognitive and behavioral characteristics associated with the 22q11.2 phenotype can be quite heterogeneous, part of the reason the syndrome is often detected very late, if at all. Though in individuals with more severe cardiac, respiratory, or speech and language problems, 22q11DS is more easily detected at a young age. The cognitive profile in 22q11DS varies between borderline IQ and mild mental retardation. Less than half children have mental retardation but a majority suffer from learning difficulties. It is also typically characterized by a verbal-visual dissociation, with verbal abilities higher than visuo-spatial and abstract reasoning. Psychiatric comorbidity is also frequent in 22q11DS, and the presence of psychotic symptoms in pre-adolescence may be unique to the syndrome. In older adolescents and young adults, social withdrawal often becomes more intense and can be an indicator of psychiatric disorder. Neuroimaging studies in 22q11DS indicate different patterns of structural alterations in affected children and adults that directly relate to cognitive impairments in the syndrome. For these reasons, we believe that treatment of persons affected by 22q11DS should include periodic evaluations and frequent clinical check-ups that integrate recommendations for medical, speech, psychiatric, and academic problems.

Source monitoring for actions in adolescents with 22q11.2 deletion syndrome (22q11DS).

BACKGROUND: Source monitoring consists in identifying the origin of mental events. Recent research suggests that confusions over internally generated mental events may represent a cognitive marker for increased proneness to psychotic symptoms and disorders. We have examined source monitoring for actions in adolescents with the 22q11.2 deletion syndrome (22q11DS), a neurogenetic disease associated with high rates of schizophrenia during adulthood, and expected to observe source monitoring deficits in comparison to IQ-matched and typically developing controls. METHOD: Eighteen adolescents with 22q11DS, 17 adolescents matched for age and IQ, and also 17 adolescents matched for age participated in this study. Our adapted action monitoring paradigm asked subjects to visualize a series of actions in three different conditions: (1) visualize themselves performing the action; (2) visualize the experimenter performing the action; or (3) simply repeat the action statements without visualization of the action performer. RESULTS: The adolescents with 22q11DS performed adequately in terms of recognition (hits), but in comparison to both control groups, they committed more source confusions on correctly recognized items. Further examination revealed that the adolescents were more likely to demonstrate confusions between exterior sources in which the self was not involved. CONCLUSIONS: Source monitoring deficits can be observed in adolescents with 22q11DS, a syndrome putting them at high risk for developing schizophrenia. These deficits are discussed in terms of early cognitive processes associated with genetic risk for schizophrenia.

A multiple case study of verbal short-term memory in velo-cardio-facial syndrome.

BACKGROUND: Velo-cardio-facial syndrome (VCFS, 22q11.2 deletion) is characterized by severely delayed language development. The current study explored the integrity of verbal short-term memory (STM), a cognitive function critically involved in language development, in eight children with VCFS. METHODS: Using a multiple case study design, we presented a series of STM tasks exploring immediate serial recall for word and non-word lists to eight children with VCFS (aged 8-12 years) and to chronological-age-matched control groups. A first task assessed the integrity of phonological coding in verbal STM by comparing recall for phonologically similar and dissimilar words. Subsequently, the interaction between verbal knowledge and STM capacity was investigated by comparing recall for high- and low-imageability words, for high- and low-frequency words, and for words and non-words. A final task assessed short-term serial order recognition for digit sequences. RESULTS: When computing the number of items recalled in the word recall tasks, independently of their serial position, only one child presented consistent difficulties. Short-term recall of non-words was normal in each child. Phonological similarity and verbal knowledge influenced STM performance to a similar extent in children with VCFS and controls. On the other hand, when applying a strict serial recall criterion, difficulties with the word and non-word recall tasks were observed in most children. Half of the patients were also impaired in the serial order recognition task. CONCLUSIONS: Despite mild intellectual disability, it is possible for short-term retention capacities for verbal item information to be at an age-appropriate level in VCFS. However, STM for serial order information could be impaired more specifically.

[Psychiatry]. / Psychiatrie.

The main innovation of the year 2004 was the introduction of a new, second-generation antipsychotic drug with a new mechanism of action (partial dopamine agonist), encouraging first clinical results, and an advantageous clinical tolerance profile. Additionally, three new galenic forms are presented: an oral, extended-release form of methylphenidate that could be useful in the treatment of attention-deficit/hyperactivity disorders; an intramuscular depot form of a second-generation antipsychotic drug (risperidone) with the advantage of improving adherence; and an intramuscular form of a second generation antipsychotic (olanzapine) that is valuable in emergency situations. Finally, we will briefly give an update on the advantages of lamotrigine in bipolar depression.

Gray matter alteration in dyslexia: converging evidence from volumetric and voxel-by-voxel MRI analyses.

Affecting up to 4-10% of the population, dyslexia is a highly prevalent, childhood onset developmental disorder adversely influencing multiple domains of adaptive functioning throughout the lifespan. The present brain imaging study was conducted in order to investigate the neuroanatomical correlates of developmental dyslexia. The MRI brain scans of 10 males with dyslexia and 14 matched controls were analyzed with (1) a classical volumetric method measuring gray and white matter lobar volumes and (2) a voxel-by-voxel method. The voxel-by-voxel method identifies changes in tissue density and localizes morphologic alterations without limiting the analyses to predefined regions. Subsequent correlations between gray matter density and neuropsychological performance on specific phonological processing tasks (rhyme judgment) were conducted. Volumetric analyses revealed significantly reduced gray matter volumes in both temporal lobes in dyslexic individuals. The voxel-by-voxel analyses further localized changes to the left temporal lobe, revealing reduced gray matter density in the middle and inferior temporal gyri. Conversely, increased gray matter density was found in the precentral gyri bilaterally. As a combined group, the dyslexic and control subjects demonstrated positive correlations between performance on the rhyme judgment tasks and gray matter density in the middle and inferior frontal gyri, and the middle temporal gyri bilaterally. The current study indicates that dyslexia is associated with a structural gray matter deficit involving a complex fronto-temporal network implicated in phonological processing.