Genetics and TS
In collaboration with the Tourette Syndrome Association International Consortium for Genetics (TSAICG), we are actively involved in identifying genes that cause susceptibility to TS. Initial results of these studies have identified a region on chromosome 2 that is associated with TS in families. We continue to pursue these studies in order to confirm the initial findings, and to identify new regions of interest along the genome.
Environment and TS
In conjunction with investigators at the Massachussetts General Hospital and in the UK, we are examining the relationship between tic disorders and the environment, including factors such as prenatal maternal smoking, birthweight, complications of pregnancy, etc. This study uses a cohort of children who were born in 1991 and 1992 in the United Kingdom and have been followed for many years (the Avon Longitudinal Study of Parents and Children, or ALSPAC). This work is based on previous studies, including some from our group, that suggest that some factors during pregnancy and delivery may contribute to the development of and/or severity of TS.
Clinical Presentations of TS
These studies focus on the variety of ways that tics and related symptoms can present in TS, and how this may relate to genetics, development, environment and culture. These studies confirm that TS is a complex disorder, with many associated symptoms. However, they also suggest that there may be subtypes of TS that may have different genetic or environmental causes. These studies are in the early phases, and there is still much more work to be done.
Neurocognitive Profiles in OCD
We have evidence from a previous study that individuals with compulsive hoarding, which is related to OCD and in some cases may be a subtype of OCD, have specific changes in neuropsychological profiles compared to individuals without hoarding, including problems with categorization, difficulties with working memory, and problems with attention. We are now extending that study and are investigating whether this profile is also seen in individuals with non-hoarding forms of OCD. This study includes obtaining neuropsychological, EEG-based, and neuroimaging (fMRI) profiles among individuals with non-hoarding OCD, unaffected family members (blood relatives), and healthy controls.
Genetics of OCD
Our genetic studies of OCD include genome-wide association studies (GWAS) in collaboration with the Obsessive Compulsive Foundation Genetics Collaborative (OCFGC), candidate gene studies in nuclear (small) families, and linkage studies in large, extended families from Costa Rica and the US. Genetic linkage analyses on our large families from Costa Rica implicate a region on chromosome 15 which has multiple brain expressed genes, including the ryanodine receptor 3. This region has also been implicated in other human and in mouse studies of compulsivity. We are now in the process of sequencing the entire genome of key individuals in these families, as well as expanding the existing families and collecting additional families to confirm the results.
We have also analyzed a large set of families from the US; these results are also very encouraging. We continue to collect individuals and families with OCD from the US for future studies, which will be needed to confirm any findings from the initial analyses.
Phenomenology and Genetic Epidemiology of OCD
These studies focus primarily on patterns of obsessive compulsive symptoms, both within OCD, and among individuals who may or may not have OCD, such as college or medical students. We have found that OC symptoms are present in relatively predictable patterns in the groups that we have studied, with most individuals having only a few OC symptoms, and a small proportion, including, but not limited to, those with OCD, having many symptoms. Along with others, we have also identified several specific types of OC symptoms, including contamination/cleaning symptoms, hoarding and related symptoms, taboo symptoms (sexual, aggressive and religious symptoms), doubting symptoms (including checking behaviors), and rituals/superstitious behaviors. Although most people with OCD will have many types of symptoms, these specific symptom types do tend to run in families, and may be useful for identifying specific susceptibility genes for OCD.
Ultimately, we hope to identify factors that predict both susceptibility to depression and anxiety, as well as factors that are related to protection from depression and anxiety (i.e., resilience). Preliminary work in over 150 school children suggests a strong relationship between low psychological resilience and clinially significant anxiety. Additional work to confirm and extend these findings is ongoing.
Genetics of CH
Our group and others have shown that CH runs in families, and that it most likely has a genetic etiology. However, genes for CH have not yet been identified. Our genetic studies of CH are ongoing, and are currently focused on studies of families who have individuals affected with CH or OCD or both. We have collected an initial set of families from Costa Rica and the US and are currently conducting genetic analysis, but are still recruiting families for this study.
Neurocognitive profiles in CH
We have evidence that individuals with CH have specific differences in neuropsychological profiles from individuals without CH, including problems with categorization, difficulties with working memory, and problems with attention. We are continuing our examination of the neuropsychological, EEG-based, and neuroimaging (fMRI) profiles among individuals with CH, individuals with non-hoarding OCD, unaffected family members of these groups, and healthy controls. We are now recruiting for participation in this study.
CH and quality of life
In the context of a study of depression in older individuals, and in conjunction with colleagues at UCSF, we are examining the relationship between quality of life, physical disability, and psychiatric disability to CH. These analyses are ongoing.
CH and ADHD
We have recently completed a study (published in the journal Depression and Anxiety) examining the overlap between CH and ADHD, and have found that ADHD symptoms are very prevalent among people with CH. In our sample of individuals with OCD, 34% of those with CH had ADHD, and another 5% had ADHD symptoms but did not meet all of the requirements for a diagnosis. This is compared to the population prevalence for ADHD of 6%.
Clinical and Phenomenological Studies
In addition to examining the rate of other psychiatric disorders in ADHD families, we are interested in the intersection between ADHD and anxiety disorders such as OCD, and between ADHD and compulsive hoarding. Our studies have shown that the rates of ADHD among OCD-affected individuals are higher than the rates of ADHD in the general population, and that in these individuals, ADHD is associated with the presence of clinically significant compulsive hoarding behaviors. We are planning to further pursue this finding, both in ADHD-affected families and individuals, and in OCD-affected families and individuals, to determine the precise nature of the relationship between ADHD,OCD, and compulsive hoardin (i.e., whether ADHD is secondary to the presence of OCD or compulsive hoarding, whether these disorders are caused by the same gene(s), or whether there other factors that lead to an increased rate of ADHD in OCD and CH).
We are collecting neuropsychological information, including measures of memory, attention, and processing speed, among others, in the ADHD families in Costa Rica. Previous evidence has suggested that ADHD-affected individuals and their family members may have specific neuropsychological patterns, and that these patterns may be useful for genetic studies. We are examining the neuropsychological profiles of the participants in our ADHD studies to see whether there are identifiable patterns within ADHD families. We are also interested in how these patterns relate to the presence or absence of other psychiatric disorders, such as mood and anxiety disorders, in these families.
Our genetic studies of ADHD are ongoing, and are in collaboration with the ADHD Molecular Genetics Network. We expect to begin the genetic analysis of 200 ADHD families from the CVCR within the year.
We will be recruiting 500 people working in a healthcare setting (e.g., physicians, nurses, medical students, residents, housekeeping staff, sitters, clerical staff, respiratory therapists, physical therapists, social workers, etc.) from healthcare systems across the US. Participants will complete an online screening once a month for eight months which probes COVID-19 trauma exposure, temperament, and psychopathological symptomology. The effects of temperament and coping on the developmental trajectory and nature of psychopathological disorder will be investigated. The development of this online screening will be useful in future research investigating not only pandemic-related stress, but traumatic exposure occurring in any stressful context.