A case report of two male siblings with autism and duplication of Xq13–q21, a region including three genes predisposing for autism

Autism spectrum disorder, severe behaviour problems and duplication of the Xq12 to Xq13 region have recently been described in three male relatives. To describe the psychiatric comorbidity and dysmorphic features, including craniosynostosis, of two male siblings with autism and duplication of the Xq13 to Xq21 region, and attempt to narrow down the number of duplicated genes proposed to be leading to global developmental delay and autism. We performed DNA sequencing of certain exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed microarray analysis of the DNA. In addition to autism, the two male siblings exhibited severe learning disability, self-injurious behaviour, temper tantrums and hyperactivity, and had no communicative language. Chromosomal analyses were normal. Neither of the two siblings showed mutations of the sequenced exons known to produce craniosynostosis. The microarray analysis detected an extra copy of a region on the long arm of chromosome X, chromosome band Xq13.1–q21.1. Comparison of our two cases with previously described patients allowed us to identify three genes predisposing for autism in the duplicated chromosomal region. Sagittal craniosynostosis is also a new finding linked to the duplication.     

Development and evaluation of the Communication over Language Barriers questionnaire (CoLB-q) in paediatric healthcare

Objective

To develop a valid and reliable questionnaire addressing the experiences of healthcare personnel of communicating over language barriers and using interpreters in paediatric healthcare.

Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring

During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers.Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by excessive androgen secretion and abnormal insulin activity and affects up to 17% of women worldwide (1). Women with PCOS are at an increased risk of developing symptoms of anxiety and depression. In fact, over 60% of women with PCOS are diagnosed with at least one psychiatric disorder, such as depression, anxiety, or an eating disorder (2). Suicide attempts have also been shown to be seven times more common in women with PCOS than in healthy controls (3). The mechanisms underlying the development of PCOS are poorly understood. Although a genetic basis for PCOS has been suggested, the intrauterine milieu might also affect the reproductive/endocrine function of a child born to a PCOS mother in a manner that is independent of genetic inheritance or sex. It is also known that daughters of mothers with PCOS are at increased risk of developing the syndrome and that sons tend to suffer from obesity and insulin resistance (4). Thus, it has been proposed that PCOS originates during fetal development and that this might be, in part, a result of maternal androgen excess (5).Maternal testosterone levels in humans have been shown to affect brain morphology and function (6) and to be correlated to neural development and mental function (7). There is evidence for a crucial role of the hippocampus and the amygdala in the development of anxiety and depression, and that these neural circuits are affected by fluctuations in sex steroids in humans and in rodents (8). We have previously demonstrated that continuous exposure to dihydrotestosterone (DHT) from puberty until adulthood in female rats down-regulates androgen receptor (AR) expression in the hypothalamus and induces anxiety-like behavior in female rats (9). The increased rates of anxiety disorders and disruptive behavioral disorders among children with genetically induced hyperandrogenism further indicate that androgen excess may contribute to a higher risk of psychopathology (10).During pregnancy, androgens are metabolized to estrogens by the placenta in women and by the ovaries in rodents. Thus, the effects of testosterone on pregnancy are partly mediated by estrogen (11). Women with PCOS exhibit high circulating androgen levels during pregnancy, which hypothetically could be related to the increased risk of mood disorders in their offspring (12).Here, we tested the hypothesis that an excess of androgens in dams during pregnancy may cause anxiety-like behavior in adult female and male offspring. We used the prenatal androgen (PNA) model, which mimics the elevation of androgens in women with PCOS during pregnancy (13). The phenotype of the PNA model in mice (14) and in rats (12) reflects reproductive and metabolic characteristics of lean women with PCOS. However, whether it reflects symptoms of anxiety (2) is unknown. We demonstrated that female PNA offspring exhibited increased anxiety-like behavior, which was prevented by blocking the AR during pregnancy, implicating AR-mediated signaling in mediating the altered behavior of PNA offspring. To understand the neuroanatomical distribution of sites affected by the PNA treatment we evaluated the gene expression of key steroid receptors [Ar, estrogen receptor-α (Erα), Erβ, and G protein-coupled estrogen receptor (Gper)] in the hypothalamus, hippocampus, and amygdala, brain areas known to be involved in the regulation of mood behavior in female offspring. The expression of the AR gene was selectively altered in the amygdala of the PNA offspring. We further show that subchronic testosterone exposure in adult females also reduced Ar expression in the amygdala. Because the amygdala is known to be involved in the regulation of mood behavior, we hypothesized that testosterone exerts an anxiogenic effect in the amygdala. We obtained support for this hypothesis by demonstrating that intra-amygdala testosterone microinjections resulted in anxiety-like behavior.     

Stability and Change of Psychopathology Symptoms Throughout Childhood and Adolescence

Child Psychiatry & Human Development - Assessing stability and change of children’s psychopathology symptoms can help elucidate whether specific behaviors are transient developmental...     

Incidence of scoliosis in cerebral palsy

Background and purpose — Surveillance of scoliosis in individuals with cerebral palsy (CP) is important for ensuring timely diagnosis and identification of curve progression. We analyzed the incidence of scoliosis in relation to age, sex, and gross motor function in a population-based cohort of individuals with CP.

Patients and methods — This was a prospective register study of all 1,025 individuals born 1990–2012 in southern Sweden (1.4 million inhabitants) in the Swedish surveillance program for CP, which included >95% of the total population of people with CP in the area. Annual clinical examinations and radiographic measurement of the Cobb angle of those with a moderate or severe scoliosis were registered. We determined the incidence of scoliosis related to age, sex, and the Gross Motor Function Classification System (GMFCS) level.

Results — The inclusion criteria were fulfilled by 962 individuals. The number of people (140/962) with scoliosis increased up to 20–25 years of age. The incidence of scoliosis was related to age and GMFCS level. In individuals at the lowest level of gross motor function (GMFCS V) scoliosis was seen in 10/131 before 5 years of age and at the age of 20 years 75% of these individuals had a Cobb angle ≥40°. No one in the highest level of motor function (GMFCS I) developed a Cobb angle ≥40°

Interpretation — Surveillance programs for scoliosis in CP should be based on age and GMFCS level and should be initiated at a young age and continued into adulthood.     

Daily life after moving into a care home--experiences from older people, relatives and contact persons

Aims and objectives. To describe older people's experiences of daily life at the care home after admittance with respect to their perceptions of participation in the decision to move. Furthermore, the aim was to study the experiences of their relatives and contact persons with respect to the daily life of the same residents. Background. When older persons move into a care home, the whole family often play an important part. Thus, it is interesting to study how newly admitted older people, their relatives and staff members experience daily life in a modern care home. Methods. Qualitative design. The participants comprised a purposive sample of 13 residents, recently admitted to a care home, 69–90 years old, both single living and married, both moving from their own homes and from different institutions. Interviews were carried out with the older people (n = 13), their relatives (n = 10) and contact persons (n = 11). Results. The majority of the residents reported satisfaction with care home living. The relatives were also satisfied, secure and appreciated the privacy and homely atmosphere of the flat. The disadvantage of one‐room flats was that the residents might have felt lonely. The relatives felt that the residents were bored, but few residents desired more activities, even if some of them longed for people to socialize with. For many older people, perhaps talking is the most important ‘activity’ at care homes. Concerning self‐determination, some residents did not find it satisfactory. Relevance to clinical practice. Staff members must pay attention to residents’ need to talk with people. For many older people, talking is perhaps the most important ‘activity’ at care homes. Nurses must safeguard residents’ self‐determination. When residents are in control of their lives, they may become satisfied with time.