Clinical features of psychotic disorders and polymorphisms in HT2A, DRD2, DRD4, SLC6A3 (DAT1), and BDNF:a family based association study

Schizophrenia is clinically heterogeneous and multidimensional, but it is not known whether this is due to etiological heterogeneity. Previous studies have not consistently reported association between any specific polymorphisms and clinical features of schizophrenia, and have primarily used case-control designs. We tested for the presence of association between clinical features and polymorphisms in the genes for the serotonin 2A receptor (HT2A), dopamine receptor types 2 and 4, dopamine transporter (SLC6A3), and brain-derived neurotrophic factor (BDNF). Two hundred seventy pedigrees were ascertained on the basis of having two or more members with schizophrenia or poor outcome schizoaffective disorder. Diagnoses were made using a structured interview based on the SCID. All patients were rated on the major symptoms of schizophrenia scale (MSSS), integrating clinical and course features throughout the course of illness. Factor analysis revealed positive, negative, and affective symptom factors. The program QTDT was used to implement a family-based test of association for quantitative traits, controlling for age and sex. We found suggestive evidence of association between the His452Tyr polymorphism in HT2A and affective symptoms (P = 0.02), the 172-bp allele of BDNF and negative symptoms (P = 0.04), and the 480-bp allele in SLC6A3 (= DAT1) and negative symptoms (P = 0.04). As total of 19 alleles were tested, we cannot rule out false positives. However, given prior evidence of involvement of the proteins encoded by these genes in psychopathology, our results suggest that more attention should be focused on the impact of these alleles on clinical features of schizophrenia.

A systematic review and meta-analysis of the ethnic density effect in psychotic disorders

A number of studies have found an ethnic density effect in psychotic disorders, where the incidence for ethnic minorities increases as the neighbourhood proportional ethnic composition decreases [Morgan and Hutchinson, Psychol Med 40:705-709, (2010); Singh, Psychol Med 39:1402-1403, (2009); Schofield et al., Psychol Med 41:1263-1269, (2010)]. However, there is a mixed picture with some studies reporting no effect [Schofield et al., Psychol Med 41:1263-1269, (2010)]. This review aimed to establish the existence of the effect by answering the review question: is there an ethnic density dose effect in the prevalence of psychotic disorders?

Task-switching deficits and repetitive behaviour in genetic neurodevelopmental disorders: Data from children with Prader-Willi syndrome chromosome 15 q11-q13 deletion and boys with Fragile X syndrome

Prader-Willi syndrome (PWS) and Fragile X syndrome (FraX) are associated with distinctive cognitive and behavioural profiles. We examined whether repetitive behaviours in the two syndromes were associated with deficits in specific executive functions. PWS, FraX, and typically developing (TD) children were assessed for executive functioning using the Test of Everyday Attention for Children and an adapted Simon spatial interference task. Relative to the TD children, children with PWS and FraX showed greater costs of attention switching on the Simon task, but after controlling for intellectual ability, these switching deficits were only significant in the PWS group. Children with PWS and FraX also showed significantly increased preference for routine and differing profiles of other specific types of repetitive behaviours. A measure of switch cost from the Simon task was positively correlated to scores on preference for routine questionnaire items and was strongly associated with scores on other items relating to a preference for predictability. It is proposed that a deficit in attention switching is a component of the endophenotypes of both PWS and FraX and is associated with specific behaviours. This proposal is discussed in the context of neurocognitive pathways between genes and behaviour.

Psychosocial, educational and communicative interventions for patients with cachexia and their family carers

Purpose of review: Cancer cachexia has a substantial impact on both patients and their family carers. It has been acknowledged as one of the two most frequent and devastating problems of advanced cancer. The impact of cachexia spans biopsychosocial realms. Symptom management in cachexia is fraught with difficulties and globally, there remains no agreed standard care or treatment for this client group. There is a need to address the psychosocial impact of cachexia for both patients and their family carers.

Recent findings: Patients living at home and their family carers are often left to manage the distressing psychosocial impacts of cancer cachexia themselves. Successful symptom management requires healthcare professionals to address the holistic impact of cancer cachexia. High quality and rigorous research details the existential impact of cachexia on patients and their family carers. This information needs to inform psychosocial, educational and communicative supportive healthcare interventions to help both patients and their family carers better cope with the effects of cachexia.

Summary: Supportive interventions need to inform both patients and their family carers of the expected impacts of cachexia, and address how to cope with them to retain a functional, supported family unit who are informed about and equipped to care for a loved one with cachexia.

Evidence-based management and intervention for autism spectrum disorders

Autism Spectrum Disorder (ASD) is diagnosed along a continuum of behavioural variants in social communication and repetitive behaviours [96]. Most individuals on the autism spectrum also experience differences in sensory perception. Some individuals on the spectrum are ‘high-functioning’ and able to cope in every day environments, while others are severely affected, non-verbal, and may have co-occurring diagnoses, such as intellectual disability, epilepsy, and/or obsessional, conduct, or mental health disorders. These individuals require substantial support, caring and careful management, and evidence-based, effective interventions.

Proposed role for COUP-TFII in regulating fetal Leydig cell steroidogenesis, perturbation of which leads to masculinization disorders in rodents

Reproductive disorders that are common/increasing in prevalence in human males may arise because of deficient androgen production/action during a fetal 'masculinization programming window'. We identify a potentially important role for Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) in Leydig cell (LC) steroidogenesis that may partly explain this. In rats, fetal LC size and intratesticular testosterone (ITT) increased ~3-fold between e15.5-e21.5 which associated with a progressive decrease in the percentage of LC expressing COUP-TFII. Exposure of fetuses to dibutyl phthalate (DBP), which induces masculinization disorders, dose-dependently prevented the age-related decrease in LC COUP-TFII expression and the normal increases in LC size and ITT. We show that nuclear COUP-TFII expression in fetal rat LC relates inversely to LC expression of steroidogenic factor-1 (SF-1)-dependent genes (StAR, Cyp11a1, Cyp17a1) with overlapping binding sites for SF-1 and COUP-TFII in their promoter regions, but does not affect an SF-1 dependent LC gene (3β-HSD) without overlapping sites. We also show that once COUP-TFII expression in LC has switched off, it is re-induced by DBP exposure, coincident with suppression of ITT. Furthermore, other treatments that reduce fetal ITT in rats (dexamethasone, diethylstilbestrol (DES)) also maintain/induce LC nuclear expression of COUP-TFII. In contrast to rats, in mice DBP neither causes persistence of fetal LC COUP-TFII nor reduces ITT, whereas DES-exposure of mice maintains COUP-TFII expression in fetal LC and decreases ITT, as in rats. These findings suggest that lifting of repression by COUP-TFII may be an important mechanism that promotes increased testosterone production by fetal LC to drive masculinization. As we also show an age-related decline in expression of COUP-TFII in human fetal LC, this mechanism may also be functional in humans, and its susceptibility to disruption by environmental chemicals, stress and pregnancy hormones could explain the origin of some human male reproductive disorders.