[show abstract][hide abstract] ABSTRACT: The central theme of personalized medicine is the premise that an individual's unique physiologic characteristics play a significant role in both disease vulnerability and in response to specific therapies. The major goals of personalized medicine are therefore to predict an individual's susceptibility to developing an illness, achieve accurate diagnosis, and optimize the most efficient and favorable response to treatment. The goal of achieving personalized medicine in psychiatry is a laudable one, because its attainment should be associated with a marked reduction in morbidity and mortality. In this review, we summarize an illustrative selection of studies that are laying the foundation towards personalizing medicine in major depressive disorder, bipolar disorder, and schizophrenia. In addition, we present emerging applications that are likely to advance personalized medicine in psychiatry, with an emphasis on novel biomarkers and neuroimaging.
BMC Medicine 05/2013; 11(1):132. · 6.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: Obsessive compulsive disorder (OCD) is a syndrome characterized by recurrent and intrusive thoughts and ritualistic behaviors or mental acts that a person feels compelled to perform. Twin studies, family studies, and segregation analyses provide compelling evidence that OCD has a strong genetic component. The SLITRK1 gene encodes a developmentally regulated stimulator of neurite outgrowth and previous studies have implicated rare variants in this gene in disorders in the OC spectrum, specifically Tourette syndrome (TS) and trichotillomania (TTM). The objective of the current study was to evaluate rare genetic variation in SLITRK1 in risk for OCD and to functionally characterize associated coding variants. We sequenced SLITRK1 coding exons in 381 individuals with OCD as well as in 356 control samples and identified three novel variants in seven individuals. We found that the combined mutation load in OCD relative to controls was significant (p = 0.036). We identified a missense N400I change in an individual with OCD, which was not found in more than 1000 control samples (P<0.05). In addition, we showed the the N400I variant failed to enhance neurite outgrowth in primary neuronal cultures, in contrast to wildtype SLITRK1, which enhanced neurite outgrowth in this assay. These important functional differences in the N400I variant, as compared to the wildtype SLITRK1 sequence, may contribute to OCD and OC spectrum symptoms. A synonymous L63L change identified in an individual with OCD and an additional missense change, T418S, was found in four individuals with OCD and in one individual without an OCD spectrum disorder. Examination of additional samples will help assess the role of rare SLITRK1 variation in OCD and in related psychiatric illness.
PLoS ONE 01/2013; 8(8):e70376. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: The XVIIIth World Congress of Psychiatric Genetics, sponsored by The International Society of Psychiatric Genetics took place in Athens, Greece on October 3-7, 2010. Approximately 950 participants gathered to discuss the latest findings in this rapidly advancing field. The following report was written by junior travel awardees, as well as others who were volunteers from student meeting attendees. Each was assigned sessions as rapporteurs. This report represents some of the areas covered in oral presentation during the conference, and reports on some of the notable major new findings described at this 2010 World Congress of Psychiatric Genetics.
[show abstract][hide abstract] ABSTRACT: Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. Over 40 chromosomal loci have been identified for autosomal dominant, recessive, and X-linked HSP. Mutations in the genes atlastin, spastin and REEP1 are estimated to account for up to 50% of autosomal-dominant HSP and currently guide the molecular diagnosis of HSP. Here, we report the mutation screening results of 120 HSP patients from North America for spastin, atlastin, and REEP1, with the latter one partially reported previously. We identified mutations in 36.7% of all tested HSP patients and describe 20 novel changes in spastin and atlastin. Our results add to a growing number of HSP disease-associated variants and confirm the high prevalence of atlastin, spastin, and REEP1 mutations in the HSP patient population.
[show abstract][hide abstract] ABSTRACT: The XVII World Congress of Psychiatric Genetics, sponsored by The International Society of Psychiatric Genetics (ISPG) took place in San Diego, California from 4 to 8 November 2009. Approximately 550 participants gathered to discuss the latest molecular genetic findings relevant to serious mental illness, including schizophrenia, mood disorders, substance abuse, autism, and attention deficit disorder. Recent advances in the field were discussed, including the genome-wide association studies results, copy number variation (CNV) in the genome, genomic imaging, and large multicenter collaborations. The following report, written by junior travel awardees who were assigned sessions as rapporteurs represents some of the areas covered in oral presentation during the conference, and reports on some of the notable major new findings described at this 2009 World Congress of Psychiatric Genetics.
[show abstract][hide abstract] ABSTRACT: Teresa Zimmers and colleagues argue that it is difficult to conceive how lethal injection research activities could be carried out in a fashion consistent with ethical norms.
PLoS Medicine 07/2008; 5(6):e126. · 15.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the relative contribution and importance of five surgical specialties (general surgery, urology, otolaryngology, neurosurgery, and orthopedics) to the total National Institutes of Health (NIH) funding at medical schools.
Publicly available NIH funding data from 1996 to 2004 were analyzed.
From 1998 through 2003 the NIH budget increased from 11.2 billion to 21.9 billion dollars. Overall, NIH funding to departments of medicine was the greatest contributor to any individual medical school's total NIH funding, comprising 28.4% of total NIH awards on average, with a correlation coefficient highly predictive of medical school's ranking for NIH awards (cc = 0.93). Total NIH funding by different surgical specialties varied greatly, both within and between institutions. Together all of the surgical subspecialties combined accounted for 4.8% of medical school NIH awards on average from the years 1996 to 2004. Among the surgical specialties, general surgery received the largest fraction of NIH dollars followed by otolaryngology, neurosurgery, urology, and orthopedics. Although general surgery had the highest overall correlation coefficient of the surgical departments during the early years of the study period (r = 0.71 in 1996), its correlation significantly decreased during the period of study (as low as r = 0.54 in 2002).
Surgical departments as an aggregate have continued to receive a stable overall fraction of NIH awards. The total funding to the different surgical departments varies considerably between institutions and does not correlate well with total institutional funding. The downward trend in the correlation of general surgery funding to total institutional funding suggests a decline in support for surgical research in this specialty nationwide.
Journal of Surgical Research 08/2007; 141(1):16-21. · 2.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Obsessive-compulsive disorder (OCD) and the spectrum of associated conditions, affect 2-4% of the population worldwide. Although heritability studies in OCD have shown a 3 - 12 times increased risk for first degree relatives, the identification of the underlying risk-conferring genetic variation using classic genetic association studies has proven to be difficult. The possibility of a larger contribution of rare genetic variants to the risk of psychiatric disorder has been suggested by several successful studies. We expect that a spectrum of risk allele frequencies exists, which includes not only common variation but also a substantial amount of rare genetic variants that contribute to OCD. This thesis is aimed at identifying and functionally characterizing rare genetic variation in the OCD spectrum. Identified statistically significant variants were scrutinized for changes related to synaptic function using high content screening and subsequent functional analyses. Identifying the genetic profile of rare variants found in the OCD spectrum cohort combined with the functional impact that these variants have has provided insight into the etiology of the OCD spectrum. With these approaches a foundation can be laid for the development of a predictive model of the OCD spectrum.