Hanna Swaab

Long-term cognitive and behavioral consequences of neonatal encephalopathy following perinatal asphyxia: a review

Neonatal encephalopathy (NE) following perinatal asphyxia (PA) is considered an important cause of later neurodevelopmental impairment in infants born at term. This review discusses long-term consequences for general cognitive functioning, educational achievement, neuropsychological functioning and behavior. In all areas reviewed, the outcome of children with mild NE is consistently positive and the outcome of children with severe NE consistently negative. However, children with moderate NE form a more heterogeneous group with respect to outcome. On average, intelligence scores are below those of children with mild NE and age-matched peers, but within the normal range. With respect to educational achievement, difficulties have been found in the domains reading, spelling and arithmetic/mathematics. So far, studies of neuropsychological functioning have yielded ambiguous results in children with moderate NE. A few studies suggest elevated rates of hyperactivity in children with moderate NE and autism in children with moderate and severe NE. Conclusion: Behavioral monitoring is required for all children with NE. In addition, systematic, detailed neuropsychological examination is needed especially for children with moderate NE.

Psychiatric Characteristics in a Self-Selected Sample of Boys With Klinefelter Syndrome

BACKGROUND. Klinefelter syndrome is the most frequent chromosomal aneuploidy with a prevalence of 1 in 700. Klinefelter syndrome has been widely associated with cognitive impairment and language problems. No previous studies have systematically investigated the association of Klinefelter syndrome with psychiatric disorders in children and adolescents. To our knowledge, the only data available are from psychiatric inventories of adults with Klinefelter syndrome. OBJECTIVE. To explore the extent of psychiatric morbidity in children with Klinefelter syndrome. METHOD. Fifty-one subjects with Klinefelter syndrome aged 6 to 19 years were included through the Dutch Klinefelter association and 2 university medical centers. The sample was screened by using structured and standardized assessment procedures covering the full range of psychiatric problems and disorders. In addition, all boys were formally evaluated for the presence of a language disorder. RESULTS. A wide range of classifications could be applied, with language disorder (65% [33 of 51]) as the most prevalent disorder, followed by attention-deficit disorders (63% [32 of 51]) and autism spectrum disorder (27% [14 of 51]). Behavioral impairment was most evident among cases classified as autism spectrum disorder and psychotic disorder (12% [6 of 51]). CONCLUSIONS. Children with Klinefelter syndrome seem to be at risk for problems in social and language development, as well as for problems in regulation of emotion and behavior. This is reflected in the broad spectrum of psychiatric classifications applicable in the present selected sample. Health care professionals should be aware of an increased a priori possibility of psychiatric problems when confronted with a child with Klinefelter syndrome.

Social Behavior and Autism Traits in a Sex Chromosomal Disorder: Klinefelter (47XXY) Syndrome

Although Klinefelter syndrome (47,XXY) has been associated with psychosocial difficulties, knowledge of the social behavioral phenotype is limited. We examined specific social abilities and autism traits in Klinefelter syndrome. Scores of 31 XXY men on the Scale for Interpersonal Behavior and the Autism Spectrum Questionnaire were compared to 24 and 20 control men respectively. XXY men reported increased distress during social interactions and less engagement in specific social behaviors. In the XXY group, levels of autism traits were significantly higher across all dimensions of the autism phenotype. These findings call for a clinical investigation of vulnerability to autism in Klinefelter syndrome. Klinefelter syndrome might serve as a model for studying a role of the X chromosome in social behavioral dysfunction and autism-like behavior.

X Chromosomal effects on social cognitive processing and emotion regulation: a study with Klinefelter men (47,XXY)

Studying Klinefelter syndrome (47,XXY), a genetically defined disorder characterized by the presence of an additional X chromosome, can reveal insights into genotype-phenotype associations. Increased vulnerability to psychiatric disorders characterized by difficulties in social interactions, such as schizophrenia and autism, has been reported for this population. The reported social difficulties in 47,XXY men may arise as a consequence of impairments in the processing of social and emotional information. The present study is the first investigation of social-emotional information processing in this X chromosomal disorder. 32 Klinefelter men and 26 men from the general population, with the groups matched for age, educational level and I.Q., participated in the study. Several tasks were included, reflecting aspects of social-emotional information processing on levels of perception, experience and expression: labeling of facial expressions of emotion, emotion-cognition interactions in decision making and emotion regulation, that refers to subjective experience and identification of emotional arousal as well as verbal expression of emotions. A discrepancy between cognitive appraisal of emotions and emotional arousal was observed in Klinefelter syndrome. Taken together, Klinefelter men seem less accurate in perception of socio-emotional cues such as angry facial expressions, they are less able to identify and verbalize their emotions, but experience increased levels of emotional arousal, in comparison to the general population. Besides describing the social-emotional phenotype of this X chromosomal disorder, the present data may prove to be an important contribution to the development of more general models describing pathways to neuropsychiatric disorders characterized by social cognitive disturbances.

