Meta-analysis of genome-wide association studies of hoarding symptoms in 27,537 individuals.

Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,537 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26-48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a "gene discovery zone". To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.

Serotonin system genes and hoarding with and without other obsessive-compulsive traits in a population-based, pediatric sample: A genetic association study.

BACKGROUND: Hoarding, originally only considered a symptom of obsessive-compulsive disorder (OCD), is now categorized as a separate disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). We studied candidate serotonergic genes and the distinctness of hoarding in children and adolescents and hypothesized that unique gene variants would be associated with hoarding alone. METHODS: We examined obsessive-compulsive (OC) traits, including hoarding, in a total of 5,213 pediatric participants in the community. We genotyped candidate serotonin genes (5-HTTLPR polymorphism in SLC6A4 for 2,018 individuals and single nucleotide polymorphisms [SNPs] across genes SLC6A4, HTR2A, and HTR1B for 4,711 individuals). In a previous study conducted by our group in the same sample, we identified a significant association between 5-HTTLPR and hoarding in males. In this study, we examined hoarding more closely by testing the association between serotonin gene variants and hoarding traits with and without other accompanying OC traits. RESULTS: The [LG +S] variant in 5-HTTLPR was significantly associated with hoarding alone in males (p-value of 0.009). There were no significant findings for 5-HTTLPR in females. There were no significant findings after correction for multiple comparisons using SNP array data, but top SNP findings suggested that variation downstream of HTR1B may be implicated in hoarding alone in females. CONCLUSIONS: Our results suggest specific serotonin gene variants are associated with hoarding traits alone, differing between sexes. Top findings are in line with our former study, suggesting that individuals with hoarding alone were driving previous results. Our paper supports hoarding disorder's new designation.

A narrative synthesis of possible causes and risk factors of hoarding behaviours.

BACKGROUND: Hoarding is a disorder characterized by excessive acquisition and persistent difficulty in discarding possessions. The behaviour has adverse emotional, physical, social, financial, and legal outcomes for the person with the disorder and family members, and might pose a significant public health problem. Hoarding has been included as a distinct disorder in the Diagnostic and Statistical Manual of Mental Disorders Fifth edition (DSM-5). The prevalence of hoarding disorder is approximately 2-6% globally. The current state of the evidence does not offer clear understanding of the causes of hoarding behaviours. A systematic review of the extant literature was carried out to determine the possible causal factors of hoarding behaviours. METHODS: This review is conducted in line with PRISMA guidelines. The following electronic databases: Medline through Ovid, EMBASE and PsycINFO were searched for relevant articles published between January 2000 and November 2018. Only articles published in English language were included. Two reviewers independently scrutinized the studies and included them in this review. RESULTS: Our search strategy returned a total of 396 references. Preliminary findings suggest that individuals with hoarding behaviours may have a genetic susceptibility; abnormal neural activity in the fronto-temporal, para-hippocampal gyrus and insular parts of the brain has also been identified. Traumatic life experiences have also been posited to predispose individuals to hoard. CONCLUSION: Although the understanding of hoarding disorder hasgrown in recent years, greater efforts are still needed to clarify the etiology and mechanisms of hoarding disorder as these may help in planning of more holistic interventions to treat the problem.

Partitioning the etiology of hoarding and obsessive-compulsive symptoms.

BACKGROUND: Until recently, hoarding was considered an obsessive-compulsive symptom (OCS). However, current evidence suggests that these two phenotypes may be clinically, and perhaps etiologically, distinct. Both hoarding and OCS have a genetic etiology, but the degree of unique and shared genetic contributions to these phenotypes has not been well studied. METHOD: Prevalence rates were assessed for hoarding and OCS in a sample of adult twin pairs (n = 7906 twins) and their family members from The Netherlands Twin Register (total sample = 15,914). Using Mplus, genetic analyses using liability threshold models were conducted for both phenotypes, for their co-morbidity, and for specific hoarding symptoms (cluttering, discarding and acquiring). RESULTS: Of the total sample, 6.7% met criteria for clinically significant hoarding; endorsement of all three hoarding symptoms was > or = 79%. Men had slightly higher rates than women. Also, 5.7% met criteria for clinically significant OCS; rates were similar in males and females. Genetic factors accounted for 36% of the variance for hoarding and 40% of the variance for OCS. The genetic correlation between hoarding and OCS was 0.10. There was no evidence of sex-specific genetic contributions for hoarding or OCS. There was evidence for a genetic contribution to all hoarding symptom subtypes. Only cluttering showed evidence of a contribution from the shared environment. CONCLUSIONS: OCS and hoarding are common in this population-based sample, have prevalence rates similar to those previously reported, and show significant heritability. Genetic factors contributed to the co-morbidity of both traits, although the genetic correlation between them was low.

