Serotonin system genes and obsessive-compulsive trait dimensions in a population-based, pediatric sample: a genetic association study.

BACKGROUND: Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. METHODS: Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. RESULTS: The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6). CONCLUSIONS: This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group.

GnRH expression and cell proliferation are associated with seasonal breeding and food hoarding in Mongolian gerbils (Meriones unguiculatus).

Seasonal brain plasticity contributes to a variety of physiological and behavioral processes. We hypothesized that variations in GnRH expression and cell proliferation facilitated seasonal breeding and food hoarding. Here, we reported seasonal changes in sexual and social behavior, GnRH expression and brain cell proliferation, and the role of photoperiod in inducing seasonal breeding and brain plasticity in Mongolian gerbils (Meriones unguiculatus). The gerbils captured in April and July had more mature sexual development, higher exploratory behavior, and preferred novelty much more than those captured in September. Male gerbils captured in April and July had consistently higher GnRH expression than those captured in September. GnRH expression was also found to be suppressed by food-induced hoarding behavior in the breeding season. Both subadult and adult gerbils from April and July had higher cell proliferation in SVZ, hypothalamus and amygdala compared to those in September. However, adult gerbils captured in September preferred familiar objects, and no seasonal differences were found in cell proliferation in hippocampal dentate gyrus among the three seasons. The laboratory study showed that photoperiod alone did not alter reproductive traits, behavior, cell proliferation or cell survival in the detected brain regions. These findings suggest that the structural variations in GnRH expression in hypothalamus and cell proliferation in hypothalamus, amygdala and hippocampus are associated with seasonal breeding and food hoarding in gerbils. It gives a new insight into the proximate physiological and neural basis for these seasonal life-history traits of breeding and food hoarding in small mammals.

Animal hoarding: The challenge for mental health, law enforcement, and animal welfare professionals.

Animal hoarding has been considered a significant problem by animal welfare and law enforcement professionals for over a century. However, it has only been recognized as an indication of a mental disorder in the last decade. I review the different forms that animal hoarding can take and the current understanding of the prevalence, demographics and possible etiology of this disorder. Conventional animal cruelty laws have often been inadequate to respond to animal hoarding cases until they reach levels that may involve serious harm to animals and people. I document how prosecution of such cases can be difficult and often does not adequately consider the mental health issues underlying the problem or the high likelihood of recidivism. Attempts to solve these problems by enacting new laws specifically addressing animal hoarding have been controversial and ineffective. I explore new approaches that coordinate a variety of community resources in response to hoarding cases that offer the best opportunity to respond to both the human and animal problems associated with animal hoarding.

A novel PSEN1 (S230N) mutation causing early-onset Alzheimer's Disease associated with prosopagnosia, hoarding, and Parkinsonism.

We describe clinical and biomarker findings in an index patient with the onset of Alzheimer's disease (AD) symptoms at age 57 and a family history consistent with an autosomal dominant pattern of inheritance. She had the atypical early features of visual agnosia and prosopagnosia followed by hoarding behavior and Parkinsonism. Structural MRI revealed global atrophy that was most severe in the lateral temporal lobes and insular cortex bilaterally. CSF biomarker assessment showed Aß42, p-tau181, and total tau levels consistent with AD. Genetic assessment revealed a novel mutation in the PSEN1 gene (S230N) in the index patient and her affected brother which was absent in her two clinically unaffected and AD-biomarker negative sisters. The serine residue at codon 230 in PSEN1 is highly conserved across species and in PSEN2, providing strong evidence for its pathogenicity in this family.

Heritability of hoarding symptoms across adolescence and young adulthood: A longitudinal twin study.

BACKGROUND: Twin studies of hoarding symptoms indicate low to moderate heritability during adolescence and considerably higher heritability in older samples, suggesting dynamic developmental etiological effects. The aim of the current study was to estimate the relative contribution of additive genetic and environmental effects to hoarding symptoms during adolescence and young adulthood and to estimate the sources of stability and change of hoarding symptoms during adolescence. METHODS: Univariate model-fitting was conducted in three cohorts of twins aged 15 (n = 7,905), 18 (n = 2,495) and 20-28 (n = 6,218). Longitudinal analyses were conducted in a subsample of twins for which data on hoarding symptoms was available at both age 15 and 18 (n = 1,701). RESULTS: Heritability estimates for hoarding symptoms at ages 15, 18 and 20-28 were 41% (95% confidence interval [CI]: 36-45%), 31% (95% CI: 22-39%) and 29% (95% CI: 24-34%) respectively. Quantitative sex-differences emerged in twins aged 15 at which point the heritability in boys was 33% (95% CI: 22-41%) and 17% (95% CI: 0-36%) in girls. Shared environmental effects played a negligible role across all samples with the exception of girls aged 15 where they accounted for a significant proportion of the variance (22%; 95% CI 6-36%). The longitudinal bivariate analyses revealed a significant phenotypic correlation of hoarding symptoms between ages 15 and 18 (0.40; 95% CI: 0.36-0.44) and a strong but imperfect genetic correlation (0.75; 95% CI: 0.57-0.94). The bivariate heritability was estimated to 65% (95% CI: 50-79%). CONCLUSIONS: Hoarding symptoms are heritable from adolescence throughout young adulthood, although heritability appears to slightly decrease over time. Shared environmental effects contribute to hoarding symptoms only in girls at age 15. The stability of hoarding symptoms between ages 15 and 18 is largely explained by genetic factors, while non-shared environmental factors primarily have a time-specific effect. The findings indicate that dynamic developmental etiological effects may be operating across the life span.

On the evolution of hoarding, risk-taking, and wealth distribution in nonhuman and human populations.

This paper applies the theory of the evolution of risk-taking in the presence of idiosyncratic and environmental risks to the example of food hoarding by animals and explores implications of the resulting theory for human attitudes toward risk.