Psychiatric morbidity and X-chromosomal origin in a Klinefelter sample

The presence of an additional X-chromosome in Klinefelter patients provides an opportunity to study the influence of this chromosome on psychiatric disorders. Previous studies have reported an excess of Klinefelter patients in psychiatric patient groups. We report an increased prevalence of psychiatric disorders including psychotic disorders in a sample of Klinefelter patients but could not find evidence of an effect of the parental origin of the extra X-chromosome on the psychiatric phenotype. Nevertheless, these findings provide further support for the role of the X-chromosome in the susceptibility to psychiatric disorders in general and psychotic disorders in particular.

Overlap of autistic and schizotypal traits in adolescents with Autism Spectrum Disorders

This study addresses the unraveling of the relationship between autism spectrum and schizophrenia spectrum traits in a population of adolescents with Autism Spectrum Disorders (ASD). Recent studies comparing isolated symptoms of both spectrum disorders as well as diagnostic criteria for each (DSM-IV-TR) suggest resemblances in the clinical phenotype. A group of 27 adolescents with ASD (11 to 18 years) and 30 typically developing adolescents, matched for age and gender, participated in this study. Within the ASD group 11 adolescents satisfied DSM-IV-TR criteria for schizotypal personality disorders. Autistic and schizotypal traits were identified by means of well validated questionnaires (Autism Questionnaire, AQ and Schizotypal Personality Questionnaire-Revised, SPQ). Significantly more schizotypal traits in adolescents with ASD were found than in typically developing controls. Besides high levels of negative symptoms, adolescents with ASD also displayed high levels of positive and disorganized symptoms. There appeared to be a relationship between the mean level of autistic symptoms and schizotypal traits, as well as specific associations between autistic symptoms and negative, disorganized and positive schizotypal symptoms within individuals. Schizotypal symptomatology in all sub dimensions that are reflected by the SPQ scores, was most prominently associated with attention switching problems of the autism symptoms from the AQ. These findings indicate that patients diagnosed with an ASD show schizophrenia spectrum traits in adolescence. Although other studies have provided empirical support for this overlap in diagnostic criteria between both spectrum disorders, the present findings add to the literature that behavioral overlap is not limited to negative schizotypal symptoms, but extends to disorganized and positive symptoms as well.

Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes

Background The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetically more homogeneous ASD groups are associated with decreased phenotypic heterogeneity with respect to their autistic symptom profile. Methodology The autistic phenotypes of ASD subjects with 22q11 deletion syndrome (22q11DS) and ASD subjects with Klinefelter Syndrome (KS) were statistically compared to the symptom profile of a large (genetically) heterogeneous ASD sample. Autism diagnostic interview-revised (ADI-R) variables were entered in different statistical analyses to assess differences in symptom homogeneity and the feasibility of discrimination of group-specific ASD-symptom profiles. Principal Findings The results showed substantially higher symptom homogeneity in both the genetic disorder ASD groups in comparison to the heterogeneous ASD sample. In addition, a robust discrimination between 22q11-ASD and KS-ASD and idiopathic ASD phenotypes was feasible on the basis of a reduced number of autistic scales and symptoms. The lack of overlap in discriminating subscales and symptoms between KS-ASD and 22q11DS-ASD suggests that their autistic symptom profiles cluster around different points in the total diagnostic space of profiles present in the general ASD population. Conclusion The findings of the current study indicate that the clinical heterogeneity of ASDs may be reduced when subgroups based on a specific genotype are extracted from the idiopathic ASD population. The current strategy involving the widely used ADI-R offers a relatively straightforward possibility for assessing genotype-phenotype ASD relationships. Reverse phenotype strategies are becoming more feasible, given the accumulating evidence for the existence of genetic variants of large effect in a substantial proportion of the ASD population.

Pathways to psychosis: a comparison of the pervasive developmental disorder subtype Multiple Complex Developmental Disorder and the "At Risk Mental State".