The structure of genetic and environmental risk factors for dimensional representations of DSM-5 obsessive-compulsive spectrum disorders.

IMPORTANCE: The new DSM-5 "Obsessive-Compulsive and Related Disorders" chapter contains a series of conditions thought to be etiologically related to obsessive-compulsive disorder (OCD). However, the evidence to support this relatedness remains incomplete. OBJECTIVE: To estimate the degree to which genetic and environmental risk factors are shared and/or unique to dimensionally scored OCD, body dysmorphic disorder (BDD), hoarding disorder (HD), trichotillomania (hair-pulling disorder) (TTM), and excoriation (skin-picking) disorder (SPD). DESIGN, SETTING, AND PARTICIPANTS: Multivariate twin modeling methods involving 5409 female members of the TwinsUK adult population-based twin register. MAIN OUTCOMES AND MEASURES: Scores on the Obsessive-Compulsive Inventory-Revised, the Dysmorphic Concern Questionnaire, the Hoarding Rating Scale, the Massachusetts General Hospital Hairpulling Scale, and the Skin Picking Scale. RESULTS: A 2-latent factor common pathway model fitted the data best; the first latent factor loaded on all 5 phenotypes, particularly on OCD, BDD, and HD. A second factor loaded exclusively on TTM and SPD. Disorder-specific genetic (for OCD, BDD, and HD only) and particularly nonshared environmental risk factors were also evident. Shared environmental influences were negligible. CONCLUSIONS AND RELEVANCE: Obsessive-compulsive and related disorders may be influenced by 2 distinct liability factors rather than a single liability factor. One of these factors was common to all disorders, and another was exclusive to TTM and SPD. Disorder-specific genetic factors unique to OCD, BDD, and HD were also apparent, whereas TTM and SPD were largely influenced by the same latent genetic factor. Environmental influences were largely disorder specific. The results help explain the apparent similarities as well as some important differences between the disorders included in the new Obsessive-Compulsive and Related Disorders chapter.

Prevalence, comorbidity and heritability of hoarding symptoms in adolescence: a population based twin study in 15-year olds.

BACKGROUND: Hoarding Disorder (HD) is often assumed to be an 'old age' problem, but many individuals diagnosed with HD retrospectively report first experiencing symptoms in childhood or adolescence. We examined the prevalence, comorbidity and etiology of hoarding symptoms in adolescence. METHODS: To determine the presence of clinically significant hoarding symptoms, a population-based sample of 15-year old twins (N = 3,974) completed the Hoarding Rating Scale-Self Report. Co-occurring Obsessive Compulsive Disorder (OCD), Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) were estimated from parental report. Model-fitting analyses divided hoarding symptom scores into additive genetic, shared, and non-shared environmental effects. RESULTS: The prevalence of clinically significant hoarding symptoms was 2% (95% CI 1.6-2.5%), with a significantly higher prevalence in girls than boys. Exclusion of the clutter criterion (as adolescents do not have control over their environment) increased the prevalence rate to 3.7% (95% CI 3.1-4.3%). Excessive acquisition was reported by 30-40% among those with clinically significant hoarding symptoms. The prevalence of co-occurring OCD (2.9%), ASD (2.9%) and ADHD (10.0%) was comparable in hoarding and non-hoarding teenagers. Model-fitting analyses suggested that, in boys, additive genetic (32%; 95% CI 13-44%) and non-shared environmental effects accounted for most of the variance. In contrast, among girls, shared and non-shared environmental effects explained most of the variance, while additive genetic factors played a negligible role. CONCLUSIONS: Hoarding symptoms are relatively prevalent in adolescents, particularly in girls, and cause distress and/or impairment. Hoarding was rarely associated with other common neurodevelopmental disorders, supporting its DSM-5 status as an independent diagnosis. The relative importance of genetic and shared environmental factors for hoarding differed across sexes. The findings are suggestive of dynamic developmental genetic and environmental effects operating from adolescence onto adulthood.

