Association between serotonin 5-HT-2C receptor gene (HTR2C) polymorphisms and obesity- and mental health-related phenotypes in a large population-based cohort

OBJECTIVE: Studies have shown that common single-nucleotide polymorphisms (SNPs) in the serotonin 5-HT-2C receptor (HTR2C) are associated with antipsychotic agent-induced weight gain and the development of behavioural and psychological symptoms. We aimed to analyse whether variation in the HTR2C is associated with obesity- and mental health-related phenotypes in a large population-based cohort. METHOD: Six tagSNPs, which capture all common genetic variation in the HTR2C gene, were genotyped in 4978 men and women from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, an ongoing prospective population-based cohort study in the United Kingdom. To confirm borderline significant associations, the -759C/T SNP (rs3813929) was genotyped in the remaining 16 003 individuals from the EPIC-Norfolk study. We assessed social and psychological circumstances using the Health and Life Experiences Questionnaire. Genmod models were used to test associations between the SNPs and the outcomes. Logistic regression was performed to test for association of SNPs with obesity- and mental health- related phenotypes. RESULTS: Of the six HTR2C SNPs, only the T allele of the -759C/T SNP showed borderline significant associations with higher body mass index (BMI) (0.23 kg m(-2); (95% confidence interval (CI): 0.01-0.44); P=0.051) and increased risk of lifetime major depressive disorder (MDD) (Odds ratio (OR): 1.13 (95% CI: 1.01-1.22), P=0.02). The associations between the -759C/T and BMI and lifetime MDD were independent. As associations only achieved borderline significance, we aimed to validate our findings on the -759C/T SNP in the full EPIC-Norfolk cohort (n=20 981). Although the association with BMI remained borderline significant (beta=0.20 kg m(-2); 95% CI: 0.04-0.44, P=0.09), that with lifetime MDD (OR: 1.01; 95% CI: 0.94-1.09, P=0.73) was not replicated. CONCLUSIONS: Our findings suggest that common HTR2C gene variants are unlikely to have a major role in obesity- and mental health-related traits in the general population.

The Effect of Mental Health Problems on Children’s Ability to Discriminate Amongst Thoughts, Feelings and Behaviours

Many young children appear to have skills sufficient to engage in basic elements of cognitive behaviour therapy (CBT). Previous research has, however, typically used children from non-clinical populations. It is important to assess children with mental health problems on cognitive skills relevant to CBT and to compare their performance to children who are not identified as having mental health difficulties. In this study 193 6 and 7 year old children were assessed using a thought–feeling–behaviour discrimination task [Quakley et al. Behav. Res. Therapy 42 (2004) 343] and a brief IQ test (the WASI). Children were assigned to groups (at risk, borderline, low risk) according to ratings of their mental health made by their teachers and parents on the Strengths and Difficulties Questionnaire [Goodman, J. Am. Acad. Child Adolescent Psych. 40 (2001) 1337]. After controlling for IQ, children ‘at risk’ of mental health problems performed significantly less well than children with a ‘low risk’ of mental health problems. Before receiving CBT, children’s meta-cognitive development should be assessed and additional help provided to those with meta-cognitive difficulties.

Patterns of hominin occupation and cultural diversity across the Gebel Akhdar of Northern Libya over the last ~200 kyr

Excavations at Haua Fteah cave in Cyrenaica, Libya, have revealed a cultural sequence that may span the last glacial–interglacial-glacial cycle. The TRANS-NAP project has been re-excavating Haua Fteah and conducting geoarchaeological survey of an ecologically diverse landscape that includes the fertile Gebel Akhdar and littoral, pre-desert, and desert biomes. A major aim of this project is to characterize cultural and environmental changes across the region and correlate the surface archaeology with that from Haua Fteah. To date, 181 sites have been recorded, ranging from the Middle Stone Age (MSA) to Late Stone Age (LSA). Their geographic distribution suggests temporal variation in patterns of hominin habitat preference, with significantly more LSA than MSA sites at higher elevations. The surface archaeology also points to substantial spatiotemporal technological variation within the MSA. These patterns may be explained by both paleoenvironmental change and paleodemographic shifts in the region, resulting in a variety of hominin adaptive responses.