BACKGROUND The comparison of high-risk populations with different developmental pathways to psychosis may lend more insight into the heterogeneity of the manifestation of the psychotic syndrome, and possible differing etiological pathways. AIM To compare high-risk traits and symptoms in two populations at risk for psychosis, i.e. (1) help-seeking adolescents presenting with prodromal symptoms meeting the criteria for At Risk Mental State (ARMS), and (2) adolescents with Multiple Complex Developmental Disorder (MCDD), a PDD-NOS subtype characterized by severe, early childhood-onset deficits in affect regulation, anxieties, disturbed social relationships, and thought disorder. METHOD 80 ARMS- and 32 MCDD-adolescents (12-18 years) were compared on prodromal symptoms (Structured Interview of Prodromal Symptoms, and Bonn Scale for the Assessment of Basic Symptoms-Prediction list), and autism traits (Social Communication Questionnaire). In addition, both high-risk groups were compared with 82 healthy controls on schizotypal traits (Schizotypal Personality Questionnaire-Revised). RESULTS Although the high-risk groups clearly differed in early developmental and treatment histories as well as autism traits, they did not differ with regard to schizotypal traits and basic symptoms, as well as disorganized and general prodromal symptoms. There were, however, group differences in positive and negative prodromal symptoms. Interestingly, 78% of the adolescents with MCDD met criteria for ARMS. CONCLUSION These findings suggest that children diagnosed with MCDD are at high risk for developing psychosis later in life, and support the notion that there are different developmental pathways to psychosis. Follow-up research is needed to compare the rates of transition to psychosis in both high-risk groups.

Misattribution of facial expressions of emotion in adolescents at increased risk of psychosis: the role of inhibitory control.

BACKGROUND By studying behavior, cognitive abilities and brain functioning in adolescents at high risk for psychosis, we can gain an insight into the vulnerability markers or protective factors in the development of psychotic symptoms. Although many high-risk studies have focused on impairments in neurocognitive functions, such as memory and attention, very few studies have investigated problems in processing social cues such as facial expressions as a possible vulnerability marker for psychosis. METHOD Thirty-six adolescents at ultra-high risk (UHR) for psychosis and 21 non-clinical controls completed a face recognition test, a facial affect labeling test and an inhibitory control test. Schizotypal traits and schizophrenia symptoms were assessed using a schizotypy questionnaire and the Positive and Negative Syndrome Scale (PANSS). RESULTS The UHR group showed impairments in labeling facial expressions of others, in addition to a spared ability to recognize facial identity. More specifically, the UHR group made more errors in labeling neutral expressions compared to the controls, and an analysis of error types indicated that neutral faces were misattributed as being angry. The degree of misattribution of neutral-as-angry faces correlated significantly with reduced inhibitory control. CONCLUSIONS Our findings suggest that misattributing social cues might contribute to vulnerability for psychosis. This social cognitive deficit may be related to problems in inhibitory control, which potentially plays an important role in the selection of appropriate social meaning. These findings may have relevance for understanding the mechanisms underlying prodromal social dysfunction, which should be targeted in future remediation interventions.

Associations between sleep characteristics, seasonal depressive symptoms, lifestyle, and ADHD symptoms in adults.

Objective: The authors explored associations between ADHD symptoms, seasonal depressive symptoms, lifestyle, and health. Method: Adult ADHD patients (n = 202) and controls (n = 189) completed the ASESA questionnaire involving lifestyle, eating pattern, and physical and psychological health, and validated measures on ADHD and sleep. ASESA is the Dutch acronym for Inattention, Sleep, Eating pattern, Mood, and General health questionnaire. Results: Indication for delayed sleep phase syndrome (DSPS) was 26% in patients and 2% in controls (p < .001). Patients reported shorter sleep, longer sleep-onset latency, and later midsleep. Shorter (R2 = .21) and later (R2 = .27) sleep were associated with hyperactivity, male gender, younger age, and seasonal depressive symptoms. Seasonal depressive symptoms were related to hyperactivity, female gender, unemployment, and late sleep (pseudo R2 = .28). Higher body mass index (BMI) was associated with shorter sleep in patients (ρ = −.16; p = .04) and controls (ρ = −.17; p = .02). Longer sleep showed lower odds for indication of metabolic syndrome (OR = −0.17; p = .053). Conclusion: DSPS is more prevalent in ADHD and needs further investigation to establish treatment to prevent chronic health issues.