Overlap and specificity of genetic and environmental influences on excessive acquisition and difficulties discarding possessions: Implications for hoarding disorder.

A reluctance to discard items, leading to severely cluttered living spaces, is the landmark feature of hoarding disorder (HD). Many, but not all, individuals with HD also excessively acquire, buy or even steal items that they do not need and for which no space is available. In DSM-5, "excessive acquisition" can be coded as a specifier of HD. Despite their consistent co-occurrence, the question of whether excessive acquisition and difficulties discarding possessions share a common etiology remains unanswered. The current study sought to flesh out this relationship by examining the extent of shared genetic and environmental influences on the association between excessive acquisition and difficulties discarding in a community sample of adult, female twins. A total of 5,022 female twins (2,529 pairs; mean age = 55.5 years) completed a self-report measure of hoarding symptoms, including items assessing excessive acquisition and difficulties discarding. The data were analyzed using bivariate twin modeling methods in the statistical program Mx. As expected, we found a strong phenotypic correlation (0.63) between excessive acquisition and difficulty discarding items. Both traits were moderately heritable. The genetic correlation between the traits was estimated to be 0.77 (95% CI: 0.69-0.85), indicating a substantial but imperfect genetic overlap. The non-shared environmental correlation (0.50 [95% CI: 0.42-0.57]), though lower, was also significant. The findings demonstrate a substantial genetic, and more modest environmental, etiological overlap between the excessive acquisition of possessions and difficulties discarding them, providing a possible explanation for their frequent co-occurrence in HD. However, given that the etiological overlap is not perfect, unique etiological influences, particularly environmental, on each phenotype seem plausible.

Clinically significant hoarding in obsessive-compulsive disorder: results from an Indian study.

BACKGROUND: Hoarding is frequently conceptualized as a symptom of obsessive-compulsive disorder (OCD), but recent evidence indicates that, in most cases, hoarding may be better conceptualized as a distinct disorder that can coexist with OCD. Most of the research on hoarding is from the Western countries. This study aimed to provide data on the prevalence and correlates of clinically significant hoarding in a large sample of patients with OCD from the Indian subcontinent. METHODS: We examined 200 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition OCD for clinically significant hoarding using the Saving Inventory-Revised, followed by a clinical interview. RESULTS: Twenty patients (10%) had clinically significant hoarding. In all cases, hoarding did not appear to be related or secondary to other OCD symptoms. None of the cases consulted for their hoarding problems. Compared with nonhoarders, hoarders hailed exclusively from an urban background and had a significantly higher frequency of certain obsessions and compulsions, bipolar disorder, generalized anxiety disorder, cluster C personality disorders, and a higher number of lifetime suicidal attempts. They also had a more severe OCD along with poorer global functioning and somewhat poorer insight into obsessive-compulsive symptoms. CONCLUSIONS: The results suggest that clinically significant hoarding is relatively prevalent in Indian patients with OCD and that it appears to be largely unrelated to the OCD phenotype. However, the presence of comorbid hoarding is associated with more severe OCD, high comorbidity, more suicidal attempts, and a lower level of functioning. The results contribute to the current nosologic debate around hoarding disorder and provide a unique transcultural perspective.

Consideration of the BDNF gene in relation to two phenotypes: hoarding and obesity.

The gene coding for the brain derived neurotrophic factor (BDNF) has emerged as an interesting candidate for multiple brain and brain disorder-related phenomena. The primary aim of the present investigation was to consider the relationship between the BDNF Val66Met variant and two phenotypes: compulsive hoarding as a symptom dimension of obsessive-compulsive disorder (OCD), and body mass index (BMI). We examined the BDNF gene in a large (N=301) clinical sample of probands with OCD. Participants were classified as hoarding or nonhoarding using a strict, multimeasure grouping approach. Results revealed that the Val/Val genotype was linked with hoarding classification and more severe hoarding behaviors, as well as greater BMI levels. Hoarding status was also associated with greater BMI scores, with individuals in the hoarding group being far more likely to be classified as obese compared with the nonhoarding group. Our findings may provide a distinct avenue through which hoarding and BMI could be linked. These findings are suggestive of a complex gene, body weight, and psychopathology relationship wherein a primitive, survival "thrifty gene" strategy may be conserved and represented in a subgroup of humans manifesting severe hoarding symptoms.